belladonna alkaloids/phenobarbital (Rx)

Gastrointestinal Conditions (Off-label)

FDA has classified as "possibly" effective in the treatment of irritable bowel syndrome (irritable colon, spastic colon, mucous colitis), acute enterocolitis, and duodenal ulcer

Tablet: 1-2 tablets PO TID-QID

Extended release tablet: 1 tablet PO q12hr; may increase to q8hr if needed

Liquid: 5-10 mL PO TID-QID

Dosing considerations

Not shown conclusively whether anticholinergic/antispasmodic drug aid in the healing of a duodenal ulcer, decrease the rate of recurrences, or prevent complications

Irritable Bowel (Off-label)

4.5-9 kg: 0.5 mL PO q4hr OR 0.75 mL PO q6hr; individualize

9-13.5 kg: 1 mL PO q4hr OR 1.5 mL PO q6hr; individualize

13.5-22.6 kg: 1.5 mL PO q4hr OR 2 mL PO q6hr; individualize

22.7-34 kg: 2.5 mL PO q4hr OR 3.75 mL PO q6hr; individualize

34-45.4 kg: 3.75 mL PO q4hr OR 5 mL PO q6hr; individualize

> 45.4 kg: 5 mL PO q4hr OR 7.5 mL PO q6hr; individualize

High incidence of anticholinergic effects and uncertain effectiveness

Avoid except in short-term palliative care to decrease oral secretions

Contraindicated (34)

• artemether/lumefantrine

  phenobarbital will decrease the level or effect of artemether/lumefantrine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Coadministration with strong CYP3A4 inducers can result in decreased serum concentrations and loss of antimalarial efficacy

• atazanavir

  phenobarbital will decrease the level or effect of atazanavir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.

• cabotegravir

  phenobarbital will decrease the level or effect of cabotegravir by increasing metabolism. Contraindicated. Cabotegravir is metabolized by UGT1A1 and UGT1A9. Strong UGT1A1 or UGT1A9 inducers decrease cabotegravir systemic exposure, thereby increasing potential for loss of virologic response.

• calcium/magnesium/potassium/sodium oxybates

  phenobarbital, calcium/magnesium/potassium/sodium oxybates. Either increases effects of the other by pharmacodynamic synergism. Contraindicated. Prescribing information for sodium oxybate states coadministration with alcohol or insomnia drugs is contraindicated because of additive CNS depression.

• cariprazine

  phenobarbital will decrease the level or effect of cariprazine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. CYP3A4 is responsible for the formation and elimination of cariprazine's active metabolites. The effect of CYP3A4 inducers on cariprazine exposure has not been evaluated and the net effect is unclear.

• cobimetinib

  phenobarbital will decrease the level or effect of cobimetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Avoid coadministration. Strong or moderate CYP3A inducers may decrease cobimetinib systemic exposure by >80% and reduce its efficacy.

• darunavir

  phenobarbital will decrease the level or effect of darunavir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Coadministration with phenobarbital may result in loss of therapeutic effect and development of resistance to darunavir

• dienogest/estradiol valerate

  phenobarbital will decrease the level or effect of dienogest/estradiol valerate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Women should not choose estradiol valerate/dienogest as their contraceptive while using strong CYP3A4 inducers due to potential decrease in contraceptive efficacy. Estradiol valerate/dienogest should not be used for at least 28 days after discontinuation of the inducer due to possibility of decreased contraceptive efficacy.

• doravirine

  phenobarbital will decrease the level or effect of doravirine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Coadministration of doravirine with a strong CYP3A inducer may decrease doravirine plasma concentrations and/or effects. Potential for loss of virologic response and possible resistance to doravirine.

• elbasvir/grazoprevir

  phenobarbital will decrease the level or effect of elbasvir/grazoprevir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. The therapeutic effect of elbasvir/grazoprevir may be reduced if coadministered with strong CYP3A inducers and is therefore contraindicated.

• elvitegravir/cobicistat/emtricitabine/tenofovir DF

  phenobarbital decreases levels of elvitegravir/cobicistat/emtricitabine/tenofovir DF by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. May lead to loss of virologic response and possible resistance.

• etravirine

  phenobarbital decreases levels of etravirine by increasing metabolism. Contraindicated.

• fostemsavir

  phenobarbital will decrease the level or effect of fostemsavir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Coadministration of fostemsavir (prodrug) with strong CYP3A4 inducers significantly decreases temsavir (active moiety) plasma concentrations, which may lead to loss of virologic response and resistance.

• isavuconazonium sulfate

  phenobarbital will decrease the level or effect of isavuconazonium sulfate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.

• ledipasvir/sofosbuvir

  phenobarbital will decrease the level or effect of ledipasvir/sofosbuvir by P-glycoprotein (MDR1) efflux transporter. Contraindicated. P-gp inducers decrease sofosbuvir levels, and therefore decrease conversion to sofosbuvir's active metabolite (GS-331007) responsible for 90% of pharmacologic effect

• lonafarnib

  phenobarbital will decrease the level or effect of lonafarnib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Lonafarnib is a sensitive CYP3A4 substrate. Coadministration with strong or moderate CYP3A4 inducers is contraindicated.

• lorlatinib

  phenobarbital will decrease the level or effect of lorlatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Coadministration of lorlatinib with strong CYP3A inducers is contraindicated. Discontinue the strong CYP3A inducer for 3 plasma half-lives before initiating lorlatinib.

• lumacaftor/ivacaftor

  phenobarbital will decrease the level or effect of lumacaftor/ivacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Strong CYP3A inducers have minimal effect on lumacaftor exposure, but decreased ivacaftor exposure (AUC) by 57%. This may reduce the effectiveness of lumacaftor/ivacaftor. Therefore, coadministration is not recommended.

• lumefantrine

  phenobarbital will decrease the level or effect of lumefantrine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Coadministration with strong CYP3A4 inducers can result in decreased serum concentrations and loss of antimalarial efficacy

• lurasidone

  phenobarbital decreases levels of lurasidone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Contraindicated.

• mavacamten

  phenobarbital will decrease the level or effect of mavacamten by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.

• naloxegol

  phenobarbital will decrease the level or effect of naloxegol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Use of naloxegol with strong CYP3A4 inducers is not recommended

• nirmatrelvir

  phenobarbital will decrease the level or effect of nirmatrelvir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Nirmatrelvir, a CYP3A4 substrate, is contraindicated with strong CYP3A4 inducers. Significantly reduced nirmatrelvir plasma concentrations may be associated with potential for loss of virologic response and possible resistance. Do not initiate nirmatrelvir/ritonavir immediately after discontinuing a strong 3A4 inducer owing to time needed for systemic clearance of the inducer.

• nirmatrelvir/ritonavir

  phenobarbital will decrease the level or effect of nirmatrelvir/ritonavir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Nirmatrelvir, a CYP3A4 substrate, is contraindicated with strong CYP3A4 inducers. Significantly reduced nirmatrelvir plasma concentrations may be associated with potential for loss of virologic response and possible resistance. Do not initiate nirmatrelvir/ritonavir immediately after discontinuing a strong 3A4 inducer owing to time needed for systemic clearance of the inducer.

• ombitasvir/paritaprevir/ritonavir & dasabuvir (DSC)

  phenobarbital will decrease the level or effect of ombitasvir/paritaprevir/ritonavir & dasabuvir (DSC) by increasing metabolism. Contraindicated. Strong CYP2C8 inducers may reduce dasabuvir levels, and therefore decreased efficacy of Viekira Pak
  
  phenobarbital will decrease the level or effect of ombitasvir/paritaprevir/ritonavir & dasabuvir (DSC) by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Strong CYP3A4 inducers may reduce partiaprevir and ritonavir levels, and therefore decreased efficacy of Viekira Pak

• panobinostat

  phenobarbital decreases levels of panobinostat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Strong CYP3A4 inducers can reduce panobinostat levels by ~70% and lead to treatment failure.

• pirfenidone

  phenobarbital will decrease the level or effect of pirfenidone by affecting hepatic enzyme CYP1A2 metabolism. Contraindicated. Use of strong CYP1A2 inducers should be discontinued before initiating pirfenidone and avoided during treatment

• praziquantel

  phenobarbital decreases levels of praziquantel by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Strong CYP450 inducers significantly decrease praziquantel blood levels.

• regorafenib

  phenobarbital, regorafenib. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Strong CYP3A4 inducers decrease regorafenib levels and increase exposure of the active metabolite M-5.

• rilpivirine

  phenobarbital decreases levels of rilpivirine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Contraindicated. Rilpivirine should not be co-administered with strong CYP 3A4 inducers. Potential for loss of virologic response and possible resistance to rilpivirine or to the NNRTI class.

• roflumilast

  phenobarbital will decrease the level or effect of roflumilast by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Coadministration not recommended; strong cytochrome P450 enzyme inducers decrease systemic exposure to roflumilast and may reduce the therapeutic effectiveness
  
  phenobarbital will decrease the level or effect of roflumilast by affecting hepatic enzyme CYP1A2 metabolism. Contraindicated. Coadministration not recommended; strong cytochrome P450 enzyme inducers decrease systemic exposure to roflumilast and may reduce the therapeutic effectiveness

• sodium oxybate

  phenobarbital, sodium oxybate. Either increases effects of the other by pharmacodynamic synergism. Contraindicated. Prescribing information for sodium oxybate states coadministration with alcohol or insomnia drugs is contraindicated because of additive CNS depression.

• vandetanib

  phenobarbital decreases levels of vandetanib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Avoid coadministration with potent CYP3A4 inducers; these drugs reduce exposure to vandetanib by up to 40%.

• voriconazole

  phenobarbital decreases levels of voriconazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.

Serious - Use Alternative (168)

• abemaciclib

  phenobarbital will decrease the level or effect of abemaciclib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration of abemaciclib with strong CYP3A4 inducers reduces plasma concentration of abemaciclib and its metabolites.

• acalabrutinib

  phenobarbital will decrease the level or effect of acalabrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of acalabrutinib with strong CYP3A inducers. If a strong CYP3A inducer must be used, increase acalabrutinib dose to 200 mg twice daily.

• adagrasib

  phenobarbital will decrease the level or effect of adagrasib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
  
  adagrasib will increase the level or effect of phenobarbital by affecting hepatic enzyme CYP2C9/10 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of adagrasib, a CYP2C9 inhibitor, with sensitive CYP2C9 substrates unless otherwise recommended in the prescribing information for these substrates.

• afatinib

  phenobarbital decreases levels of afatinib by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug. Increase afatinib daily dose by 10 mg as tolerated if chronic therapy with P-gp inducer required; resume previous afatinib dose 2-3 days after P-gp inducer discontinued.

• alosetron

  phenobarbital will decrease the level or effect of alosetron by affecting hepatic enzyme CYP1A2 metabolism. Avoid or Use Alternate Drug.

• alpelisib

  phenobarbital will decrease the level or effect of alpelisib by pharmacodynamic synergism. Avoid or Use Alternate Drug. Avoid coadministration of alpelisib (CYP3A4 substrate) with strong CYP3A4 inducers.
  
  phenobarbital will decrease the level or effect of alpelisib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• antithrombin alfa

  phenobarbital decreases effects of antithrombin alfa by increasing metabolism. Avoid or Use Alternate Drug.

• antithrombin III

  phenobarbital decreases effects of antithrombin III by increasing metabolism. Avoid or Use Alternate Drug.

• apalutamide

  apalutamide will decrease the level or effect of phenobarbital by affecting hepatic enzyme CYP2C19 metabolism. Avoid or Use Alternate Drug. Coadministration of apalutamide, a strong CYP2C19 inducer, with drugs that are CYP2C19 substrates can result in lower exposure to these medications. Avoid or substitute another drug for these medications when possible. Evaluate for loss of therapeutic effect if medication must be coadministered.

• apixaban

  phenobarbital will decrease the level or effect of apixaban by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.

• apremilast

  phenobarbital will decrease the level or effect of apremilast by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration with strong CYP inducers results in a significant decrease of systemic exposure of apremilast, which may result in loss of efficacy

• argatroban

  phenobarbital decreases effects of argatroban by increasing metabolism. Avoid or Use Alternate Drug.

• avapritinib

  phenobarbital will decrease the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• axitinib

  phenobarbital decreases levels of axitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Selection of concomitant medication with no or minimal CYP3A4 induction potential is recommended.

• bedaquiline

  phenobarbital will decrease the level or effect of bedaquiline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of bedaquiline with strong CYP3A4 inducers due to potential for decreased therapeutic effect

• bemiparin

  phenobarbital decreases effects of bemiparin by increasing metabolism. Avoid or Use Alternate Drug.

• benzhydrocodone/acetaminophen

  benzhydrocodone/acetaminophen, phenobarbital. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.
  
  benzhydrocodone/acetaminophen and phenobarbital both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• berotralstat

  phenobarbital decreases levels of berotralstat by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug.

• bictegravir

  phenobarbital will decrease the level or effect of bictegravir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration of strong CYP3A and UGT1A1 inducers can substantially decrease bictegravir plasma concentrations. This may result in the loss of therapeutic effect and development of resistance to bictegravir. Coadministration with another anticonvulsant should be considered.

• bivalirudin

  phenobarbital decreases effects of bivalirudin by increasing metabolism. Avoid or Use Alternate Drug.

• bosutinib

  phenobarbital decreases levels of bosutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Strong CYP3A4 inducers decreased bosutinib plasma concentration by ~85%.

• bremelanotide

  bremelanotide will decrease the level or effect of phenobarbital by Other (see comment). Avoid or Use Alternate Drug. Bremelanotide may slow gastric emptying and potentially reduces the rate and extent of absorption of concomitantly administered oral medications. Avoid use when taking any oral drug that is dependent on threshold concentrations for efficacy. Interactions listed are representative examples and do not include all possible clinical examples.

• brigatinib

  phenobarbital will decrease the level or effect of brigatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration with strong CYP3A4 inducers may decrease brigatinib efficacy.

• buprenorphine subdermal implant

  buprenorphine subdermal implant and phenobarbital both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• buprenorphine transdermal

  buprenorphine transdermal and phenobarbital both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• cabozantinib

  phenobarbital will decrease the level or effect of cabozantinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of cabozantinib with strong CYP3A4 inducers. If a strong CYP3A4 inducer is required, increase cabozantinib dose by 40 mg/day (Cometriq) or by 20 mg/day (Cabometyx). Resume previous dose 2-3 days after strong CYP3A4 inducer discontinued.

• capmatinib

  phenobarbital will decrease the level or effect of capmatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• ceritinib

  phenobarbital decreases levels of ceritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• cobicistat

  phenobarbital will decrease the level or effect of cobicistat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration is necessary, monitor for lack or loss of virologic response from cobicistat

• copanlisib

  phenobarbital will decrease the level or effect of copanlisib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of copanlisib with strong CYP3A4 inducers.

• dabigatran

  phenobarbital will decrease the level or effect of dabigatran by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug. Avoid coadministration. P-gp inducers reduce systemic exposure of dabigatran

• dabrafenib

  phenobarbital decreases levels of dabrafenib by increasing metabolism. Avoid or Use Alternate Drug. Strong CYP2C8 inducers may decrease dabrafenib levels.
  
  phenobarbital decreases levels of dabrafenib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• dalteparin

  phenobarbital decreases effects of dalteparin by increasing metabolism. Avoid or Use Alternate Drug.

• dantrolene

  phenobarbital will decrease the level or effect of dantrolene by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• daridorexant

  phenobarbital will decrease the level or effect of daridorexant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• darolutamide

  phenobarbital will increase the level or effect of darolutamide by Other (see comment). Avoid or Use Alternate Drug. Darolutamide is a P-gp and CYP3A4 substrate. Avoid coadminstration of darolutamide with combined P-gp and strong or moderate CYP3A4 inducers.

• deflazacort

  phenobarbital will decrease the level or effect of deflazacort by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of deflazacort with moderate or strong CYP3A4 inducers.

• dexlansoprazole

  phenobarbital will decrease the level or effect of dexlansoprazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• dihydroergotamine

  phenobarbital will decrease the level or effect of dihydroergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• dihydroergotamine intranasal

  phenobarbital will decrease the level or effect of dihydroergotamine intranasal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• dolutegravir

  phenobarbital will decrease the level or effect of dolutegravir by increasing metabolism. Avoid or Use Alternate Drug. Avoid coadministration; insufficient data to recommend dosage adjustment

• dronedarone

  phenobarbital will decrease the level or effect of dronedarone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• duloxetine

  phenobarbital will decrease the level or effect of duloxetine by affecting hepatic enzyme CYP1A2 metabolism. Avoid or Use Alternate Drug.

• duvelisib

  phenobarbital will decrease the level or effect of duvelisib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration with a strong CYP3A inducer decreases duvelisib area under the curve (AUC), which may reduce duvelisib efficacy.

• edoxaban

  phenobarbital will decrease the level or effect of edoxaban by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug. Avoid coadministration of edoxaban with potent P-gp inducers

• elacestrant

  phenobarbital will decrease the level or effect of elacestrant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• eliglustat

  phenobarbital will decrease the level or effect of eliglustat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Strong CYP3A inducers significantly decreases eliglustat exposure; coadministration not recommended

• elvitegravir

  phenobarbital will decrease the level or effect of elvitegravir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid; coadministration with CYP3A inducers may result in decreased plasma concentrations of elvitegravir and/or a concomitantly administered protease inhibitor and lead to loss of therapeutic effect and to possible resistance

• encorafenib

  phenobarbital will decrease the level or effect of encorafenib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• enoxaparin

  phenobarbital decreases effects of enoxaparin by increasing metabolism. Avoid or Use Alternate Drug.

• entrectinib

  phenobarbital will decrease the level or effect of entrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• enzalutamide

  phenobarbital will decrease the level or effect of enzalutamide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• erdafitinib

  phenobarbital will decrease the level or effect of erdafitinib by altering metabolism. Avoid or Use Alternate Drug. Avoid coadministration of strong CYP2C9 or CYP3A4 inducers with erdafitinib.

• ergotamine

  phenobarbital will decrease the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• erythromycin base

  phenobarbital will decrease the level or effect of erythromycin base by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• erythromycin ethylsuccinate

  phenobarbital will decrease the level or effect of erythromycin ethylsuccinate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• erythromycin lactobionate

  phenobarbital will decrease the level or effect of erythromycin lactobionate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• erythromycin stearate

  phenobarbital will decrease the level or effect of erythromycin stearate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• esomeprazole

  phenobarbital will decrease the level or effect of esomeprazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• eszopiclone

  phenobarbital will decrease the level or effect of eszopiclone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• ethinylestradiol

  phenobarbital will decrease the level or effect of ethinylestradiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. The efficacy of hormonal contraceptives may be reduced. Use of a nonhormonal contraceptive is recommended.

• everolimus

  phenobarbital will decrease the level or effect of everolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
  
  phenobarbital will decrease the level or effect of everolimus by P-glycoprotein (MDR1) efflux transporter. Contraindicated.

• fedratinib

  phenobarbital will decrease the level or effect of fedratinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Effect of coadministering a strong CYP3A4 inducer with fedratinib has not been studied.

• fexinidazole

  phenobarbital will increase the level or effect of fexinidazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. CYP450 inducers may significantly increase plasma concentrations of fexinidazole?s active metabolites: fexinidazole sulfoxide (M1) and fexinidazole sulfone (M2). M2 plasma concentrations associated with increased QT prolongation risks.

• finerenone

  phenobarbital will decrease the level or effect of finerenone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• flurazepam

  phenobarbital will decrease the level or effect of flurazepam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• fondaparinux

  phenobarbital decreases effects of fondaparinux by increasing metabolism. Avoid or Use Alternate Drug.

• fostamatinib

  phenobarbital will decrease the level or effect of fostamatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• ganaxolone

  phenobarbital will decrease the level or effect of ganaxolone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of ganaxolone with moderate or strong CYP3A4 inducers. If coadministration unavoidable, consider increasing ganaxolone dose; however, do not exceed maximum daily dose for weight.

• gilteritinib

  phenobarbital will decrease the level or effect of gilteritinib by Other (see comment). Avoid or Use Alternate Drug. Gilteritinib is a P-gp and CYP3A4 substrates. Coadministration of gilteritinib with a combined P-gp and strong CYP3A inducer decreases gilteritinib exposure and efficacy.

• glasdegib

  phenobarbital will decrease the level or effect of glasdegib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of glasdegib with strong CYP3A inducers.

• heparin

  phenobarbital decreases effects of heparin by increasing metabolism. Avoid or Use Alternate Drug.

• hydrocodone

  hydrocodone, phenobarbital. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.

• ibrutinib

  phenobarbital decreases levels of ibrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Strong CYP3A inducers decrease ibrutinib plasma concentrations by ~10-fold.

• idelalisib

  phenobarbital will decrease the level or effect of idelalisib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration; strong CYP3A4 inducers significantly decrease idelalisib systemic exposure

• infigratinib

  phenobarbital will decrease the level or effect of infigratinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• irinotecan

  phenobarbital will decrease the level or effect of irinotecan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• irinotecan liposomal

  phenobarbital will decrease the level or effect of irinotecan liposomal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• isocarboxazid

  isocarboxazid, phenobarbital. Other (see comment). Avoid or Use Alternate Drug. Comment: CNS depressants such as barbiturates should not be used in combination with isocarboxazid.

• isosorbide dinitrate

  phenobarbital will decrease the level or effect of isosorbide dinitrate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• isosorbide mononitrate

  phenobarbital will decrease the level or effect of isosorbide mononitrate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• istradefylline

  phenobarbital will decrease the level or effect of istradefylline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of istradefylline with strong CYP3A4 inducers.

• ivabradine

  phenobarbital will decrease the level or effect of ivabradine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of ivabradine with moderate CYP3A4 inducers.

• ivacaftor

  phenobarbital decreases levels of ivacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration with strong CYP3A4 inducers; systemic exposure of ivacaftor substantially reduced (ie, ~9-fold).

• ivosidenib

  phenobarbital will decrease the level or effect of ivosidenib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration of ivosidenib with strong CYP3A4 inducers decreased ivosidenib plasma concentrations.

• ixazomib

  phenobarbital will decrease the level or effect of ixazomib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of ixazomib with strong CYP3A inducers. Strong inducers have been shown to decrease ixazomib Cmax by 54% and AUC by 74%.

• larotrectinib

  phenobarbital will decrease the level or effect of larotrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration of larotrectinib with strong CYP3A4 inducers is unavoidable, double larotrectinib dose. Resume prior larotrectinib dose once CYP3A4 inducer discontinued for 3-5 half-lives

• lefamulin

  phenobarbital will decrease the level or effect of lefamulin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of lefamulin with strong or moderate CYP3A inducers unless the benefit outweighs risks. Monitor for reduced efficacy.

• lemborexant

  phenobarbital will decrease the level or effect of lemborexant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• lenacapavir

  phenobarbital will decrease the level or effect of lenacapavir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of lenacapavir with moderate CYP3A4 inducers.

• leniolisib

  phenobarbital will decrease the level or effect of leniolisib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• letermovir

  phenobarbital will decrease the level or effect of letermovir by Other (see comment). Avoid or Use Alternate Drug. Coadministration of letermovir with UCT1A1/3 inducers is not recommended.
  
  phenobarbital will decrease the level or effect of letermovir by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug. Coadministration of letermovir with P-gp inducers is not recommended.

• lomitapide

  phenobarbital will decrease the level or effect of lomitapide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• lovastatin

  phenobarbital will decrease the level or effect of lovastatin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• lumateperone

  phenobarbital will decrease the level or effect of lumateperone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• lurbinectedin

  phenobarbital will decrease the level or effect of lurbinectedin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• macimorelin

  phenobarbital will decrease the level or effect of macimorelin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Potential for false positive test results if macimorelin and strong CYP3A4 inducers are coadministered. Discontinue strong CYP3A4 inducer, allowing for sufficient washout time, before testing.

• macitentan

  phenobarbital will decrease the level or effect of macitentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministering macitentan with strong CYP3A4 inducers

• mestranol

  phenobarbital decreases levels of mestranol by increasing metabolism. Avoid or Use Alternate Drug. May result in contraceptive failure.

• methoxyflurane

  phenobarbital increases toxicity of methoxyflurane by increasing metabolism. Contraindicated. Increased metabolism of methoxyflurane to nephrotoxic compounds.

• methylene blue

  methylene blue and belladonna alkaloids both increase serotonin levels. Avoid or Use Alternate Drug. If drug combination must be administered, monitor for evidence of serotonergic or opioid-related toxicities

• metoclopramide intranasal

  phenobarbital, metoclopramide intranasal. Either increases effects of the other by Other (see comment). Avoid or Use Alternate Drug. Comment: Avoid use of metoclopramide intranasal or interacting drug, depending on importance of drug to patient.

• midostaurin

  phenobarbital will decrease the level or effect of midostaurin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Strong CYP3A4 inducers may decrease midostaurin concentrations resulting in reduced efficacy.

• mobocertinib

  phenobarbital will decrease the level or effect of mobocertinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• modafinil

  phenobarbital will decrease the level or effect of modafinil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• naldemedine

  phenobarbital will decrease the level or effect of naldemedine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration with strong CYP3A4 inducers.

• neratinib

  phenobarbital will decrease the level or effect of neratinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of neratinib with strong/moderate CYP3A4 inducers.

• netupitant/palonosetron

  phenobarbital will decrease the level or effect of netupitant/palonosetron by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Netupitant is mainly metabolized by CYP3A4; avoid use in patients who are chronically using a strong CYP3A4 inducer

• nintedanib

  phenobarbital decreases levels of nintedanib by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug. Avoid coadministration, particularly for P-gp inducers that are also CYP3A4 inducers; nintedanib is a substrate of P-gp and to a less extent CYP3A4.

• norethindrone

  phenobarbital will decrease the level or effect of norethindrone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration unless benefit outweighs risk. When coadministered, hormonal contraceptives are not a reliable method of effective birth control. Concomitant use may increase incidence of menstruation associated adverse effects (amenorrhea, dysmenorrhea, menorrhagia).

• norethindrone acetate

  phenobarbital will decrease the level or effect of norethindrone acetate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration unless benefit outweighs risk. When coadministered, hormonal contraceptives are not a reliable method of effective birth control. Concomitant use may increase incidence of menstruation associated adverse effects (amenorrhea, dysmenorrhea, menorrhagia).

• norethindrone transdermal

  phenobarbital will decrease the level or effect of norethindrone transdermal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration unless benefit outweighs risk. When coadministered, hormonal contraceptives are not a reliable method of effective birth control. Concomitant use may increase incidence of menstruation associated adverse effects (amenorrhea, dysmenorrhea, menorrhagia).

• olaparib

  phenobarbital will decrease the level or effect of olaparib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of olaparib with strong CYP3A4 inducers.

• olopatadine intranasal

  phenobarbital and olopatadine intranasal both increase sedation. Avoid or Use Alternate Drug. Coadministration increases risk of CNS depression, which can lead to additive impairment of psychomotor performance and cause daytime impairment.

• olutasidenib

  phenobarbital will decrease the level or effect of olutasidenib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Strong or moderate CYP3A inducers decrease olutasidenib (a CYP3A4 substrate) plasma concentrations and efficacy.

• omaveloxolone

  phenobarbital will decrease the level or effect of omaveloxolone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• omeprazole

  phenobarbital will decrease the level or effect of omeprazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• osimertinib

  phenobarbital will decrease the level or effect of osimertinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid concomitant use of osimertinib with strong CYP3A inducers.

• ozanimod

  phenobarbital will decrease the level or effect of ozanimod by Other (see comment). Avoid or Use Alternate Drug. Coadministration of ozanimod (a CYP2C8 substrate) with strong CYP2C8 inducers decreases the exposure of the active metabolites (CC112273 and CC1084037) of ozanimod, which may decrease the effiicacy of ozanimod. Therefore, coadministration of ozanimod with strong CYP2C8 inducers is not recommended.

• palbociclib

  phenobarbital will decrease the level or effect of palbociclib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Strong CYP3A inducers decrease palbociclib plasma exposure by ~85%.

• pemigatinib

  phenobarbital will decrease the level or effect of pemigatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• perampanel

  phenobarbital will decrease the level or effect of perampanel by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• pexidartinib

  phenobarbital will decrease the level or effect of pexidartinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• phenindione

  phenobarbital decreases effects of phenindione by increasing metabolism. Avoid or Use Alternate Drug.

• pomalidomide

  phenobarbital decreases levels of pomalidomide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
  
  phenobarbital decreases levels of pomalidomide by affecting hepatic enzyme CYP1A2 metabolism. Avoid or Use Alternate Drug.

• ponatinib

  phenobarbital decreases levels of ponatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid unless the coadministration outweighs the possible risk of ponatinib underexposure; monitor for signs of reduced efficacy.

• pralsetinib

  phenobarbital will decrease the level or effect of pralsetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If unable to avoid, double current pralsetinib dose starting on Day 7 of coadministration with strong CYP3A inducer. After inducer has been discontinued for at least 14 days, resume previous pralsetinib dose.

• pramlintide

  pramlintide, belladonna alkaloids. Either increases effects of the other by pharmacodynamic synergism. Contraindicated. Synergistic inhibition of GI motility.

• pretomanid

  phenobarbital will decrease the level or effect of pretomanid by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Pretomanid is a CYP3A4 substrate. Avoid coadministration of strong or moderate CYP3A4 inducers

• protamine

  phenobarbital decreases effects of protamine by increasing metabolism. Avoid or Use Alternate Drug.

• ranolazine

  phenobarbital will decrease the level or effect of ranolazine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• ribociclib

  phenobarbital will decrease the level or effect of ribociclib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration of ribociclib with strong CYP3A inducers should be avoided.

• rimegepant

  phenobarbital will decrease the level or effect of rimegepant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• ripretinib

  phenobarbital will decrease the level or effect of ripretinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration with a strong CYP3A inhibitor will decrease systemic exposure to ripretinib and its active metabolite (DP-5439), which may decrease risk of adverse reactions.

• rivaroxaban

  phenobarbital will decrease the level or effect of rivaroxaban by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.

• rolapitant

  phenobarbital will decrease the level or effect of rolapitant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Long-term coadministration of strong CYP3A4 inducers with rolapitant may significantly decrease rolapitant efficacy.

• romidepsin

  phenobarbital will decrease the level or effect of romidepsin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• ropeginterferon alfa 2b

  ropeginterferon alfa 2b and phenobarbital both increase Other (see comment). Avoid or Use Alternate Drug. Narcotics, hypnotics or sedatives can produce additive neuropsychiatric side effects. Avoid use and monitor patients receiving the combination for effects of excessive CNS toxicity.

• selinexor

  selinexor, phenobarbital. unspecified interaction mechanism. Avoid or Use Alternate Drug. Patients treated with selinexor may experience neurological toxicities. Avoid taking selinexor with other medications that may cause dizziness or confusion.

• selpercatinib

  phenobarbital will decrease the level or effect of selpercatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• selumetinib

  phenobarbital will decrease the level or effect of selumetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• sildenafil

  phenobarbital will decrease the level or effect of sildenafil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Potent CYP3A4 inducers are expected to cause substantial decreases in sildenafil plasma levels

• silodosin

  phenobarbital will decrease the level or effect of silodosin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• simvastatin

  phenobarbital will decrease the level or effect of simvastatin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• siponimod

  phenobarbital will decrease the level or effect of siponimod by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration of siponimod with a drug that causes moderate CYP2C9 plus a moderate or strong CYP3A4 inducer is not recommended. Coadministration with moderate or strong CYP3A4 inducers alone is not recommended for patients with CYP2C9*1/*3 and*2/*3 genotype.

• sirolimus

  phenobarbital will decrease the level or effect of sirolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• sofosbuvir

  phenobarbital will decrease the level or effect of sofosbuvir by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug. P-gp inducers decrease sofosbuvir levels, and therefore decrease conversion to sofosbuvir's active metabolite (GS-331007) responsible for 90% of pharmacologic effect

• sofosbuvir/velpatasvir

  phenobarbital will decrease the level or effect of sofosbuvir/velpatasvir by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug. Sofosbuvir and velpatasvir are substrates of the drug transporter P-gp. Potent P-gp inducers may significantly decrease sofosbuvir and velpatasvir plasma concentrations, leading to potentially reduced therapeutic effect.
  
  phenobarbital will decrease the level or effect of sofosbuvir/velpatasvir by affecting hepatic enzyme CYP2B6 metabolism. Avoid or Use Alternate Drug. Velpatasvir is a substrate of CYP2B6, CYP2C8, and CYP3A4. Drugs that are moderate-to-potent inducers of CYP2B6, CYP2C8, or CYP3A4 may significantly decrease velpatasvir plasma concentrations, leading to potentially reduced therapeutic effect.
  
  phenobarbital will decrease the level or effect of sofosbuvir/velpatasvir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Velpatasvir is a substrate of CYP2B6, CYP2C8, and CYP3A4. Drugs that are moderate-to-potent inducers of CYP2B6, CYP2C8, or CYP3A4 may significantly decrease velpatasvir plasma concentrations, leading to potentially reduced therapeutic effect.

• sonidegib

  phenobarbital will decrease the level or effect of sonidegib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of sonidegib with strong or moderate CYP3A4 inducers.

• sorafenib

  phenobarbital will decrease the level or effect of sorafenib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• sotagliflozin

  phenobarbital will decrease the level or effect of sotagliflozin by Other (see comment). Avoid or Use Alternate Drug. Glucuronidation by UGT1A9, to form the 3-O-glucuronide, was identified as a major metabolic pathway for sotagliflozin. Coadministration of UGT1A9 inducers may decrease exposure to sotagliflozin, which may decrease efficacy.

• sotorasib

  phenobarbital will decrease the level or effect of sotorasib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• sparsentan

  phenobarbital will decrease the level or effect of sparsentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• stiripentol

  phenobarbital will decrease the level or effect of stiripentol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If unable to avoid coadministration of stiripentol with strong CYP3A4 inducers, increase stiripentol dose.
  
  phenobarbital will decrease the level or effect of stiripentol by affecting hepatic enzyme CYP1A2 metabolism. Avoid or Use Alternate Drug. If unable to avoid coadministration of stiripentol with strong CYP1A2 inducers, increase stiripentol dose.
  
  stiripentol, phenobarbital. Either increases effects of the other by sedation. Avoid or Use Alternate Drug. Concomitant use stiripentol with other CNS depressants, including alcohol, may increase the risk of sedation and somnolence.

• sufentanil SL

  sufentanil SL, phenobarbital. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration may result in hypotension, profound sedation, respiratory depression, coma, and death. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.

• tamsulosin

  phenobarbital will decrease the level or effect of tamsulosin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• tazemetostat

  phenobarbital will decrease the level or effect of tazemetostat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• tetracycline

  phenobarbital will decrease the level or effect of tetracycline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• tezacaftor

  phenobarbital will decrease the level or effect of tezacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• tivozanib

  phenobarbital will decrease the level or effect of tivozanib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• tizanidine

  phenobarbital will decrease the level or effect of tizanidine by affecting hepatic enzyme CYP1A2 metabolism. Avoid or Use Alternate Drug.

• tolvaptan

  phenobarbital will decrease the level or effect of tolvaptan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• trabectedin

  phenobarbital will decrease the level or effect of trabectedin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• tucatinib

  phenobarbital will decrease the level or effect of tucatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
  
  phenobarbital will decrease the level or effect of tucatinib by Other (see comment). Avoid or Use Alternate Drug. Coadministration of tucatinib (a CYP2C8 substrate) with a strong or moderate CYP2C8 inducer decreases tucatinib plasma concentrations.

• ubrogepant

  phenobarbital will decrease the level or effect of ubrogepant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• ulipristal

  phenobarbital will decrease the level or effect of ulipristal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• umeclidinium bromide/vilanterol inhaled

  belladonna alkaloids, umeclidinium bromide/vilanterol inhaled. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Concomitant use with other anticholinergic-containing drugs may lead to additive anticholinergic adverse effects.

• upadacitinib

  phenobarbital will decrease the level or effect of upadacitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid upadacitinib coadministration with strong CYP3A4 inducers.

Monitor Closely (504)

• abiraterone

  phenobarbital decreases levels of abiraterone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Avoid coadministration of abiraterone with strong CYP3A4 inducers; if a strong CYP3A4 inducer must be used, increase abiraterone dosage frequency from once daily to twice daily.

• acebutolol

  phenobarbital decreases levels of acebutolol by increasing metabolism. Use Caution/Monitor. Consider a higher beta-blocker dose during coadministration of phenobarbital. Atenolol, sotalol, nadolol less likely to be affected than other beta blockers.

• aclidinium

  belladonna alkaloids and aclidinium both decrease cholinergic effects/transmission. Use Caution/Monitor.

• acrivastine

  acrivastine and phenobarbital both increase sedation. Use Caution/Monitor.

• albuterol

  phenobarbital increases and albuterol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• alfentanil

  phenobarbital and alfentanil both increase sedation. Use Caution/Monitor.

• almotriptan

  phenobarbital will decrease the level or effect of almotriptan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• alprazolam

  phenobarbital will decrease the level or effect of alprazolam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
  
  phenobarbital and alprazolam both increase sedation. Use Caution/Monitor.

• amantadine

  belladonna alkaloids, amantadine. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Potential for increased anticholinergic adverse effects.

• amikacin

  phenobarbital will decrease the level or effect of amikacin by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• amiodarone

  phenobarbital will decrease the level or effect of amiodarone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• amisulpride

  amisulpride and phenobarbital both increase sedation. Use Caution/Monitor.

• amitriptyline

  phenobarbital will decrease the level or effect of amitriptyline by affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor.
  
  phenobarbital will decrease the level or effect of amitriptyline by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
  
  phenobarbital will decrease the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely.
  
  belladonna alkaloids and amitriptyline both decrease cholinergic effects/transmission. Modify Therapy/Monitor Closely.
  
  phenobarbital and amitriptyline both increase sedation. Use Caution/Monitor.

• amlodipine

  phenobarbital will decrease the level or effect of amlodipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• amoxapine

  belladonna alkaloids and amoxapine both decrease cholinergic effects/transmission. Use Caution/Monitor.

• amobarbital

  amobarbital and phenobarbital both increase sedation. Use Caution/Monitor.

• amoxapine

  phenobarbital and amoxapine both increase sedation. Use Caution/Monitor.

• anticholinergic/sedative combos

  anticholinergic/sedative combos and belladonna alkaloids both decrease cholinergic effects/transmission. Use Caution/Monitor.

• apomorphine

  phenobarbital and apomorphine both increase sedation. Use Caution/Monitor.

• aprepitant

  phenobarbital will decrease the level or effect of aprepitant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• arformoterol

  phenobarbital increases and arformoterol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• aripiprazole

  aripiprazole increases effects of belladonna alkaloids by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.
  
  phenobarbital will decrease the level or effect of aripiprazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
  
  phenobarbital and aripiprazole both increase sedation. Use Caution/Monitor.
  
  belladonna alkaloids decreases levels of aripiprazole by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
  
  belladonna alkaloids decreases levels of aripiprazole by pharmacodynamic antagonism. Use Caution/Monitor.

• armodafinil

  phenobarbital increases and armodafinil decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• atracurium

  atracurium and belladonna alkaloids both decrease cholinergic effects/transmission. Use Caution/Monitor.

• artesunate

  phenobarbital will decrease the level or effect of artesunate by increasing metabolism. Use Caution/Monitor. Coadministration may decrease AUC and peak plasma concentration of active artesunate metabolite (DHA) by inducing UGT. Monitor for decreased efficacy.

• asenapine

  asenapine and phenobarbital both increase sedation. Use Caution/Monitor.

• asenapine transdermal

  asenapine transdermal and phenobarbital both increase sedation. Use Caution/Monitor.

• atenolol

  phenobarbital decreases levels of atenolol by increasing metabolism. Use Caution/Monitor. Consider a higher beta-blocker dose during coadministration of phenobarbital. Atenolol, sotalol, nadolol less likely to be affected than other beta blockers.

• atogepant

  phenobarbital will decrease the level or effect of atogepant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Recommended atogepant dosage with concomitant use of strong or moderate CYP3A4 inducers is 30 mg or 60 mg qDay.

• atorvastatin

  phenobarbital will decrease the level or effect of atorvastatin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
  
  phenobarbital will decrease the level or effect of atorvastatin by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• atropine

  atropine and belladonna alkaloids both decrease cholinergic effects/transmission. Use Caution/Monitor.

• atropine IV/IM

  atropine IV/IM and belladonna alkaloids both decrease cholinergic effects/transmission. Use Caution/Monitor.

• avanafil

  phenobarbital will decrease the level or effect of avanafil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. For patients with ED, monitor response carefully because of potential for decreased effectiveness.

• avapritinib

  avapritinib and phenobarbital both increase sedation. Use Caution/Monitor.

• avatrombopag

  phenobarbital will decrease the level or effect of avatrombopag by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. When treating ITP, coadministration of avatrombopag with a moderate or strong dual CYP2C9/3A4 inducer requires an increased avatrombopag starting dose. Refer to drug monograph for specific recommendations.

• azelastine

  azelastine and phenobarbital both increase sedation. Use Caution/Monitor.

• baclofen

  phenobarbital and baclofen both increase sedation. Use Caution/Monitor.

• bazedoxifene/conjugated estrogens

  phenobarbital will decrease the level or effect of bazedoxifene/conjugated estrogens by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
  
  phenobarbital will decrease the level or effect of bazedoxifene/conjugated estrogens by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
  
  phenobarbital decreases levels of bazedoxifene/conjugated estrogens by increasing metabolism. Use Caution/Monitor. A reduction in bazedoxifene exposure may be associated with an increase risk of endometrial hyperplasia.

• belladonna and opium

  phenobarbital and belladonna and opium both increase sedation. Use Caution/Monitor.
  
  belladonna alkaloids and belladonna and opium both decrease cholinergic effects/transmission. Use Caution/Monitor.

• belumosudil

  phenobarbital will decrease the level or effect of belumosudil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Increase belumosudil dosage to 200 mg PO BID when coadministered with strong CYP3A inducers.

• benperidol

  belladonna alkaloids decreases levels of benperidol by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
  
  belladonna alkaloids decreases levels of benperidol by pharmacodynamic antagonism. Use Caution/Monitor.
  
  benperidol increases effects of belladonna alkaloids by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.

• benazepril

  phenobarbital, benazepril. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Enhanced hypotensive effects.

• bendamustine

  phenobarbital decreases levels of bendamustine by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor. Concentrations of active metabolites may be increased.

• benperidol

  phenobarbital and benperidol both increase sedation. Use Caution/Monitor.

• benzhydrocodone/acetaminophen

  phenobarbital will decrease the level or effect of benzhydrocodone/acetaminophen by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Caution when discontinuing CYP3A4 inducers that are coadministered with benzhydrocodone (prodrug of hydrocodone); plasma concentrations of hydrocodone may increase and can result in potentially fatal respiratory depression.

• benzphetamine

  phenobarbital increases and benzphetamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• benztropine

  belladonna alkaloids and benztropine both decrease cholinergic effects/transmission. Use Caution/Monitor. Additive anticholinergic adverse effects may be seen with concurrent use.

• betaxolol

  phenobarbital decreases levels of betaxolol by increasing metabolism. Use Caution/Monitor. Consider a higher beta-blocker dose during coadministration of phenobarbital. Atenolol, sotalol, nadolol less likely to be affected than other beta blockers.

• bethanechol

  bethanechol increases and belladonna alkaloids decreases cholinergic effects/transmission. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• bexagliflozin

  phenobarbital will decrease the level or effect of bexagliflozin by Other (see comment). Modify Therapy/Monitor Closely. Bexagliflozin is a major substrate of UGT1A9. If coadministered with a UGT1A9 inducer, consider adding another antihyperglycemic agent in patients requiring additional glycemic control.

• bexarotene

  phenobarbital will decrease the level or effect of bexarotene by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• bisoprolol

  phenobarbital decreases levels of bisoprolol by increasing metabolism. Use Caution/Monitor. Consider a higher beta-blocker dose during coadministration of phenobarbital. Atenolol, sotalol, nadolol less likely to be affected than other beta blockers.

• blinatumomab

  blinatumomab increases levels of phenobarbital by decreasing metabolism. Modify Therapy/Monitor Closely. Treatment initiation causes transient release of cytokines that may suppress CYP450 enzymes; highest drug-drug interaction risk is during the first 9 days of the first cycle and the first 2 days of the 2nd cycle in patients who are receiving concomitant CYP450 substrates, particularly those with a narrow therapeutic index.

• bortezomib

  phenobarbital will decrease the level or effect of bortezomib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• brentuximab vedotin

  phenobarbital decreases levels of brentuximab vedotin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• brexanolone

  brexanolone, phenobarbital. Either increases toxicity of the other by sedation. Use Caution/Monitor.

• brexpiprazole

  phenobarbital will decrease the level or effect of brexpiprazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Double brexpiprazole dose over 1-2 weeks if administered with a strong CYP3A4 inducer.
  
  brexpiprazole and phenobarbital both increase sedation. Use Caution/Monitor.

• brimonidine

  brimonidine and phenobarbital both increase sedation. Use Caution/Monitor.

• brivaracetam

  phenobarbital will decrease the level or effect of brivaracetam by affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor. Brivaracetam plasma concentration decreased by 19%.
  
  brivaracetam and phenobarbital both increase sedation. Use Caution/Monitor.

• brodalumab

  brodalumab, phenobarbital. Other (see comment). Use Caution/Monitor. Comment: Formation of CYP450 enzymes can be altered by increased levels of certain cytokines during chronic inflammation; thus, brodalumab could normalize the formation of CYP450 enzymes. Upon initiation or discontinuation of brodalumab in patients who are receiving concomitant CYP450 substrates, particularly those with a narrow therapeutic index, consider monitoring for therapeutic effect.

• bromocriptine

  phenobarbital will decrease the level or effect of bromocriptine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• brompheniramine

  brompheniramine and phenobarbital both increase sedation. Use Caution/Monitor.

• budesonide

  phenobarbital will decrease the level or effect of budesonide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
  
  phenobarbital will decrease the level or effect of budesonide by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• bupivacaine implant

  phenobarbital, bupivacaine implant. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: Local anesthetics may increase the risk of developing methemoglobinemia when concurrently exposed to drugs that also cause methemoglobinemia.

• buprenorphine

  phenobarbital and buprenorphine both increase sedation. Use Caution/Monitor.
  
  phenobarbital will decrease the level or effect of buprenorphine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• buprenorphine buccal

  phenobarbital and buprenorphine buccal both increase sedation. Use Caution/Monitor.
  
  phenobarbital will decrease the level or effect of buprenorphine buccal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• buprenorphine subdermal implant

  phenobarbital will decrease the level or effect of buprenorphine subdermal implant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Monitor patients already on buprenorphine subdermal implant who require newly-initiated treatment with CYP3A4 inducer for signs and symptoms of withdrawal. If the dose of the concomitant CYP3A4 inducer cannot be reduced or discontinued, implant removal may be necessary and the patient should then be treated with a buprenorphine dosage form that permits dose adjustments. If a CYP3A4 inducer is discontinued in a patient who has been stabilized on buprenorphine, monitor the patient for overmedication.

• buprenorphine transdermal

  phenobarbital will decrease the level or effect of buprenorphine transdermal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• buprenorphine, long-acting injection

  phenobarbital will decrease the level or effect of buprenorphine, long-acting injection by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Patients who transfer to buprenorphine long-acting injection from transmucosal buprenorphine coadministered with CYP3A4 inducers should be monitored to ensure buprenorphine plasma levels are adequate. If the buprenorphine dose is inadequate and the CYP3A4 inducer cannot be reduced or discontinued, transition the patient back to a buprenorphine formulation that permits dose adjustments.

• bupropion

  phenobarbital will decrease the level or effect of bupropion by increasing metabolism. Use Caution/Monitor. Decrease levels of bupropion.

• buspirone

  phenobarbital will decrease the level or effect of buspirone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• butabarbital

  butabarbital and phenobarbital both increase sedation. Use Caution/Monitor.

• butalbital

  butalbital and phenobarbital both increase sedation. Use Caution/Monitor.

• butorphanol

  phenobarbital and butorphanol both increase sedation. Use Caution/Monitor.

• cabazitaxel

  phenobarbital will decrease the level or effect of cabazitaxel by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Coadministration of strong CYP3A4 inducers may decrease cabazitaxel concentrations. Avoid coadministration.

• caffeine

  phenobarbital increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• calcifediol

  phenobarbital, calcifediol. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Drugs that stimulate microsomal hydroxylation reduce the half-life of calcifediol.

• calcitriol

  phenobarbital will decrease the level or effect of calcitriol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• canagliflozin

  phenobarbital decreases levels of canagliflozin by increasing metabolism. Use Caution/Monitor. Coadministration with potent UGT enzyme inducers: Consider increasing dose to 300 mg qDay if 100 mg/day tolerate and additional glycemic control required (eGFR must be >60 mL/min/1.73 m2 to increase dose); if eGFR <60 mL/min/1.73 m2, consider using a different antihyperglycemic agent.

• cannabidiol

  phenobarbital will decrease the level or effect of cannabidiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Consider an increase in cannabidiol dosage (based on clinical response and tolerability) when coadministered with a strong CYP3A4 inducer.
  
  cannabidiol will increase the level or effect of phenobarbital by affecting hepatic enzyme CYP2C19 metabolism. Modify Therapy/Monitor Closely. Consider reducing the dose of sensitive CYP2C19 substrates, as clinically appropriate, when coadministered with cannabidiol.

• captopril

  phenobarbital, captopril. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Both drugs lower blood pressure. Monitor blood pressure.

• carbachol

  carbachol increases and belladonna alkaloids decreases cholinergic effects/transmission. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• carbamazepine

  phenobarbital will decrease the level or effect of carbamazepine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• carbinoxamine

  carbinoxamine and phenobarbital both increase sedation. Use Caution/Monitor.

• carisoprodol

  phenobarbital and carisoprodol both increase sedation. Use Caution/Monitor.

• carvedilol

  phenobarbital will decrease the level or effect of carvedilol by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor.
  
  phenobarbital decreases levels of carvedilol by increasing metabolism. Use Caution/Monitor. Consider a higher beta-blocker dose during coadministration of phenobarbital. Atenolol, sotalol, nadolol less likely to be affected than other beta blockers.

• celiprolol

  phenobarbital decreases levels of celiprolol by increasing metabolism. Use Caution/Monitor. Atenolol, sotalol, nadolol less likely to be affected than other beta blockers.

• cenobamate

  cenobamate will increase the level or effect of phenobarbital by unspecified interaction mechanism. Modify Therapy/Monitor Closely. Concomitant use of phenobarbital with multiple doses of cenobamate 200 mg qDay increased carbamazepine mean Cmax and AUC by 34% and 37%. Consider a dose reduction of phenobarbital, as clinically appropriate, when used concomitantly with cenobamate.
  
  cenobamate will increase the level or effect of phenobarbital by affecting hepatic enzyme CYP2C19 metabolism. Modify Therapy/Monitor Closely. Consider a dose reduction of CYP2C19 substrates, as clinically appropriate, when used concomitantly with cenobamate.
  
  cenobamate, phenobarbital. Either increases effects of the other by sedation. Use Caution/Monitor.

• cevimeline

  cevimeline increases and belladonna alkaloids decreases cholinergic effects/transmission. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• chloral hydrate

  phenobarbital and chloral hydrate both increase sedation. Use Caution/Monitor.

• chloramphenicol

  chloramphenicol increases levels of phenobarbital by decreasing metabolism. Use Caution/Monitor.

• chlordiazepoxide

  phenobarbital and chlordiazepoxide both increase sedation. Use Caution/Monitor.
  
  phenobarbital will decrease the level or effect of chlordiazepoxide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• chloroquine

  phenobarbital will decrease the level or effect of chloroquine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• chlorpheniramine

  chlorpheniramine and phenobarbital both increase sedation. Use Caution/Monitor.

• chlorpromazine

  phenobarbital and chlorpromazine both increase sedation. Use Caution/Monitor.
  
  chlorpromazine increases effects of belladonna alkaloids by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.
  
  belladonna alkaloids decreases levels of chlorpromazine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
  
  belladonna alkaloids decreases levels of chlorpromazine by pharmacodynamic antagonism. Use Caution/Monitor.

• chlorzoxazone

  phenobarbital and chlorzoxazone both increase sedation. Use Caution/Monitor.

• cisatracurium

  belladonna alkaloids and cisatracurium both decrease cholinergic effects/transmission. Use Caution/Monitor.

• cilostazol

  phenobarbital will decrease the level or effect of cilostazol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• cinacalcet

  phenobarbital will decrease the level or effect of cinacalcet by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• cinnarizine

  cinnarizine and phenobarbital both increase sedation. Use Caution/Monitor.

• citalopram

  phenobarbital will decrease the level or effect of citalopram by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• clemastine

  clemastine and phenobarbital both increase sedation. Use Caution/Monitor.

• clobazam

  phenobarbital, clobazam. Other (see comment). Use Caution/Monitor. Comment: Concomitant administration can increase the potential for CNS effects (e.g., increased sedation or respiratory depression).

• clomipramine

  phenobarbital will decrease the level or effect of clomipramine by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.
  
  phenobarbital and clomipramine both increase sedation. Use Caution/Monitor.
  
  belladonna alkaloids and clomipramine both decrease cholinergic effects/transmission. Use Caution/Monitor.
  
  phenobarbital will decrease the level or effect of clomipramine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely.

• clonazepam

  phenobarbital and clonazepam both increase sedation. Use Caution/Monitor.
  
  phenobarbital will decrease the level or effect of clonazepam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• clozapine

  belladonna alkaloids decreases levels of clozapine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
  
  belladonna alkaloids decreases levels of clozapine by pharmacodynamic antagonism. Use Caution/Monitor.
  
  clozapine increases effects of belladonna alkaloids by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.

• clopidogrel

  phenobarbital will increase the level or effect of clopidogrel by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. CYP3A4 inducers may increase the metabolism of clopidogrel to its active metabolite. Monitor patients for potential increase in antiplatelet effects when CYP3A4 inducers are used in combination with clopidogrel

• clorazepate

  phenobarbital and clorazepate both increase sedation. Use Caution/Monitor.
  
  phenobarbital will decrease the level or effect of clorazepate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• clozapine

  phenobarbital will decrease the level or effect of clozapine by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.
  
  phenobarbital will decrease the level or effect of clozapine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
  
  phenobarbital and clozapine both increase sedation. Use Caution/Monitor.

• codeine

  phenobarbital and codeine both increase sedation. Use Caution/Monitor.

• colchicine

  phenobarbital will decrease the level or effect of colchicine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• conivaptan

  phenobarbital will decrease the level or effect of conivaptan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• conjugated estrogens

  phenobarbital will decrease the level or effect of conjugated estrogens by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
  
  phenobarbital will decrease the level or effect of conjugated estrogens by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• conjugated estrogens, vaginal

  phenobarbital will decrease the level or effect of conjugated estrogens, vaginal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
  
  phenobarbital will decrease the level or effect of conjugated estrogens, vaginal by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• cortisone

  phenobarbital will decrease the level or effect of cortisone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
  
  phenobarbital will decrease the level or effect of cortisone by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• crizotinib

  phenobarbital decreases levels of crizotinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Concomitant use of strong CYP3A inducers should be avoided. .

• cyclizine

  belladonna alkaloids and cyclizine both decrease cholinergic effects/transmission. Use Caution/Monitor.
  
  cyclizine and phenobarbital both increase sedation. Use Caution/Monitor.

• cyclobenzaprine

  phenobarbital and cyclobenzaprine both increase sedation. Use Caution/Monitor.
  
  belladonna alkaloids and cyclobenzaprine both decrease cholinergic effects/transmission. Use Caution/Monitor.

• cyclophosphamide

  phenobarbital will decrease the level or effect of cyclophosphamide by affecting hepatic enzyme CYP2B6 metabolism. Use Caution/Monitor.

• darifenacin

  belladonna alkaloids and darifenacin both decrease cholinergic effects/transmission. Use Caution/Monitor.

• cyclosporine

  phenobarbital will decrease the level or effect of cyclosporine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
  
  phenobarbital will decrease the level or effect of cyclosporine by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• cyproheptadine

  cyproheptadine and phenobarbital both increase sedation. Use Caution/Monitor.

• dantrolene

  phenobarbital and dantrolene both increase sedation. Use Caution/Monitor.

• dapsone topical

  phenobarbital increases toxicity of dapsone topical by altering metabolism. Modify Therapy/Monitor Closely. May induce methemoglobinemia.

• daridorexant

  phenobarbital and daridorexant both increase sedation. Modify Therapy/Monitor Closely. Coadministration increases risk of CNS depression, which can lead to additive impairment of psychomotor performance and cause daytime impairment.

• darifenacin

  phenobarbital will decrease the level or effect of darifenacin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• dasatinib

  phenobarbital will decrease the level or effect of dasatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• deferasirox

  phenobarbital decreases levels of deferasirox by Other (see comment). Use Caution/Monitor. Comment: Avoid concomitant use of potent UGT inducers with deferasirox. If co-administration is required then consider increasing initial dose of deferasirox to 30 mg/kg and monitor ferritin levels and clinical response.

• deflazacort

  phenobarbital will decrease the level or effect of deflazacort by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• desipramine

  phenobarbital and desipramine both increase sedation. Use Caution/Monitor.

• dexamethasone

  phenobarbital will decrease the level or effect of dexamethasone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
  
  phenobarbital will decrease the level or effect of dexamethasone by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• dexchlorpheniramine

  dexchlorpheniramine and phenobarbital both increase sedation. Use Caution/Monitor.

• dexfenfluramine

  phenobarbital increases and dexfenfluramine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• dexmedetomidine

  phenobarbital and dexmedetomidine both increase sedation. Use Caution/Monitor.

• dexmethylphenidate

  phenobarbital increases and dexmethylphenidate decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• dextroamphetamine

  phenobarbital increases and dextroamphetamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• dextromoramide

  phenobarbital and dextromoramide both increase sedation. Use Caution/Monitor.

• diamorphine

  phenobarbital and diamorphine both increase sedation. Use Caution/Monitor.

• diazepam

  phenobarbital will decrease the level or effect of diazepam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
  
  phenobarbital and diazepam both increase sedation. Use Caution/Monitor.

• diazepam intranasal

  phenobarbital will decrease the level or effect of diazepam intranasal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Strong or moderate CYP3A4 inducers may increase rate of diazepam elimination; therefore, efficacy of diazepam may be decreased.
  
  diazepam intranasal, phenobarbital. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Coadministration may potentiate the CNS-depressant effects of each drug.

• dicyclomine

  belladonna alkaloids and dicyclomine both decrease cholinergic effects/transmission. Use Caution/Monitor.

• diethylpropion

  phenobarbital increases and diethylpropion decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• difelikefalin

  difelikefalin and phenobarbital both increase sedation. Use Caution/Monitor.

• difenoxin hcl

  phenobarbital and difenoxin hcl both increase sedation. Use Caution/Monitor.

• digoxin

  phenobarbital will decrease the level or effect of digoxin by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• diltiazem

  phenobarbital will decrease the level or effect of diltiazem by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• dimenhydrinate

  dimenhydrinate and phenobarbital both increase sedation. Use Caution/Monitor.

• diphenhydramine

  belladonna alkaloids and diphenhydramine both decrease cholinergic effects/transmission. Use Caution/Monitor.
  
  diphenhydramine and phenobarbital both increase sedation. Use Caution/Monitor.

• diphenoxylate hcl

  phenobarbital and diphenoxylate hcl both increase sedation. Use Caution/Monitor.

• donepezil

  donepezil increases and belladonna alkaloids decreases cholinergic effects/transmission. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• dipipanone

  phenobarbital and dipipanone both increase sedation. Use Caution/Monitor.

• dobutamine

  phenobarbital increases and dobutamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• docetaxel

  phenobarbital will decrease the level or effect of docetaxel by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• dopamine

  phenobarbital increases and dopamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• dopexamine

  phenobarbital increases and dopexamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• dosulepin

  belladonna alkaloids and dosulepin both decrease cholinergic effects/transmission. Use Caution/Monitor.
  
  phenobarbital and dosulepin both increase sedation. Use Caution/Monitor.

• doxepin

  phenobarbital and doxepin both increase sedation. Use Caution/Monitor.
  
  belladonna alkaloids and doxepin both decrease cholinergic effects/transmission. Use Caution/Monitor.

• doxorubicin

  phenobarbital will decrease the level or effect of doxorubicin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
  
  phenobarbital decreases levels of doxorubicin by increasing elimination. Use Caution/Monitor.

• droperidol

  belladonna alkaloids decreases levels of droperidol by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
  
  belladonna alkaloids decreases levels of droperidol by pharmacodynamic antagonism. Use Caution/Monitor.
  
  droperidol increases effects of belladonna alkaloids by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.

• doxorubicin liposomal

  phenobarbital will decrease the level or effect of doxorubicin liposomal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
  
  phenobarbital decreases levels of doxorubicin liposomal by increasing elimination. Use Caution/Monitor.

• doxycycline

  phenobarbital decreases levels of doxycycline by increasing metabolism. Use Caution/Monitor.

• doxylamine

  phenobarbital and doxylamine both increase sedation. Use Caution/Monitor.

• dronabinol

  phenobarbital will decrease the level or effect of dronabinol by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor. Dronabinol is a CYP2C9 substrate.
  
  phenobarbital will decrease the level or effect of dronabinol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Dronabinol is a CYP3A4 substrate.

• droperidol

  phenobarbital and droperidol both increase sedation. Use Caution/Monitor.

• dulaglutide

  dulaglutide, phenobarbital. Other (see comment). Use Caution/Monitor. Comment: Dulaglutide slows gastric emptying and may impact absorption of concomitantly administered oral medications; be particularly cautious when coadministered with drugs that have a narrow therapeutic index.

• dupilumab

  dupilumab, phenobarbital. Other (see comment). Use Caution/Monitor. Comment: Formation of CYP450 enzymes can be altered by increased levels of certain cytokines during chronic inflammation; thus, dupilumab could normalize the formation of CYP450 enzymes. Upon initiation or discontinuation of dupilumab in patients who are receiving concomitant CYP450 substrates, particularly those with a narrow therapeutic index, consider monitoring for therapeutic effect.

• duvelisib

  phenobarbital will decrease the level or effect of duvelisib by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• echothiophate iodide

  echothiophate iodide increases and belladonna alkaloids decreases cholinergic effects/transmission. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• elagolix

  elagolix will increase the level or effect of phenobarbital by affecting hepatic enzyme CYP2C19 metabolism. Modify Therapy/Monitor Closely. Elagolix is a weak CYP2C19 inhibitor. Caution with sensitive CYP2C19 substrates.
  
  phenobarbital will decrease the level or effect of elagolix by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• eletriptan

  phenobarbital will decrease the level or effect of eletriptan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• eltrombopag

  phenobarbital will decrease the level or effect of eltrombopag by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.
  
  phenobarbital will decrease the level or effect of eltrombopag by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor.

• enfortumab vedotin

  phenobarbital will decrease the level or effect of enfortumab vedotin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• ephedrine

  phenobarbital increases and ephedrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• epinephrine

  phenobarbital increases and epinephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• epinephrine racemic

  phenobarbital increases and epinephrine racemic decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• erlotinib

  phenobarbital will decrease the level or effect of erlotinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• escitalopram

  phenobarbital will decrease the level or effect of escitalopram by affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor.
  
  phenobarbital will decrease the level or effect of escitalopram by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• eslicarbazepine acetate

  phenobarbital will decrease the level or effect of eslicarbazepine acetate by increasing metabolism. Use Caution/Monitor. Higher dosage of eslicarbazepine may be necessary
  
  eslicarbazepine acetate will increase the level or effect of phenobarbital by affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor.

• esmolol

  phenobarbital decreases levels of esmolol by increasing metabolism. Use Caution/Monitor. Consider a higher beta-blocker dose during coadministration of phenobarbital. Atenolol, sotalol, nadolol less likely to be affected than other beta blockers.

• esomeprazole

  phenobarbital will decrease the level or effect of esomeprazole by affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor.

• estazolam

  phenobarbital and estazolam both increase sedation. Use Caution/Monitor.

• estradiol

  phenobarbital will decrease the level or effect of estradiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
  
  phenobarbital will decrease the level or effect of estradiol by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• estradiol vaginal

  phenobarbital will decrease the level or effect of estradiol vaginal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• estrogens conjugated synthetic

  phenobarbital will decrease the level or effect of estrogens conjugated synthetic by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
  
  phenobarbital will decrease the level or effect of estrogens conjugated synthetic by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• estrogens esterified

  phenobarbital will decrease the level or effect of estrogens esterified by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• estropipate

  phenobarbital will decrease the level or effect of estropipate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
  
  phenobarbital will decrease the level or effect of estropipate by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• ethanol

  phenobarbital and ethanol both increase sedation. Use Caution/Monitor.

• ethosuximide

  phenobarbital will decrease the level or effect of ethosuximide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• ethotoin

  phenobarbital will decrease the level or effect of ethotoin by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor.

• etomidate

  etomidate and phenobarbital both increase sedation. Use Caution/Monitor.

• etonogestrel

  phenobarbital will decrease the level or effect of etonogestrel by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• etoposide

  phenobarbital will decrease the level or effect of etoposide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• etravirine

  phenobarbital will decrease the level or effect of etravirine by affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor.
  
  phenobarbital will decrease the level or effect of etravirine by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor.
  
  phenobarbital will decrease the level or effect of etravirine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• exemestane

  phenobarbital will decrease the level or effect of exemestane by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. For patients receiving exemestane with a potent CYP3A4 inducer the recommended dose of exemestane is 50 mg daily after a meal.

• fedratinib

  fedratinib will increase the level or effect of phenobarbital by affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP2C19 substrates as necessary.

• felbamate

  phenobarbital will decrease the level or effect of felbamate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• felodipine

  phenobarbital will decrease the level or effect of felodipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• fenfluramine

  phenobarbital increases and fenfluramine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  phenobarbital will decrease the level or effect of fenfluramine by Other (see comment). Modify Therapy/Monitor Closely. Coadministration with drugs that increase serotonin may increase the risk of serotonin syndrome.

• fentanyl

  phenobarbital will decrease the level or effect of fentanyl by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Coadministration of fentanyl with CYP3A4 inducers could lead to a decrease in fentanyl plasma concentrations, lack of efficacy or, possibly, development of a withdrawal syndrome in a patient who has developed physical dependence to fentanyl. After stopping a CYP3A4 inducer, as the effects of the inducer decline, the fentanyl plasma concentration will increase which could increase or prolong both the therapeutic and adverse effects.

• fentanyl intranasal

  phenobarbital will decrease the level or effect of fentanyl intranasal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Coadministration of fentanyl with CYP3A4 inducers could lead to a decrease in fentanyl plasma concentrations, lack of efficacy or, possibly, development of a withdrawal syndrome in a patient who has developed physical dependence to fentanyl. After stopping a CYP3A4 inducer, as the effects of the inducer decline, the fentanyl plasma concentration will increase which could increase or prolong both the therapeutic and adverse effects.

• fentanyl transdermal

  phenobarbital will decrease the level or effect of fentanyl transdermal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Coadministration of fentanyl with CYP3A4 inducers could lead to a decrease in fentanyl plasma concentrations, lack of efficacy or, possibly, development of a withdrawal syndrome in a patient who has developed physical dependence to fentanyl. After stopping a CYP3A4 inducer, as the effects of the inducer decline, the fentanyl plasma concentration will increase which could increase or prolong both the therapeutic and adverse effects.

• fentanyl transmucosal

  phenobarbital will decrease the level or effect of fentanyl transmucosal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Coadministration of fentanyl with CYP3A4 inducers could lead to a decrease in fentanyl plasma concentrations, lack of efficacy or, possibly, development of a withdrawal syndrome in a patient who has developed physical dependence to fentanyl. After stopping a CYP3A4 inducer, as the effects of the inducer decline, the fentanyl plasma concentration will increase which could increase or prolong both the therapeutic and adverse effects.

• ferric maltol

  ferric maltol, phenobarbital. Either increases levels of the other by unspecified interaction mechanism. Modify Therapy/Monitor Closely. Coadministration of ferric maltol with certain oral medications may decrease the bioavailability of either ferric maltol and some oral drugs. For oral drugs where reductions in bioavailability may cause clinically significant effects on its safety or efficacy, separate administration of ferric maltol from these drugs. Duration of separation may depend on the absorption of the medication concomitantly administered (eg, time to peak concentration, whether the drug is an immediate or extended release product).

• fesoterodine

  belladonna alkaloids and fesoterodine both decrease cholinergic effects/transmission. Use Caution/Monitor.
  
  phenobarbital will decrease the level or effect of fesoterodine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• fexinidazole

  fexinidazole will increase the level or effect of phenobarbital by affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor.

• flavoxate

  belladonna alkaloids and flavoxate both decrease cholinergic effects/transmission. Use Caution/Monitor.

• flibanserin

  phenobarbital will decrease the level or effect of flibanserin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Strong CYP3A4 inducers substantially decrease flibanserin systemic exposure.

• fludrocortisone

  phenobarbital will decrease the level or effect of fludrocortisone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
  
  phenobarbital will decrease the level or effect of fludrocortisone by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• fluphenazine

  belladonna alkaloids decreases levels of fluphenazine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
  
  belladonna alkaloids decreases levels of fluphenazine by pharmacodynamic antagonism. Use Caution/Monitor.
  
  fluphenazine increases effects of belladonna alkaloids by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.
  
  phenobarbital and fluphenazine both increase sedation. Use Caution/Monitor.

• flurazepam

  phenobarbital and flurazepam both increase sedation. Use Caution/Monitor.

• galantamine

  galantamine increases and belladonna alkaloids decreases cholinergic effects/transmission. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• fluticasone furoate

  phenobarbital will decrease the level or effect of fluticasone furoate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• fluticasone inhaled

  phenobarbital will decrease the level or effect of fluticasone inhaled by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• formoterol

  phenobarbital increases and formoterol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• fosamprenavir

  phenobarbital will decrease the level or effect of fosamprenavir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• fosaprepitant

  phenobarbital will decrease the level or effect of fosaprepitant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• fosphenytoin

  phenobarbital will decrease the level or effect of fosphenytoin by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor.

• gefitinib

  phenobarbital will decrease the level or effect of gefitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Increase gefitinib to 500 mg daily if coadministered with a strong CYP3A4 inducer. Resume gefitinib dose at 250 mg/day 7 days after discontinuing the strong inducer.

• gentamicin

  phenobarbital will decrease the level or effect of gentamicin by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• glecaprevir/pibrentasvir

  phenobarbital will decrease the level or effect of glecaprevir/pibrentasvir by increasing metabolism. Use Caution/Monitor. Coadministration of drugs that induce CYP3A4 and P-gp with glecaprevir/pibrentasvir may decrease glecaprevir/pibrentasvir plasma concentrations. Potential for loss of therapeutic effect.
  
  phenobarbital will decrease the level or effect of glecaprevir/pibrentasvir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• glyburide

  phenobarbital decreases levels of glyburide by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor. Strong CYP2C9 inducers may increase glyburide metabolism.

• glycopyrrolate

  belladonna alkaloids and glycopyrrolate both decrease cholinergic effects/transmission. Use Caution/Monitor.

• glycopyrrolate inhaled

  belladonna alkaloids and glycopyrrolate inhaled both decrease cholinergic effects/transmission. Use Caution/Monitor.

• gotu kola

  gotu kola increases effects of phenobarbital by pharmacodynamic synergism. Use Caution/Monitor. May enhance CNS depression.

• guanfacine

  phenobarbital will decrease the level or effect of guanfacine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Strong or moderate CYP3A4 inducers significantly reduce guanfacine plasma concentrations and elimination half-life. If coadministered, more frequent dosing of the IR product may be required to achieve or maintain the desired hypotensive response. For patients with ADHD, FDA-approved labeling for ER guanfacine recommends that, if coadministered, doubling the recommended dose of guanfacine should be considered.

• guselkumab

  guselkumab, phenobarbital. Other (see comment). Use Caution/Monitor. Comment: Formation of CYP450 enzymes can be altered by increased levels of certain cytokines during chronic inflammation; thus, normalizing the formation of CYP450 enzymes. Upon initiation or discontinuation of guselkumab in patients who are receiving concomitant CYP450 substrates, particularly those with a narrow therapeutic index, consider monitoring for therapeutic effect.

• haloperidol

  haloperidol increases effects of belladonna alkaloids by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.
  
  phenobarbital and haloperidol both increase sedation. Use Caution/Monitor.
  
  belladonna alkaloids decreases levels of haloperidol by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
  
  belladonna alkaloids decreases levels of haloperidol by pharmacodynamic antagonism. Use Caution/Monitor.
  
  phenobarbital will decrease the level or effect of haloperidol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• hawthorn

  hawthorn increases effects of phenobarbital by pharmacodynamic synergism. Use Caution/Monitor. May enhance CNS depression.

• henbane

  belladonna alkaloids and henbane both decrease cholinergic effects/transmission. Use Caution/Monitor.

• hemin

  phenobarbital decreases effects of hemin by pharmacodynamic antagonism. Use Caution/Monitor. Drugs that increase delta-aminolevulinic acid synthetase may decrease hemin effect.

• homatropine

  belladonna alkaloids and homatropine both decrease cholinergic effects/transmission. Use Caution/Monitor.

• hops

  hops increases effects of phenobarbital by pharmacodynamic synergism. Use Caution/Monitor. May enhance CNS depression.

• huperzine A

  huperzine A increases and belladonna alkaloids decreases cholinergic effects/transmission. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• hydrocodone

  phenobarbital will decrease the level or effect of hydrocodone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Caution when discontinuing CYP3A4 inducers that are coadministered with hydrocodone; plasma concentrations of hydrocodone may increase and can result in potentially fatal respiratory depression

• hydrocortisone

  phenobarbital will decrease the level or effect of hydrocortisone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
  
  phenobarbital will decrease the level or effect of hydrocortisone by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• hydromorphone

  phenobarbital and hydromorphone both increase sedation. Use Caution/Monitor.

• hydroxyprogesterone caproate (DSC)

  phenobarbital will decrease the level or effect of hydroxyprogesterone caproate (DSC) by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• hydroxyzine

  hydroxyzine and phenobarbital both increase sedation. Use Caution/Monitor.

• hyoscyamine

  belladonna alkaloids and hyoscyamine both decrease cholinergic effects/transmission. Use Caution/Monitor.

• hyoscyamine spray

  belladonna alkaloids and hyoscyamine spray both decrease cholinergic effects/transmission. Use Caution/Monitor.

• ifosfamide

  phenobarbital increases effects of ifosfamide by affecting hepatic enzyme CYP2B6 metabolism. Use Caution/Monitor. Coadministration of ifosfamide with CYP2B6 inducers may increase metabolism of ifosfamide to its metabolite. Monitor for increased effects/toxicities if combined with CYP2B6 inducers.
  
  phenobarbital increases toxicity of ifosfamide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. CYP3A4 inducers may increase the metabolism of ifosfamide to its active alkylating metabolites. CYP3A4 inducers may increase the formation of the neurotoxic/nephrotoxic ifosfamide metabolite, chloroacetaldehyde. Closely monitor patients taking ifosfamide with CYP3A4 inducers for toxicities and consider dose adjustment.

• iloperidone

  iloperidone increases effects of belladonna alkaloids by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.
  
  belladonna alkaloids decreases levels of iloperidone by pharmacodynamic antagonism. Use Caution/Monitor.
  
  phenobarbital and iloperidone both increase sedation. Use Caution/Monitor.
  
  belladonna alkaloids decreases levels of iloperidone by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
  
  phenobarbital will decrease the level or effect of iloperidone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• imatinib

  phenobarbital will decrease the level or effect of imatinib by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• imipramine

  belladonna alkaloids and imipramine both decrease cholinergic effects/transmission. Use Caution/Monitor.

• imipramine

  phenobarbital will decrease the level or effect of imipramine by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.
  
  phenobarbital will decrease the level or effect of imipramine by affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor.
  
  phenobarbital will decrease the level or effect of imipramine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely.
  
  phenobarbital and imipramine both increase sedation. Use Caution/Monitor.

• incobotulinumtoxinA

  belladonna alkaloids, incobotulinumtoxinA. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Use of anticholinergic drugs after administration of botulinum toxin-containing products may potentiate systemic anticholinergic effects.

• indinavir

  phenobarbital will decrease the level or effect of indinavir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
  
  phenobarbital will decrease the level or effect of indinavir by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• ipratropium

  belladonna alkaloids and ipratropium both decrease cholinergic effects/transmission. Use Caution/Monitor. Due to the poor systemic absorption of ipratropium, interaction unlikely at regularly recommended dosages.

• isoproterenol

  phenobarbital increases and isoproterenol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• itraconazole

  phenobarbital will decrease the level or effect of itraconazole by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• ivermectin

  phenobarbital will decrease the level or effect of ivermectin by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• ixabepilone

  phenobarbital will decrease the level or effect of ixabepilone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• ixekizumab

  ixekizumab, phenobarbital. Other (see comment). Use Caution/Monitor. Comment: Formation of CYP450 enzymes can be altered by increased levels of certain cytokines during chronic inflammation; thus, ixekizumab could normalize the formation of CYP450 enzymes. Upon initiation or discontinuation of ixekizumab in patients who are receiving concomitant CYP450 substrates, particularly those with a narrow therapeutic index, consider monitoring for therapeutic effect.

• kava

  kava increases effects of phenobarbital by pharmacodynamic synergism. Use Caution/Monitor. May enhance CNS depression.

• ketamine

  ketamine and phenobarbital both increase sedation. Use Caution/Monitor.

• ketotifen, ophthalmic

  phenobarbital and ketotifen, ophthalmic both increase sedation. Use Caution/Monitor.

• labetalol

  phenobarbital decreases levels of labetalol by increasing metabolism. Use Caution/Monitor. Consider a higher beta-blocker dose during coadministration of phenobarbital. Atenolol, sotalol, nadolol less likely to be affected than other beta blockers.

• lamotrigine

  phenobarbital decreases levels of lamotrigine by increasing hepatic clearance. Use Caution/Monitor.

• lansoprazole

  phenobarbital will decrease the level or effect of lansoprazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• lapatinib

  phenobarbital will decrease the level or effect of lapatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
  
  phenobarbital will decrease the level or effect of lapatinib by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• lasmiditan

  lasmiditan, phenobarbital. Either increases effects of the other by sedation. Use Caution/Monitor. Coadministration of lasmiditan and other CNS depressant drugs, including alcohol have not been evaluated in clinical studies. Lasmiditan may cause sedation, as well as other cognitive and/or neuropsychiatric adverse reactions.

• lemborexant

  lemborexant, phenobarbital. Either increases effects of the other by sedation. Modify Therapy/Monitor Closely. Dosage adjustment may be necessary if lemborexant is coadministered with other CNS depressants because of potentially additive effects.

• lesinurad

  phenobarbital will decrease the level or effect of lesinurad by affecting hepatic enzyme CYP2C9/10 metabolism. Modify Therapy/Monitor Closely.

• levalbuterol

  phenobarbital increases and levalbuterol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• levamlodipine

  phenobarbital will decrease the level or effect of levamlodipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. No information is available on the quantitative effects of CYP3A4 inducers on amlodipine. Closely monitor blood pressure when amlodipine is coadministered with CYP3A4 inducers.

• levonorgestrel intrauterine

  phenobarbital decreases levels of levonorgestrel intrauterine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• levonorgestrel oral

  phenobarbital decreases levels of levonorgestrel oral by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• levonorgestrel oral/ethinylestradiol/ferrous bisglycinate

  phenobarbital will decrease the level or effect of levonorgestrel oral/ethinylestradiol/ferrous bisglycinate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. The efficacy of hormonal contraceptives may be reduced. Use an alternative method of contraception or a backup method when enzyme inducers are used with combined hormonal contraceptives (CHCs), and continue backup contraception for 28 days after discontinuing enzyme inducer to ensure contraceptive reliability.

• levorphanol

  phenobarbital and levorphanol both increase sedation. Use Caution/Monitor.

• lidocaine

  phenobarbital will decrease the level or effect of lidocaine by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.

• linagliptin

  phenobarbital will decrease the level or effect of linagliptin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Use of alternative treatments is strongly recommended when linagliptin is to be administered with a CYP3A4 inducer.

• lisdexamfetamine

  phenobarbital increases and lisdexamfetamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• lofepramine

  belladonna alkaloids and lofepramine both decrease cholinergic effects/transmission. Use Caution/Monitor.
  
  phenobarbital and lofepramine both increase sedation. Use Caution/Monitor.

• lofexidine

  phenobarbital and lofexidine both increase sedation. Use Caution/Monitor.

• loxapine

  belladonna alkaloids decreases levels of loxapine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
  
  belladonna alkaloids decreases levels of loxapine by pharmacodynamic antagonism. Use Caution/Monitor.
  
  loxapine increases effects of belladonna alkaloids by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.

• loperamide

  phenobarbital will decrease the level or effect of loperamide by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• lopinavir

  phenobarbital will decrease the level or effect of lopinavir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• loprazolam

  phenobarbital and loprazolam both increase sedation. Use Caution/Monitor.

• loratadine

  phenobarbital will decrease the level or effect of loratadine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• lorazepam

  phenobarbital and lorazepam both increase sedation. Use Caution/Monitor.

• lormetazepam

  phenobarbital and lormetazepam both increase sedation. Use Caution/Monitor.

• losartan

  phenobarbital will decrease the level or effect of losartan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• lovastatin

  phenobarbital will decrease the level or effect of lovastatin by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• loxapine

  phenobarbital and loxapine both increase sedation. Use Caution/Monitor.

• loxapine inhaled

  phenobarbital and loxapine inhaled both increase sedation. Use Caution/Monitor.
  
  loxapine inhaled increases effects of belladonna alkaloids by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.
  
  belladonna alkaloids decreases levels of loxapine inhaled by pharmacodynamic antagonism. Use Caution/Monitor.

• lumacaftor/ivacaftor

  lumacaftor/ivacaftor, phenobarbital. affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor. In vitro studies suggest that lumacaftor may induce and ivacaftor may inhibit CYP2C19 substrates. .

• maprotiline

  belladonna alkaloids and maprotiline both decrease cholinergic effects/transmission. Use Caution/Monitor.

• lurasidone

  lurasidone, phenobarbital. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: Potential for increased CNS depressant effects when used concurrently; monitor for increased adverse effects and toxicity.

• maprotiline

  phenobarbital and maprotiline both increase sedation. Use Caution/Monitor.

• maraviroc

  phenobarbital will decrease the level or effect of maraviroc by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
  
  phenobarbital will decrease the level or effect of maraviroc by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• marijuana

  phenobarbital and marijuana both increase sedation. Use Caution/Monitor.
  
  phenobarbital will decrease the level or effect of marijuana by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• meclizine

  belladonna alkaloids and meclizine both decrease cholinergic effects/transmission. Use Caution/Monitor.

• medroxyprogesterone

  phenobarbital will decrease the level or effect of medroxyprogesterone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Contraceptirve failure possible

• mefloquine

  phenobarbital, mefloquine. Either decreases effects of the other by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• melatonin

  phenobarbital and melatonin both increase sedation. Use Caution/Monitor.

• meperidine

  phenobarbital and meperidine both increase sedation. Use Caution/Monitor.

• meprobamate

  phenobarbital and meprobamate both increase sedation. Use Caution/Monitor.

• mestranol

  phenobarbital will decrease the level or effect of mestranol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
  
  phenobarbital will decrease the level or effect of mestranol by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• metaproterenol

  phenobarbital increases and metaproterenol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• metaxalone

  phenobarbital and metaxalone both increase sedation. Use Caution/Monitor.

• methadone

  phenobarbital will decrease the level or effect of methadone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
  
  phenobarbital and methadone both increase sedation. Use Caution/Monitor.

• methamphetamine

  phenobarbital increases and methamphetamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• methocarbamol

  phenobarbital and methocarbamol both increase sedation. Use Caution/Monitor.

• methscopolamine

  belladonna alkaloids and methscopolamine both decrease cholinergic effects/transmission. Use Caution/Monitor.

• methylenedioxymethamphetamine

  phenobarbital increases and methylenedioxymethamphetamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• methylphenidate

  methylphenidate will increase the level or effect of phenobarbital by unknown mechanism. Use Caution/Monitor. Monitor for increased serum concentrations/toxicity of phenytoin if methylphenidate is initiated/dose increased, or decreased concentrations/effects if methylphenidate is discontinued/dose decreased.

• methylphenidate transdermal

  methylphenidate transdermal will increase the level or effect of phenobarbital by decreasing metabolism. Modify Therapy/Monitor Closely. Consider decreasing the dose of these drugs when given coadministered with methylphenidate. Monitor for drug toxiticities when initiating or discontinuing methylphenidate.

• methylprednisolone

  phenobarbital will decrease the level or effect of methylprednisolone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
  
  phenobarbital will decrease the level or effect of methylprednisolone by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• metoprolol

  phenobarbital decreases levels of metoprolol by increasing metabolism. Use Caution/Monitor. Consider a higher beta-blocker dose during coadministration of phenobarbital. Atenolol, sotalol, nadolol less likely to be affected than other beta blockers.

• mexiletine

  phenobarbital will decrease the level or effect of mexiletine by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.

• midazolam

  phenobarbital will decrease the level or effect of midazolam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
  
  phenobarbital and midazolam both increase sedation. Use Caution/Monitor.

• midazolam intranasal

  midazolam intranasal, phenobarbital. Either increases toxicity of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Concomitant use of barbiturates, alcohol, or other CNS depressants may increase the risk of hypoventilation, airway obstruction, desaturation, or apnea and may contribute to profound and/or prolonged drug effect.

• midodrine

  phenobarbital increases and midodrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• mifepristone

  phenobarbital will decrease the level or effect of mifepristone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. CYP3A4 inducers have not been studied, coadministration not recommended by manufacturer

• mipomersen

  mipomersen, phenobarbital. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: Both drugs have potential to increase hepatic enzymes; monitor LFTs.

• mirtazapine

  phenobarbital and mirtazapine both increase sedation. Use Caution/Monitor.
  
  phenobarbital will decrease the level or effect of mirtazapine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• modafinil

  phenobarbital increases and modafinil decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• morphine

  phenobarbital and morphine both increase sedation. Use Caution/Monitor.

• motherwort

  phenobarbital and motherwort both increase sedation. Use Caution/Monitor.

• moxonidine

  phenobarbital and moxonidine both increase sedation. Use Caution/Monitor.

• nabilone

  phenobarbital and nabilone both increase sedation. Use Caution/Monitor.

• nadolol

  phenobarbital decreases levels of nadolol by increasing metabolism. Use Caution/Monitor. Consider a higher beta-blocker dose during coadministration of phenobarbital. Atenolol, sotalol, nadolol less likely to be affected than other beta blockers.

• nalbuphine

  phenobarbital and nalbuphine both increase sedation. Use Caution/Monitor.

• nateglinide

  phenobarbital will decrease the level or effect of nateglinide by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor.

• nebivolol

  phenobarbital decreases levels of nebivolol by increasing metabolism. Use Caution/Monitor. Consider a higher beta-blocker dose during coadministration of phenobarbital. Atenolol, sotalol, nadolol less likely to be affected than other beta blockers.

• nefazodone

  phenobarbital will decrease the level or effect of nefazodone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• nelfinavir

  phenobarbital will decrease the level or effect of nelfinavir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
  
  phenobarbital will decrease the level or effect of nelfinavir by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• neomycin PO

  phenobarbital will decrease the level or effect of neomycin PO by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• neostigmine

  neostigmine increases and belladonna alkaloids decreases cholinergic effects/transmission. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• nevirapine

  phenobarbital, nevirapine. Either decreases effects of the other by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• nicardipine

  phenobarbital will decrease the level or effect of nicardipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• nifedipine

  phenobarbital will decrease the level or effect of nifedipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely.

• nilotinib

  phenobarbital will decrease the level or effect of nilotinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
  
  phenobarbital will decrease the level or effect of nilotinib by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• nisoldipine

  phenobarbital will decrease the level or effect of nisoldipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• norepinephrine

  phenobarbital increases and norepinephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• norgestrel

  phenobarbital will decrease the level or effect of norgestrel by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• nortriptyline

  phenobarbital and nortriptyline both increase sedation. Use Caution/Monitor.
  
  belladonna alkaloids and nortriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.

• olanzapine

  belladonna alkaloids decreases levels of olanzapine by pharmacodynamic antagonism. Use Caution/Monitor.
  
  phenobarbital and olanzapine both increase sedation. Use Caution/Monitor.
  
  belladonna alkaloids decreases levels of olanzapine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
  
  olanzapine increases effects of belladonna alkaloids by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.
  
  phenobarbital will decrease the level or effect of olanzapine by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.

• oliceridine

  phenobarbital will decrease the level or effect of oliceridine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. If coadministration with a CYP3A4 inducer is necessary, consider increasing oliceridine dose until stable drug effects are achieved; monitor for signs of opioid withdrawal. If inducer is discontinued, consider oliceridine dosage reduction and monitor for signs of respiratory depression.
  
  belladonna alkaloids increases toxicity of oliceridine by Other (see comment). Use Caution/Monitor. Comment: Anticholinergic drugs may increase risk of urinary retention and/or severe constipation, which may lead to paralytic ileus. Monitor for signs of urinary retention or reduced gastric motility if oliceridine is coadministered with anticholinergics.

• omeprazole

  phenobarbital will decrease the level or effect of omeprazole by affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor.

• onabotulinumtoxinA

  belladonna alkaloids and onabotulinumtoxinA both decrease cholinergic effects/transmission. Use Caution/Monitor.

• ondansetron

  phenobarbital will decrease the level or effect of ondansetron by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. No dosage adjustment for ondansetron is recommended for patients on these drugs.

• opium tincture

  phenobarbital and opium tincture both increase sedation. Use Caution/Monitor.

• oritavancin

  oritavancin will increase the level or effect of phenobarbital by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor. Oritavancin is a weak CYP2C9 inhibitor; caution if coadministered with CYP2C9 substrates that have a narrow therapeutic index

• orlistat

  orlistat decreases levels of phenobarbital by inhibition of GI absorption. Applies only to oral form of both agents. Modify Therapy/Monitor Closely. Risk of convulsions.

• orphenadrine

  belladonna alkaloids and orphenadrine both decrease cholinergic effects/transmission. Use Caution/Monitor.
  
  phenobarbital and orphenadrine both increase sedation. Use Caution/Monitor.

• osilodrostat

  phenobarbital will decrease the level or effect of osilodrostat by Other (see comment). Modify Therapy/Monitor Closely. Osilodrostat is a CYP3A4 and CYP2B6 subtrate. Monitor cortisol concentration and patient?s signs and symptoms during coadministration and discontinuation with strong CYP3A4 and/or CYP2B6 inducers. Adjust dose of osilodrostat if necessary.

• oxybutynin

  belladonna alkaloids and oxybutynin both decrease cholinergic effects/transmission. Use Caution/Monitor.

• ospemifene

  phenobarbital decreases levels of ospemifene by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
  
  phenobarbital decreases levels of ospemifene by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor.

• oxazepam

  phenobarbital and oxazepam both increase sedation. Use Caution/Monitor.

• oxybutynin topical

  belladonna alkaloids and oxybutynin topical both decrease cholinergic effects/transmission. Use Caution/Monitor.

• oxybutynin transdermal

  belladonna alkaloids and oxybutynin transdermal both decrease cholinergic effects/transmission. Use Caution/Monitor.

• oxycodone

  phenobarbital and oxycodone both increase sedation. Use Caution/Monitor.
  
  phenobarbital decreases levels of oxycodone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• oxymorphone

  phenobarbital and oxymorphone both increase sedation. Use Caution/Monitor.

• paclitaxel

  phenobarbital will decrease the level or effect of paclitaxel by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
  
  phenobarbital will decrease the level or effect of paclitaxel by Other (see comment). Use Caution/Monitor. Paclitaxel levels/efficacy may decrease when coadministered with CYP2C8 inducers

• paclitaxel protein bound

  phenobarbital will decrease the level or effect of paclitaxel protein bound by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
  
  phenobarbital will decrease the level or effect of paclitaxel protein bound by Other (see comment). Use Caution/Monitor. Paclitaxel levels/efficacy may decrease when coadministered with CYP2C8 inducers

• paliperidone

  belladonna alkaloids decreases levels of paliperidone by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
  
  belladonna alkaloids decreases levels of paliperidone by pharmacodynamic antagonism. Use Caution/Monitor.
  
  phenobarbital will decrease the level or effect of paliperidone by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
  
  phenobarbital and paliperidone both increase sedation. Use Caution/Monitor.
  
  paliperidone increases effects of belladonna alkaloids by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.

• pancuronium

  belladonna alkaloids and pancuronium both decrease cholinergic effects/transmission. Use Caution/Monitor.

• papaveretum

  phenobarbital and papaveretum both increase sedation. Use Caution/Monitor.

• papaverine

  phenobarbital and papaverine both increase sedation. Use Caution/Monitor.

• parecoxib

  phenobarbital will decrease the level or effect of parecoxib by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor.

• paromomycin

  phenobarbital will decrease the level or effect of paromomycin by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• passion flower

  passion flower increases effects of phenobarbital by pharmacodynamic synergism. Use Caution/Monitor. May enhance CNS depression.

• pazopanib

  phenobarbital will decrease the level or effect of pazopanib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• penbutolol

  phenobarbital decreases levels of penbutolol by increasing metabolism. Use Caution/Monitor. Consider a higher beta-blocker dose during coadministration of phenobarbital. Atenolol, sotalol, nadolol less likely to be affected than other beta blockers.

• pentazocine

  phenobarbital and pentazocine both increase sedation. Use Caution/Monitor.

• pentobarbital

  pentobarbital and phenobarbital both increase sedation. Use Caution/Monitor.

• perphenazine

  perphenazine increases effects of belladonna alkaloids by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.
  
  phenobarbital and perphenazine both increase sedation. Use Caution/Monitor.
  
  belladonna alkaloids decreases levels of perphenazine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
  
  belladonna alkaloids decreases levels of perphenazine by pharmacodynamic antagonism. Use Caution/Monitor.

• phendimetrazine

  phenobarbital increases and phendimetrazine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• physostigmine

  physostigmine increases and belladonna alkaloids decreases cholinergic effects/transmission. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• phentermine

  phenobarbital increases and phentermine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• phenylephrine

  phenobarbital increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• phenylephrine PO

  phenobarbital increases and phenylephrine PO decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor. .

• phenytoin

  phenobarbital will decrease the level or effect of phenytoin by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor.

• pholcodine

  phenobarbital and pholcodine both increase sedation. Use Caution/Monitor.

• pilocarpine

  pilocarpine increases and belladonna alkaloids decreases cholinergic effects/transmission. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• pimavanserin

  phenobarbital will decrease the level or effect of pimavanserin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Avoid coadministration if possible. Monitor for reduced pimavanserin efficacy. An increase in pimavanserin dosage may be needed.

• pimozide

  pimozide increases effects of belladonna alkaloids by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.
  
  belladonna alkaloids decreases levels of pimozide by pharmacodynamic antagonism. Use Caution/Monitor.
  
  phenobarbital and pimozide both increase sedation. Use Caution/Monitor.
  
  belladonna alkaloids decreases levels of pimozide by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.

• pindolol

  phenobarbital decreases levels of pindolol by increasing metabolism. Use Caution/Monitor. Consider a higher beta-blocker dose during coadministration of phenobarbital. Atenolol, sotalol, nadolol less likely to be affected than other beta blockers.

• pralidoxime

  belladonna alkaloids and pralidoxime both decrease cholinergic effects/transmission. Use Caution/Monitor.

• pirbuterol

  phenobarbital increases and pirbuterol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• pitolisant

  phenobarbital will decrease the level or effect of pitolisant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Pitolisant exposure is decreased by 50% if coadministered with strong CYP3A4 inducers. For patients stable on pitolisant 8.9 mg/day or 17.8 mg/day, double the pitolisant dose (ie, 17.8 mg or 35.6 mg, respectively) over 7 days. If the strong CYP3A4 inducer is discontinued, reduce pitolisant dosage by half.

• polatuzumab vedotin

  phenobarbital will decrease the level or effect of polatuzumab vedotin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Polatuzumab undergoes catabolism to small peptides, amino acids, monomethyl auristatin E (MMAE), and unconjugated MMAE-related catabolites. MMAE is a CYP3A4 substrate. Coadministration of polatuzumab vedotin with a strong CYP3A4 inducer may decrease unconjugated MMAE AUC.

• posaconazole

  phenobarbital will decrease the level or effect of posaconazole by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
  
  phenobarbital decreases levels of posaconazole by increasing metabolism. Use Caution/Monitor.

• prednisolone

  phenobarbital will decrease the level or effect of prednisolone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
  
  phenobarbital will decrease the level or effect of prednisolone by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• prednisone

  phenobarbital will decrease the level or effect of prednisone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
  
  phenobarbital will decrease the level or effect of prednisone by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• primaquine

  phenobarbital will decrease the level or effect of primaquine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely.

• primidone

  phenobarbital and primidone both increase sedation. Use Caution/Monitor.

• prochlorperazine

  belladonna alkaloids decreases levels of prochlorperazine by pharmacodynamic antagonism. Use Caution/Monitor.
  
  prochlorperazine increases effects of belladonna alkaloids by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.
  
  phenobarbital and prochlorperazine both increase sedation. Use Caution/Monitor.
  
  belladonna alkaloids decreases levels of prochlorperazine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.

• progesterone intravaginal gel

  phenobarbital will decrease the level or effect of progesterone intravaginal gel by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely.

• promethazine

  belladonna alkaloids decreases levels of promethazine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
  
  belladonna alkaloids decreases levels of promethazine by pharmacodynamic antagonism. Use Caution/Monitor.
  
  promethazine increases effects of belladonna alkaloids by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.

• progesterone micronized

  phenobarbital will decrease the level or effect of progesterone micronized by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely.

• progesterone, natural

  phenobarbital will decrease the level or effect of progesterone, natural by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely.

• promethazine

  promethazine and phenobarbital both increase sedation. Use Caution/Monitor.

• propafenone

  phenobarbital decreases levels of propafenone by increasing metabolism. Use Caution/Monitor.

• propantheline

  belladonna alkaloids and propantheline both decrease cholinergic effects/transmission. Use Caution/Monitor.

• propofol

  propofol and phenobarbital both increase sedation. Use Caution/Monitor.

• propranolol

  phenobarbital decreases levels of propranolol by increasing metabolism. Use Caution/Monitor. Consider a higher beta-blocker dose during coadministration of phenobarbital. Atenolol, sotalol, nadolol less likely to be affected than other beta blockers.

• propylhexedrine

  phenobarbital increases and propylhexedrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• protriptyline

  belladonna alkaloids and protriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.
  
  phenobarbital and protriptyline both increase sedation. Use Caution/Monitor.

• pyridostigmine

  pyridostigmine increases and belladonna alkaloids decreases cholinergic effects/transmission. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• quazepam

  phenobarbital and quazepam both increase sedation. Use Caution/Monitor.
  
  phenobarbital will decrease the level or effect of quazepam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• quetiapine

  belladonna alkaloids decreases levels of quetiapine by pharmacodynamic antagonism. Use Caution/Monitor.
  
  phenobarbital will decrease the level or effect of quetiapine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
  
  phenobarbital and quetiapine both increase sedation. Use Caution/Monitor.
  
  belladonna alkaloids decreases levels of quetiapine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
  
  quetiapine increases effects of belladonna alkaloids by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.

• quinidine

  phenobarbital will decrease the level or effect of quinidine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• rapacuronium

  belladonna alkaloids and rapacuronium both decrease cholinergic effects/transmission. Use Caution/Monitor.

• ramelteon

  phenobarbital will decrease the level or effect of ramelteon by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.
  
  phenobarbital and ramelteon both increase sedation. Use Caution/Monitor.

• rasagiline

  phenobarbital will decrease the level or effect of rasagiline by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.

• repaglinide

  phenobarbital will decrease the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• rifabutin

  phenobarbital will decrease the level or effect of rifabutin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely.

• rifampin

  rifampin decreases levels of phenobarbital by increasing metabolism. Use Caution/Monitor.

• rimabotulinumtoxinB

  belladonna alkaloids, rimabotulinumtoxinB. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Anticholinergics may enhance botulinum toxin effects. Closely monitor for increased neuromuscular blockade.

• riociguat

  phenobarbital will decrease the level or effect of riociguat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Data not available for dose adjustment

• risperidone

  belladonna alkaloids decreases levels of risperidone by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
  
  belladonna alkaloids decreases levels of risperidone by pharmacodynamic antagonism. Use Caution/Monitor.
  
  phenobarbital and risperidone both increase sedation. Use Caution/Monitor.
  
  phenobarbital will decrease the level or effect of risperidone by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
  
  risperidone increases effects of belladonna alkaloids by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.

• ritonavir

  phenobarbital will decrease the level or effect of ritonavir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
  
  phenobarbital will decrease the level or effect of ritonavir by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• rocuronium

  belladonna alkaloids and rocuronium both decrease cholinergic effects/transmission. Use Caution/Monitor.

• ropinirole

  phenobarbital will decrease the level or effect of ropinirole by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.

• rucaparib

  rucaparib will increase the level or effect of phenobarbital by affecting hepatic enzyme CYP2C19 metabolism. Modify Therapy/Monitor Closely. Adjust dosage of CYP2C19 substrates, if clinically indicated.

• rufinamide

  phenobarbital decreases levels of rufinamide by increasing metabolism. Use Caution/Monitor.

• ruxolitinib

  phenobarbital will decrease the level or effect of ruxolitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• ruxolitinib topical

  phenobarbital will decrease the level or effect of ruxolitinib topical by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• salmeterol

  phenobarbital increases and salmeterol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• saquinavir

  phenobarbital will decrease the level or effect of saquinavir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
  
  phenobarbital will decrease the level or effect of saquinavir by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• sarilumab

  sarilumab, phenobarbital. Other (see comment). Use Caution/Monitor. Comment: Formation of CYP450 enzymes can be altered by increased levels of cytokines such as IL-6. Elevated IL-6 concentration may down-regulate CYP activity, such as in patients with RA, and, hence, increase drug levels compared with subjects without RA. Blockade of IL-6 signaling by IL-6 antagonists (eg, sarilumab) might reverse the inhibitory effect of IL-6 and restore CYP activity, leading to decreased drug concentrations. Caution when initiating or discontinuing sarilumab if coadministered with CYP450 substrates, especially those with a narrow therapeutic index.

• scopolamine

  belladonna alkaloids and scopolamine both decrease cholinergic effects/transmission. Use Caution/Monitor.

• scullcap

  phenobarbital and scullcap both increase sedation. Use Caution/Monitor.

• secobarbital

  phenobarbital and secobarbital both increase sedation. Use Caution/Monitor.

• secukinumab

  secukinumab, phenobarbital. Other (see comment). Use Caution/Monitor. Comment: Formation of CYP450 enzymes can be altered by increased levels of certain cytokines during chronic inflammation; thus, secukinumab could normalize the formation of CYP450 enzymes. Upon initiation or discontinuation of secukinumab in patients who are receiving concomitant CYP450 substrates, particularly those with a narrow therapeutic index, consider monitoring for therapeutic effect.

• selexipag

  phenobarbital will decrease the level or effect of selexipag by increasing metabolism. Modify Therapy/Monitor Closely. Increase selexipag dose (up to 2-fold) if coadministered with strong CYP2C8 inducers.

• sevelamer

  sevelamer decreases levels of phenobarbital by increasing elimination. Use Caution/Monitor.

• sevoflurane

  sevoflurane and phenobarbital both increase sedation. Use Caution/Monitor.

• shepherd's purse

  phenobarbital and shepherd's purse both increase sedation. Use Caution/Monitor.

• silodosin

  phenobarbital will decrease the level or effect of silodosin by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• sirolimus

  phenobarbital will decrease the level or effect of sirolimus by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• solifenacin

  phenobarbital will decrease the level or effect of solifenacin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
  
  belladonna alkaloids and solifenacin both decrease cholinergic effects/transmission. Use Caution/Monitor.

• sorafenib

  phenobarbital decreases levels of sorafenib by increasing metabolism. Use Caution/Monitor.

• succinylcholine

  succinylcholine increases and belladonna alkaloids decreases cholinergic effects/transmission. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• sotalol

  phenobarbital decreases levels of sotalol by increasing metabolism. Use Caution/Monitor. Consider a higher beta-blocker dose during coadministration of phenobarbital. Atenolol, sotalol, nadolol less likely to be affected than other beta blockers.

• sparsentan

  sparsentan will increase the level or effect of phenobarbital by affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor. Sparsentan (a CYP2C19 inducer) decreases exposure of CYP2C19 substrates and reduces efficacy related to these substrates.

• stiripentol

  stiripentol will increase the level or effect of phenobarbital by affecting hepatic enzyme CYP2C19 metabolism. Modify Therapy/Monitor Closely. Consider reducing the dose of CYP2C19 substrates, if adverse reactions are experienced when administered concomitantly with stiripentol.

• streptomycin

  phenobarbital will decrease the level or effect of streptomycin by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• sufentanil

  phenobarbital and sufentanil both increase sedation. Use Caution/Monitor.

• sufentanil SL

  phenobarbital decreases effects of sufentanil SL by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Coadministration of CYP3A4 inducers may decrease sufentanil levels and efficacy, possibly precipitating withdrawal syndrome in patients who have developed physical dependence to sufentanil. Discontinuation of concomitantly used CYP3A4 inducers may increase sufentanil plasma concentration.

• sunitinib

  phenobarbital will decrease the level or effect of sunitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• suvorexant

  phenobarbital will decrease the level or effect of suvorexant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Strong CYP3A4 inducers may decrease suvorexant efficacy; if increased suvorexant dose required, do not exceed 20 mg/day

• tacrolimus

  phenobarbital will decrease the level or effect of tacrolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
  
  phenobarbital will decrease the level or effect of tacrolimus by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• tadalafil

  phenobarbital will decrease the level or effect of tadalafil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Avoid combination in pulmonary HTN patients. For patients with ED, monitor response to tadalafil carefully because of potential for decreased effectiveness.

• tamoxifen

  phenobarbital will decrease the level or effect of tamoxifen by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor.
  
  phenobarbital will decrease the level or effect of tamoxifen by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• tapentadol

  phenobarbital and tapentadol both increase sedation. Use Caution/Monitor.

• tasimelteon

  phenobarbital will decrease the level or effect of tasimelteon by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Avoid coadministration of tasimelteon with strong CYP3A4 inducers

• teclistamab

  teclistamab will increase the level or effect of phenobarbital by altering metabolism. Use Caution/Monitor. Teclistamab causes release of cytokines that may suppress activity of CYP450 enzymes, resulting in increased exposure of CYP substrates. Monitor for increased concentrations or toxicities of sensitive CYP substrates. Adjust dose of CYP substrate drug as needed.

• tecovirimat

  tecovirimat will increase the level or effect of phenobarbital by affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor. Tecovirimat is a weak inhibitor of CYP2C8 and CYP2C19. Monitor for adverse effects if coadministered with sensitive substrates of these enzymes.

• temazepam

  phenobarbital and temazepam both increase sedation. Use Caution/Monitor.

• temsirolimus

  phenobarbital will decrease the level or effect of temsirolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• teniposide

  phenobarbital will decrease the level or effect of teniposide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• terbinafine

  phenobarbital will decrease the level or effect of terbinafine by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.
  
  phenobarbital will decrease the level or effect of terbinafine by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor.
  
  phenobarbital will decrease the level or effect of terbinafine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• terbutaline

  phenobarbital increases and terbutaline decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• tetracaine

  tetracaine, phenobarbital. Other (see comment). Use Caution/Monitor. Comment: Monitor for signs of methemoglobinemia when methemoglobin-inducing drugs are coadministered.

• thalidomide

  thalidomide increases effects of phenobarbital by unspecified interaction mechanism. Use Caution/Monitor. Increased sedative effects.

• theophylline

  phenobarbital will decrease the level or effect of theophylline by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.
  
  phenobarbital will decrease the level or effect of theophylline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• thioridazine

  thioridazine increases effects of belladonna alkaloids by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.
  
  belladonna alkaloids decreases levels of thioridazine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
  
  belladonna alkaloids decreases levels of thioridazine by pharmacodynamic antagonism. Use Caution/Monitor.
  
  phenobarbital and thioridazine both increase sedation. Use Caution/Monitor.

• thiothixene

  phenobarbital and thiothixene both increase sedation. Use Caution/Monitor.
  
  belladonna alkaloids decreases levels of thiothixene by pharmacodynamic antagonism. Use Caution/Monitor.
  
  thiothixene increases effects of belladonna alkaloids by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.
  
  belladonna alkaloids decreases levels of thiothixene by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.

• tiagabine

  phenobarbital will decrease the level or effect of tiagabine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• tiotropium

  belladonna alkaloids and tiotropium both decrease cholinergic effects/transmission. Use Caution/Monitor.

• ticagrelor

  phenobarbital decreases levels of ticagrelor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Avoid use of ticagrelor with potent CYP3A inducers.

• timolol

  phenobarbital decreases levels of timolol by increasing metabolism. Use Caution/Monitor. Consider a higher beta-blocker dose during coadministration of phenobarbital. Atenolol, sotalol, nadolol less likely to be affected than other beta blockers.

• tinidazole

  phenobarbital will decrease the level or effect of tinidazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• tipranavir

  phenobarbital will decrease the level or effect of tipranavir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• tobramycin

  phenobarbital will decrease the level or effect of tobramycin by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• tofacitinib

  phenobarbital will decrease the level or effect of tofacitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Loss of, or decreased response to tofacitinib may occur when coadministered with potent CYP3A4 inducers

• tolterodine

  belladonna alkaloids and tolterodine both decrease cholinergic effects/transmission. Use Caution/Monitor.
  
  phenobarbital will decrease the level or effect of tolterodine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• tolvaptan

  phenobarbital will decrease the level or effect of tolvaptan by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• trifluoperazine

  belladonna alkaloids decreases levels of trifluoperazine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
  
  belladonna alkaloids decreases levels of trifluoperazine by pharmacodynamic antagonism. Use Caution/Monitor.
  
  trifluoperazine increases effects of belladonna alkaloids by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.

• topiramate

  phenobarbital and topiramate both increase sedation. Modify Therapy/Monitor Closely.

• toremifene

  phenobarbital decreases levels of toremifene by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. CYP3A4 inducers increase rate of toremifene metabolism, lowering the steady-state concentration in serum.

• tramadol

  phenobarbital and tramadol both increase sedation. Use Caution/Monitor.
  
  phenobarbital will decrease the level or effect of tramadol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Decreased AUC of tramadol and the active metabolite (O-desmethyltramadol) when coadministered with strong CYP3A4 and CYP2B6 inducers

• trazodone

  phenobarbital will decrease the level or effect of trazodone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
  
  phenobarbital and trazodone both increase sedation. Use Caution/Monitor.

• triamcinolone acetonide injectable suspension

  phenobarbital will decrease the level or effect of triamcinolone acetonide injectable suspension by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• triazolam

  phenobarbital will decrease the level or effect of triazolam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
  
  phenobarbital and triazolam both increase sedation. Use Caution/Monitor.

• triclabendazole

  triclabendazole will increase the level or effect of phenobarbital by affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor. If plasma concentrations of the CYP2C19 substrates are elevated during triclabendazole, recheck plasma concentration of the CYP2C19 substrates after discontinuation of triclabendazole.

• triclofos

  phenobarbital and triclofos both increase sedation. Use Caution/Monitor.

• trifluoperazine

  phenobarbital and trifluoperazine both increase sedation. Use Caution/Monitor.

• trihexyphenidyl

  belladonna alkaloids and trihexyphenidyl both decrease cholinergic effects/transmission. Use Caution/Monitor. Potential for additive anticholinergic effects.

• trimipramine

  phenobarbital and trimipramine both increase sedation. Use Caution/Monitor.
  
  phenobarbital will decrease the level or effect of trimipramine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
  
  belladonna alkaloids and trimipramine both decrease cholinergic effects/transmission. Use Caution/Monitor.

• triprolidine

  triprolidine and phenobarbital both increase sedation. Use Caution/Monitor.

• trospium chloride

  belladonna alkaloids and trospium chloride both decrease cholinergic effects/transmission. Use Caution/Monitor.

• trofinetide

  trofinetide will increase the level or effect of phenobarbital by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Monitor CYP3A4 substrates for which a small increase in plasma concentration may lead to serious toxicities if coadministered with trofinetide (a weak CYP3A4 inhibitor).

• umeclidinium bromide

  umeclidinium bromide and belladonna alkaloids both decrease cholinergic effects/transmission. Use Caution/Monitor. If possible, avoid coadministration of additional anticholinergic agents

• ustekinumab

  ustekinumab, phenobarbital. Other (see comment). Use Caution/Monitor. Comment: Formation of CYP450 enzymes can be altered by increased levels of certain cytokines during chronic inflammation; thus, normalizing the formation of CYP450 enzymes. Upon initiation or discontinuation of ustekinumab in patients who are receiving concomitant CYP450 substrates, particularly those with a narrow therapeutic index, consider monitoring for therapeutic effect.

• vardenafil

  phenobarbital will decrease the level or effect of vardenafil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• vecuronium

  belladonna alkaloids and vecuronium both decrease cholinergic effects/transmission. Use Caution/Monitor.

• verapamil

  phenobarbital will decrease the level or effect of verapamil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• vilanterol/fluticasone furoate inhaled

  phenobarbital will decrease the level or effect of vilanterol/fluticasone furoate inhaled by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• vilazodone

  phenobarbital decreases levels of vilazodone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Consider increasing vilazodone dose up to 2-fold (not to exceed 80 mg/day) when coadministered with strong CYP3A4 inducers for >14 days.

• vinblastine

  phenobarbital will decrease the level or effect of vinblastine by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• vincristine

  phenobarbital will decrease the level or effect of vincristine by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• vincristine liposomal

  phenobarbital will decrease the level or effect of vincristine liposomal by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• vitamin D

  phenobarbital decreases effects of vitamin D by Other (see comment). Use Caution/Monitor. Comment: Vitamin D supplementation or dosage adjustments may be required in patients who are receiving chronic treatment with anticonvulsants.

• vortioxetine

  phenobarbital increases levels of vortioxetine by increasing metabolism. Modify Therapy/Monitor Closely. Consider increasing the vortioxetine dose when coadministered with strong CYP inducers for >14 days; not to exceed 3 times original vortioxetine dose.

• warfarin

  phenobarbital will decrease the level or effect of warfarin by affecting hepatic enzyme CYP2C9/10 metabolism. Modify Therapy/Monitor Closely.

• xylometazoline

  phenobarbital increases and xylometazoline decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• yohimbine

  phenobarbital increases and yohimbine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• ziconotide

  phenobarbital and ziconotide both increase sedation. Use Caution/Monitor.

• ziprasidone

  belladonna alkaloids decreases levels of ziprasidone by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
  
  phenobarbital and ziprasidone both increase sedation. Use Caution/Monitor.
  
  belladonna alkaloids decreases levels of ziprasidone by pharmacodynamic antagonism. Use Caution/Monitor.
  
  ziprasidone increases effects of belladonna alkaloids by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.

• zotepine

  belladonna alkaloids decreases levels of zotepine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
  
  phenobarbital and zotepine both increase sedation. Use Caution/Monitor.
  
  belladonna alkaloids decreases levels of zotepine by pharmacodynamic antagonism. Use Caution/Monitor.

Minor (154)

• acetaminophen

  phenobarbital decreases levels of acetaminophen by increasing metabolism. Minor/Significance Unknown. Enhanced metabolism incr levels of hepatotoxic metabolites.

• acetaminophen IV

  phenobarbital decreases levels of acetaminophen IV by increasing metabolism. Minor/Significance Unknown. Enhanced metabolism incr levels of hepatotoxic metabolites.

• acetaminophen rectal

  phenobarbital decreases levels of acetaminophen rectal by increasing metabolism. Minor/Significance Unknown. Enhanced metabolism incr levels of hepatotoxic metabolites.

• acetazolamide

  acetazolamide, phenobarbital. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Increased risk of anticonvulsant induced osteomalacia.

• alfentanil

  phenobarbital will decrease the level or effect of alfentanil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• alfuzosin

  phenobarbital will decrease the level or effect of alfuzosin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• alosetron

  phenobarbital will decrease the level or effect of alosetron by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.
  
  phenobarbital will decrease the level or effect of alosetron by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• alvimopan

  phenobarbital will decrease the level or effect of alvimopan by P-glycoprotein (MDR1) efflux transporter. Minor/Significance Unknown.

• ambrisentan

  phenobarbital will decrease the level or effect of ambrisentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• amitriptyline

  phenobarbital, amitriptyline. Other (see comment). Minor/Significance Unknown. Comment: Barbiturates may increase adverse effects, including respiratory depression, produced by toxic doses of TCAs. With therapeutic doses of TCAs, barbiturates increase metabolism and decrease blood concentrations of TCAs.

• amoxapine

  phenobarbital, amoxapine. Other (see comment). Minor/Significance Unknown. Comment: Barbiturates may increase adverse effects, including respiratory depression, produced by toxic doses of TCAs. With therapeutic doses of TCAs, barbiturates increase metabolism and decrease blood concentrations of TCAs.

• amphotericin B deoxycholate

  phenobarbital decreases levels of amphotericin B deoxycholate by inhibition of GI absorption. Applies only to oral form of both agents. Minor/Significance Unknown.

• antipyrine

  phenobarbital will decrease the level or effect of antipyrine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.

• armodafinil

  phenobarbital will decrease the level or effect of armodafinil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
  
  phenobarbital will decrease the level or effect of armodafinil by P-glycoprotein (MDR1) efflux transporter. Minor/Significance Unknown.

• ascorbic acid

  phenobarbital decreases levels of ascorbic acid by increasing elimination. Minor/Significance Unknown.

• asenapine

  phenobarbital will decrease the level or effect of asenapine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.

• ashwagandha

  ashwagandha increases effects of phenobarbital by pharmacodynamic synergism. Minor/Significance Unknown. May enhance CNS depression.

• atracurium

  phenobarbital decreases effects of atracurium by pharmacodynamic antagonism. Minor/Significance Unknown.

• biotin

  phenobarbital decreases levels of biotin by unspecified interaction mechanism. Minor/Significance Unknown. Biotin supplementation may be necessary.

• bosentan

  phenobarbital will decrease the level or effect of bosentan by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.
  
  phenobarbital will decrease the level or effect of bosentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• brimonidine

  brimonidine increases effects of phenobarbital by pharmacodynamic synergism. Minor/Significance Unknown. Increased CNS depression.

• brinzolamide

  brinzolamide, phenobarbital. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Increased risk of anticonvulsant induced osteomalacia.

• caffeine

  phenobarbital will decrease the level or effect of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.

• celecoxib

  phenobarbital will decrease the level or effect of celecoxib by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

• cevimeline

  phenobarbital will decrease the level or effect of cevimeline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• chloramphenicol

  phenobarbital decreases levels of chloramphenicol by increasing metabolism. Minor/Significance Unknown.

• chlorpromazine

  phenobarbital decreases levels of chlorpromazine by increasing metabolism. Minor/Significance Unknown.

• cimetidine

  phenobarbital will decrease the level or effect of cimetidine by affecting hepatic enzyme CYP2C19 metabolism. Minor/Significance Unknown.

• cisatracurium

  phenobarbital decreases effects of cisatracurium by pharmacodynamic antagonism. Minor/Significance Unknown.

• clarithromycin

  phenobarbital will decrease the level or effect of clarithromycin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
  
  phenobarbital decreases levels of clarithromycin by increasing elimination. Minor/Significance Unknown.

• clomipramine

  phenobarbital, clomipramine. Other (see comment). Minor/Significance Unknown. Comment: Barbiturates may increase adverse effects, including respiratory depression, produced by toxic doses of TCAs. With therapeutic doses of TCAs, barbiturates increase metabolism and decrease blood concentrations of TCAs.

• clotrimazole

  phenobarbital decreases levels of clotrimazole by inhibition of GI absorption. Applies only to oral form of both agents. Minor/Significance Unknown.

• cocaine topical

  phenobarbital will decrease the level or effect of cocaine topical by affecting hepatic enzyme CYP2B6 metabolism. Minor/Significance Unknown.

• cyanocobalamin

  phenobarbital decreases levels of cyanocobalamin by inhibition of GI absorption. Applies only to oral form of both agents. Minor/Significance Unknown.

• dapsone

  phenobarbital will decrease the level or effect of dapsone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• desipramine

  belladonna alkaloids and desipramine both decrease cholinergic effects/transmission. Minor/Significance Unknown.
  
  phenobarbital, desipramine. Other (see comment). Minor/Significance Unknown. Comment: Barbiturates may increase adverse effects, including respiratory depression, produced by toxic doses of TCAs. With therapeutic doses of TCAs, barbiturates increase metabolism and decrease blood concentrations of TCAs.

• dexmethylphenidate

  dexmethylphenidate increases effects of phenobarbital by decreasing metabolism. Minor/Significance Unknown.

• dimenhydrinate

  dimenhydrinate increases toxicity of belladonna alkaloids by pharmacodynamic synergism. Minor/Significance Unknown. Additive anticholinergic effects.

• diazepam

  phenobarbital will decrease the level or effect of diazepam by affecting hepatic enzyme CYP2C19 metabolism. Minor/Significance Unknown.

• diclofenac

  phenobarbital will decrease the level or effect of diclofenac by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

• disopyramide

  phenobarbital will decrease the level or effect of disopyramide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• docetaxel

  phenobarbital will decrease the level or effect of docetaxel by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• donepezil

  phenobarbital will decrease the level or effect of donepezil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
  
  donepezil decreases effects of belladonna alkaloids by pharmacodynamic antagonism. Minor/Significance Unknown.

• dosulepin

  phenobarbital, dosulepin. Other (see comment). Minor/Significance Unknown. Comment: Barbiturates may increase adverse effects, including respiratory depression, produced by toxic doses of TCAs. With therapeutic doses of TCAs, barbiturates increase metabolism and decrease blood concentrations of TCAs.

• galantamine

  galantamine decreases effects of belladonna alkaloids by pharmacodynamic antagonism. Minor/Significance Unknown.

• doxepin

  phenobarbital, doxepin. Other (see comment). Minor/Significance Unknown. Comment: Barbiturates may increase adverse effects, including respiratory depression, produced by toxic doses of TCAs. With therapeutic doses of TCAs, barbiturates increase metabolism and decrease blood concentrations of TCAs.

• dutasteride

  phenobarbital will decrease the level or effect of dutasteride by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• efavirenz

  phenobarbital will decrease the level or effect of efavirenz by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• eplerenone

  phenobarbital will decrease the level or effect of eplerenone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• erythromycin base

  phenobarbital decreases levels of erythromycin base by increasing elimination. Minor/Significance Unknown.

• erythromycin ethylsuccinate

  phenobarbital decreases levels of erythromycin ethylsuccinate by increasing elimination. Minor/Significance Unknown.

• erythromycin lactobionate

  phenobarbital decreases levels of erythromycin lactobionate by increasing elimination. Minor/Significance Unknown.

• erythromycin stearate

  phenobarbital decreases levels of erythromycin stearate by increasing elimination. Minor/Significance Unknown.

• ethosuximide

  ethosuximide decreases effects of phenobarbital by pharmacodynamic antagonism. Minor/Significance Unknown.

• ethotoin

  phenobarbital decreases levels of ethotoin by increasing metabolism. Minor/Significance Unknown. Phenobarbital may occasionally not change or even increase (via competitive inhibition) phenytoin levels.

• eucalyptus

  phenobarbital will decrease the level or effect of eucalyptus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
  
  phenobarbital and eucalyptus both increase sedation. Minor/Significance Unknown.

• felbamate

  felbamate increases levels of phenobarbital by decreasing metabolism. Minor/Significance Unknown.

• fexofenadine

  phenobarbital will decrease the level or effect of fexofenadine by P-glycoprotein (MDR1) efflux transporter. Minor/Significance Unknown.

• finasteride

  phenobarbital will decrease the level or effect of finasteride by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• fluconazole

  phenobarbital decreases levels of fluconazole by inhibition of GI absorption. Applies only to oral form of both agents. Minor/Significance Unknown.

• flurbiprofen

  phenobarbital will decrease the level or effect of flurbiprofen by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

• fluvastatin

  phenobarbital will decrease the level or effect of fluvastatin by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

• folic acid

  folic acid decreases levels of phenobarbital by increasing metabolism. Minor/Significance Unknown.
  
  phenobarbital decreases levels of folic acid by inhibition of GI absorption. Applies only to oral form of both agents. Minor/Significance Unknown.

• fosphenytoin

  phenobarbital decreases levels of fosphenytoin by increasing metabolism. Minor/Significance Unknown. Phenobarbital may occasionally not change or even increase (via competitive inhibition) phenytoin levels.

• frovatriptan

  phenobarbital will decrease the level or effect of frovatriptan by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.

• furosemide

  phenobarbital decreases levels of furosemide by inhibition of GI absorption. Applies only to oral form of both agents. Minor/Significance Unknown.

• galantamine

  phenobarbital will decrease the level or effect of galantamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• green tea

  phenobarbital will decrease the level or effect of green tea by increasing metabolism. Minor/Significance Unknown. Green tea products may contain caffeine. The metabolism of xanthines, such as caffeine, can be increased by concurrent use with barbiturates.

• griseofulvin

  phenobarbital decreases levels of griseofulvin by inhibition of GI absorption. Applies only to oral form of both agents. Minor/Significance Unknown.

• haloperidol

  haloperidol, phenobarbital. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Risk of hyperthermia if haloperidol admin. during barbiturate withdrawal.

• ibuprofen

  phenobarbital will decrease the level or effect of ibuprofen by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

• ibuprofen IV

  phenobarbital will decrease the level or effect of ibuprofen IV by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

• imatinib

  phenobarbital will decrease the level or effect of imatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• imipramine

  phenobarbital, imipramine. Other (see comment). Minor/Significance Unknown. Comment: Barbiturates may increase adverse effects, including respiratory depression, produced by toxic doses of TCAs. With therapeutic doses of TCAs, barbiturates increase metabolism and decrease blood concentrations of TCAs.

• isocarboxazid

  isocarboxazid increases levels of phenobarbital by decreasing metabolism. Minor/Significance Unknown. Theoretical interaction.

• isradipine

  phenobarbital will decrease the level or effect of isradipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• itraconazole

  phenobarbital will decrease the level or effect of itraconazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
  
  phenobarbital decreases levels of itraconazole by inhibition of GI absorption. Applies only to oral form of both agents. Minor/Significance Unknown.

• ketoconazole

  phenobarbital will decrease the level or effect of ketoconazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
  
  phenobarbital decreases levels of ketoconazole by inhibition of GI absorption. Applies only to oral form of both agents. Minor/Significance Unknown.

• L-methylfolate

  L-methylfolate decreases levels of phenobarbital by increasing metabolism. Minor/Significance Unknown.
  
  phenobarbital decreases levels of L-methylfolate by inhibition of GI absorption. Applies only to oral form of both agents. Minor/Significance Unknown.

• lansoprazole

  phenobarbital will decrease the level or effect of lansoprazole by affecting hepatic enzyme CYP2C19 metabolism. Minor/Significance Unknown.

• levocarnitine

  phenobarbital decreases levels of levocarnitine by unspecified interaction mechanism. Minor/Significance Unknown.

• levodopa

  belladonna alkaloids, levodopa. Other (see comment). Minor/Significance Unknown. Comment: Anticholinergic agents may enhance the therapeutic effects of levodopa; however, anticholinergic agents can exacerbate tardive dyskinesia. In high dosage, anticholinergics may decrease the effects of levodopa by delaying its GI absorption. .

• levoketoconazole

  phenobarbital will decrease the level or effect of levoketoconazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
  
  phenobarbital decreases levels of levoketoconazole by inhibition of GI absorption. Applies only to oral form of both agents. Minor/Significance Unknown.

• levothyroxine

  phenobarbital decreases levels of levothyroxine by increasing metabolism. Minor/Significance Unknown.

• linezolid

  linezolid increases levels of phenobarbital by decreasing metabolism. Minor/Significance Unknown. Theoretical interaction.

• liothyronine

  phenobarbital decreases levels of liothyronine by increasing metabolism. Minor/Significance Unknown.

• lofepramine

  phenobarbital, lofepramine. Other (see comment). Minor/Significance Unknown. Comment: Barbiturates may increase adverse effects, including respiratory depression, produced by toxic doses of TCAs. With therapeutic doses of TCAs, barbiturates increase metabolism and decrease blood concentrations of TCAs.

• loratadine

  phenobarbital will decrease the level or effect of loratadine by P-glycoprotein (MDR1) efflux transporter. Minor/Significance Unknown.

• losartan

  phenobarbital will decrease the level or effect of losartan by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

• maprotiline

  phenobarbital, maprotiline. Other (see comment). Minor/Significance Unknown. Comment: Barbiturates may increase adverse effects, including respiratory depression, produced by toxic doses of TCAs. With therapeutic doses of TCAs, barbiturates increase metabolism and decrease blood concentrations of TCAs.

• meloxicam

  phenobarbital will decrease the level or effect of meloxicam by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

• methazolamide

  methazolamide, phenobarbital. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Increased risk of anticonvulsant induced osteomalacia.

• methsuximide

  methsuximide decreases effects of phenobarbital by pharmacodynamic antagonism. Minor/Significance Unknown.

• metyrapone

  phenobarbital decreases effects of metyrapone by unspecified interaction mechanism. Minor/Significance Unknown.

• miconazole vaginal

  phenobarbital decreases levels of miconazole vaginal by inhibition of GI absorption. Applies only to oral form of both agents. Minor/Significance Unknown.

• montelukast

  phenobarbital will decrease the level or effect of montelukast by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• nettle

  nettle increases effects of phenobarbital by pharmacodynamic synergism. Minor/Significance Unknown. (High dose nettle; theoretical interaction) May enhance CNS depression.

• nimodipine

  phenobarbital will decrease the level or effect of nimodipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• nitrendipine

  phenobarbital will decrease the level or effect of nitrendipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• nortriptyline

  phenobarbital, nortriptyline. Other (see comment). Minor/Significance Unknown. Comment: Barbiturates may increase adverse effects, including respiratory depression, produced by toxic doses of TCAs. With therapeutic doses of TCAs, barbiturates increase metabolism and decrease blood concentrations of TCAs.

• onabotulinumtoxinA

  phenobarbital decreases effects of onabotulinumtoxinA by pharmacodynamic antagonism. Minor/Significance Unknown.

• ondansetron

  phenobarbital will decrease the level or effect of ondansetron by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.

• oxcarbazepine

  phenobarbital decreases levels of oxcarbazepine by increasing metabolism. Minor/Significance Unknown.

• oxybutynin

  phenobarbital will decrease the level or effect of oxybutynin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• paclitaxel

  phenobarbital will decrease the level or effect of paclitaxel by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• paclitaxel protein bound

  phenobarbital will decrease the level or effect of paclitaxel protein bound by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• pancuronium

  phenobarbital decreases effects of pancuronium by pharmacodynamic antagonism. Minor/Significance Unknown.

• pantoprazole

  phenobarbital will decrease the level or effect of pantoprazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• parecoxib

  phenobarbital will decrease the level or effect of parecoxib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• phenelzine

  phenelzine increases levels of phenobarbital by decreasing metabolism. Minor/Significance Unknown. Theoretical interaction.

• phenytoin

  phenobarbital decreases levels of phenytoin by increasing metabolism. Minor/Significance Unknown. Phenobarbital may occasionally not change or even increase (via competitive inhibition) phenytoin levels.

• pimozide

  phenobarbital will decrease the level or effect of pimozide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• pioglitazone

  phenobarbital will decrease the level or effect of pioglitazone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• piroxicam

  phenobarbital will decrease the level or effect of piroxicam by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

• posaconazole

  phenobarbital decreases levels of posaconazole by inhibition of GI absorption. Applies only to oral form of both agents. Minor/Significance Unknown.

• procarbazine

  procarbazine increases levels of phenobarbital by decreasing metabolism. Minor/Significance Unknown. Theoretical interaction.

• propafenone

  phenobarbital will decrease the level or effect of propafenone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• protriptyline

  phenobarbital, protriptyline. Other (see comment). Minor/Significance Unknown. Comment: Barbiturates may increase adverse effects, including respiratory depression, produced by toxic doses of TCAs. With therapeutic doses of TCAs, barbiturates increase metabolism and decrease blood concentrations of TCAs.

• pyridoxine

  pyridoxine decreases levels of phenobarbital by increasing metabolism. Minor/Significance Unknown.

• pyridoxine (Antidote)

  pyridoxine (Antidote) decreases levels of phenobarbital by increasing metabolism. Minor/Significance Unknown.

• quinine

  phenobarbital will decrease the level or effect of quinine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• rabeprazole

  phenobarbital will decrease the level or effect of rabeprazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• ramelteon

  phenobarbital will decrease the level or effect of ramelteon by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.
  
  phenobarbital will decrease the level or effect of ramelteon by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• rapacuronium

  phenobarbital decreases effects of rapacuronium by pharmacodynamic antagonism. Minor/Significance Unknown.

• riluzole

  phenobarbital will decrease the level or effect of riluzole by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.

• rocuronium

  phenobarbital decreases effects of rocuronium by pharmacodynamic antagonism. Minor/Significance Unknown.

• rose hips

  phenobarbital decreases levels of rose hips by increasing elimination. Minor/Significance Unknown.

• sage

  phenobarbital and sage both increase sedation. Minor/Significance Unknown.
  
  sage decreases effects of phenobarbital by pharmacodynamic antagonism. Minor/Significance Unknown. Theoretical interaction; some species of sage may cause convulsions.

• saxagliptin

  phenobarbital will decrease the level or effect of saxagliptin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• selegiline transdermal

  selegiline transdermal increases levels of phenobarbital by decreasing metabolism. Minor/Significance Unknown. Theoretical interaction.

• serdexmethylphenidate/dexmethylphenidate

  serdexmethylphenidate/dexmethylphenidate increases effects of phenobarbital by decreasing metabolism. Minor/Significance Unknown.

• Siberian ginseng

  Siberian ginseng increases effects of phenobarbital by pharmacodynamic synergism. Minor/Significance Unknown. May enhance CNS depression.

• succinylcholine

  phenobarbital decreases effects of succinylcholine by pharmacodynamic antagonism. Minor/Significance Unknown.

• sufentanil

  phenobarbital will decrease the level or effect of sufentanil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• sulfamethoxazole

  phenobarbital will decrease the level or effect of sulfamethoxazole by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

• thioridazine

  thioridazine decreases levels of phenobarbital by unspecified interaction mechanism. Minor/Significance Unknown.

• thyroid desiccated

  phenobarbital decreases levels of thyroid desiccated by increasing metabolism. Minor/Significance Unknown.

• tiagabine

  phenobarbital decreases levels of tiagabine by increasing metabolism. Minor/Significance Unknown.

• tibolone

  phenobarbital decreases levels of tibolone by increasing metabolism. Minor/Significance Unknown. Theoretical interaction.

• tolbutamide

  phenobarbital will decrease the level or effect of tolbutamide by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

• topiramate

  phenobarbital decreases levels of topiramate by increasing metabolism. Minor/Significance Unknown.

• tranylcypromine

  tranylcypromine increases levels of phenobarbital by decreasing metabolism. Minor/Significance Unknown. Theoretical interaction.

• trazodone

  belladonna alkaloids and trazodone both decrease cholinergic effects/transmission. Minor/Significance Unknown.
  
  phenobarbital, trazodone. Other (see comment). Minor/Significance Unknown. Comment: Barbiturates may increase adverse effects, including respiratory depression, produced by toxic doses of TCAs. With therapeutic doses of TCAs, barbiturates increase metabolism and decrease blood concentrations of TCAs.

• trimipramine

  phenobarbital, trimipramine. Other (see comment). Minor/Significance Unknown. Comment: Barbiturates may increase adverse effects, including respiratory depression, produced by toxic doses of TCAs. With therapeutic doses of TCAs, barbiturates increase metabolism and decrease blood concentrations of TCAs.

• valproic acid

  valproic acid increases levels of phenobarbital by unspecified interaction mechanism. Minor/Significance Unknown.

• vecuronium

  phenobarbital decreases effects of vecuronium by pharmacodynamic antagonism. Minor/Significance Unknown.

• vinblastine

  phenobarbital will decrease the level or effect of vinblastine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• vincristine

  phenobarbital will decrease the level or effect of vincristine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• vincristine liposomal

  phenobarbital will decrease the level or effect of vincristine liposomal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• vinorelbine

  phenobarbital will decrease the level or effect of vinorelbine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• zaleplon

  phenobarbital will decrease the level or effect of zaleplon by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• ziprasidone

  phenobarbital will decrease the level or effect of ziprasidone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• zolpidem

  phenobarbital will decrease the level or effect of zolpidem by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• zonisamide

  phenobarbital will decrease the level or effect of zonisamide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• abemaciclib

  Serious - Use Alternative (1)phenobarbital will decrease the level or effect of abemaciclib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration of abemaciclib with strong CYP3A4 inducers reduces plasma concentration of abemaciclib and its metabolites.

• abiraterone

  Monitor Closely (1)phenobarbital decreases levels of abiraterone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Avoid coadministration of abiraterone with strong CYP3A4 inducers; if a strong CYP3A4 inducer must be used, increase abiraterone dosage frequency from once daily to twice daily.

• acalabrutinib

  Serious - Use Alternative (1)phenobarbital will decrease the level or effect of acalabrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of acalabrutinib with strong CYP3A inducers. If a strong CYP3A inducer must be used, increase acalabrutinib dose to 200 mg twice daily.

• acebutolol

  Monitor Closely (1)phenobarbital decreases levels of acebutolol by increasing metabolism. Use Caution/Monitor. Consider a higher beta-blocker dose during coadministration of phenobarbital. Atenolol, sotalol, nadolol less likely to be affected than other beta blockers.

• acetaminophen

  Minor (1)phenobarbital decreases levels of acetaminophen by increasing metabolism. Minor/Significance Unknown. Enhanced metabolism incr levels of hepatotoxic metabolites.

• acetaminophen IV

  Minor (1)phenobarbital decreases levels of acetaminophen IV by increasing metabolism. Minor/Significance Unknown. Enhanced metabolism incr levels of hepatotoxic metabolites.

• acetaminophen rectal

  Minor (1)phenobarbital decreases levels of acetaminophen rectal by increasing metabolism. Minor/Significance Unknown. Enhanced metabolism incr levels of hepatotoxic metabolites.

• acetazolamide

  Minor (1)acetazolamide, phenobarbital. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Increased risk of anticonvulsant induced osteomalacia.

• aclidinium

  Monitor Closely (1)belladonna alkaloids and aclidinium both decrease cholinergic effects/transmission. Use Caution/Monitor.

• acrivastine

  Monitor Closely (1)acrivastine and phenobarbital both increase sedation. Use Caution/Monitor.

• adagrasib

  Serious - Use Alternative (2)phenobarbital will decrease the level or effect of adagrasib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
  
  adagrasib will increase the level or effect of phenobarbital by affecting hepatic enzyme CYP2C9/10 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of adagrasib, a CYP2C9 inhibitor, with sensitive CYP2C9 substrates unless otherwise recommended in the prescribing information for these substrates.

• afatinib

  Serious - Use Alternative (1)phenobarbital decreases levels of afatinib by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug. Increase afatinib daily dose by 10 mg as tolerated if chronic therapy with P-gp inducer required; resume previous afatinib dose 2-3 days after P-gp inducer discontinued.

• albuterol

  Monitor Closely (1)phenobarbital increases and albuterol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• alfentanil

  Monitor Closely (1)phenobarbital and alfentanil both increase sedation. Use Caution/Monitor.Minor (1)phenobarbital will decrease the level or effect of alfentanil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• alfuzosin

  Minor (1)phenobarbital will decrease the level or effect of alfuzosin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• almotriptan

  Monitor Closely (1)phenobarbital will decrease the level or effect of almotriptan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• alosetron

  Serious - Use Alternative (1)phenobarbital will decrease the level or effect of alosetron by affecting hepatic enzyme CYP1A2 metabolism. Avoid or Use Alternate Drug.Minor (2)phenobarbital will decrease the level or effect of alosetron by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.
  
  phenobarbital will decrease the level or effect of alosetron by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• alpelisib

  Serious - Use Alternative (2)phenobarbital will decrease the level or effect of alpelisib by pharmacodynamic synergism. Avoid or Use Alternate Drug. Avoid coadministration of alpelisib (CYP3A4 substrate) with strong CYP3A4 inducers.
  
  phenobarbital will decrease the level or effect of alpelisib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• alprazolam

  Monitor Closely (2)phenobarbital will decrease the level or effect of alprazolam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
  
  phenobarbital and alprazolam both increase sedation. Use Caution/Monitor.

• alvimopan

  Minor (1)phenobarbital will decrease the level or effect of alvimopan by P-glycoprotein (MDR1) efflux transporter. Minor/Significance Unknown.

• amantadine

  Monitor Closely (1)belladonna alkaloids, amantadine. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Potential for increased anticholinergic adverse effects.

• ambrisentan

  Minor (1)phenobarbital will decrease the level or effect of ambrisentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• amikacin

  Monitor Closely (1)phenobarbital will decrease the level or effect of amikacin by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• amiodarone

  Monitor Closely (1)phenobarbital will decrease the level or effect of amiodarone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• amisulpride

  Monitor Closely (1)amisulpride and phenobarbital both increase sedation. Use Caution/Monitor.

• amitriptyline

  Monitor Closely (5)phenobarbital will decrease the level or effect of amitriptyline by affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor.
  
  phenobarbital will decrease the level or effect of amitriptyline by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
  
  phenobarbital will decrease the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely.
  
  belladonna alkaloids and amitriptyline both decrease cholinergic effects/transmission. Modify Therapy/Monitor Closely.
  
  phenobarbital and amitriptyline both increase sedation. Use Caution/Monitor.Minor (1)phenobarbital, amitriptyline. Other (see comment). Minor/Significance Unknown. Comment: Barbiturates may increase adverse effects, including respiratory depression, produced by toxic doses of TCAs. With therapeutic doses of TCAs, barbiturates increase metabolism and decrease blood concentrations of TCAs.

• amlodipine

  Monitor Closely (1)phenobarbital will decrease the level or effect of amlodipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• amobarbital

  Monitor Closely (1)amobarbital and phenobarbital both increase sedation. Use Caution/Monitor.

• amoxapine

  Monitor Closely (2)phenobarbital and amoxapine both increase sedation. Use Caution/Monitor.
  
  belladonna alkaloids and amoxapine both decrease cholinergic effects/transmission. Use Caution/Monitor.Minor (1)phenobarbital, amoxapine. Other (see comment). Minor/Significance Unknown. Comment: Barbiturates may increase adverse effects, including respiratory depression, produced by toxic doses of TCAs. With therapeutic doses of TCAs, barbiturates increase metabolism and decrease blood concentrations of TCAs.

• amphotericin B deoxycholate

  Minor (1)phenobarbital decreases levels of amphotericin B deoxycholate by inhibition of GI absorption. Applies only to oral form of both agents. Minor/Significance Unknown.

• anticholinergic/sedative combos

  Monitor Closely (1)anticholinergic/sedative combos and belladonna alkaloids both decrease cholinergic effects/transmission. Use Caution/Monitor.

• antipyrine

  Minor (1)phenobarbital will decrease the level or effect of antipyrine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.

• antithrombin alfa

  Serious - Use Alternative (1)phenobarbital decreases effects of antithrombin alfa by increasing metabolism. Avoid or Use Alternate Drug.

• antithrombin III

  Serious - Use Alternative (1)phenobarbital decreases effects of antithrombin III by increasing metabolism. Avoid or Use Alternate Drug.

• apalutamide

  Serious - Use Alternative (1)apalutamide will decrease the level or effect of phenobarbital by affecting hepatic enzyme CYP2C19 metabolism. Avoid or Use Alternate Drug. Coadministration of apalutamide, a strong CYP2C19 inducer, with drugs that are CYP2C19 substrates can result in lower exposure to these medications. Avoid or substitute another drug for these medications when possible. Evaluate for loss of therapeutic effect if medication must be coadministered.

• apixaban

  Serious - Use Alternative (1)phenobarbital will decrease the level or effect of apixaban by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.

• apomorphine

  Monitor Closely (1)phenobarbital and apomorphine both increase sedation. Use Caution/Monitor.

• apremilast

  Serious - Use Alternative (1)phenobarbital will decrease the level or effect of apremilast by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration with strong CYP inducers results in a significant decrease of systemic exposure of apremilast, which may result in loss of efficacy

• aprepitant

  Monitor Closely (1)phenobarbital will decrease the level or effect of aprepitant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• arformoterol

  Monitor Closely (1)phenobarbital increases and arformoterol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• argatroban

  Serious - Use Alternative (1)phenobarbital decreases effects of argatroban by increasing metabolism. Avoid or Use Alternate Drug.

• aripiprazole

  Monitor Closely (5)aripiprazole increases effects of belladonna alkaloids by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.
  
  phenobarbital will decrease the level or effect of aripiprazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
  
  phenobarbital and aripiprazole both increase sedation. Use Caution/Monitor.
  
  belladonna alkaloids decreases levels of aripiprazole by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
  
  belladonna alkaloids decreases levels of aripiprazole by pharmacodynamic antagonism. Use Caution/Monitor.

• armodafinil

  Monitor Closely (1)phenobarbital increases and armodafinil decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.Minor (2)phenobarbital will decrease the level or effect of armodafinil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
  
  phenobarbital will decrease the level or effect of armodafinil by P-glycoprotein (MDR1) efflux transporter. Minor/Significance Unknown.

• artemether/lumefantrine

  Contraindicated (1)phenobarbital will decrease the level or effect of artemether/lumefantrine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Coadministration with strong CYP3A4 inducers can result in decreased serum concentrations and loss of antimalarial efficacy

• artesunate

  Monitor Closely (1)phenobarbital will decrease the level or effect of artesunate by increasing metabolism. Use Caution/Monitor. Coadministration may decrease AUC and peak plasma concentration of active artesunate metabolite (DHA) by inducing UGT. Monitor for decreased efficacy.

• ascorbic acid

  Minor (1)phenobarbital decreases levels of ascorbic acid by increasing elimination. Minor/Significance Unknown.

• asenapine

  Monitor Closely (1)asenapine and phenobarbital both increase sedation. Use Caution/Monitor.Minor (1)phenobarbital will decrease the level or effect of asenapine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.

• asenapine transdermal

  Monitor Closely (1)asenapine transdermal and phenobarbital both increase sedation. Use Caution/Monitor.

• ashwagandha

  Minor (1)ashwagandha increases effects of phenobarbital by pharmacodynamic synergism. Minor/Significance Unknown. May enhance CNS depression.

• atazanavir

  Contraindicated (1)phenobarbital will decrease the level or effect of atazanavir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.

• atenolol

  Monitor Closely (1)phenobarbital decreases levels of atenolol by increasing metabolism. Use Caution/Monitor. Consider a higher beta-blocker dose during coadministration of phenobarbital. Atenolol, sotalol, nadolol less likely to be affected than other beta blockers.

• atogepant

  Monitor Closely (1)phenobarbital will decrease the level or effect of atogepant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Recommended atogepant dosage with concomitant use of strong or moderate CYP3A4 inducers is 30 mg or 60 mg qDay.

• atorvastatin

  Monitor Closely (2)phenobarbital will decrease the level or effect of atorvastatin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
  
  phenobarbital will decrease the level or effect of atorvastatin by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• atracurium

  Monitor Closely (1)atracurium and belladonna alkaloids both decrease cholinergic effects/transmission. Use Caution/Monitor.Minor (1)phenobarbital decreases effects of atracurium by pharmacodynamic antagonism. Minor/Significance Unknown.

• atropine

  Monitor Closely (1)atropine and belladonna alkaloids both decrease cholinergic effects/transmission. Use Caution/Monitor.

• atropine IV/IM

  Monitor Closely (1)atropine IV/IM and belladonna alkaloids both decrease cholinergic effects/transmission. Use Caution/Monitor.

• avanafil

  Monitor Closely (1)phenobarbital will decrease the level or effect of avanafil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. For patients with ED, monitor response carefully because of potential for decreased effectiveness.

• avapritinib

  Monitor Closely (1)avapritinib and phenobarbital both increase sedation. Use Caution/Monitor.Serious - Use Alternative (1)phenobarbital will decrease the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• avatrombopag

  Monitor Closely (1)phenobarbital will decrease the level or effect of avatrombopag by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. When treating ITP, coadministration of avatrombopag with a moderate or strong dual CYP2C9/3A4 inducer requires an increased avatrombopag starting dose. Refer to drug monograph for specific recommendations.

• axitinib

  Serious - Use Alternative (1)phenobarbital decreases levels of axitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Selection of concomitant medication with no or minimal CYP3A4 induction potential is recommended.

• azelastine

  Monitor Closely (1)azelastine and phenobarbital both increase sedation. Use Caution/Monitor.

• baclofen

  Monitor Closely (1)phenobarbital and baclofen both increase sedation. Use Caution/Monitor.

• bazedoxifene/conjugated estrogens

  Monitor Closely (3)phenobarbital will decrease the level or effect of bazedoxifene/conjugated estrogens by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
  
  phenobarbital will decrease the level or effect of bazedoxifene/conjugated estrogens by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
  
  phenobarbital decreases levels of bazedoxifene/conjugated estrogens by increasing metabolism. Use Caution/Monitor. A reduction in bazedoxifene exposure may be associated with an increase risk of endometrial hyperplasia.

• bedaquiline

  Serious - Use Alternative (1)phenobarbital will decrease the level or effect of bedaquiline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of bedaquiline with strong CYP3A4 inducers due to potential for decreased therapeutic effect

• belladonna and opium

  Monitor Closely (2)phenobarbital and belladonna and opium both increase sedation. Use Caution/Monitor.
  
  belladonna alkaloids and belladonna and opium both decrease cholinergic effects/transmission. Use Caution/Monitor.

• belumosudil

  Monitor Closely (1)phenobarbital will decrease the level or effect of belumosudil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Increase belumosudil dosage to 200 mg PO BID when coadministered with strong CYP3A inducers.

• bemiparin

  Serious - Use Alternative (1)phenobarbital decreases effects of bemiparin by increasing metabolism. Avoid or Use Alternate Drug.

• benazepril

  Monitor Closely (1)phenobarbital, benazepril. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Enhanced hypotensive effects.

• bendamustine

  Monitor Closely (1)phenobarbital decreases levels of bendamustine by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor. Concentrations of active metabolites may be increased.

• benperidol

  Monitor Closely (4)benperidol increases effects of belladonna alkaloids by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.
  
  belladonna alkaloids decreases levels of benperidol by pharmacodynamic antagonism. Use Caution/Monitor.
  
  phenobarbital and benperidol both increase sedation. Use Caution/Monitor.
  
  belladonna alkaloids decreases levels of benperidol by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.

• benzhydrocodone/acetaminophen

  Monitor Closely (1)phenobarbital will decrease the level or effect of benzhydrocodone/acetaminophen by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Caution when discontinuing CYP3A4 inducers that are coadministered with benzhydrocodone (prodrug of hydrocodone); plasma concentrations of hydrocodone may increase and can result in potentially fatal respiratory depression.Serious - Use Alternative (2)benzhydrocodone/acetaminophen, phenobarbital. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.
  
  benzhydrocodone/acetaminophen and phenobarbital both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• benzphetamine

  Monitor Closely (1)phenobarbital increases and benzphetamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• benztropine

  Monitor Closely (1)belladonna alkaloids and benztropine both decrease cholinergic effects/transmission. Use Caution/Monitor. Additive anticholinergic adverse effects may be seen with concurrent use.

• berotralstat

  Serious - Use Alternative (1)phenobarbital decreases levels of berotralstat by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug.

• betaxolol

  Monitor Closely (1)phenobarbital decreases levels of betaxolol by increasing metabolism. Use Caution/Monitor. Consider a higher beta-blocker dose during coadministration of phenobarbital. Atenolol, sotalol, nadolol less likely to be affected than other beta blockers.

• bethanechol

  Monitor Closely (1)bethanechol increases and belladonna alkaloids decreases cholinergic effects/transmission. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• bexagliflozin

  Monitor Closely (1)phenobarbital will decrease the level or effect of bexagliflozin by Other (see comment). Modify Therapy/Monitor Closely. Bexagliflozin is a major substrate of UGT1A9. If coadministered with a UGT1A9 inducer, consider adding another antihyperglycemic agent in patients requiring additional glycemic control.

• bexarotene

  Monitor Closely (1)phenobarbital will decrease the level or effect of bexarotene by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• bictegravir

  Serious - Use Alternative (1)phenobarbital will decrease the level or effect of bictegravir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration of strong CYP3A and UGT1A1 inducers can substantially decrease bictegravir plasma concentrations. This may result in the loss of therapeutic effect and development of resistance to bictegravir. Coadministration with another anticonvulsant should be considered.

• biotin

  Minor (1)phenobarbital decreases levels of biotin by unspecified interaction mechanism. Minor/Significance Unknown. Biotin supplementation may be necessary.

• bisoprolol

  Monitor Closely (1)phenobarbital decreases levels of bisoprolol by increasing metabolism. Use Caution/Monitor. Consider a higher beta-blocker dose during coadministration of phenobarbital. Atenolol, sotalol, nadolol less likely to be affected than other beta blockers.

• bivalirudin

  Serious - Use Alternative (1)phenobarbital decreases effects of bivalirudin by increasing metabolism. Avoid or Use Alternate Drug.

• blinatumomab

  Monitor Closely (1)blinatumomab increases levels of phenobarbital by decreasing metabolism. Modify Therapy/Monitor Closely. Treatment initiation causes transient release of cytokines that may suppress CYP450 enzymes; highest drug-drug interaction risk is during the first 9 days of the first cycle and the first 2 days of the 2nd cycle in patients who are receiving concomitant CYP450 substrates, particularly those with a narrow therapeutic index.

• bortezomib

  Monitor Closely (1)phenobarbital will decrease the level or effect of bortezomib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• bosentan

  Minor (2)phenobarbital will decrease the level or effect of bosentan by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.
  
  phenobarbital will decrease the level or effect of bosentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• bosutinib

  Serious - Use Alternative (1)phenobarbital decreases levels of bosutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Strong CYP3A4 inducers decreased bosutinib plasma concentration by ~85%.

• bremelanotide

  Serious - Use Alternative (1)bremelanotide will decrease the level or effect of phenobarbital by Other (see comment). Avoid or Use Alternate Drug. Bremelanotide may slow gastric emptying and potentially reduces the rate and extent of absorption of concomitantly administered oral medications. Avoid use when taking any oral drug that is dependent on threshold concentrations for efficacy. Interactions listed are representative examples and do not include all possible clinical examples.

• brentuximab vedotin

  Monitor Closely (1)phenobarbital decreases levels of brentuximab vedotin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• brexanolone

  Monitor Closely (1)brexanolone, phenobarbital. Either increases toxicity of the other by sedation. Use Caution/Monitor.

• brexpiprazole

  Monitor Closely (2)brexpiprazole and phenobarbital both increase sedation. Use Caution/Monitor.
  
  phenobarbital will decrease the level or effect of brexpiprazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Double brexpiprazole dose over 1-2 weeks if administered with a strong CYP3A4 inducer.

• brigatinib

  Serious - Use Alternative (1)phenobarbital will decrease the level or effect of brigatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration with strong CYP3A4 inducers may decrease brigatinib efficacy.

• brimonidine

  Monitor Closely (1)brimonidine and phenobarbital both increase sedation. Use Caution/Monitor.Minor (1)brimonidine increases effects of phenobarbital by pharmacodynamic synergism. Minor/Significance Unknown. Increased CNS depression.

• brinzolamide

  Minor (1)brinzolamide, phenobarbital. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Increased risk of anticonvulsant induced osteomalacia.

• brivaracetam

  Monitor Closely (2)phenobarbital will decrease the level or effect of brivaracetam by affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor. Brivaracetam plasma concentration decreased by 19%.
  
  brivaracetam and phenobarbital both increase sedation. Use Caution/Monitor.

• brodalumab

  Monitor Closely (1)brodalumab, phenobarbital. Other (see comment). Use Caution/Monitor. Comment: Formation of CYP450 enzymes can be altered by increased levels of certain cytokines during chronic inflammation; thus, brodalumab could normalize the formation of CYP450 enzymes. Upon initiation or discontinuation of brodalumab in patients who are receiving concomitant CYP450 substrates, particularly those with a narrow therapeutic index, consider monitoring for therapeutic effect.

• bromocriptine

  Monitor Closely (1)phenobarbital will decrease the level or effect of bromocriptine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• brompheniramine

  Monitor Closely (1)brompheniramine and phenobarbital both increase sedation. Use Caution/Monitor.

• budesonide

  Monitor Closely (2)phenobarbital will decrease the level or effect of budesonide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
  
  phenobarbital will decrease the level or effect of budesonide by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• bupivacaine implant

  Monitor Closely (1)phenobarbital, bupivacaine implant. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: Local anesthetics may increase the risk of developing methemoglobinemia when concurrently exposed to drugs that also cause methemoglobinemia.

• buprenorphine

  Monitor Closely (2)phenobarbital will decrease the level or effect of buprenorphine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
  
  phenobarbital and buprenorphine both increase sedation. Use Caution/Monitor.

• buprenorphine buccal

  Monitor Closely (2)phenobarbital will decrease the level or effect of buprenorphine buccal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
  
  phenobarbital and buprenorphine buccal both increase sedation. Use Caution/Monitor.

• buprenorphine subdermal implant

  Monitor Closely (1)phenobarbital will decrease the level or effect of buprenorphine subdermal implant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Monitor patients already on buprenorphine subdermal implant who require newly-initiated treatment with CYP3A4 inducer for signs and symptoms of withdrawal. If the dose of the concomitant CYP3A4 inducer cannot be reduced or discontinued, implant removal may be necessary and the patient should then be treated with a buprenorphine dosage form that permits dose adjustments. If a CYP3A4 inducer is discontinued in a patient who has been stabilized on buprenorphine, monitor the patient for overmedication.Serious - Use Alternative (1)buprenorphine subdermal implant and phenobarbital both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• buprenorphine transdermal

  Monitor Closely (1)phenobarbital will decrease the level or effect of buprenorphine transdermal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.Serious - Use Alternative (1)buprenorphine transdermal and phenobarbital both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• buprenorphine, long-acting injection

  Monitor Closely (1)phenobarbital will decrease the level or effect of buprenorphine, long-acting injection by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Patients who transfer to buprenorphine long-acting injection from transmucosal buprenorphine coadministered with CYP3A4 inducers should be monitored to ensure buprenorphine plasma levels are adequate. If the buprenorphine dose is inadequate and the CYP3A4 inducer cannot be reduced or discontinued, transition the patient back to a buprenorphine formulation that permits dose adjustments.

• bupropion

  Monitor Closely (1)phenobarbital will decrease the level or effect of bupropion by increasing metabolism. Use Caution/Monitor. Decrease levels of bupropion.

• buspirone

  Monitor Closely (1)phenobarbital will decrease the level or effect of buspirone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• butabarbital

  Monitor Closely (1)butabarbital and phenobarbital both increase sedation. Use Caution/Monitor.

• butalbital

  Monitor Closely (1)butalbital and phenobarbital both increase sedation. Use Caution/Monitor.

• butorphanol

  Monitor Closely (1)phenobarbital and butorphanol both increase sedation. Use Caution/Monitor.

• cabazitaxel

  Monitor Closely (1)phenobarbital will decrease the level or effect of cabazitaxel by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Coadministration of strong CYP3A4 inducers may decrease cabazitaxel concentrations. Avoid coadministration.

• cabotegravir

  Contraindicated (1)phenobarbital will decrease the level or effect of cabotegravir by increasing metabolism. Contraindicated. Cabotegravir is metabolized by UGT1A1 and UGT1A9. Strong UGT1A1 or UGT1A9 inducers decrease cabotegravir systemic exposure, thereby increasing potential for loss of virologic response.

• cabozantinib

  Serious - Use Alternative (1)phenobarbital will decrease the level or effect of cabozantinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of cabozantinib with strong CYP3A4 inducers. If a strong CYP3A4 inducer is required, increase cabozantinib dose by 40 mg/day (Cometriq) or by 20 mg/day (Cabometyx). Resume previous dose 2-3 days after strong CYP3A4 inducer discontinued.

• caffeine

  Monitor Closely (1)phenobarbital increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.Minor (1)phenobarbital will decrease the level or effect of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.

• calcifediol

  Monitor Closely (1)phenobarbital, calcifediol. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Drugs that stimulate microsomal hydroxylation reduce the half-life of calcifediol.

• calcitriol

  Monitor Closely (1)phenobarbital will decrease the level or effect of calcitriol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• calcium/magnesium/potassium/sodium oxybates

  Contraindicated (1)phenobarbital, calcium/magnesium/potassium/sodium oxybates. Either increases effects of the other by pharmacodynamic synergism. Contraindicated. Prescribing information for sodium oxybate states coadministration with alcohol or insomnia drugs is contraindicated because of additive CNS depression.

• canagliflozin

  Monitor Closely (1)phenobarbital decreases levels of canagliflozin by increasing metabolism. Use Caution/Monitor. Coadministration with potent UGT enzyme inducers: Consider increasing dose to 300 mg qDay if 100 mg/day tolerate and additional glycemic control required (eGFR must be >60 mL/min/1.73 m2 to increase dose); if eGFR <60 mL/min/1.73 m2, consider using a different antihyperglycemic agent.

• cannabidiol

  Monitor Closely (2)phenobarbital will decrease the level or effect of cannabidiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Consider an increase in cannabidiol dosage (based on clinical response and tolerability) when coadministered with a strong CYP3A4 inducer.
  
  cannabidiol will increase the level or effect of phenobarbital by affecting hepatic enzyme CYP2C19 metabolism. Modify Therapy/Monitor Closely. Consider reducing the dose of sensitive CYP2C19 substrates, as clinically appropriate, when coadministered with cannabidiol.

• capmatinib

  Serious - Use Alternative (1)phenobarbital will decrease the level or effect of capmatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• captopril

  Monitor Closely (1)phenobarbital, captopril. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Both drugs lower blood pressure. Monitor blood pressure.

• carbachol

  Monitor Closely (1)carbachol increases and belladonna alkaloids decreases cholinergic effects/transmission. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• carbamazepine

  Monitor Closely (1)phenobarbital will decrease the level or effect of carbamazepine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• carbinoxamine

  Monitor Closely (1)carbinoxamine and phenobarbital both increase sedation. Use Caution/Monitor.

• cariprazine

  Contraindicated (1)phenobarbital will decrease the level or effect of cariprazine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. CYP3A4 is responsible for the formation and elimination of cariprazine's active metabolites. The effect of CYP3A4 inducers on cariprazine exposure has not been evaluated and the net effect is unclear.

• carisoprodol

  Monitor Closely (1)phenobarbital and carisoprodol both increase sedation. Use Caution/Monitor.

• carvedilol

  Monitor Closely (2)phenobarbital will decrease the level or effect of carvedilol by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor.
  
  phenobarbital decreases levels of carvedilol by increasing metabolism. Use Caution/Monitor. Consider a higher beta-blocker dose during coadministration of phenobarbital. Atenolol, sotalol, nadolol less likely to be affected than other beta blockers.

• celecoxib

  Minor (1)phenobarbital will decrease the level or effect of celecoxib by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

• celiprolol

  Monitor Closely (1)phenobarbital decreases levels of celiprolol by increasing metabolism. Use Caution/Monitor. Atenolol, sotalol, nadolol less likely to be affected than other beta blockers.

• cenobamate

  Monitor Closely (3)cenobamate, phenobarbital. Either increases effects of the other by sedation. Use Caution/Monitor.
  
  cenobamate will increase the level or effect of phenobarbital by unspecified interaction mechanism. Modify Therapy/Monitor Closely. Concomitant use of phenobarbital with multiple doses of cenobamate 200 mg qDay increased carbamazepine mean Cmax and AUC by 34% and 37%. Consider a dose reduction of phenobarbital, as clinically appropriate, when used concomitantly with cenobamate.
  
  cenobamate will increase the level or effect of phenobarbital by affecting hepatic enzyme CYP2C19 metabolism. Modify Therapy/Monitor Closely. Consider a dose reduction of CYP2C19 substrates, as clinically appropriate, when used concomitantly with cenobamate.

• ceritinib

  Serious - Use Alternative (1)phenobarbital decreases levels of ceritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• cevimeline

  Monitor Closely (1)cevimeline increases and belladonna alkaloids decreases cholinergic effects/transmission. Effect of interaction is not clear, use caution. Use Caution/Monitor.Minor (1)phenobarbital will decrease the level or effect of cevimeline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• chloral hydrate

  Monitor Closely (1)phenobarbital and chloral hydrate both increase sedation. Use Caution/Monitor.

• chloramphenicol

  Monitor Closely (1)chloramphenicol increases levels of phenobarbital by decreasing metabolism. Use Caution/Monitor.Minor (1)phenobarbital decreases levels of chloramphenicol by increasing metabolism. Minor/Significance Unknown.

• chlordiazepoxide

  Monitor Closely (2)phenobarbital and chlordiazepoxide both increase sedation. Use Caution/Monitor.
  
  phenobarbital will decrease the level or effect of chlordiazepoxide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• chloroquine

  Monitor Closely (1)phenobarbital will decrease the level or effect of chloroquine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• chlorpheniramine

  Monitor Closely (1)chlorpheniramine and phenobarbital both increase sedation. Use Caution/Monitor.

• chlorpromazine

  Monitor Closely (4)phenobarbital and chlorpromazine both increase sedation. Use Caution/Monitor.
  
  chlorpromazine increases effects of belladonna alkaloids by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.
  
  belladonna alkaloids decreases levels of chlorpromazine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
  
  belladonna alkaloids decreases levels of chlorpromazine by pharmacodynamic antagonism. Use Caution/Monitor.Minor (1)phenobarbital decreases levels of chlorpromazine by increasing metabolism. Minor/Significance Unknown.

• chlorzoxazone

  Monitor Closely (1)phenobarbital and chlorzoxazone both increase sedation. Use Caution/Monitor.

• cilostazol

  Monitor Closely (1)phenobarbital will decrease the level or effect of cilostazol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• cimetidine

  Minor (1)phenobarbital will decrease the level or effect of cimetidine by affecting hepatic enzyme CYP2C19 metabolism. Minor/Significance Unknown.

• cinacalcet

  Monitor Closely (1)phenobarbital will decrease the level or effect of cinacalcet by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• cinnarizine

  Monitor Closely (1)cinnarizine and phenobarbital both increase sedation. Use Caution/Monitor.

• cisatracurium

  Monitor Closely (1)belladonna alkaloids and cisatracurium both decrease cholinergic effects/transmission. Use Caution/Monitor.Minor (1)phenobarbital decreases effects of cisatracurium by pharmacodynamic antagonism. Minor/Significance Unknown.

• citalopram

  Monitor Closely (1)phenobarbital will decrease the level or effect of citalopram by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• clarithromycin

  Minor (2)phenobarbital will decrease the level or effect of clarithromycin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
  
  phenobarbital decreases levels of clarithromycin by increasing elimination. Minor/Significance Unknown.

• clemastine

  Monitor Closely (1)clemastine and phenobarbital both increase sedation. Use Caution/Monitor.

• clobazam

  Monitor Closely (1)phenobarbital, clobazam. Other (see comment). Use Caution/Monitor. Comment: Concomitant administration can increase the potential for CNS effects (e.g., increased sedation or respiratory depression).

• clomipramine

  Monitor Closely (4)phenobarbital will decrease the level or effect of clomipramine by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.
  
  phenobarbital and clomipramine both increase sedation. Use Caution/Monitor.
  
  belladonna alkaloids and clomipramine both decrease cholinergic effects/transmission. Use Caution/Monitor.
  
  phenobarbital will decrease the level or effect of clomipramine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely.Minor (1)phenobarbital, clomipramine. Other (see comment). Minor/Significance Unknown. Comment: Barbiturates may increase adverse effects, including respiratory depression, produced by toxic doses of TCAs. With therapeutic doses of TCAs, barbiturates increase metabolism and decrease blood concentrations of TCAs.

• clonazepam

  Monitor Closely (2)phenobarbital and clonazepam both increase sedation. Use Caution/Monitor.
  
  phenobarbital will decrease the level or effect of clonazepam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• clopidogrel

  Monitor Closely (1)phenobarbital will increase the level or effect of clopidogrel by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. CYP3A4 inducers may increase the metabolism of clopidogrel to its active metabolite. Monitor patients for potential increase in antiplatelet effects when CYP3A4 inducers are used in combination with clopidogrel

• clorazepate

  Monitor Closely (2)phenobarbital and clorazepate both increase sedation. Use Caution/Monitor.
  
  phenobarbital will decrease the level or effect of clorazepate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• clotrimazole

  Minor (1)phenobarbital decreases levels of clotrimazole by inhibition of GI absorption. Applies only to oral form of both agents. Minor/Significance Unknown.

• clozapine

  Monitor Closely (6)phenobarbital and clozapine both increase sedation. Use Caution/Monitor.
  
  phenobarbital will decrease the level or effect of clozapine by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.
  
  belladonna alkaloids decreases levels of clozapine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
  
  belladonna alkaloids decreases levels of clozapine by pharmacodynamic antagonism. Use Caution/Monitor.
  
  clozapine increases effects of belladonna alkaloids by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.
  
  phenobarbital will decrease the level or effect of clozapine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• cobicistat

  Serious - Use Alternative (1)phenobarbital will decrease the level or effect of cobicistat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration is necessary, monitor for lack or loss of virologic response from cobicistat

• cobimetinib

  Contraindicated (1)phenobarbital will decrease the level or effect of cobimetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Avoid coadministration. Strong or moderate CYP3A inducers may decrease cobimetinib systemic exposure by >80% and reduce its efficacy.

• cocaine topical

  Minor (1)phenobarbital will decrease the level or effect of cocaine topical by affecting hepatic enzyme CYP2B6 metabolism. Minor/Significance Unknown.

• codeine

  Monitor Closely (1)phenobarbital and codeine both increase sedation. Use Caution/Monitor.

• colchicine

  Monitor Closely (1)phenobarbital will decrease the level or effect of colchicine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• conivaptan

  Monitor Closely (1)phenobarbital will decrease the level or effect of conivaptan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• conjugated estrogens

  Monitor Closely (2)phenobarbital will decrease the level or effect of conjugated estrogens by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
  
  phenobarbital will decrease the level or effect of conjugated estrogens by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• conjugated estrogens, vaginal

  Monitor Closely (2)phenobarbital will decrease the level or effect of conjugated estrogens, vaginal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
  
  phenobarbital will decrease the level or effect of conjugated estrogens, vaginal by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• copanlisib

  Serious - Use Alternative (1)phenobarbital will decrease the level or effect of copanlisib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of copanlisib with strong CYP3A4 inducers.

• cortisone

  Monitor Closely (2)phenobarbital will decrease the level or effect of cortisone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
  
  phenobarbital will decrease the level or effect of cortisone by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• crizotinib

  Monitor Closely (1)phenobarbital decreases levels of crizotinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Concomitant use of strong CYP3A inducers should be avoided. .

• cyanocobalamin

  Minor (1)phenobarbital decreases levels of cyanocobalamin by inhibition of GI absorption. Applies only to oral form of both agents. Minor/Significance Unknown.

• cyclizine

  Monitor Closely (2)belladonna alkaloids and cyclizine both decrease cholinergic effects/transmission. Use Caution/Monitor.
  
  cyclizine and phenobarbital both increase sedation. Use Caution/Monitor.

• cyclobenzaprine

  Monitor Closely (2)phenobarbital and cyclobenzaprine both increase sedation. Use Caution/Monitor.
  
  belladonna alkaloids and cyclobenzaprine both decrease cholinergic effects/transmission. Use Caution/Monitor.

• cyclophosphamide

  Monitor Closely (1)phenobarbital will decrease the level or effect of cyclophosphamide by affecting hepatic enzyme CYP2B6 metabolism. Use Caution/Monitor.

• cyclosporine

  Monitor Closely (2)phenobarbital will decrease the level or effect of cyclosporine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
  
  phenobarbital will decrease the level or effect of cyclosporine by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• cyproheptadine

  Monitor Closely (1)cyproheptadine and phenobarbital both increase sedation. Use Caution/Monitor.

• dabigatran

  Serious - Use Alternative (1)phenobarbital will decrease the level or effect of dabigatran by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug. Avoid coadministration. P-gp inducers reduce systemic exposure of dabigatran

• dabrafenib

  Serious - Use Alternative (2)phenobarbital decreases levels of dabrafenib by increasing metabolism. Avoid or Use Alternate Drug. Strong CYP2C8 inducers may decrease dabrafenib levels.
  
  phenobarbital decreases levels of dabrafenib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• dalteparin

  Serious - Use Alternative (1)phenobarbital decreases effects of dalteparin by increasing metabolism. Avoid or Use Alternate Drug.

• dantrolene

  Monitor Closely (1)phenobarbital and dantrolene both increase sedation. Use Caution/Monitor.Serious - Use Alternative (1)phenobarbital will decrease the level or effect of dantrolene by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• dapsone

  Minor (1)phenobarbital will decrease the level or effect of dapsone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• dapsone topical

  Monitor Closely (1)phenobarbital increases toxicity of dapsone topical by altering metabolism. Modify Therapy/Monitor Closely. May induce methemoglobinemia.

• daridorexant

  Monitor Closely (1)phenobarbital and daridorexant both increase sedation. Modify Therapy/Monitor Closely. Coadministration increases risk of CNS depression, which can lead to additive impairment of psychomotor performance and cause daytime impairment. Serious - Use Alternative (1)phenobarbital will decrease the level or effect of daridorexant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• darifenacin

  Monitor Closely (2)belladonna alkaloids and darifenacin both decrease cholinergic effects/transmission. Use Caution/Monitor.
  
  phenobarbital will decrease the level or effect of darifenacin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• darolutamide

  Serious - Use Alternative (1)phenobarbital will increase the level or effect of darolutamide by Other (see comment). Avoid or Use Alternate Drug. Darolutamide is a P-gp and CYP3A4 substrate. Avoid coadminstration of darolutamide with combined P-gp and strong or moderate CYP3A4 inducers.

• darunavir

  Contraindicated (1)phenobarbital will decrease the level or effect of darunavir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Coadministration with phenobarbital may result in loss of therapeutic effect and development of resistance to darunavir

• dasatinib

  Monitor Closely (1)phenobarbital will decrease the level or effect of dasatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• deferasirox

  Monitor Closely (1)phenobarbital decreases levels of deferasirox by Other (see comment). Use Caution/Monitor. Comment: Avoid concomitant use of potent UGT inducers with deferasirox. If co-administration is required then consider increasing initial dose of deferasirox to 30 mg/kg and monitor ferritin levels and clinical response.

• deflazacort

  Monitor Closely (1)phenobarbital will decrease the level or effect of deflazacort by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.Serious - Use Alternative (1)phenobarbital will decrease the level or effect of deflazacort by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of deflazacort with moderate or strong CYP3A4 inducers.

• desipramine

  Monitor Closely (1)phenobarbital and desipramine both increase sedation. Use Caution/Monitor.Minor (2)belladonna alkaloids and desipramine both decrease cholinergic effects/transmission. Minor/Significance Unknown.
  
  phenobarbital, desipramine. Other (see comment). Minor/Significance Unknown. Comment: Barbiturates may increase adverse effects, including respiratory depression, produced by toxic doses of TCAs. With therapeutic doses of TCAs, barbiturates increase metabolism and decrease blood concentrations of TCAs.

• dexamethasone

  Monitor Closely (2)phenobarbital will decrease the level or effect of dexamethasone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
  
  phenobarbital will decrease the level or effect of dexamethasone by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• dexchlorpheniramine

  Monitor Closely (1)dexchlorpheniramine and phenobarbital both increase sedation. Use Caution/Monitor.

• dexfenfluramine

  Monitor Closely (1)phenobarbital increases and dexfenfluramine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• dexlansoprazole

  Serious - Use Alternative (1)phenobarbital will decrease the level or effect of dexlansoprazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• dexmedetomidine

  Monitor Closely (1)phenobarbital and dexmedetomidine both increase sedation. Use Caution/Monitor.

• dexmethylphenidate

  Monitor Closely (1)phenobarbital increases and dexmethylphenidate decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.Minor (1)dexmethylphenidate increases effects of phenobarbital by decreasing metabolism. Minor/Significance Unknown.

• dextroamphetamine

  Monitor Closely (1)phenobarbital increases and dextroamphetamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• dextromoramide

  Monitor Closely (1)phenobarbital and dextromoramide both increase sedation. Use Caution/Monitor.

• diamorphine

  Monitor Closely (1)phenobarbital and diamorphine both increase sedation. Use Caution/Monitor.

• diazepam

  Monitor Closely (2)phenobarbital will decrease the level or effect of diazepam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
  
  phenobarbital and diazepam both increase sedation. Use Caution/Monitor.Minor (1)phenobarbital will decrease the level or effect of diazepam by affecting hepatic enzyme CYP2C19 metabolism. Minor/Significance Unknown.

• diazepam intranasal

  Monitor Closely (2)phenobarbital will decrease the level or effect of diazepam intranasal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Strong or moderate CYP3A4 inducers may increase rate of diazepam elimination; therefore, efficacy of diazepam may be decreased.
  
  diazepam intranasal, phenobarbital. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Coadministration may potentiate the CNS-depressant effects of each drug.

• diclofenac

  Minor (1)phenobarbital will decrease the level or effect of diclofenac by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

• dicyclomine

  Monitor Closely (1)belladonna alkaloids and dicyclomine both decrease cholinergic effects/transmission. Use Caution/Monitor.

• dienogest/estradiol valerate

  Contraindicated (1)phenobarbital will decrease the level or effect of dienogest/estradiol valerate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Women should not choose estradiol valerate/dienogest as their contraceptive while using strong CYP3A4 inducers due to potential decrease in contraceptive efficacy. Estradiol valerate/dienogest should not be used for at least 28 days after discontinuation of the inducer due to possibility of decreased contraceptive efficacy.

• diethylpropion

  Monitor Closely (1)phenobarbital increases and diethylpropion decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• difelikefalin

  Monitor Closely (1)difelikefalin and phenobarbital both increase sedation. Use Caution/Monitor.

• difenoxin hcl

  Monitor Closely (1)phenobarbital and difenoxin hcl both increase sedation. Use Caution/Monitor.

• digoxin

  Monitor Closely (1)phenobarbital will decrease the level or effect of digoxin by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• dihydroergotamine

  Serious - Use Alternative (1)phenobarbital will decrease the level or effect of dihydroergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• dihydroergotamine intranasal

  Serious - Use Alternative (1)phenobarbital will decrease the level or effect of dihydroergotamine intranasal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• diltiazem

  Monitor Closely (1)phenobarbital will decrease the level or effect of diltiazem by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• dimenhydrinate

  Monitor Closely (1)dimenhydrinate and phenobarbital both increase sedation. Use Caution/Monitor.Minor (1)dimenhydrinate increases toxicity of belladonna alkaloids by pharmacodynamic synergism. Minor/Significance Unknown. Additive anticholinergic effects.

• diphenhydramine

  Monitor Closely (2)belladonna alkaloids and diphenhydramine both decrease cholinergic effects/transmission. Use Caution/Monitor.
  
  diphenhydramine and phenobarbital both increase sedation. Use Caution/Monitor.

• diphenoxylate hcl

  Monitor Closely (1)phenobarbital and diphenoxylate hcl both increase sedation. Use Caution/Monitor.

• dipipanone

  Monitor Closely (1)phenobarbital and dipipanone both increase sedation. Use Caution/Monitor.

• disopyramide

  Minor (1)phenobarbital will decrease the level or effect of disopyramide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• dobutamine

  Monitor Closely (1)phenobarbital increases and dobutamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• docetaxel

  Monitor Closely (1)phenobarbital will decrease the level or effect of docetaxel by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.Minor (1)phenobarbital will decrease the level or effect of docetaxel by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• dolutegravir

  Serious - Use Alternative (1)phenobarbital will decrease the level or effect of dolutegravir by increasing metabolism. Avoid or Use Alternate Drug. Avoid coadministration; insufficient data to recommend dosage adjustment

• donepezil

  Monitor Closely (1)donepezil increases and belladonna alkaloids decreases cholinergic effects/transmission. Effect of interaction is not clear, use caution. Use Caution/Monitor.Minor (2)phenobarbital will decrease the level or effect of donepezil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
  
  donepezil decreases effects of belladonna alkaloids by pharmacodynamic antagonism. Minor/Significance Unknown.

• dopamine

  Monitor Closely (1)phenobarbital increases and dopamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• dopexamine

  Monitor Closely (1)phenobarbital increases and dopexamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• doravirine

  Contraindicated (1)phenobarbital will decrease the level or effect of doravirine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Coadministration of doravirine with a strong CYP3A inducer may decrease doravirine plasma concentrations and/or effects. Potential for loss of virologic response and possible resistance to doravirine.

• dosulepin

  Monitor Closely (2)belladonna alkaloids and dosulepin both decrease cholinergic effects/transmission. Use Caution/Monitor.
  
  phenobarbital and dosulepin both increase sedation. Use Caution/Monitor.Minor (1)phenobarbital, dosulepin. Other (see comment). Minor/Significance Unknown. Comment: Barbiturates may increase adverse effects, including respiratory depression, produced by toxic doses of TCAs. With therapeutic doses of TCAs, barbiturates increase metabolism and decrease blood concentrations of TCAs.

• doxepin

  Monitor Closely (2)phenobarbital and doxepin both increase sedation. Use Caution/Monitor.
  
  belladonna alkaloids and doxepin both decrease cholinergic effects/transmission. Use Caution/Monitor.Minor (1)phenobarbital, doxepin. Other (see comment). Minor/Significance Unknown. Comment: Barbiturates may increase adverse effects, including respiratory depression, produced by toxic doses of TCAs. With therapeutic doses of TCAs, barbiturates increase metabolism and decrease blood concentrations of TCAs.

• doxorubicin

  Monitor Closely (2)phenobarbital will decrease the level or effect of doxorubicin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
  
  phenobarbital decreases levels of doxorubicin by increasing elimination. Use Caution/Monitor.

• doxorubicin liposomal

  Monitor Closely (2)phenobarbital will decrease the level or effect of doxorubicin liposomal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
  
  phenobarbital decreases levels of doxorubicin liposomal by increasing elimination. Use Caution/Monitor.

• doxycycline

  Monitor Closely (1)phenobarbital decreases levels of doxycycline by increasing metabolism. Use Caution/Monitor.

• doxylamine

  Monitor Closely (1)phenobarbital and doxylamine both increase sedation. Use Caution/Monitor.

• dronabinol

  Monitor Closely (2)phenobarbital will decrease the level or effect of dronabinol by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor. Dronabinol is a CYP2C9 substrate.
  
  phenobarbital will decrease the level or effect of dronabinol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Dronabinol is a CYP3A4 substrate.

• dronedarone

  Serious - Use Alternative (1)phenobarbital will decrease the level or effect of dronedarone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• droperidol

  Monitor Closely (4)belladonna alkaloids decreases levels of droperidol by pharmacodynamic antagonism. Use Caution/Monitor.
  
  phenobarbital and droperidol both increase sedation. Use Caution/Monitor.
  
  belladonna alkaloids decreases levels of droperidol by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
  
  droperidol increases effects of belladonna alkaloids by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.

• dulaglutide

  Monitor Closely (1)dulaglutide, phenobarbital. Other (see comment). Use Caution/Monitor. Comment: Dulaglutide slows gastric emptying and may impact absorption of concomitantly administered oral medications; be particularly cautious when coadministered with drugs that have a narrow therapeutic index.

• duloxetine

  Serious - Use Alternative (1)phenobarbital will decrease the level or effect of duloxetine by affecting hepatic enzyme CYP1A2 metabolism. Avoid or Use Alternate Drug.

• dupilumab

  Monitor Closely (1)dupilumab, phenobarbital. Other (see comment). Use Caution/Monitor. Comment: Formation of CYP450 enzymes can be altered by increased levels of certain cytokines during chronic inflammation; thus, dupilumab could normalize the formation of CYP450 enzymes. Upon initiation or discontinuation of dupilumab in patients who are receiving concomitant CYP450 substrates, particularly those with a narrow therapeutic index, consider monitoring for therapeutic effect.

• dutasteride

  Minor (1)phenobarbital will decrease the level or effect of dutasteride by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• duvelisib

  Monitor Closely (1)phenobarbital will decrease the level or effect of duvelisib by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.Serious - Use Alternative (1)phenobarbital will decrease the level or effect of duvelisib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration with a strong CYP3A inducer decreases duvelisib area under the curve (AUC), which may reduce duvelisib efficacy.

• echothiophate iodide

  Monitor Closely (1)echothiophate iodide increases and belladonna alkaloids decreases cholinergic effects/transmission. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• edoxaban

  Serious - Use Alternative (1)phenobarbital will decrease the level or effect of edoxaban by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug. Avoid coadministration of edoxaban with potent P-gp inducers

• efavirenz

  Minor (1)phenobarbital will decrease the level or effect of efavirenz by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• elacestrant

  Serious - Use Alternative (1)phenobarbital will decrease the level or effect of elacestrant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• elagolix

  Monitor Closely (2)phenobarbital will decrease the level or effect of elagolix by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
  
  elagolix will increase the level or effect of phenobarbital by affecting hepatic enzyme CYP2C19 metabolism. Modify Therapy/Monitor Closely. Elagolix is a weak CYP2C19 inhibitor. Caution with sensitive CYP2C19 substrates.

• elbasvir/grazoprevir

  Contraindicated (1)phenobarbital will decrease the level or effect of elbasvir/grazoprevir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. The therapeutic effect of elbasvir/grazoprevir may be reduced if coadministered with strong CYP3A inducers and is therefore contraindicated.

• eletriptan

  Monitor Closely (1)phenobarbital will decrease the level or effect of eletriptan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• eliglustat

  Serious - Use Alternative (1)phenobarbital will decrease the level or effect of eliglustat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Strong CYP3A inducers significantly decreases eliglustat exposure; coadministration not recommended

• eltrombopag

  Monitor Closely (2)phenobarbital will decrease the level or effect of eltrombopag by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.
  
  phenobarbital will decrease the level or effect of eltrombopag by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor.

• elvitegravir

  Serious - Use Alternative (1)phenobarbital will decrease the level or effect of elvitegravir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid; coadministration with CYP3A inducers may result in decreased plasma concentrations of elvitegravir and/or a concomitantly administered protease inhibitor and lead to loss of therapeutic effect and to possible resistance

• elvitegravir/cobicistat/emtricitabine/tenofovir DF

  Contraindicated (1)phenobarbital decreases levels of elvitegravir/cobicistat/emtricitabine/tenofovir DF by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. May lead to loss of virologic response and possible resistance.

• encorafenib

  Serious - Use Alternative (1)phenobarbital will decrease the level or effect of encorafenib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• enfortumab vedotin

  Monitor Closely (1)phenobarbital will decrease the level or effect of enfortumab vedotin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• enoxaparin

  Serious - Use Alternative (1)phenobarbital decreases effects of enoxaparin by increasing metabolism. Avoid or Use Alternate Drug.

• entrectinib

  Serious - Use Alternative (1)phenobarbital will decrease the level or effect of entrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• enzalutamide

  Serious - Use Alternative (1)phenobarbital will decrease the level or effect of enzalutamide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• ephedrine

  Monitor Closely (1)phenobarbital increases and ephedrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• epinephrine

  Monitor Closely (1)phenobarbital increases and epinephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• epinephrine racemic

  Monitor Closely (1)phenobarbital increases and epinephrine racemic decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• eplerenone

  Minor (1)phenobarbital will decrease the level or effect of eplerenone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• erdafitinib

  Serious - Use Alternative (1)phenobarbital will decrease the level or effect of erdafitinib by altering metabolism. Avoid or Use Alternate Drug. Avoid coadministration of strong CYP2C9 or CYP3A4 inducers with erdafitinib.

• ergotamine

  Serious - Use Alternative (1)phenobarbital will decrease the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• erlotinib

  Monitor Closely (1)phenobarbital will decrease the level or effect of erlotinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• erythromycin base

  Serious - Use Alternative (1)phenobarbital will decrease the level or effect of erythromycin base by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.Minor (1)phenobarbital decreases levels of erythromycin base by increasing elimination. Minor/Significance Unknown.

• erythromycin ethylsuccinate

  Serious - Use Alternative (1)phenobarbital will decrease the level or effect of erythromycin ethylsuccinate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.Minor (1)phenobarbital decreases levels of erythromycin ethylsuccinate by increasing elimination. Minor/Significance Unknown.

• erythromycin lactobionate

  Serious - Use Alternative (1)phenobarbital will decrease the level or effect of erythromycin lactobionate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.Minor (1)phenobarbital decreases levels of erythromycin lactobionate by increasing elimination. Minor/Significance Unknown.

• erythromycin stearate

  Serious - Use Alternative (1)phenobarbital will decrease the level or effect of erythromycin stearate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.Minor (1)phenobarbital decreases levels of erythromycin stearate by increasing elimination. Minor/Significance Unknown.

• escitalopram

  Monitor Closely (2)phenobarbital will decrease the level or effect of escitalopram by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
  
  phenobarbital will decrease the level or effect of escitalopram by affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor.

• eslicarbazepine acetate

  Monitor Closely (2)phenobarbital will decrease the level or effect of eslicarbazepine acetate by increasing metabolism. Use Caution/Monitor. Higher dosage of eslicarbazepine may be necessary
  
  eslicarbazepine acetate will increase the level or effect of phenobarbital by affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor.

• esmolol

  Monitor Closely (1)phenobarbital decreases levels of esmolol by increasing metabolism. Use Caution/Monitor. Consider a higher beta-blocker dose during coadministration of phenobarbital. Atenolol, sotalol, nadolol less likely to be affected than other beta blockers.

• esomeprazole

  Monitor Closely (1)phenobarbital will decrease the level or effect of esomeprazole by affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor.Serious - Use Alternative (1)phenobarbital will decrease the level or effect of esomeprazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• estazolam

  Monitor Closely (1)phenobarbital and estazolam both increase sedation. Use Caution/Monitor.

• estradiol

  Monitor Closely (2)phenobarbital will decrease the level or effect of estradiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
  
  phenobarbital will decrease the level or effect of estradiol by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• estradiol vaginal

  Monitor Closely (1)phenobarbital will decrease the level or effect of estradiol vaginal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• estrogens conjugated synthetic

  Monitor Closely (2)phenobarbital will decrease the level or effect of estrogens conjugated synthetic by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
  
  phenobarbital will decrease the level or effect of estrogens conjugated synthetic by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• estrogens esterified

  Monitor Closely (1)phenobarbital will decrease the level or effect of estrogens esterified by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• estropipate

  Monitor Closely (2)phenobarbital will decrease the level or effect of estropipate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
  
  phenobarbital will decrease the level or effect of estropipate by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• eszopiclone

  Serious - Use Alternative (1)phenobarbital will decrease the level or effect of eszopiclone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• ethanol

  Monitor Closely (1)phenobarbital and ethanol both increase sedation. Use Caution/Monitor.

• ethinylestradiol

  Serious - Use Alternative (1)phenobarbital will decrease the level or effect of ethinylestradiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. The efficacy of hormonal contraceptives may be reduced. Use of a nonhormonal contraceptive is recommended.

• ethosuximide

  Monitor Closely (1)phenobarbital will decrease the level or effect of ethosuximide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.Minor (1)ethosuximide decreases effects of phenobarbital by pharmacodynamic antagonism. Minor/Significance Unknown.

• ethotoin

  Monitor Closely (1)phenobarbital will decrease the level or effect of ethotoin by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor.Minor (1)phenobarbital decreases levels of ethotoin by increasing metabolism. Minor/Significance Unknown. Phenobarbital may occasionally not change or even increase (via competitive inhibition) phenytoin levels.

• etomidate

  Monitor Closely (1)etomidate and phenobarbital both increase sedation. Use Caution/Monitor.

• etonogestrel

  Monitor Closely (1)phenobarbital will decrease the level or effect of etonogestrel by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• etoposide

  Monitor Closely (1)phenobarbital will decrease the level or effect of etoposide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• etravirine

  Contraindicated (1)phenobarbital decreases levels of etravirine by increasing metabolism. Contraindicated.Monitor Closely (3)phenobarbital will decrease the level or effect of etravirine by affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor.
  
  phenobarbital will decrease the level or effect of etravirine by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor.
  
  phenobarbital will decrease the level or effect of etravirine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• eucalyptus

  Minor (2)phenobarbital will decrease the level or effect of eucalyptus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
  
  phenobarbital and eucalyptus both increase sedation. Minor/Significance Unknown.

• everolimus

  Serious - Use Alternative (2)phenobarbital will decrease the level or effect of everolimus by P-glycoprotein (MDR1) efflux transporter. Contraindicated.
  
  phenobarbital will decrease the level or effect of everolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• exemestane

  Monitor Closely (1)phenobarbital will decrease the level or effect of exemestane by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. For patients receiving exemestane with a potent CYP3A4 inducer the recommended dose of exemestane is 50 mg daily after a meal.

• fedratinib

  Monitor Closely (1)fedratinib will increase the level or effect of phenobarbital by affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP2C19 substrates as necessary.Serious - Use Alternative (1)phenobarbital will decrease the level or effect of fedratinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Effect of coadministering a strong CYP3A4 inducer with fedratinib has not been studied.

• felbamate

  Monitor Closely (1)phenobarbital will decrease the level or effect of felbamate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.Minor (1)felbamate increases levels of phenobarbital by decreasing metabolism. Minor/Significance Unknown.

• felodipine

  Monitor Closely (1)phenobarbital will decrease the level or effect of felodipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• fenfluramine

  Monitor Closely (2)phenobarbital will decrease the level or effect of fenfluramine by Other (see comment). Modify Therapy/Monitor Closely. Coadministration with drugs that increase serotonin may increase the risk of serotonin syndrome.
  
  phenobarbital increases and fenfluramine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• fentanyl

  Monitor Closely (1)phenobarbital will decrease the level or effect of fentanyl by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Coadministration of fentanyl with CYP3A4 inducers could lead to a decrease in fentanyl plasma concentrations, lack of efficacy or, possibly, development of a withdrawal syndrome in a patient who has developed physical dependence to fentanyl. After stopping a CYP3A4 inducer, as the effects of the inducer decline, the fentanyl plasma concentration will increase which could increase or prolong both the therapeutic and adverse effects.

• fentanyl intranasal

  Monitor Closely (1)phenobarbital will decrease the level or effect of fentanyl intranasal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Coadministration of fentanyl with CYP3A4 inducers could lead to a decrease in fentanyl plasma concentrations, lack of efficacy or, possibly, development of a withdrawal syndrome in a patient who has developed physical dependence to fentanyl. After stopping a CYP3A4 inducer, as the effects of the inducer decline, the fentanyl plasma concentration will increase which could increase or prolong both the therapeutic and adverse effects.

• fentanyl transdermal

  Monitor Closely (1)phenobarbital will decrease the level or effect of fentanyl transdermal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Coadministration of fentanyl with CYP3A4 inducers could lead to a decrease in fentanyl plasma concentrations, lack of efficacy or, possibly, development of a withdrawal syndrome in a patient who has developed physical dependence to fentanyl. After stopping a CYP3A4 inducer, as the effects of the inducer decline, the fentanyl plasma concentration will increase which could increase or prolong both the therapeutic and adverse effects.

• fentanyl transmucosal

  Monitor Closely (1)phenobarbital will decrease the level or effect of fentanyl transmucosal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Coadministration of fentanyl with CYP3A4 inducers could lead to a decrease in fentanyl plasma concentrations, lack of efficacy or, possibly, development of a withdrawal syndrome in a patient who has developed physical dependence to fentanyl. After stopping a CYP3A4 inducer, as the effects of the inducer decline, the fentanyl plasma concentration will increase which could increase or prolong both the therapeutic and adverse effects.

• ferric maltol

  Monitor Closely (1)ferric maltol, phenobarbital. Either increases levels of the other by unspecified interaction mechanism. Modify Therapy/Monitor Closely. Coadministration of ferric maltol with certain oral medications may decrease the bioavailability of either ferric maltol and some oral drugs. For oral drugs where reductions in bioavailability may cause clinically significant effects on its safety or efficacy, separate administration of ferric maltol from these drugs. Duration of separation may depend on the absorption of the medication concomitantly administered (eg, time to peak concentration, whether the drug is an immediate or extended release product).

• fesoterodine

  Monitor Closely (2)belladonna alkaloids and fesoterodine both decrease cholinergic effects/transmission. Use Caution/Monitor.
  
  phenobarbital will decrease the level or effect of fesoterodine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• fexinidazole

  Monitor Closely (1)fexinidazole will increase the level or effect of phenobarbital by affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor.Serious - Use Alternative (1)phenobarbital will increase the level or effect of fexinidazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. CYP450 inducers may significantly increase plasma concentrations of fexinidazole?s active metabolites: fexinidazole sulfoxide (M1) and fexinidazole sulfone (M2). M2 plasma concentrations associated with increased QT prolongation risks.

• fexofenadine

  Minor (1)phenobarbital will decrease the level or effect of fexofenadine by P-glycoprotein (MDR1) efflux transporter. Minor/Significance Unknown.

• finasteride

  Minor (1)phenobarbital will decrease the level or effect of finasteride by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• finerenone

  Serious - Use Alternative (1)phenobarbital will decrease the level or effect of finerenone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• flavoxate

  Monitor Closely (1)belladonna alkaloids and flavoxate both decrease cholinergic effects/transmission. Use Caution/Monitor.

• flibanserin

  Monitor Closely (1)phenobarbital will decrease the level or effect of flibanserin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Strong CYP3A4 inducers substantially decrease flibanserin systemic exposure.

• fluconazole

  Minor (1)phenobarbital decreases levels of fluconazole by inhibition of GI absorption. Applies only to oral form of both agents. Minor/Significance Unknown.

• fludrocortisone

  Monitor Closely (2)phenobarbital will decrease the level or effect of fludrocortisone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
  
  phenobarbital will decrease the level or effect of fludrocortisone by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• fluphenazine

  Monitor Closely (4)belladonna alkaloids decreases levels of fluphenazine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
  
  belladonna alkaloids decreases levels of fluphenazine by pharmacodynamic antagonism. Use Caution/Monitor.
  
  fluphenazine increases effects of belladonna alkaloids by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.
  
  phenobarbital and fluphenazine both increase sedation. Use Caution/Monitor.

• flurazepam

  Monitor Closely (1)phenobarbital and flurazepam both increase sedation. Use Caution/Monitor.Serious - Use Alternative (1)phenobarbital will decrease the level or effect of flurazepam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• flurbiprofen

  Minor (1)phenobarbital will decrease the level or effect of flurbiprofen by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

• fluticasone furoate

  Monitor Closely (1)phenobarbital will decrease the level or effect of fluticasone furoate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• fluticasone inhaled

  Monitor Closely (1)phenobarbital will decrease the level or effect of fluticasone inhaled by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• fluvastatin

  Minor (1)phenobarbital will decrease the level or effect of fluvastatin by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

• folic acid

  Minor (2)folic acid decreases levels of phenobarbital by increasing metabolism. Minor/Significance Unknown.
  
  phenobarbital decreases levels of folic acid by inhibition of GI absorption. Applies only to oral form of both agents. Minor/Significance Unknown.

• fondaparinux

  Serious - Use Alternative (1)phenobarbital decreases effects of fondaparinux by increasing metabolism. Avoid or Use Alternate Drug.

• formoterol

  Monitor Closely (1)phenobarbital increases and formoterol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• fosamprenavir

  Monitor Closely (1)phenobarbital will decrease the level or effect of fosamprenavir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• fosaprepitant

  Monitor Closely (1)phenobarbital will decrease the level or effect of fosaprepitant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• fosphenytoin

  Monitor Closely (1)phenobarbital will decrease the level or effect of fosphenytoin by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor.Minor (1)phenobarbital decreases levels of fosphenytoin by increasing metabolism. Minor/Significance Unknown. Phenobarbital may occasionally not change or even increase (via competitive inhibition) phenytoin levels.

• fostamatinib

  Serious - Use Alternative (1)phenobarbital will decrease the level or effect of fostamatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• fostemsavir

  Contraindicated (1)phenobarbital will decrease the level or effect of fostemsavir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Coadministration of fostemsavir (prodrug) with strong CYP3A4 inducers significantly decreases temsavir (active moiety) plasma concentrations, which may lead to loss of virologic response and resistance.

• frovatriptan

  Minor (1)phenobarbital will decrease the level or effect of frovatriptan by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.

• furosemide

  Minor (1)phenobarbital decreases levels of furosemide by inhibition of GI absorption. Applies only to oral form of both agents. Minor/Significance Unknown.

• galantamine

  Monitor Closely (1)galantamine increases and belladonna alkaloids decreases cholinergic effects/transmission. Effect of interaction is not clear, use caution. Use Caution/Monitor.Minor (2)phenobarbital will decrease the level or effect of galantamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
  
  galantamine decreases effects of belladonna alkaloids by pharmacodynamic antagonism. Minor/Significance Unknown.

• ganaxolone

  Serious - Use Alternative (1)phenobarbital will decrease the level or effect of ganaxolone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of ganaxolone with moderate or strong CYP3A4 inducers. If coadministration unavoidable, consider increasing ganaxolone dose; however, do not exceed maximum daily dose for weight.

• gefitinib

  Monitor Closely (1)phenobarbital will decrease the level or effect of gefitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Increase gefitinib to 500 mg daily if coadministered with a strong CYP3A4 inducer. Resume gefitinib dose at 250 mg/day 7 days after discontinuing the strong inducer.

• gentamicin

  Monitor Closely (1)phenobarbital will decrease the level or effect of gentamicin by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• gilteritinib

  Serious - Use Alternative (1)phenobarbital will decrease the level or effect of gilteritinib by Other (see comment). Avoid or Use Alternate Drug. Gilteritinib is a P-gp and CYP3A4 substrates. Coadministration of gilteritinib with a combined P-gp and strong CYP3A inducer decreases gilteritinib exposure and efficacy.

• glasdegib

  Serious - Use Alternative (1)phenobarbital will decrease the level or effect of glasdegib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of glasdegib with strong CYP3A inducers.

• glecaprevir/pibrentasvir

  Monitor Closely (2)phenobarbital will decrease the level or effect of glecaprevir/pibrentasvir by increasing metabolism. Use Caution/Monitor. Coadministration of drugs that induce CYP3A4 and P-gp with glecaprevir/pibrentasvir may decrease glecaprevir/pibrentasvir plasma concentrations. Potential for loss of therapeutic effect.
  
  phenobarbital will decrease the level or effect of glecaprevir/pibrentasvir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• glyburide

  Monitor Closely (1)phenobarbital decreases levels of glyburide by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor. Strong CYP2C9 inducers may increase glyburide metabolism.

• glycopyrrolate

  Monitor Closely (1)belladonna alkaloids and glycopyrrolate both decrease cholinergic effects/transmission. Use Caution/Monitor.

• glycopyrrolate inhaled

  Monitor Closely (1)belladonna alkaloids and glycopyrrolate inhaled both decrease cholinergic effects/transmission. Use Caution/Monitor.

• gotu kola

  Monitor Closely (1)gotu kola increases effects of phenobarbital by pharmacodynamic synergism. Use Caution/Monitor. May enhance CNS depression.

• green tea

  Minor (1)phenobarbital will decrease the level or effect of green tea by increasing metabolism. Minor/Significance Unknown. Green tea products may contain caffeine. The metabolism of xanthines, such as caffeine, can be increased by concurrent use with barbiturates.

• griseofulvin

  Minor (1)phenobarbital decreases levels of griseofulvin by inhibition of GI absorption. Applies only to oral form of both agents. Minor/Significance Unknown.

• guanfacine

  Monitor Closely (1)phenobarbital will decrease the level or effect of guanfacine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Strong or moderate CYP3A4 inducers significantly reduce guanfacine plasma concentrations and elimination half-life. If coadministered, more frequent dosing of the IR product may be required to achieve or maintain the desired hypotensive response. For patients with ADHD, FDA-approved labeling for ER guanfacine recommends that, if coadministered, doubling the recommended dose of guanfacine should be considered.

• guselkumab

  Monitor Closely (1)guselkumab, phenobarbital. Other (see comment). Use Caution/Monitor. Comment: Formation of CYP450 enzymes can be altered by increased levels of certain cytokines during chronic inflammation; thus, normalizing the formation of CYP450 enzymes. Upon initiation or discontinuation of guselkumab in patients who are receiving concomitant CYP450 substrates, particularly those with a narrow therapeutic index, consider monitoring for therapeutic effect.

• haloperidol

  Monitor Closely (5)haloperidol increases effects of belladonna alkaloids by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.
  
  phenobarbital and haloperidol both increase sedation. Use Caution/Monitor.
  
  belladonna alkaloids decreases levels of haloperidol by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
  
  phenobarbital will decrease the level or effect of haloperidol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
  
  belladonna alkaloids decreases levels of haloperidol by pharmacodynamic antagonism. Use Caution/Monitor.Minor (1)haloperidol, phenobarbital. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Risk of hyperthermia if haloperidol admin. during barbiturate withdrawal.

• hawthorn

  Monitor Closely (1)hawthorn increases effects of phenobarbital by pharmacodynamic synergism. Use Caution/Monitor. May enhance CNS depression.

• hemin

  Monitor Closely (1)phenobarbital decreases effects of hemin by pharmacodynamic antagonism. Use Caution/Monitor. Drugs that increase delta-aminolevulinic acid synthetase may decrease hemin effect.

• henbane

  Monitor Closely (1)belladonna alkaloids and henbane both decrease cholinergic effects/transmission. Use Caution/Monitor.

• heparin

  Serious - Use Alternative (1)phenobarbital decreases effects of heparin by increasing metabolism. Avoid or Use Alternate Drug.

• homatropine

  Monitor Closely (1)belladonna alkaloids and homatropine both decrease cholinergic effects/transmission. Use Caution/Monitor.

• hops

  Monitor Closely (1)hops increases effects of phenobarbital by pharmacodynamic synergism. Use Caution/Monitor. May enhance CNS depression.

• huperzine A

  Monitor Closely (1)huperzine A increases and belladonna alkaloids decreases cholinergic effects/transmission. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• hydrocodone

  Monitor Closely (1)phenobarbital will decrease the level or effect of hydrocodone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Caution when discontinuing CYP3A4 inducers that are coadministered with hydrocodone; plasma concentrations of hydrocodone may increase and can result in potentially fatal respiratory depressionSerious - Use Alternative (1)hydrocodone, phenobarbital. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.

• hydrocortisone

  Monitor Closely (2)phenobarbital will decrease the level or effect of hydrocortisone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
  
  phenobarbital will decrease the level or effect of hydrocortisone by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• hydromorphone

  Monitor Closely (1)phenobarbital and hydromorphone both increase sedation. Use Caution/Monitor.

• hydroxyprogesterone caproate (DSC)

  Monitor Closely (1)phenobarbital will decrease the level or effect of hydroxyprogesterone caproate (DSC) by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• hydroxyzine

  Monitor Closely (1)hydroxyzine and phenobarbital both increase sedation. Use Caution/Monitor.

• hyoscyamine

  Monitor Closely (1)belladonna alkaloids and hyoscyamine both decrease cholinergic effects/transmission. Use Caution/Monitor.

• hyoscyamine spray

  Monitor Closely (1)belladonna alkaloids and hyoscyamine spray both decrease cholinergic effects/transmission. Use Caution/Monitor.

• ibrutinib

  Serious - Use Alternative (1)phenobarbital decreases levels of ibrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Strong CYP3A inducers decrease ibrutinib plasma concentrations by ~10-fold.

• ibuprofen

  Minor (1)phenobarbital will decrease the level or effect of ibuprofen by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

• ibuprofen IV

  Minor (1)phenobarbital will decrease the level or effect of ibuprofen IV by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

• idelalisib

  Serious - Use Alternative (1)phenobarbital will decrease the level or effect of idelalisib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration; strong CYP3A4 inducers significantly decrease idelalisib systemic exposure

• ifosfamide

  Monitor Closely (2)phenobarbital increases effects of ifosfamide by affecting hepatic enzyme CYP2B6 metabolism. Use Caution/Monitor. Coadministration of ifosfamide with CYP2B6 inducers may increase metabolism of ifosfamide to its metabolite. Monitor for increased effects/toxicities if combined with CYP2B6 inducers.
  
  phenobarbital increases toxicity of ifosfamide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. CYP3A4 inducers may increase the metabolism of ifosfamide to its active alkylating metabolites. CYP3A4 inducers may increase the formation of the neurotoxic/nephrotoxic ifosfamide metabolite, chloroacetaldehyde. Closely monitor patients taking ifosfamide with CYP3A4 inducers for toxicities and consider dose adjustment.

• iloperidone

  Monitor Closely (5)iloperidone increases effects of belladonna alkaloids by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.
  
  belladonna alkaloids decreases levels of iloperidone by pharmacodynamic antagonism. Use Caution/Monitor.
  
  phenobarbital and iloperidone both increase sedation. Use Caution/Monitor.
  
  belladonna alkaloids decreases levels of iloperidone by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
  
  phenobarbital will decrease the level or effect of iloperidone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• imatinib

  Monitor Closely (1)phenobarbital will decrease the level or effect of imatinib by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.Minor (1)phenobarbital will decrease the level or effect of imatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• imipramine

  Monitor Closely (5)phenobarbital and imipramine both increase sedation. Use Caution/Monitor.
  
  belladonna alkaloids and imipramine both decrease cholinergic effects/transmission. Use Caution/Monitor.
  
  phenobarbital will decrease the level or effect of imipramine by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.
  
  phenobarbital will decrease the level or effect of imipramine by affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor.
  
  phenobarbital will decrease the level or effect of imipramine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely.Minor (1)phenobarbital, imipramine. Other (see comment). Minor/Significance Unknown. Comment: Barbiturates may increase adverse effects, including respiratory depression, produced by toxic doses of TCAs. With therapeutic doses of TCAs, barbiturates increase metabolism and decrease blood concentrations of TCAs.

• incobotulinumtoxinA

  Monitor Closely (1)belladonna alkaloids, incobotulinumtoxinA. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Use of anticholinergic drugs after administration of botulinum toxin-containing products may potentiate systemic anticholinergic effects.

• indinavir

  Monitor Closely (2)phenobarbital will decrease the level or effect of indinavir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
  
  phenobarbital will decrease the level or effect of indinavir by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• infigratinib

  Serious - Use Alternative (1)phenobarbital will decrease the level or effect of infigratinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• ipratropium

  Monitor Closely (1)belladonna alkaloids and ipratropium both decrease cholinergic effects/transmission. Use Caution/Monitor. Due to the poor systemic absorption of ipratropium, interaction unlikely at regularly recommended dosages.

• irinotecan

  Serious - Use Alternative (1)phenobarbital will decrease the level or effect of irinotecan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• irinotecan liposomal

  Serious - Use Alternative (1)phenobarbital will decrease the level or effect of irinotecan liposomal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• isavuconazonium sulfate

  Contraindicated (1)phenobarbital will decrease the level or effect of isavuconazonium sulfate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.

• isocarboxazid

  Serious - Use Alternative (1)isocarboxazid, phenobarbital. Other (see comment). Avoid or Use Alternate Drug. Comment: CNS depressants such as barbiturates should not be used in combination with isocarboxazid.Minor (1)isocarboxazid increases levels of phenobarbital by decreasing metabolism. Minor/Significance Unknown. Theoretical interaction.

• isoproterenol

  Monitor Closely (1)phenobarbital increases and isoproterenol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• isosorbide dinitrate

  Serious - Use Alternative (1)phenobarbital will decrease the level or effect of isosorbide dinitrate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• isosorbide mononitrate

  Serious - Use Alternative (1)phenobarbital will decrease the level or effect of isosorbide mononitrate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• isradipine

  Minor (1)phenobarbital will decrease the level or effect of isradipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• istradefylline

  Serious - Use Alternative (1)phenobarbital will decrease the level or effect of istradefylline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of istradefylline with strong CYP3A4 inducers.

• itraconazole

  Monitor Closely (1)phenobarbital will decrease the level or effect of itraconazole by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.Minor (2)phenobarbital will decrease the level or effect of itraconazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
  
  phenobarbital decreases levels of itraconazole by inhibition of GI absorption. Applies only to oral form of both agents. Minor/Significance Unknown.

• ivabradine

  Serious - Use Alternative (1)phenobarbital will decrease the level or effect of ivabradine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of ivabradine with moderate CYP3A4 inducers.

• ivacaftor

  Serious - Use Alternative (1)phenobarbital decreases levels of ivacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration with strong CYP3A4 inducers; systemic exposure of ivacaftor substantially reduced (ie, ~9-fold).

• ivermectin

  Monitor Closely (1)phenobarbital will decrease the level or effect of ivermectin by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• ivosidenib

  Serious - Use Alternative (1)phenobarbital will decrease the level or effect of ivosidenib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration of ivosidenib with strong CYP3A4 inducers decreased ivosidenib plasma concentrations.

• ixabepilone

  Monitor Closely (1)phenobarbital will decrease the level or effect of ixabepilone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• ixazomib

  Serious - Use Alternative (1)phenobarbital will decrease the level or effect of ixazomib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of ixazomib with strong CYP3A inducers. Strong inducers have been shown to decrease ixazomib Cmax by 54% and AUC by 74%.

• ixekizumab

  Monitor Closely (1)ixekizumab, phenobarbital. Other (see comment). Use Caution/Monitor. Comment: Formation of CYP450 enzymes can be altered by increased levels of certain cytokines during chronic inflammation; thus, ixekizumab could normalize the formation of CYP450 enzymes. Upon initiation or discontinuation of ixekizumab in patients who are receiving concomitant CYP450 substrates, particularly those with a narrow therapeutic index, consider monitoring for therapeutic effect.

• kava

  Monitor Closely (1)kava increases effects of phenobarbital by pharmacodynamic synergism. Use Caution/Monitor. May enhance CNS depression.

• ketamine

  Monitor Closely (1)ketamine and phenobarbital both increase sedation. Use Caution/Monitor.

• ketoconazole

  Minor (2)phenobarbital will decrease the level or effect of ketoconazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
  
  phenobarbital decreases levels of ketoconazole by inhibition of GI absorption. Applies only to oral form of both agents. Minor/Significance Unknown.

• ketotifen, ophthalmic

  Monitor Closely (1)phenobarbital and ketotifen, ophthalmic both increase sedation. Use Caution/Monitor.

• L-methylfolate

  Minor (2)L-methylfolate decreases levels of phenobarbital by increasing metabolism. Minor/Significance Unknown.
  
  phenobarbital decreases levels of L-methylfolate by inhibition of GI absorption. Applies only to oral form of both agents. Minor/Significance Unknown.

• labetalol

  Monitor Closely (1)phenobarbital decreases levels of labetalol by increasing metabolism. Use Caution/Monitor. Consider a higher beta-blocker dose during coadministration of phenobarbital. Atenolol, sotalol, nadolol less likely to be affected than other beta blockers.

• lamotrigine

  Monitor Closely (1)phenobarbital decreases levels of lamotrigine by increasing hepatic clearance. Use Caution/Monitor.

• lansoprazole

  Monitor Closely (1)phenobarbital will decrease the level or effect of lansoprazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.Minor (1)phenobarbital will decrease the level or effect of lansoprazole by affecting hepatic enzyme CYP2C19 metabolism. Minor/Significance Unknown.

• lapatinib

  Monitor Closely (2)phenobarbital will decrease the level or effect of lapatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
  
  phenobarbital will decrease the level or effect of lapatinib by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• larotrectinib

  Serious - Use Alternative (1)phenobarbital will decrease the level or effect of larotrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration of larotrectinib with strong CYP3A4 inducers is unavoidable, double larotrectinib dose. Resume prior larotrectinib dose once CYP3A4 inducer discontinued for 3-5 half-lives

• lasmiditan

  Monitor Closely (1)lasmiditan, phenobarbital. Either increases effects of the other by sedation. Use Caution/Monitor. Coadministration of lasmiditan and other CNS depressant drugs, including alcohol have not been evaluated in clinical studies. Lasmiditan may cause sedation, as well as other cognitive and/or neuropsychiatric adverse reactions.

• ledipasvir/sofosbuvir

  Contraindicated (1)phenobarbital will decrease the level or effect of ledipasvir/sofosbuvir by P-glycoprotein (MDR1) efflux transporter. Contraindicated. P-gp inducers decrease sofosbuvir levels, and therefore decrease conversion to sofosbuvir's active metabolite (GS-331007) responsible for 90% of pharmacologic effect

• lefamulin

  Serious - Use Alternative (1)phenobarbital will decrease the level or effect of lefamulin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of lefamulin with strong or moderate CYP3A inducers unless the benefit outweighs risks. Monitor for reduced efficacy.

• lemborexant

  Monitor Closely (1)lemborexant, phenobarbital. Either increases effects of the other by sedation. Modify Therapy/Monitor Closely. Dosage adjustment may be necessary if lemborexant is coadministered with other CNS depressants because of potentially additive effects.Serious - Use Alternative (1)phenobarbital will decrease the level or effect of lemborexant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• lenacapavir

  Serious - Use Alternative (1)phenobarbital will decrease the level or effect of lenacapavir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of lenacapavir with moderate CYP3A4 inducers.

• leniolisib

  Serious - Use Alternative (1)phenobarbital will decrease the level or effect of leniolisib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• lesinurad

  Monitor Closely (1)phenobarbital will decrease the level or effect of lesinurad by affecting hepatic enzyme CYP2C9/10 metabolism. Modify Therapy/Monitor Closely.

• letermovir

  Serious - Use Alternative (2)phenobarbital will decrease the level or effect of letermovir by Other (see comment). Avoid or Use Alternate Drug. Coadministration of letermovir with UCT1A1/3 inducers is not recommended.
  
  phenobarbital will decrease the level or effect of letermovir by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug. Coadministration of letermovir with P-gp inducers is not recommended.

• levalbuterol

  Monitor Closely (1)phenobarbital increases and levalbuterol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• levamlodipine

  Monitor Closely (1)phenobarbital will decrease the level or effect of levamlodipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. No information is available on the quantitative effects of CYP3A4 inducers on amlodipine. Closely monitor blood pressure when amlodipine is coadministered with CYP3A4 inducers.

• levocarnitine

  Minor (1)phenobarbital decreases levels of levocarnitine by unspecified interaction mechanism. Minor/Significance Unknown.

• levodopa

  Minor (1)belladonna alkaloids, levodopa. Other (see comment). Minor/Significance Unknown. Comment: Anticholinergic agents may enhance the therapeutic effects of levodopa; however, anticholinergic agents can exacerbate tardive dyskinesia. In high dosage, anticholinergics may decrease the effects of levodopa by delaying its GI absorption. .

• levoketoconazole

  Minor (2)phenobarbital will decrease the level or effect of levoketoconazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
  
  phenobarbital decreases levels of levoketoconazole by inhibition of GI absorption. Applies only to oral form of both agents. Minor/Significance Unknown.

• levonorgestrel intrauterine

  Monitor Closely (1)phenobarbital decreases levels of levonorgestrel intrauterine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• levonorgestrel oral

  Monitor Closely (1)phenobarbital decreases levels of levonorgestrel oral by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• levonorgestrel oral/ethinylestradiol/ferrous bisglycinate

  Monitor Closely (1)phenobarbital will decrease the level or effect of levonorgestrel oral/ethinylestradiol/ferrous bisglycinate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. The efficacy of hormonal contraceptives may be reduced. Use an alternative method of contraception or a backup method when enzyme inducers are used with combined hormonal contraceptives (CHCs), and continue backup contraception for 28 days after discontinuing enzyme inducer to ensure contraceptive reliability.

• levorphanol

  Monitor Closely (1)phenobarbital and levorphanol both increase sedation. Use Caution/Monitor.

• levothyroxine

  Minor (1)phenobarbital decreases levels of levothyroxine by increasing metabolism. Minor/Significance Unknown.

• lidocaine

  Monitor Closely (1)phenobarbital will decrease the level or effect of lidocaine by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.

• linagliptin

  Monitor Closely (1)phenobarbital will decrease the level or effect of linagliptin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Use of alternative treatments is strongly recommended when linagliptin is to be administered with a CYP3A4 inducer.

• linezolid

  Minor (1)linezolid increases levels of phenobarbital by decreasing metabolism. Minor/Significance Unknown. Theoretical interaction.

• liothyronine

  Minor (1)phenobarbital decreases levels of liothyronine by increasing metabolism. Minor/Significance Unknown.

• lisdexamfetamine

  Monitor Closely (1)phenobarbital increases and lisdexamfetamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• lofepramine

  Monitor Closely (2)belladonna alkaloids and lofepramine both decrease cholinergic effects/transmission. Use Caution/Monitor.
  
  phenobarbital and lofepramine both increase sedation. Use Caution/Monitor.Minor (1)phenobarbital, lofepramine. Other (see comment). Minor/Significance Unknown. Comment: Barbiturates may increase adverse effects, including respiratory depression, produced by toxic doses of TCAs. With therapeutic doses of TCAs, barbiturates increase metabolism and decrease blood concentrations of TCAs.

• lofexidine

  Monitor Closely (1)phenobarbital and lofexidine both increase sedation. Use Caution/Monitor.

• lomitapide

  Serious - Use Alternative (1)phenobarbital will decrease the level or effect of lomitapide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• lonafarnib

  Contraindicated (1)phenobarbital will decrease the level or effect of lonafarnib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Lonafarnib is a sensitive CYP3A4 substrate. Coadministration with strong or moderate CYP3A4 inducers is contraindicated.

• loperamide

  Monitor Closely (1)phenobarbital will decrease the level or effect of loperamide by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• lopinavir

  Monitor Closely (1)phenobarbital will decrease the level or effect of lopinavir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• loprazolam

  Monitor Closely (1)phenobarbital and loprazolam both increase sedation. Use Caution/Monitor.

• loratadine

  Monitor Closely (1)phenobarbital will decrease the level or effect of loratadine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.Minor (1)phenobarbital will decrease the level or effect of loratadine by P-glycoprotein (MDR1) efflux transporter. Minor/Significance Unknown.

• lorazepam

  Monitor Closely (1)phenobarbital and lorazepam both increase sedation. Use Caution/Monitor.

• lorlatinib

  Contraindicated (1)phenobarbital will decrease the level or effect of lorlatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Coadministration of lorlatinib with strong CYP3A inducers is contraindicated. Discontinue the strong CYP3A inducer for 3 plasma half-lives before initiating lorlatinib.

• lormetazepam

  Monitor Closely (1)phenobarbital and lormetazepam both increase sedation. Use Caution/Monitor.

• losartan

  Monitor Closely (1)phenobarbital will decrease the level or effect of losartan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.Minor (1)phenobarbital will decrease the level or effect of losartan by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

• lovastatin

  Monitor Closely (1)phenobarbital will decrease the level or effect of lovastatin by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.Serious - Use Alternative (1)phenobarbital will decrease the level or effect of lovastatin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• loxapine

  Monitor Closely (4)phenobarbital and loxapine both increase sedation. Use Caution/Monitor.
  
  loxapine increases effects of belladonna alkaloids by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.
  
  belladonna alkaloids decreases levels of loxapine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
  
  belladonna alkaloids decreases levels of loxapine by pharmacodynamic antagonism. Use Caution/Monitor.

• loxapine inhaled

  Monitor Closely (3)phenobarbital and loxapine inhaled both increase sedation. Use Caution/Monitor.
  
  loxapine inhaled increases effects of belladonna alkaloids by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.
  
  belladonna alkaloids decreases levels of loxapine inhaled by pharmacodynamic antagonism. Use Caution/Monitor.

• lumacaftor/ivacaftor

  Contraindicated (1)phenobarbital will decrease the level or effect of lumacaftor/ivacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Strong CYP3A inducers have minimal effect on lumacaftor exposure, but decreased ivacaftor exposure (AUC) by 57%. This may reduce the effectiveness of lumacaftor/ivacaftor. Therefore, coadministration is not recommended.Monitor Closely (1)lumacaftor/ivacaftor, phenobarbital. affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor. In vitro studies suggest that lumacaftor may induce and ivacaftor may inhibit CYP2C19 substrates. .

• lumateperone

  Serious - Use Alternative (1)phenobarbital will decrease the level or effect of lumateperone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• lumefantrine

  Contraindicated (1)phenobarbital will decrease the level or effect of lumefantrine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Coadministration with strong CYP3A4 inducers can result in decreased serum concentrations and loss of antimalarial efficacy

• lurasidone

  Contraindicated (1)phenobarbital decreases levels of lurasidone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Contraindicated.Monitor Closely (1)lurasidone, phenobarbital. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: Potential for increased CNS depressant effects when used concurrently; monitor for increased adverse effects and toxicity.

• lurbinectedin

  Serious - Use Alternative (1)phenobarbital will decrease the level or effect of lurbinectedin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• macimorelin

  Serious - Use Alternative (1)phenobarbital will decrease the level or effect of macimorelin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Potential for false positive test results if macimorelin and strong CYP3A4 inducers are coadministered. Discontinue strong CYP3A4 inducer, allowing for sufficient washout time, before testing.

• macitentan

  Serious - Use Alternative (1)phenobarbital will decrease the level or effect of macitentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministering macitentan with strong CYP3A4 inducers

• maprotiline

  Monitor Closely (2)belladonna alkaloids and maprotiline both decrease cholinergic effects/transmission. Use Caution/Monitor.
  
  phenobarbital and maprotiline both increase sedation. Use Caution/Monitor.Minor (1)phenobarbital, maprotiline. Other (see comment). Minor/Significance Unknown. Comment: Barbiturates may increase adverse effects, including respiratory depression, produced by toxic doses of TCAs. With therapeutic doses of TCAs, barbiturates increase metabolism and decrease blood concentrations of TCAs.

• maraviroc

  Monitor Closely (2)phenobarbital will decrease the level or effect of maraviroc by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
  
  phenobarbital will decrease the level or effect of maraviroc by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• marijuana

  Monitor Closely (2)phenobarbital and marijuana both increase sedation. Use Caution/Monitor.
  
  phenobarbital will decrease the level or effect of marijuana by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• mavacamten

  Contraindicated (1)phenobarbital will decrease the level or effect of mavacamten by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.

• meclizine

  Monitor Closely (1)belladonna alkaloids and meclizine both decrease cholinergic effects/transmission. Use Caution/Monitor.

• medroxyprogesterone

  Monitor Closely (1)phenobarbital will decrease the level or effect of medroxyprogesterone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Contraceptirve failure possible

• mefloquine

  Monitor Closely (1)phenobarbital, mefloquine. Either decreases effects of the other by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• melatonin

  Monitor Closely (1)phenobarbital and melatonin both increase sedation. Use Caution/Monitor.

• meloxicam

  Minor (1)phenobarbital will decrease the level or effect of meloxicam by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

• meperidine

  Monitor Closely (1)phenobarbital and meperidine both increase sedation. Use Caution/Monitor.

• meprobamate

  Monitor Closely (1)phenobarbital and meprobamate both increase sedation. Use Caution/Monitor.

• mestranol

  Monitor Closely (2)phenobarbital will decrease the level or effect of mestranol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
  
  phenobarbital will decrease the level or effect of mestranol by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.Serious - Use Alternative (1)phenobarbital decreases levels of mestranol by increasing metabolism. Avoid or Use Alternate Drug. May result in contraceptive failure.

• metaproterenol

  Monitor Closely (1)phenobarbital increases and metaproterenol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• metaxalone

  Monitor Closely (1)phenobarbital and metaxalone both increase sedation. Use Caution/Monitor.

• methadone

  Monitor Closely (2)phenobarbital will decrease the level or effect of methadone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
  
  phenobarbital and methadone both increase sedation. Use Caution/Monitor.

• methamphetamine

  Monitor Closely (1)phenobarbital increases and methamphetamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• methazolamide

  Minor (1)methazolamide, phenobarbital. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Increased risk of anticonvulsant induced osteomalacia.

• methocarbamol

  Monitor Closely (1)phenobarbital and methocarbamol both increase sedation. Use Caution/Monitor.

• methoxyflurane

  Serious - Use Alternative (1)phenobarbital increases toxicity of methoxyflurane by increasing metabolism. Contraindicated. Increased metabolism of methoxyflurane to nephrotoxic compounds.

• methscopolamine

  Monitor Closely (1)belladonna alkaloids and methscopolamine both decrease cholinergic effects/transmission. Use Caution/Monitor.

• methsuximide

  Minor (1)methsuximide decreases effects of phenobarbital by pharmacodynamic antagonism. Minor/Significance Unknown.

• methylene blue

  Serious - Use Alternative (1)methylene blue and belladonna alkaloids both increase serotonin levels. Avoid or Use Alternate Drug. If drug combination must be administered, monitor for evidence of serotonergic or opioid-related toxicities

• methylenedioxymethamphetamine

  Monitor Closely (1)phenobarbital increases and methylenedioxymethamphetamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• methylphenidate

  Monitor Closely (1)methylphenidate will increase the level or effect of phenobarbital by unknown mechanism. Use Caution/Monitor. Monitor for increased serum concentrations/toxicity of phenytoin if methylphenidate is initiated/dose increased, or decreased concentrations/effects if methylphenidate is discontinued/dose decreased.

• methylphenidate transdermal

  Monitor Closely (1)methylphenidate transdermal will increase the level or effect of phenobarbital by decreasing metabolism. Modify Therapy/Monitor Closely. Consider decreasing the dose of these drugs when given coadministered with methylphenidate. Monitor for drug toxiticities when initiating or discontinuing methylphenidate.

• methylprednisolone

  Monitor Closely (2)phenobarbital will decrease the level or effect of methylprednisolone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
  
  phenobarbital will decrease the level or effect of methylprednisolone by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• metoclopramide intranasal

  Serious - Use Alternative (1)phenobarbital, metoclopramide intranasal. Either increases effects of the other by Other (see comment). Avoid or Use Alternate Drug. Comment: Avoid use of metoclopramide intranasal or interacting drug, depending on importance of drug to patient.

• metoprolol

  Monitor Closely (1)phenobarbital decreases levels of metoprolol by increasing metabolism. Use Caution/Monitor. Consider a higher beta-blocker dose during coadministration of phenobarbital. Atenolol, sotalol, nadolol less likely to be affected than other beta blockers.

• metyrapone

  Minor (1)phenobarbital decreases effects of metyrapone by unspecified interaction mechanism. Minor/Significance Unknown.

• mexiletine

  Monitor Closely (1)phenobarbital will decrease the level or effect of mexiletine by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.

• miconazole vaginal

  Minor (1)phenobarbital decreases levels of miconazole vaginal by inhibition of GI absorption. Applies only to oral form of both agents. Minor/Significance Unknown.

• midazolam

  Monitor Closely (2)phenobarbital will decrease the level or effect of midazolam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
  
  phenobarbital and midazolam both increase sedation. Use Caution/Monitor.

• midazolam intranasal

  Monitor Closely (1)midazolam intranasal, phenobarbital. Either increases toxicity of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Concomitant use of barbiturates, alcohol, or other CNS depressants may increase the risk of hypoventilation, airway obstruction, desaturation, or apnea and may contribute to profound and/or prolonged drug effect.

• midodrine

  Monitor Closely (1)phenobarbital increases and midodrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• midostaurin

  Serious - Use Alternative (1)phenobarbital will decrease the level or effect of midostaurin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Strong CYP3A4 inducers may decrease midostaurin concentrations resulting in reduced efficacy.

• mifepristone

  Monitor Closely (1)phenobarbital will decrease the level or effect of mifepristone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. CYP3A4 inducers have not been studied, coadministration not recommended by manufacturer

• mipomersen

  Monitor Closely (1)mipomersen, phenobarbital. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: Both drugs have potential to increase hepatic enzymes; monitor LFTs.

• mirtazapine

  Monitor Closely (2)phenobarbital will decrease the level or effect of mirtazapine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
  
  phenobarbital and mirtazapine both increase sedation. Use Caution/Monitor.

• mobocertinib

  Serious - Use Alternative (1)phenobarbital will decrease the level or effect of mobocertinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• modafinil

  Monitor Closely (1)phenobarbital increases and modafinil decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.Serious - Use Alternative (1)phenobarbital will decrease the level or effect of modafinil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• montelukast

  Minor (1)phenobarbital will decrease the level or effect of montelukast by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• morphine

  Monitor Closely (1)phenobarbital and morphine both increase sedation. Use Caution/Monitor.

• motherwort

  Monitor Closely (1)phenobarbital and motherwort both increase sedation. Use Caution/Monitor.

• moxonidine

  Monitor Closely (1)phenobarbital and moxonidine both increase sedation. Use Caution/Monitor.

• nabilone

  Monitor Closely (1)phenobarbital and nabilone both increase sedation. Use Caution/Monitor.

• nadolol

  Monitor Closely (1)phenobarbital decreases levels of nadolol by increasing metabolism. Use Caution/Monitor. Consider a higher beta-blocker dose during coadministration of phenobarbital. Atenolol, sotalol, nadolol less likely to be affected than other beta blockers.

• nalbuphine

  Monitor Closely (1)phenobarbital and nalbuphine both increase sedation. Use Caution/Monitor.

• naldemedine

  Serious - Use Alternative (1)phenobarbital will decrease the level or effect of naldemedine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration with strong CYP3A4 inducers.

• naloxegol

  Contraindicated (1)phenobarbital will decrease the level or effect of naloxegol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Use of naloxegol with strong CYP3A4 inducers is not recommended

• nateglinide

  Monitor Closely (1)phenobarbital will decrease the level or effect of nateglinide by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor.

• nebivolol

  Monitor Closely (1)phenobarbital decreases levels of nebivolol by increasing metabolism. Use Caution/Monitor. Consider a higher beta-blocker dose during coadministration of phenobarbital. Atenolol, sotalol, nadolol less likely to be affected than other beta blockers.

• nefazodone

  Monitor Closely (1)phenobarbital will decrease the level or effect of nefazodone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• nelfinavir

  Monitor Closely (2)phenobarbital will decrease the level or effect of nelfinavir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
  
  phenobarbital will decrease the level or effect of nelfinavir by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• neomycin PO

  Monitor Closely (1)phenobarbital will decrease the level or effect of neomycin PO by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• neostigmine

  Monitor Closely (1)neostigmine increases and belladonna alkaloids decreases cholinergic effects/transmission. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• neratinib

  Serious - Use Alternative (1)phenobarbital will decrease the level or effect of neratinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of neratinib with strong/moderate CYP3A4 inducers.

• nettle

  Minor (1)nettle increases effects of phenobarbital by pharmacodynamic synergism. Minor/Significance Unknown. (High dose nettle; theoretical interaction) May enhance CNS depression.

• netupitant/palonosetron

  Serious - Use Alternative (1)phenobarbital will decrease the level or effect of netupitant/palonosetron by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Netupitant is mainly metabolized by CYP3A4; avoid use in patients who are chronically using a strong CYP3A4 inducer

• nevirapine

  Monitor Closely (1)phenobarbital, nevirapine. Either decreases effects of the other by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• nicardipine

  Monitor Closely (1)phenobarbital will decrease the level or effect of nicardipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• nifedipine

  Monitor Closely (1)phenobarbital will decrease the level or effect of nifedipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely.

• nilotinib

  Monitor Closely (2)phenobarbital will decrease the level or effect of nilotinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
  
  phenobarbital will decrease the level or effect of nilotinib by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• nimodipine

  Minor (1)phenobarbital will decrease the level or effect of nimodipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• nintedanib

  Serious - Use Alternative (1)phenobarbital decreases levels of nintedanib by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug. Avoid coadministration, particularly for P-gp inducers that are also CYP3A4 inducers; nintedanib is a substrate of P-gp and to a less extent CYP3A4.

• nirmatrelvir

  Contraindicated (1)phenobarbital will decrease the level or effect of nirmatrelvir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Nirmatrelvir, a CYP3A4 substrate, is contraindicated with strong CYP3A4 inducers. Significantly reduced nirmatrelvir plasma concentrations may be associated with potential for loss of virologic response and possible resistance. Do not initiate nirmatrelvir/ritonavir immediately after discontinuing a strong 3A4 inducer owing to time needed for systemic clearance of the inducer.

• nirmatrelvir/ritonavir

  Contraindicated (1)phenobarbital will decrease the level or effect of nirmatrelvir/ritonavir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Nirmatrelvir, a CYP3A4 substrate, is contraindicated with strong CYP3A4 inducers. Significantly reduced nirmatrelvir plasma concentrations may be associated with potential for loss of virologic response and possible resistance. Do not initiate nirmatrelvir/ritonavir immediately after discontinuing a strong 3A4 inducer owing to time needed for systemic clearance of the inducer.

• nisoldipine

  Monitor Closely (1)phenobarbital will decrease the level or effect of nisoldipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• nitrendipine

  Minor (1)phenobarbital will decrease the level or effect of nitrendipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• norepinephrine

  Monitor Closely (1)phenobarbital increases and norepinephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• norethindrone

  Serious - Use Alternative (1)phenobarbital will decrease the level or effect of norethindrone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration unless benefit outweighs risk. When coadministered, hormonal contraceptives are not a reliable method of effective birth control. Concomitant use may increase incidence of menstruation associated adverse effects (amenorrhea, dysmenorrhea, menorrhagia).

• norethindrone acetate

  Serious - Use Alternative (1)phenobarbital will decrease the level or effect of norethindrone acetate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration unless benefit outweighs risk. When coadministered, hormonal contraceptives are not a reliable method of effective birth control. Concomitant use may increase incidence of menstruation associated adverse effects (amenorrhea, dysmenorrhea, menorrhagia).

• norethindrone transdermal

  Serious - Use Alternative (1)phenobarbital will decrease the level or effect of norethindrone transdermal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration unless benefit outweighs risk. When coadministered, hormonal contraceptives are not a reliable method of effective birth control. Concomitant use may increase incidence of menstruation associated adverse effects (amenorrhea, dysmenorrhea, menorrhagia).

• norgestrel

  Monitor Closely (1)phenobarbital will decrease the level or effect of norgestrel by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• nortriptyline

  Monitor Closely (2)phenobarbital and nortriptyline both increase sedation. Use Caution/Monitor.
  
  belladonna alkaloids and nortriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.Minor (1)phenobarbital, nortriptyline. Other (see comment). Minor/Significance Unknown. Comment: Barbiturates may increase adverse effects, including respiratory depression, produced by toxic doses of TCAs. With therapeutic doses of TCAs, barbiturates increase metabolism and decrease blood concentrations of TCAs.

• olanzapine

  Monitor Closely (5)belladonna alkaloids decreases levels of olanzapine by pharmacodynamic antagonism. Use Caution/Monitor.
  
  phenobarbital and olanzapine both increase sedation. Use Caution/Monitor.
  
  belladonna alkaloids decreases levels of olanzapine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
  
  olanzapine increases effects of belladonna alkaloids by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.
  
  phenobarbital will decrease the level or effect of olanzapine by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.

• olaparib

  Serious - Use Alternative (1)phenobarbital will decrease the level or effect of olaparib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of olaparib with strong CYP3A4 inducers.

• oliceridine

  Monitor Closely (2)phenobarbital will decrease the level or effect of oliceridine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. If coadministration with a CYP3A4 inducer is necessary, consider increasing oliceridine dose until stable drug effects are achieved; monitor for signs of opioid withdrawal. If inducer is discontinued, consider oliceridine dosage reduction and monitor for signs of respiratory depression.
  
  belladonna alkaloids increases toxicity of oliceridine by Other (see comment). Use Caution/Monitor. Comment: Anticholinergic drugs may increase risk of urinary retention and/or severe constipation, which may lead to paralytic ileus. Monitor for signs of urinary retention or reduced gastric motility if oliceridine is coadministered with anticholinergics.

• olopatadine intranasal

  Serious - Use Alternative (1)phenobarbital and olopatadine intranasal both increase sedation. Avoid or Use Alternate Drug. Coadministration increases risk of CNS depression, which can lead to additive impairment of psychomotor performance and cause daytime impairment.

• olutasidenib

  Serious - Use Alternative (1)phenobarbital will decrease the level or effect of olutasidenib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Strong or moderate CYP3A inducers decrease olutasidenib (a CYP3A4 substrate) plasma concentrations and efficacy.

• omaveloxolone

  Serious - Use Alternative (1)phenobarbital will decrease the level or effect of omaveloxolone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• ombitasvir/paritaprevir/ritonavir & dasabuvir (DSC)

  Contraindicated (2)phenobarbital will decrease the level or effect of ombitasvir/paritaprevir/ritonavir & dasabuvir (DSC) by increasing metabolism. Contraindicated. Strong CYP2C8 inducers may reduce dasabuvir levels, and therefore decreased efficacy of Viekira Pak
  
  phenobarbital will decrease the level or effect of ombitasvir/paritaprevir/ritonavir & dasabuvir (DSC) by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Strong CYP3A4 inducers may reduce partiaprevir and ritonavir levels, and therefore decreased efficacy of Viekira Pak

• omeprazole

  Monitor Closely (1)phenobarbital will decrease the level or effect of omeprazole by affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor.Serious - Use Alternative (1)phenobarbital will decrease the level or effect of omeprazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• onabotulinumtoxinA

  Monitor Closely (1)belladonna alkaloids and onabotulinumtoxinA both decrease cholinergic effects/transmission. Use Caution/Monitor.Minor (1)phenobarbital decreases effects of onabotulinumtoxinA by pharmacodynamic antagonism. Minor/Significance Unknown.

• ondansetron

  Monitor Closely (1)phenobarbital will decrease the level or effect of ondansetron by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. No dosage adjustment for ondansetron is recommended for patients on these drugs.Minor (1)phenobarbital will decrease the level or effect of ondansetron by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.

• opium tincture

  Monitor Closely (1)phenobarbital and opium tincture both increase sedation. Use Caution/Monitor.

• oritavancin

  Monitor Closely (1)oritavancin will increase the level or effect of phenobarbital by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor. Oritavancin is a weak CYP2C9 inhibitor; caution if coadministered with CYP2C9 substrates that have a narrow therapeutic index

• orlistat

  Monitor Closely (1)orlistat decreases levels of phenobarbital by inhibition of GI absorption. Applies only to oral form of both agents. Modify Therapy/Monitor Closely. Risk of convulsions.

• orphenadrine

  Monitor Closely (2)belladonna alkaloids and orphenadrine both decrease cholinergic effects/transmission. Use Caution/Monitor.
  
  phenobarbital and orphenadrine both increase sedation. Use Caution/Monitor.

• osilodrostat

  Monitor Closely (1)phenobarbital will decrease the level or effect of osilodrostat by Other (see comment). Modify Therapy/Monitor Closely. Osilodrostat is a CYP3A4 and CYP2B6 subtrate. Monitor cortisol concentration and patient?s signs and symptoms during coadministration and discontinuation with strong CYP3A4 and/or CYP2B6 inducers. Adjust dose of osilodrostat if necessary.

• osimertinib

  Serious - Use Alternative (1)phenobarbital will decrease the level or effect of osimertinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid concomitant use of osimertinib with strong CYP3A inducers.

• ospemifene

  Monitor Closely (2)phenobarbital decreases levels of ospemifene by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
  
  phenobarbital decreases levels of ospemifene by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor.

• oxazepam

  Monitor Closely (1)phenobarbital and oxazepam both increase sedation. Use Caution/Monitor.

• oxcarbazepine

  Minor (1)phenobarbital decreases levels of oxcarbazepine by increasing metabolism. Minor/Significance Unknown.

• oxybutynin

  Monitor Closely (1)belladonna alkaloids and oxybutynin both decrease cholinergic effects/transmission. Use Caution/Monitor.Minor (1)phenobarbital will decrease the level or effect of oxybutynin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• oxybutynin topical

  Monitor Closely (1)belladonna alkaloids and oxybutynin topical both decrease cholinergic effects/transmission. Use Caution/Monitor.

• oxybutynin transdermal

  Monitor Closely (1)belladonna alkaloids and oxybutynin transdermal both decrease cholinergic effects/transmission. Use Caution/Monitor.

• oxycodone

  Monitor Closely (2)phenobarbital decreases levels of oxycodone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
  
  phenobarbital and oxycodone both increase sedation. Use Caution/Monitor.

• oxymorphone

  Monitor Closely (1)phenobarbital and oxymorphone both increase sedation. Use Caution/Monitor.

• ozanimod

  Serious - Use Alternative (1)phenobarbital will decrease the level or effect of ozanimod by Other (see comment). Avoid or Use Alternate Drug. Coadministration of ozanimod (a CYP2C8 substrate) with strong CYP2C8 inducers decreases the exposure of the active metabolites (CC112273 and CC1084037) of ozanimod, which may decrease the effiicacy of ozanimod. Therefore, coadministration of ozanimod with strong CYP2C8 inducers is not recommended.

• paclitaxel

  Monitor Closely (2)phenobarbital will decrease the level or effect of paclitaxel by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
  
  phenobarbital will decrease the level or effect of paclitaxel by Other (see comment). Use Caution/Monitor. Paclitaxel levels/efficacy may decrease when coadministered with CYP2C8 inducers Minor (1)phenobarbital will decrease the level or effect of paclitaxel by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• paclitaxel protein bound

  Monitor Closely (2)phenobarbital will decrease the level or effect of paclitaxel protein bound by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
  
  phenobarbital will decrease the level or effect of paclitaxel protein bound by Other (see comment). Use Caution/Monitor. Paclitaxel levels/efficacy may decrease when coadministered with CYP2C8 inducers Minor (1)phenobarbital will decrease the level or effect of paclitaxel protein bound by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• palbociclib

  Serious - Use Alternative (1)phenobarbital will decrease the level or effect of palbociclib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Strong CYP3A inducers decrease palbociclib plasma exposure by ~85%.

• paliperidone

  Monitor Closely (5)belladonna alkaloids decreases levels of paliperidone by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
  
  belladonna alkaloids decreases levels of paliperidone by pharmacodynamic antagonism. Use Caution/Monitor.
  
  phenobarbital will decrease the level or effect of paliperidone by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
  
  phenobarbital and paliperidone both increase sedation. Use Caution/Monitor.
  
  paliperidone increases effects of belladonna alkaloids by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.

• pancuronium

  Monitor Closely (1)belladonna alkaloids and pancuronium both decrease cholinergic effects/transmission. Use Caution/Monitor.Minor (1)phenobarbital decreases effects of pancuronium by pharmacodynamic antagonism. Minor/Significance Unknown.

• panobinostat

  Contraindicated (1)phenobarbital decreases levels of panobinostat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Strong CYP3A4 inducers can reduce panobinostat levels by ~70% and lead to treatment failure.

• pantoprazole

  Minor (1)phenobarbital will decrease the level or effect of pantoprazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• papaveretum

  Monitor Closely (1)phenobarbital and papaveretum both increase sedation. Use Caution/Monitor.

• papaverine

  Monitor Closely (1)phenobarbital and papaverine both increase sedation. Use Caution/Monitor.

• parecoxib

  Monitor Closely (1)phenobarbital will decrease the level or effect of parecoxib by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor.Minor (1)phenobarbital will decrease the level or effect of parecoxib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• paromomycin

  Monitor Closely (1)phenobarbital will decrease the level or effect of paromomycin by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• passion flower

  Monitor Closely (1)passion flower increases effects of phenobarbital by pharmacodynamic synergism. Use Caution/Monitor. May enhance CNS depression.

• pazopanib

  Monitor Closely (1)phenobarbital will decrease the level or effect of pazopanib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• pemigatinib

  Serious - Use Alternative (1)phenobarbital will decrease the level or effect of pemigatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• penbutolol

  Monitor Closely (1)phenobarbital decreases levels of penbutolol by increasing metabolism. Use Caution/Monitor. Consider a higher beta-blocker dose during coadministration of phenobarbital. Atenolol, sotalol, nadolol less likely to be affected than other beta blockers.

• pentazocine

  Monitor Closely (1)phenobarbital and pentazocine both increase sedation. Use Caution/Monitor.

• pentobarbital

  Monitor Closely (1)pentobarbital and phenobarbital both increase sedation. Use Caution/Monitor.

• perampanel

  Serious - Use Alternative (1)phenobarbital will decrease the level or effect of perampanel by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• perphenazine

  Monitor Closely (4)perphenazine increases effects of belladonna alkaloids by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.
  
  phenobarbital and perphenazine both increase sedation. Use Caution/Monitor.
  
  belladonna alkaloids decreases levels of perphenazine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
  
  belladonna alkaloids decreases levels of perphenazine by pharmacodynamic antagonism. Use Caution/Monitor.

• pexidartinib

  Serious - Use Alternative (1)phenobarbital will decrease the level or effect of pexidartinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• phendimetrazine

  Monitor Closely (1)phenobarbital increases and phendimetrazine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• phenelzine

  Minor (1)phenelzine increases levels of phenobarbital by decreasing metabolism. Minor/Significance Unknown. Theoretical interaction.

• phenindione

  Serious - Use Alternative (1)phenobarbital decreases effects of phenindione by increasing metabolism. Avoid or Use Alternate Drug.

• phentermine

  Monitor Closely (1)phenobarbital increases and phentermine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• phenylephrine

  Monitor Closely (1)phenobarbital increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• phenylephrine PO

  Monitor Closely (1)phenobarbital increases and phenylephrine PO decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor. .

• phenytoin

  Monitor Closely (1)phenobarbital will decrease the level or effect of phenytoin by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor.Minor (1)phenobarbital decreases levels of phenytoin by increasing metabolism. Minor/Significance Unknown. Phenobarbital may occasionally not change or even increase (via competitive inhibition) phenytoin levels.

• pholcodine

  Monitor Closely (1)phenobarbital and pholcodine both increase sedation. Use Caution/Monitor.

• physostigmine

  Monitor Closely (1)physostigmine increases and belladonna alkaloids decreases cholinergic effects/transmission. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• pilocarpine

  Monitor Closely (1)pilocarpine increases and belladonna alkaloids decreases cholinergic effects/transmission. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• pimavanserin

  Monitor Closely (1)phenobarbital will decrease the level or effect of pimavanserin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Avoid coadministration if possible. Monitor for reduced pimavanserin efficacy. An increase in pimavanserin dosage may be needed.

• pimozide

  Monitor Closely (4)pimozide increases effects of belladonna alkaloids by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.
  
  belladonna alkaloids decreases levels of pimozide by pharmacodynamic antagonism. Use Caution/Monitor.
  
  phenobarbital and pimozide both increase sedation. Use Caution/Monitor.
  
  belladonna alkaloids decreases levels of pimozide by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.Minor (1)phenobarbital will decrease the level or effect of pimozide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• pindolol

  Monitor Closely (1)phenobarbital decreases levels of pindolol by increasing metabolism. Use Caution/Monitor. Consider a higher beta-blocker dose during coadministration of phenobarbital. Atenolol, sotalol, nadolol less likely to be affected than other beta blockers.

• pioglitazone

  Minor (1)phenobarbital will decrease the level or effect of pioglitazone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• pirbuterol

  Monitor Closely (1)phenobarbital increases and pirbuterol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• pirfenidone

  Contraindicated (1)phenobarbital will decrease the level or effect of pirfenidone by affecting hepatic enzyme CYP1A2 metabolism. Contraindicated. Use of strong CYP1A2 inducers should be discontinued before initiating pirfenidone and avoided during treatment

• piroxicam

  Minor (1)phenobarbital will decrease the level or effect of piroxicam by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

• pitolisant

  Monitor Closely (1)phenobarbital will decrease the level or effect of pitolisant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Pitolisant exposure is decreased by 50% if coadministered with strong CYP3A4 inducers. For patients stable on pitolisant 8.9 mg/day or 17.8 mg/day, double the pitolisant dose (ie, 17.8 mg or 35.6 mg, respectively) over 7 days. If the strong CYP3A4 inducer is discontinued, reduce pitolisant dosage by half.

• polatuzumab vedotin

  Monitor Closely (1)phenobarbital will decrease the level or effect of polatuzumab vedotin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Polatuzumab undergoes catabolism to small peptides, amino acids, monomethyl auristatin E (MMAE), and unconjugated MMAE-related catabolites. MMAE is a CYP3A4 substrate. Coadministration of polatuzumab vedotin with a strong CYP3A4 inducer may decrease unconjugated MMAE AUC.

• pomalidomide

  Serious - Use Alternative (2)phenobarbital decreases levels of pomalidomide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
  
  phenobarbital decreases levels of pomalidomide by affecting hepatic enzyme CYP1A2 metabolism. Avoid or Use Alternate Drug.

• ponatinib

  Serious - Use Alternative (1)phenobarbital decreases levels of ponatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid unless the coadministration outweighs the possible risk of ponatinib underexposure; monitor for signs of reduced efficacy.

• posaconazole

  Monitor Closely (2)phenobarbital will decrease the level or effect of posaconazole by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
  
  phenobarbital decreases levels of posaconazole by increasing metabolism. Use Caution/Monitor.Minor (1)phenobarbital decreases levels of posaconazole by inhibition of GI absorption. Applies only to oral form of both agents. Minor/Significance Unknown.

• pralidoxime

  Monitor Closely (1)belladonna alkaloids and pralidoxime both decrease cholinergic effects/transmission. Use Caution/Monitor.

• pralsetinib

  Serious - Use Alternative (1)phenobarbital will decrease the level or effect of pralsetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If unable to avoid, double current pralsetinib dose starting on Day 7 of coadministration with strong CYP3A inducer. After inducer has been discontinued for at least 14 days, resume previous pralsetinib dose.

• pramlintide

  Serious - Use Alternative (1)pramlintide, belladonna alkaloids. Either increases effects of the other by pharmacodynamic synergism. Contraindicated. Synergistic inhibition of GI motility.

• praziquantel

  Contraindicated (1)phenobarbital decreases levels of praziquantel by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Strong CYP450 inducers significantly decrease praziquantel blood levels.

• prednisolone

  Monitor Closely (2)phenobarbital will decrease the level or effect of prednisolone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
  
  phenobarbital will decrease the level or effect of prednisolone by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• prednisone

  Monitor Closely (2)phenobarbital will decrease the level or effect of prednisone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
  
  phenobarbital will decrease the level or effect of prednisone by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• pretomanid

  Serious - Use Alternative (1)phenobarbital will decrease the level or effect of pretomanid by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Pretomanid is a CYP3A4 substrate. Avoid coadministration of strong or moderate CYP3A4 inducers

• primaquine

  Monitor Closely (1)phenobarbital will decrease the level or effect of primaquine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely.

• primidone

  Monitor Closely (1)phenobarbital and primidone both increase sedation. Use Caution/Monitor.

• procarbazine

  Minor (1)procarbazine increases levels of phenobarbital by decreasing metabolism. Minor/Significance Unknown. Theoretical interaction.

• prochlorperazine

  Monitor Closely (4)belladonna alkaloids decreases levels of prochlorperazine by pharmacodynamic antagonism. Use Caution/Monitor.
  
  prochlorperazine increases effects of belladonna alkaloids by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.
  
  phenobarbital and prochlorperazine both increase sedation. Use Caution/Monitor.
  
  belladonna alkaloids decreases levels of prochlorperazine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.

• progesterone intravaginal gel

  Monitor Closely (1)phenobarbital will decrease the level or effect of progesterone intravaginal gel by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely.

• progesterone micronized

  Monitor Closely (1)phenobarbital will decrease the level or effect of progesterone micronized by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely.

• progesterone, natural

  Monitor Closely (1)phenobarbital will decrease the level or effect of progesterone, natural by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely.

• promethazine

  Monitor Closely (4)belladonna alkaloids decreases levels of promethazine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
  
  promethazine and phenobarbital both increase sedation. Use Caution/Monitor.
  
  belladonna alkaloids decreases levels of promethazine by pharmacodynamic antagonism. Use Caution/Monitor.
  
  promethazine increases effects of belladonna alkaloids by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.

• propafenone

  Monitor Closely (1)phenobarbital decreases levels of propafenone by increasing metabolism. Use Caution/Monitor.Minor (1)phenobarbital will decrease the level or effect of propafenone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• propantheline

  Monitor Closely (1)belladonna alkaloids and propantheline both decrease cholinergic effects/transmission. Use Caution/Monitor.

• propofol

  Monitor Closely (1)propofol and phenobarbital both increase sedation. Use Caution/Monitor.

• propranolol

  Monitor Closely (1)phenobarbital decreases levels of propranolol by increasing metabolism. Use Caution/Monitor. Consider a higher beta-blocker dose during coadministration of phenobarbital. Atenolol, sotalol, nadolol less likely to be affected than other beta blockers.

• propylhexedrine

  Monitor Closely (1)phenobarbital increases and propylhexedrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• protamine

  Serious - Use Alternative (1)phenobarbital decreases effects of protamine by increasing metabolism. Avoid or Use Alternate Drug.

• protriptyline

  Monitor Closely (2)belladonna alkaloids and protriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.
  
  phenobarbital and protriptyline both increase sedation. Use Caution/Monitor.Minor (1)phenobarbital, protriptyline. Other (see comment). Minor/Significance Unknown. Comment: Barbiturates may increase adverse effects, including respiratory depression, produced by toxic doses of TCAs. With therapeutic doses of TCAs, barbiturates increase metabolism and decrease blood concentrations of TCAs.

• pyridostigmine

  Monitor Closely (1)pyridostigmine increases and belladonna alkaloids decreases cholinergic effects/transmission. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• pyridoxine

  Minor (1)pyridoxine decreases levels of phenobarbital by increasing metabolism. Minor/Significance Unknown.

• pyridoxine (Antidote)

  Minor (1)pyridoxine (Antidote) decreases levels of phenobarbital by increasing metabolism. Minor/Significance Unknown.

• quazepam

  Monitor Closely (2)phenobarbital and quazepam both increase sedation. Use Caution/Monitor.
  
  phenobarbital will decrease the level or effect of quazepam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• quetiapine

  Monitor Closely (5)phenobarbital will decrease the level or effect of quetiapine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
  
  phenobarbital and quetiapine both increase sedation. Use Caution/Monitor.
  
  belladonna alkaloids decreases levels of quetiapine by pharmacodynamic antagonism. Use Caution/Monitor.
  
  belladonna alkaloids decreases levels of quetiapine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
  
  quetiapine increases effects of belladonna alkaloids by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.

• quinidine

  Monitor Closely (1)phenobarbital will decrease the level or effect of quinidine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• quinine

  Minor (1)phenobarbital will decrease the level or effect of quinine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• rabeprazole

  Minor (1)phenobarbital will decrease the level or effect of rabeprazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• ramelteon

  Monitor Closely (2)phenobarbital will decrease the level or effect of ramelteon by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.
  
  phenobarbital and ramelteon both increase sedation. Use Caution/Monitor.Minor (2)phenobarbital will decrease the level or effect of ramelteon by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.
  
  phenobarbital will decrease the level or effect of ramelteon by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• ranolazine

  Serious - Use Alternative (1)phenobarbital will decrease the level or effect of ranolazine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• rapacuronium

  Monitor Closely (1)belladonna alkaloids and rapacuronium both decrease cholinergic effects/transmission. Use Caution/Monitor.Minor (1)phenobarbital decreases effects of rapacuronium by pharmacodynamic antagonism. Minor/Significance Unknown.

• rasagiline

  Monitor Closely (1)phenobarbital will decrease the level or effect of rasagiline by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.

• regorafenib

  Contraindicated (1)phenobarbital, regorafenib. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Strong CYP3A4 inducers decrease regorafenib levels and increase exposure of the active metabolite M-5.

• repaglinide

  Monitor Closely (1)phenobarbital will decrease the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• ribociclib

  Serious - Use Alternative (1)phenobarbital will decrease the level or effect of ribociclib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration of ribociclib with strong CYP3A inducers should be avoided.

• rifabutin

  Monitor Closely (1)phenobarbital will decrease the level or effect of rifabutin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely.

• rifampin

  Monitor Closely (1)rifampin decreases levels of phenobarbital by increasing metabolism. Use Caution/Monitor.

• rilpivirine

  Contraindicated (1)phenobarbital decreases levels of rilpivirine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Contraindicated. Rilpivirine should not be co-administered with strong CYP 3A4 inducers. Potential for loss of virologic response and possible resistance to rilpivirine or to the NNRTI class.

• riluzole

  Minor (1)phenobarbital will decrease the level or effect of riluzole by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.

• rimabotulinumtoxinB

  Monitor Closely (1)belladonna alkaloids, rimabotulinumtoxinB. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Anticholinergics may enhance botulinum toxin effects. Closely monitor for increased neuromuscular blockade.

• rimegepant

  Serious - Use Alternative (1)phenobarbital will decrease the level or effect of rimegepant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• riociguat

  Monitor Closely (1)phenobarbital will decrease the level or effect of riociguat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Data not available for dose adjustment

• ripretinib

  Serious - Use Alternative (1)phenobarbital will decrease the level or effect of ripretinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration with a strong CYP3A inhibitor will decrease systemic exposure to ripretinib and its active metabolite (DP-5439), which may decrease risk of adverse reactions.

• risperidone

  Monitor Closely (5)belladonna alkaloids decreases levels of risperidone by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
  
  phenobarbital and risperidone both increase sedation. Use Caution/Monitor.
  
  belladonna alkaloids decreases levels of risperidone by pharmacodynamic antagonism. Use Caution/Monitor.
  
  phenobarbital will decrease the level or effect of risperidone by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
  
  risperidone increases effects of belladonna alkaloids by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.

• ritonavir

  Monitor Closely (2)phenobarbital will decrease the level or effect of ritonavir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
  
  phenobarbital will decrease the level or effect of ritonavir by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• rivaroxaban

  Serious - Use Alternative (1)phenobarbital will decrease the level or effect of rivaroxaban by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.

• rocuronium

  Monitor Closely (1)belladonna alkaloids and rocuronium both decrease cholinergic effects/transmission. Use Caution/Monitor.Minor (1)phenobarbital decreases effects of rocuronium by pharmacodynamic antagonism. Minor/Significance Unknown.

• roflumilast

  Contraindicated (2)phenobarbital will decrease the level or effect of roflumilast by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Coadministration not recommended; strong cytochrome P450 enzyme inducers decrease systemic exposure to roflumilast and may reduce the therapeutic effectiveness
  
  phenobarbital will decrease the level or effect of roflumilast by affecting hepatic enzyme CYP1A2 metabolism. Contraindicated. Coadministration not recommended; strong cytochrome P450 enzyme inducers decrease systemic exposure to roflumilast and may reduce the therapeutic effectiveness

• rolapitant

  Serious - Use Alternative (1)phenobarbital will decrease the level or effect of rolapitant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Long-term coadministration of strong CYP3A4 inducers with rolapitant may significantly decrease rolapitant efficacy.

• romidepsin

  Serious - Use Alternative (1)phenobarbital will decrease the level or effect of romidepsin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• ropeginterferon alfa 2b

  Serious - Use Alternative (1)ropeginterferon alfa 2b and phenobarbital both increase Other (see comment). Avoid or Use Alternate Drug. Narcotics, hypnotics or sedatives can produce additive neuropsychiatric side effects. Avoid use and monitor patients receiving the combination for effects of excessive CNS toxicity.

• ropinirole

  Monitor Closely (1)phenobarbital will decrease the level or effect of ropinirole by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.

• rose hips

  Minor (1)phenobarbital decreases levels of rose hips by increasing elimination. Minor/Significance Unknown.

• rucaparib

  Monitor Closely (1)rucaparib will increase the level or effect of phenobarbital by affecting hepatic enzyme CYP2C19 metabolism. Modify Therapy/Monitor Closely. Adjust dosage of CYP2C19 substrates, if clinically indicated.

• rufinamide

  Monitor Closely (1)phenobarbital decreases levels of rufinamide by increasing metabolism. Use Caution/Monitor.

• ruxolitinib

  Monitor Closely (1)phenobarbital will decrease the level or effect of ruxolitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• ruxolitinib topical

  Monitor Closely (1)phenobarbital will decrease the level or effect of ruxolitinib topical by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• sage

  Minor (2)phenobarbital and sage both increase sedation. Minor/Significance Unknown.
  
  sage decreases effects of phenobarbital by pharmacodynamic antagonism. Minor/Significance Unknown. Theoretical interaction; some species of sage may cause convulsions.

• salmeterol

  Monitor Closely (1)phenobarbital increases and salmeterol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• saquinavir

  Monitor Closely (2)phenobarbital will decrease the level or effect of saquinavir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
  
  phenobarbital will decrease the level or effect of saquinavir by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• sarilumab

  Monitor Closely (1)sarilumab, phenobarbital. Other (see comment). Use Caution/Monitor. Comment: Formation of CYP450 enzymes can be altered by increased levels of cytokines such as IL-6. Elevated IL-6 concentration may down-regulate CYP activity, such as in patients with RA, and, hence, increase drug levels compared with subjects without RA. Blockade of IL-6 signaling by IL-6 antagonists (eg, sarilumab) might reverse the inhibitory effect of IL-6 and restore CYP activity, leading to decreased drug concentrations. Caution when initiating or discontinuing sarilumab if coadministered with CYP450 substrates, especially those with a narrow therapeutic index.

• saxagliptin

  Minor (1)phenobarbital will decrease the level or effect of saxagliptin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• scopolamine

  Monitor Closely (1)belladonna alkaloids and scopolamine both decrease cholinergic effects/transmission. Use Caution/Monitor.

• scullcap

  Monitor Closely (1)phenobarbital and scullcap both increase sedation. Use Caution/Monitor.

• secobarbital

  Monitor Closely (1)phenobarbital and secobarbital both increase sedation. Use Caution/Monitor.

• secukinumab

  Monitor Closely (1)secukinumab, phenobarbital. Other (see comment). Use Caution/Monitor. Comment: Formation of CYP450 enzymes can be altered by increased levels of certain cytokines during chronic inflammation; thus, secukinumab could normalize the formation of CYP450 enzymes. Upon initiation or discontinuation of secukinumab in patients who are receiving concomitant CYP450 substrates, particularly those with a narrow therapeutic index, consider monitoring for therapeutic effect.

• selegiline transdermal

  Minor (1)selegiline transdermal increases levels of phenobarbital by decreasing metabolism. Minor/Significance Unknown. Theoretical interaction.

• selexipag

  Monitor Closely (1)phenobarbital will decrease the level or effect of selexipag by increasing metabolism. Modify Therapy/Monitor Closely. Increase selexipag dose (up to 2-fold) if coadministered with strong CYP2C8 inducers.

• selinexor

  Serious - Use Alternative (1)selinexor, phenobarbital. unspecified interaction mechanism. Avoid or Use Alternate Drug. Patients treated with selinexor may experience neurological toxicities. Avoid taking selinexor with other medications that may cause dizziness or confusion.

• selpercatinib

  Serious - Use Alternative (1)phenobarbital will decrease the level or effect of selpercatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• selumetinib

  Serious - Use Alternative (1)phenobarbital will decrease the level or effect of selumetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• serdexmethylphenidate/dexmethylphenidate

  Minor (1)serdexmethylphenidate/dexmethylphenidate increases effects of phenobarbital by decreasing metabolism. Minor/Significance Unknown.

• sevelamer

  Monitor Closely (1)sevelamer decreases levels of phenobarbital by increasing elimination. Use Caution/Monitor.

• sevoflurane

  Monitor Closely (1)sevoflurane and phenobarbital both increase sedation. Use Caution/Monitor.

• shepherd's purse

  Monitor Closely (1)phenobarbital and shepherd's purse both increase sedation. Use Caution/Monitor.

• Siberian ginseng

  Minor (1)Siberian ginseng increases effects of phenobarbital by pharmacodynamic synergism. Minor/Significance Unknown. May enhance CNS depression.

• sildenafil

  Serious - Use Alternative (1)phenobarbital will decrease the level or effect of sildenafil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Potent CYP3A4 inducers are expected to cause substantial decreases in sildenafil plasma levels

• silodosin

  Monitor Closely (1)phenobarbital will decrease the level or effect of silodosin by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.Serious - Use Alternative (1)phenobarbital will decrease the level or effect of silodosin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• simvastatin

  Serious - Use Alternative (1)phenobarbital will decrease the level or effect of simvastatin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• siponimod

  Serious - Use Alternative (1)phenobarbital will decrease the level or effect of siponimod by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration of siponimod with a drug that causes moderate CYP2C9 plus a moderate or strong CYP3A4 inducer is not recommended. Coadministration with moderate or strong CYP3A4 inducers alone is not recommended for patients with CYP2C9*1/*3 and*2/*3 genotype.

• sirolimus

  Monitor Closely (1)phenobarbital will decrease the level or effect of sirolimus by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.Serious - Use Alternative (1)phenobarbital will decrease the level or effect of sirolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• sodium oxybate

  Contraindicated (1)phenobarbital, sodium oxybate. Either increases effects of the other by pharmacodynamic synergism. Contraindicated. Prescribing information for sodium oxybate states coadministration with alcohol or insomnia drugs is contraindicated because of additive CNS depression.

• sofosbuvir

  Serious - Use Alternative (1)phenobarbital will decrease the level or effect of sofosbuvir by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug. P-gp inducers decrease sofosbuvir levels, and therefore decrease conversion to sofosbuvir's active metabolite (GS-331007) responsible for 90% of pharmacologic effect

• sofosbuvir/velpatasvir

  Serious - Use Alternative (3)phenobarbital will decrease the level or effect of sofosbuvir/velpatasvir by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug. Sofosbuvir and velpatasvir are substrates of the drug transporter P-gp. Potent P-gp inducers may significantly decrease sofosbuvir and velpatasvir plasma concentrations, leading to potentially reduced therapeutic effect.
  
  phenobarbital will decrease the level or effect of sofosbuvir/velpatasvir by affecting hepatic enzyme CYP2B6 metabolism. Avoid or Use Alternate Drug. Velpatasvir is a substrate of CYP2B6, CYP2C8, and CYP3A4. Drugs that are moderate-to-potent inducers of CYP2B6, CYP2C8, or CYP3A4 may significantly decrease velpatasvir plasma concentrations, leading to potentially reduced therapeutic effect.
  
  phenobarbital will decrease the level or effect of sofosbuvir/velpatasvir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Velpatasvir is a substrate of CYP2B6, CYP2C8, and CYP3A4. Drugs that are moderate-to-potent inducers of CYP2B6, CYP2C8, or CYP3A4 may significantly decrease velpatasvir plasma concentrations, leading to potentially reduced therapeutic effect.

• solifenacin

  Monitor Closely (2)phenobarbital will decrease the level or effect of solifenacin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
  
  belladonna alkaloids and solifenacin both decrease cholinergic effects/transmission. Use Caution/Monitor.

• sonidegib

  Serious - Use Alternative (1)phenobarbital will decrease the level or effect of sonidegib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of sonidegib with strong or moderate CYP3A4 inducers.

• sorafenib

  Monitor Closely (1)phenobarbital decreases levels of sorafenib by increasing metabolism. Use Caution/Monitor.Serious - Use Alternative (1)phenobarbital will decrease the level or effect of sorafenib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• sotagliflozin

  Serious - Use Alternative (1)phenobarbital will decrease the level or effect of sotagliflozin by Other (see comment). Avoid or Use Alternate Drug. Glucuronidation by UGT1A9, to form the 3-O-glucuronide, was identified as a major metabolic pathway for sotagliflozin. Coadministration of UGT1A9 inducers may decrease exposure to sotagliflozin, which may decrease efficacy.

• sotalol

  Monitor Closely (1)phenobarbital decreases levels of sotalol by increasing metabolism. Use Caution/Monitor. Consider a higher beta-blocker dose during coadministration of phenobarbital. Atenolol, sotalol, nadolol less likely to be affected than other beta blockers.

• sotorasib

  Serious - Use Alternative (1)phenobarbital will decrease the level or effect of sotorasib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• sparsentan

  Monitor Closely (1)sparsentan will increase the level or effect of phenobarbital by affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor. Sparsentan (a CYP2C19 inducer) decreases exposure of CYP2C19 substrates and reduces efficacy related to these substrates. Serious - Use Alternative (1)phenobarbital will decrease the level or effect of sparsentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• stiripentol

  Monitor Closely (1)stiripentol will increase the level or effect of phenobarbital by affecting hepatic enzyme CYP2C19 metabolism. Modify Therapy/Monitor Closely. Consider reducing the dose of CYP2C19 substrates, if adverse reactions are experienced when administered concomitantly with stiripentol.Serious - Use Alternative (3)phenobarbital will decrease the level or effect of stiripentol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If unable to avoid coadministration of stiripentol with strong CYP3A4 inducers, increase stiripentol dose.
  
  phenobarbital will decrease the level or effect of stiripentol by affecting hepatic enzyme CYP1A2 metabolism. Avoid or Use Alternate Drug. If unable to avoid coadministration of stiripentol with strong CYP1A2 inducers, increase stiripentol dose.
  
  stiripentol, phenobarbital. Either increases effects of the other by sedation. Avoid or Use Alternate Drug. Concomitant use stiripentol with other CNS depressants, including alcohol, may increase the risk of sedation and somnolence.

• streptomycin

  Monitor Closely (1)phenobarbital will decrease the level or effect of streptomycin by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• succinylcholine

  Monitor Closely (1)succinylcholine increases and belladonna alkaloids decreases cholinergic effects/transmission. Effect of interaction is not clear, use caution. Use Caution/Monitor.Minor (1)phenobarbital decreases effects of succinylcholine by pharmacodynamic antagonism. Minor/Significance Unknown.

• sufentanil

  Monitor Closely (1)phenobarbital and sufentanil both increase sedation. Use Caution/Monitor.Minor (1)phenobarbital will decrease the level or effect of sufentanil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• sufentanil SL

  Monitor Closely (1)phenobarbital decreases effects of sufentanil SL by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Coadministration of CYP3A4 inducers may decrease sufentanil levels and efficacy, possibly precipitating withdrawal syndrome in patients who have developed physical dependence to sufentanil. Discontinuation of concomitantly used CYP3A4 inducers may increase sufentanil plasma concentration.Serious - Use Alternative (1)sufentanil SL, phenobarbital. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration may result in hypotension, profound sedation, respiratory depression, coma, and death. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.

• sulfamethoxazole

  Minor (1)phenobarbital will decrease the level or effect of sulfamethoxazole by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

• sunitinib

  Monitor Closely (1)phenobarbital will decrease the level or effect of sunitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• suvorexant

  Monitor Closely (1)phenobarbital will decrease the level or effect of suvorexant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Strong CYP3A4 inducers may decrease suvorexant efficacy; if increased suvorexant dose required, do not exceed 20 mg/day

• tacrolimus

  Monitor Closely (2)phenobarbital will decrease the level or effect of tacrolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
  
  phenobarbital will decrease the level or effect of tacrolimus by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• tadalafil

  Monitor Closely (1)phenobarbital will decrease the level or effect of tadalafil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Avoid combination in pulmonary HTN patients. For patients with ED, monitor response to tadalafil carefully because of potential for decreased effectiveness.

• tamoxifen

  Monitor Closely (2)phenobarbital will decrease the level or effect of tamoxifen by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor.
  
  phenobarbital will decrease the level or effect of tamoxifen by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• tamsulosin

  Serious - Use Alternative (1)phenobarbital will decrease the level or effect of tamsulosin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• tapentadol

  Monitor Closely (1)phenobarbital and tapentadol both increase sedation. Use Caution/Monitor.

• tasimelteon

  Monitor Closely (1)phenobarbital will decrease the level or effect of tasimelteon by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Avoid coadministration of tasimelteon with strong CYP3A4 inducers

• tazemetostat

  Serious - Use Alternative (1)phenobarbital will decrease the level or effect of tazemetostat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• teclistamab

  Monitor Closely (1)teclistamab will increase the level or effect of phenobarbital by altering metabolism. Use Caution/Monitor. Teclistamab causes release of cytokines that may suppress activity of CYP450 enzymes, resulting in increased exposure of CYP substrates. Monitor for increased concentrations or toxicities of sensitive CYP substrates. Adjust dose of CYP substrate drug as needed.

• tecovirimat

  Monitor Closely (1)tecovirimat will increase the level or effect of phenobarbital by affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor. Tecovirimat is a weak inhibitor of CYP2C8 and CYP2C19. Monitor for adverse effects if coadministered with sensitive substrates of these enzymes.

• temazepam

  Monitor Closely (1)phenobarbital and temazepam both increase sedation. Use Caution/Monitor.

• temsirolimus

  Monitor Closely (1)phenobarbital will decrease the level or effect of temsirolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• teniposide

  Monitor Closely (1)phenobarbital will decrease the level or effect of teniposide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• terbinafine

  Monitor Closely (3)phenobarbital will decrease the level or effect of terbinafine by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.
  
  phenobarbital will decrease the level or effect of terbinafine by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor.
  
  phenobarbital will decrease the level or effect of terbinafine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• terbutaline

  Monitor Closely (1)phenobarbital increases and terbutaline decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• tetracaine

  Monitor Closely (1)tetracaine, phenobarbital. Other (see comment). Use Caution/Monitor. Comment: Monitor for signs of methemoglobinemia when methemoglobin-inducing drugs are coadministered.

• tetracycline

  Serious - Use Alternative (1)phenobarbital will decrease the level or effect of tetracycline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• tezacaftor

  Serious - Use Alternative (1)phenobarbital will decrease the level or effect of tezacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• thalidomide

  Monitor Closely (1)thalidomide increases effects of phenobarbital by unspecified interaction mechanism. Use Caution/Monitor. Increased sedative effects.

• theophylline

  Monitor Closely (2)phenobarbital will decrease the level or effect of theophylline by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.
  
  phenobarbital will decrease the level or effect of theophylline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• thioridazine

  Monitor Closely (4)thioridazine increases effects of belladonna alkaloids by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.
  
  belladonna alkaloids decreases levels of thioridazine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
  
  phenobarbital and thioridazine both increase sedation. Use Caution/Monitor.
  
  belladonna alkaloids decreases levels of thioridazine by pharmacodynamic antagonism. Use Caution/Monitor.Minor (1)thioridazine decreases levels of phenobarbital by unspecified interaction mechanism. Minor/Significance Unknown.

• thiothixene

  Monitor Closely (4)phenobarbital and thiothixene both increase sedation. Use Caution/Monitor.
  
  belladonna alkaloids decreases levels of thiothixene by pharmacodynamic antagonism. Use Caution/Monitor.
  
  thiothixene increases effects of belladonna alkaloids by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.
  
  belladonna alkaloids decreases levels of thiothixene by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.

• thyroid desiccated

  Minor (1)phenobarbital decreases levels of thyroid desiccated by increasing metabolism. Minor/Significance Unknown.

• tiagabine

  Monitor Closely (1)phenobarbital will decrease the level or effect of tiagabine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.Minor (1)phenobarbital decreases levels of tiagabine by increasing metabolism. Minor/Significance Unknown.

• tibolone

  Minor (1)phenobarbital decreases levels of tibolone by increasing metabolism. Minor/Significance Unknown. Theoretical interaction.

• ticagrelor

  Monitor Closely (1)phenobarbital decreases levels of ticagrelor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Avoid use of ticagrelor with potent CYP3A inducers.

• timolol

  Monitor Closely (1)phenobarbital decreases levels of timolol by increasing metabolism. Use Caution/Monitor. Consider a higher beta-blocker dose during coadministration of phenobarbital. Atenolol, sotalol, nadolol less likely to be affected than other beta blockers.

• tinidazole

  Monitor Closely (1)phenobarbital will decrease the level or effect of tinidazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• tiotropium

  Monitor Closely (1)belladonna alkaloids and tiotropium both decrease cholinergic effects/transmission. Use Caution/Monitor.

• tipranavir

  Monitor Closely (1)phenobarbital will decrease the level or effect of tipranavir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• tivozanib

  Serious - Use Alternative (1)phenobarbital will decrease the level or effect of tivozanib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• tizanidine

  Serious - Use Alternative (1)phenobarbital will decrease the level or effect of tizanidine by affecting hepatic enzyme CYP1A2 metabolism. Avoid or Use Alternate Drug.

• tobramycin

  Monitor Closely (1)phenobarbital will decrease the level or effect of tobramycin by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• tofacitinib

  Monitor Closely (1)phenobarbital will decrease the level or effect of tofacitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Loss of, or decreased response to tofacitinib may occur when coadministered with potent CYP3A4 inducers

• tolbutamide

  Minor (1)phenobarbital will decrease the level or effect of tolbutamide by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

• tolterodine

  Monitor Closely (2)belladonna alkaloids and tolterodine both decrease cholinergic effects/transmission. Use Caution/Monitor.
  
  phenobarbital will decrease the level or effect of tolterodine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• tolvaptan

  Monitor Closely (1)phenobarbital will decrease the level or effect of tolvaptan by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.Serious - Use Alternative (1)phenobarbital will decrease the level or effect of tolvaptan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• topiramate

  Monitor Closely (1)phenobarbital and topiramate both increase sedation. Modify Therapy/Monitor Closely.Minor (1)phenobarbital decreases levels of topiramate by increasing metabolism. Minor/Significance Unknown.

• toremifene

  Monitor Closely (1)phenobarbital decreases levels of toremifene by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. CYP3A4 inducers increase rate of toremifene metabolism, lowering the steady-state concentration in serum.

• trabectedin

  Serious - Use Alternative (1)phenobarbital will decrease the level or effect of trabectedin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• tramadol

  Monitor Closely (2)phenobarbital will decrease the level or effect of tramadol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Decreased AUC of tramadol and the active metabolite (O-desmethyltramadol) when coadministered with strong CYP3A4 and CYP2B6 inducers
  
  phenobarbital and tramadol both increase sedation. Use Caution/Monitor.

• tranylcypromine

  Minor (1)tranylcypromine increases levels of phenobarbital by decreasing metabolism. Minor/Significance Unknown. Theoretical interaction.

• trazodone

  Monitor Closely (2)phenobarbital will decrease the level or effect of trazodone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
  
  phenobarbital and trazodone both increase sedation. Use Caution/Monitor.Minor (2)belladonna alkaloids and trazodone both decrease cholinergic effects/transmission. Minor/Significance Unknown.
  
  phenobarbital, trazodone. Other (see comment). Minor/Significance Unknown. Comment: Barbiturates may increase adverse effects, including respiratory depression, produced by toxic doses of TCAs. With therapeutic doses of TCAs, barbiturates increase metabolism and decrease blood concentrations of TCAs.

• triamcinolone acetonide injectable suspension

  Monitor Closely (1)phenobarbital will decrease the level or effect of triamcinolone acetonide injectable suspension by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• triazolam

  Monitor Closely (2)phenobarbital will decrease the level or effect of triazolam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
  
  phenobarbital and triazolam both increase sedation. Use Caution/Monitor.

• triclabendazole

  Monitor Closely (1)triclabendazole will increase the level or effect of phenobarbital by affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor. If plasma concentrations of the CYP2C19 substrates are elevated during triclabendazole, recheck plasma concentration of the CYP2C19 substrates after discontinuation of triclabendazole.

• triclofos

  Monitor Closely (1)phenobarbital and triclofos both increase sedation. Use Caution/Monitor.

• trifluoperazine

  Monitor Closely (4)belladonna alkaloids decreases levels of trifluoperazine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
  
  phenobarbital and trifluoperazine both increase sedation. Use Caution/Monitor.
  
  belladonna alkaloids decreases levels of trifluoperazine by pharmacodynamic antagonism. Use Caution/Monitor.
  
  trifluoperazine increases effects of belladonna alkaloids by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.

• trihexyphenidyl

  Monitor Closely (1)belladonna alkaloids and trihexyphenidyl both decrease cholinergic effects/transmission. Use Caution/Monitor. Potential for additive anticholinergic effects.

• trimipramine

  Monitor Closely (3)phenobarbital and trimipramine both increase sedation. Use Caution/Monitor.
  
  phenobarbital will decrease the level or effect of trimipramine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
  
  belladonna alkaloids and trimipramine both decrease cholinergic effects/transmission. Use Caution/Monitor.Minor (1)phenobarbital, trimipramine. Other (see comment). Minor/Significance Unknown. Comment: Barbiturates may increase adverse effects, including respiratory depression, produced by toxic doses of TCAs. With therapeutic doses of TCAs, barbiturates increase metabolism and decrease blood concentrations of TCAs.

• triprolidine

  Monitor Closely (1)triprolidine and phenobarbital both increase sedation. Use Caution/Monitor.

• trofinetide

  Monitor Closely (1)trofinetide will increase the level or effect of phenobarbital by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Monitor CYP3A4 substrates for which a small increase in plasma concentration may lead to serious toxicities if coadministered with trofinetide (a weak CYP3A4 inhibitor).

• trospium chloride

  Monitor Closely (1)belladonna alkaloids and trospium chloride both decrease cholinergic effects/transmission. Use Caution/Monitor.

• tucatinib

  Serious - Use Alternative (2)phenobarbital will decrease the level or effect of tucatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
  
  phenobarbital will decrease the level or effect of tucatinib by Other (see comment). Avoid or Use Alternate Drug. Coadministration of tucatinib (a CYP2C8 substrate) with a strong or moderate CYP2C8 inducer decreases tucatinib plasma concentrations.

• ubrogepant

  Serious - Use Alternative (1)phenobarbital will decrease the level or effect of ubrogepant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• ulipristal

  Serious - Use Alternative (1)phenobarbital will decrease the level or effect of ulipristal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• umeclidinium bromide

  Monitor Closely (1)umeclidinium bromide and belladonna alkaloids both decrease cholinergic effects/transmission. Use Caution/Monitor. If possible, avoid coadministration of additional anticholinergic agents

• umeclidinium bromide/vilanterol inhaled

  Serious - Use Alternative (1)belladonna alkaloids, umeclidinium bromide/vilanterol inhaled. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Concomitant use with other anticholinergic-containing drugs may lead to additive anticholinergic adverse effects.

• upadacitinib

  Serious - Use Alternative (1)phenobarbital will decrease the level or effect of upadacitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid upadacitinib coadministration with strong CYP3A4 inducers.

• ustekinumab

  Monitor Closely (1)ustekinumab, phenobarbital. Other (see comment). Use Caution/Monitor. Comment: Formation of CYP450 enzymes can be altered by increased levels of certain cytokines during chronic inflammation; thus, normalizing the formation of CYP450 enzymes. Upon initiation or discontinuation of ustekinumab in patients who are receiving concomitant CYP450 substrates, particularly those with a narrow therapeutic index, consider monitoring for therapeutic effect.

• valbenazine

  Serious - Use Alternative (1)phenobarbital will decrease the level or effect of valbenazine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Concomitant use not recommended.

• valerian

  Serious - Use Alternative (1)valerian increases effects of phenobarbital by pharmacodynamic synergism. Avoid or Use Alternate Drug. May enhance CNS depression.

• valproic acid

  Minor (1)valproic acid increases levels of phenobarbital by unspecified interaction mechanism. Minor/Significance Unknown.

• vandetanib

  Contraindicated (1)phenobarbital decreases levels of vandetanib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Avoid coadministration with potent CYP3A4 inducers; these drugs reduce exposure to vandetanib by up to 40%.

• vardenafil

  Monitor Closely (1)phenobarbital will decrease the level or effect of vardenafil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• vecuronium

  Monitor Closely (1)belladonna alkaloids and vecuronium both decrease cholinergic effects/transmission. Use Caution/Monitor.Minor (1)phenobarbital decreases effects of vecuronium by pharmacodynamic antagonism. Minor/Significance Unknown.

• velpatasvir

  Serious - Use Alternative (1)phenobarbital will decrease the level or effect of velpatasvir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• vemurafenib

  Serious - Use Alternative (1)phenobarbital decreases levels of vemurafenib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• venetoclax

  Serious - Use Alternative (1)phenobarbital will decrease the level or effect of venetoclax by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of venetoclax with strong or moderate CYP3A inducers. Consider alternative treatment with agents that have less CYP3A induction.

• verapamil

  Monitor Closely (1)phenobarbital will decrease the level or effect of verapamil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• vilanterol/fluticasone furoate inhaled

  Monitor Closely (1)phenobarbital will decrease the level or effect of vilanterol/fluticasone furoate inhaled by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• vilazodone

  Monitor Closely (1)phenobarbital decreases levels of vilazodone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Consider increasing vilazodone dose up to 2-fold (not to exceed 80 mg/day) when coadministered with strong CYP3A4 inducers for >14 days.

• vinblastine

  Monitor Closely (1)phenobarbital will decrease the level or effect of vinblastine by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.Minor (1)phenobarbital will decrease the level or effect of vinblastine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• vincristine

  Monitor Closely (1)phenobarbital will decrease the level or effect of vincristine by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.Minor (1)phenobarbital will decrease the level or effect of vincristine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• vincristine liposomal

  Monitor Closely (1)phenobarbital will decrease the level or effect of vincristine liposomal by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.Minor (1)phenobarbital will decrease the level or effect of vincristine liposomal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• vinorelbine

  Minor (1)phenobarbital will decrease the level or effect of vinorelbine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• vitamin D

  Monitor Closely (1)phenobarbital decreases effects of vitamin D by Other (see comment). Use Caution/Monitor. Comment: Vitamin D supplementation or dosage adjustments may be required in patients who are receiving chronic treatment with anticonvulsants.

• voclosporin

  Serious - Use Alternative (1)phenobarbital will decrease the level or effect of voclosporin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• vonoprazan

  Serious - Use Alternative (1)phenobarbital will decrease the level or effect of vonoprazan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• vorapaxar

  Serious - Use Alternative (1)phenobarbital decreases levels of vorapaxar by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• voriconazole

  Contraindicated (1)phenobarbital decreases levels of voriconazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.

• vortioxetine

  Monitor Closely (1)phenobarbital increases levels of vortioxetine by increasing metabolism. Modify Therapy/Monitor Closely. Consider increasing the vortioxetine dose when coadministered with strong CYP inducers for >14 days; not to exceed 3 times original vortioxetine dose.Serious - Use Alternative (1)phenobarbital will decrease the level or effect of vortioxetine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• voxelotor

  Serious - Use Alternative (1)phenobarbital will decrease the level or effect of voxelotor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Voxelotor is primarily metabolized by CYP3A4. Avoid coadministration with moderate or strong CYP3A4 inducers. If unable to avoid coadministration, increase voxelotor dose (see Dosage Modifications).

• voxilaprevir

  Serious - Use Alternative (1)phenobarbital will decrease the level or effect of voxilaprevir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• warfarin

  Monitor Closely (1)phenobarbital will decrease the level or effect of warfarin by affecting hepatic enzyme CYP2C9/10 metabolism. Modify Therapy/Monitor Closely.

• xylometazoline

  Monitor Closely (1)phenobarbital increases and xylometazoline decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• yohimbine

  Monitor Closely (1)phenobarbital increases and yohimbine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• zaleplon

  Minor (1)phenobarbital will decrease the level or effect of zaleplon by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• zanubrutinib

  Serious - Use Alternative (1)phenobarbital will decrease the level or effect of zanubrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• ziconotide

  Monitor Closely (1)phenobarbital and ziconotide both increase sedation. Use Caution/Monitor.

• ziprasidone

  Monitor Closely (4)belladonna alkaloids decreases levels of ziprasidone by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
  
  phenobarbital and ziprasidone both increase sedation. Use Caution/Monitor.
  
  belladonna alkaloids decreases levels of ziprasidone by pharmacodynamic antagonism. Use Caution/Monitor.
  
  ziprasidone increases effects of belladonna alkaloids by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.Minor (1)phenobarbital will decrease the level or effect of ziprasidone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• zolpidem

  Minor (1)phenobarbital will decrease the level or effect of zolpidem by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• zonisamide

  Minor (1)phenobarbital will decrease the level or effect of zonisamide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• zotepine

  Monitor Closely (3)belladonna alkaloids decreases levels of zotepine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
  
  phenobarbital and zotepine both increase sedation. Use Caution/Monitor.
  
  belladonna alkaloids decreases levels of zotepine by pharmacodynamic antagonism. Use Caution/Monitor.