Dosing & Uses
Dosage Forms & Strengths
capsule, immediate-release
- 30mg
- 100mg
capsule, extended-release
- 100mg
- 200mg
- 300mg
tablet, chewable
- 50mg
oral suspension
- 125mg/5mL
injectable solution
- 50mg/mL
Seizures
Status epilepticus
- Load 10-15 mg/kg or 15-20 mg/kg at 25-50 mg/min, THEN
- Maintenance: 100 mg IV/PO q6-8hr PRN
- Administer IV slowly; not to exceed 50 mg/min
Anticonvulsant
-
Tablet
- 100 mg PO TID
- Maintenance: 300-400 mg/day; increase to 600 mg/day if necessary
- May adjust dose no sooner than 7-10 day intervals when indicated
-
Suspension
- 125 mg PO TID, initially
- Increase to 625 mg/day if necessary
- May adjust dose no sooner than 7-10 day intervals when indicated
-
Extended release
- Loading dose: 1 g divided into 3 doses (400, 300, 300 mg) administered at 2 hr intervals; initiate dosage 24 hr after loading dose
- Loading dose not for administration to patients with a history of renal or hepatic disease; reserve for patients who require rapid steady serum levels, when IV administration not desirable, and for patients in a clinic or hospital setting where phenytoin levels can be closely monitored
- Treatment (naive): 100 mg PO TID initially
- May adjust dose no sooner than 7-10 day intervals
- Therapeutic range: 10-20 mcg/mL (total) or 1-2 mcg/mL free drug
Dosage Forms & Strengths
capsule, immediate-release
- 30mg
- 100mg
capsule, extended-release
- 100mg
- 200mg
- 300mg
tablet
- 50mg
oral suspension
- 125mg/5mL
injectable solution
- 50mg/mL
Status Epilepticus
15-20 mg/kg IV in single or divided dose; if necessary may administer additional dose of 5-10 mg/kg 10 min after loading dose
Maintenance: 4-8 mg/kg/day IV divided twice daily
Control of Tonic-Clonic and Complex Partial Seizures
Initial dosage
Neonates (<28 days)
- Initial: 5-8 mg/kg/day IV/PO divided q8-12hr
Age-based maintenance dose
- 6 months-4 years: Usual range, 8-10 mg/kg/day IV/PO divided two to three times daily
- 4-7 years: Usual range, 7.5-9 mg/kg/day IV/PO divided two to three times daily
- 7-10 years: Usual range, 7-8 mg/kg/day IV/PO divided two to three times daily
- 10-16 years: Usual range, 6-7 mg/kg/day IV/PO divided two to three times daily
Anticonvulsant (Nonemergent)
Children and adolescents
Immediate release
- Tablet and suspension
- 5 mg/kg/day PO in 2-3 divided doses, initially; may make dose adjustments no sooner than 7-10 day intervals
- Maintenance: 4-8 mg/kg/day PO; not to exceed 300 mg/day; higher doses may be considered in infant and young children (range: 8-10 mg/kg/day in divided doses)
Extended release
- 5 mg/kg/day PO, initially in 2-3 equally divided doses; may adjust dose no sooner than 7-10-day intervals
- Maintenance: 4-8 mg/kg/day PO not to exceed 300 mg/day
Dosing Considerations
<6 years: Potential toxic dose, 20 mg/kg
Therapeutic range: 10-20 mcg/mL (total) or 1-2 mcg/mL free drug
ALWAYS administer IV slowly; not to exceed 1-3 mg/kg/min
Interactions
Interaction Checker
No Results

Contraindicated
Serious - Use Alternative
Significant - Monitor Closely
Minor

Contraindicated (32)
- apixaban
phenytoin will decrease the level or effect of apixaban by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Reduces anticoagulant effect by decreasing apixaban systemic exposure
- artemether/lumefantrine
phenytoin 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
phenytoin will decrease the level or effect of atazanavir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.
- cabotegravir
phenytoin 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.
- cariprazine
phenytoin 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
phenytoin 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
phenytoin will decrease the level or effect of darunavir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Coadministration with phenytoin may result in loss of therapeutic effect and development of resistance to darunavir
- dienogest/estradiol valerate
phenytoin 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.
- dofetilide
phenytoin, dofetilide. Either increases effects of the other by pharmacodynamic synergism. Contraindicated. Additive cardiac effects.
- doravirine
phenytoin 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
phenytoin 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
phenytoin 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.
- fostemsavir
phenytoin 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
phenytoin will decrease the level or effect of isavuconazonium sulfate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.
- ledipasvir/sofosbuvir
phenytoin 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
- lenacapavir
phenytoin will decrease the level or effect of lenacapavir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Coadministration of lenacapavir with strong CYP3A inducers is contraindicated.
- lonafarnib
phenytoin 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
phenytoin 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
phenytoin 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
phenytoin 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
phenytoin decreases levels of lurasidone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Contraindicated.
- mavacamten
phenytoin will decrease the level or effect of mavacamten by affecting hepatic enzyme CYP2C19 metabolism. Contraindicated.
phenytoin will decrease the level or effect of mavacamten by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. - naloxegol
phenytoin 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
phenytoin 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
phenytoin 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)
phenytoin 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
phenytoin 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
phenytoin 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.
- praziquantel
phenytoin decreases levels of praziquantel by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Strong CYP450 inducers significantly decrease praziquantel blood levels.
- regorafenib
phenytoin, regorafenib. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Strong CYP3A4 inducers decrease regorafenib levels and increase exposure of the active metabolite M-5.
- rilpivirine
phenytoin 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
phenytoin 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
- vandetanib
phenytoin 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%.
Serious - Use Alternative (177)
- abemaciclib
phenytoin 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.
- abrocitinib
phenytoin will decrease the level or effect of abrocitinib by increasing metabolism. Avoid or Use Alternate Drug. Abrocitinib is a CYP2C9 and CYP2C19 substrate. Drugs that are strong inducers of CYP2C19 or CYP2C9 decreases the combined exposure of abrocitinib and its active metabolites, resulting in loss of or reduced clinical response.
- acalabrutinib
phenytoin 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
phenytoin 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 phenytoin 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
phenytoin 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.
- alpelisib
phenytoin 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.
phenytoin will decrease the level or effect of alpelisib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. - apalutamide
apalutamide will decrease the level or effect of phenytoin 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.
- apremilast
phenytoin 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
- avapritinib
phenytoin will decrease the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- axitinib
phenytoin 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
phenytoin 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
- berotralstat
phenytoin decreases levels of berotralstat by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug.
- bictegravir
phenytoin 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.
- bosutinib
phenytoin 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 phenytoin 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
phenytoin 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.
- cabozantinib
phenytoin 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.
- calcium/magnesium/potassium/sodium oxybates
phenytoin, calcium/magnesium/potassium/sodium oxybates. Either increases effects 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.
- capmatinib
phenytoin will decrease the level or effect of capmatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- ceritinib
phenytoin decreases levels of ceritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
ceritinib increases levels of phenytoin by affecting hepatic enzyme CYP2C9/10 metabolism. Avoid or Use Alternate Drug. Avoid concurrent use of CYP2C9 substrates known to have narrow therapeutic indices or substrates primarily metabolized by CYP2C9 during treatment with ceritinib; if use of these medications is unavoidable, consider dose. - cobicistat
phenytoin 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
phenytoin 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.
- cyclosporine
phenytoin decreases levels of cyclosporine by increasing metabolism. Avoid or Use Alternate Drug.
- dabigatran
phenytoin 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
phenytoin decreases levels of dabrafenib by increasing metabolism. Avoid or Use Alternate Drug. Strong CYP2C8 inducers may decrease dabrafenib levels.
phenytoin decreases levels of dabrafenib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. - dantrolene
phenytoin will decrease the level or effect of dantrolene by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- daridorexant
phenytoin will decrease the level or effect of daridorexant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- darolutamide
phenytoin will decrease 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
phenytoin 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.
- dihydroergotamine
phenytoin will decrease the level or effect of dihydroergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.
- dihydroergotamine intranasal
phenytoin will decrease the level or effect of dihydroergotamine intranasal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.
- dolutegravir
phenytoin will decrease the level or effect of dolutegravir by increasing metabolism. Avoid or Use Alternate Drug. Avoid coadministration; insufficient data to recommend dosage adjustment
- dopamine
phenytoin, dopamine. Mechanism: pharmacodynamic synergism. Avoid or Use Alternate Drug. Increased risk of hypotension.
- dronedarone
phenytoin will decrease the level or effect of dronedarone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.
- duvelisib
phenytoin 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
phenytoin 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
phenytoin will decrease the level or effect of elacestrant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- eliglustat
phenytoin 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
phenytoin 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
phenytoin will decrease the level or effect of encorafenib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- entrectinib
phenytoin will decrease the level or effect of entrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- enzalutamide
phenytoin will decrease the level or effect of enzalutamide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- erdafitinib
phenytoin 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
phenytoin will decrease the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.
- erythromycin base
phenytoin will decrease the level or effect of erythromycin base by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.
- erythromycin ethylsuccinate
phenytoin will decrease the level or effect of erythromycin ethylsuccinate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.
- erythromycin lactobionate
phenytoin will decrease the level or effect of erythromycin lactobionate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.
- erythromycin stearate
phenytoin will decrease the level or effect of erythromycin stearate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.
- ethinylestradiol
phenytoin 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.
- etravirine
phenytoin will decrease the level or effect of etravirine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Etravirine and phenytoin should not be coadministered. Concomitant use of etravirine and phenytoin may result in decreased etravirine plasma concentrations and loss of therapeutic effect of etravirine.
phenytoin will decrease the level or effect of etravirine by increasing metabolism. Avoid or Use Alternate Drug. Concomitant use of etravirine and phenytoin may result in decreased etravirine plasma concentrations and loss of therapeutic effect of etravirine.
etravirine will increase the level or effect of phenytoin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Etravirine and phenytoin should not be coadministered. Concomitant use of etravirine and phenytoin may result in decreased etravirine plasma concentrations and loss of therapeutic effect of etravirine. In addition, etravirine may inhibit the CYP metabolism of phenytoin, resulting in increased phenytoin concentrations.
phenytoin will decrease the level or effect of etravirine by affecting hepatic enzyme CYP2C9/10 metabolism. Avoid or Use Alternate Drug. - everolimus
phenytoin will decrease the level or effect of everolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.
phenytoin will decrease the level or effect of everolimus by P-glycoprotein (MDR1) efflux transporter. Contraindicated. - fedratinib
phenytoin 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
phenytoin 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
phenytoin will decrease the level or effect of finerenone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- fostamatinib
phenytoin will decrease the level or effect of fostamatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- futibatinib
phenytoin will decrease the level or effect of futibatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration of futibatinib with drugs that are dual P-gp and strong CYP3A inducers may decrease futibatinib efficacy.
- ganaxolone
phenytoin 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
phenytoin 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
phenytoin 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
phenytoin will decrease the level or effect of glecaprevir/pibrentasvir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- haloperidol
phenytoin will decrease the level or effect of haloperidol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- ibrutinib
phenytoin 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
phenytoin 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
phenytoin will decrease the level or effect of infigratinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- irinotecan
phenytoin will decrease the level or effect of irinotecan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- irinotecan liposomal
phenytoin will decrease the level or effect of irinotecan liposomal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- isosorbide dinitrate
phenytoin will decrease the level or effect of isosorbide dinitrate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- isosorbide mononitrate
phenytoin will decrease the level or effect of isosorbide mononitrate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- istradefylline
phenytoin 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
phenytoin decreases levels of itraconazole by increasing metabolism. Avoid or Use Alternate Drug.
- ivabradine
phenytoin 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
phenytoin 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
phenytoin 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.
ivosidenib will decrease the level or effect of phenytoin by affecting hepatic enzyme CYP2C9/10 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of sensitive CYP2C9 substrates with ivosidenib or replace with alternate therapies. If coadministration is unavoidable, monitor patients for loss of therapeutic effect of these drugs. - ixazomib
phenytoin 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%.
- lansoprazole
phenytoin will decrease the level or effect of lansoprazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Consider alternative for one of the interacting drugs
phenytoin will decrease the level or effect of lansoprazole by affecting hepatic enzyme CYP2C19 metabolism. Avoid or Use Alternate Drug. Consider alternative for one of the interacting drugs - larotrectinib
phenytoin 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
phenytoin 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
phenytoin will decrease the level or effect of lemborexant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- leniolisib
phenytoin will decrease the level or effect of leniolisib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- letermovir
phenytoin 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.
phenytoin 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. - lidocaine
phenytoin decreases levels of lidocaine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- lomitapide
phenytoin will decrease the level or effect of lomitapide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- losartan
phenytoin will decrease the level or effect of losartan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- lovastatin
phenytoin will decrease the level or effect of lovastatin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.
- lumateperone
phenytoin will decrease the level or effect of lumateperone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- lurbinectedin
phenytoin will decrease the level or effect of lurbinectedin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- macimorelin
phenytoin 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
phenytoin 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
- mebendazole
phenytoin decreases levels of mebendazole by increasing metabolism. Contraindicated.
- mefloquine
phenytoin will decrease the level or effect of mefloquine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- mestranol
phenytoin decreases levels of mestranol by increasing metabolism. Avoid or Use Alternate Drug. May result in contraceptive failure.
- methadone
phenytoin decreases levels of methadone by increasing metabolism. Contraindicated.
- metoclopramide intranasal
phenytoin, 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
phenytoin 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
phenytoin will decrease the level or effect of mobocertinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- naldemedine
phenytoin 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
phenytoin 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
phenytoin 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
- nifedipine
phenytoin will decrease the level or effect of nifedipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Phenytoin decreases systemic exposure of nifedipine by about 70%
- nintedanib
phenytoin 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.
- nitazoxanide
nitazoxanide, phenytoin. Either increases levels of the other by Mechanism: plasma protein binding competition. Avoid or Use Alternate Drug.
- norethindrone
phenytoin 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
phenytoin 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
phenytoin 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
phenytoin will decrease the level or effect of norgestrel by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Contraceptive failure is possible owing to decreased serum concentration of norgestrel. Advise patients to use an alternative method of contraception or a back-up method during coadministration, and to continue back-up contraception for 28 days after discontinuing the strong CYP3A4 inducer to ensure contraceptive reliability
- olaparib
phenytoin 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
phenytoin 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
phenytoin 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
phenytoin will decrease the level or effect of omaveloxolone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- osimertinib
phenytoin 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
phenytoin 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
phenytoin 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%.
- palovarotene
phenytoin will decrease the level or effect of palovarotene by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- pemigatinib
phenytoin will decrease the level or effect of pemigatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- perampanel
phenytoin will decrease the level or effect of perampanel by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- pexidartinib
phenytoin will decrease the level or effect of pexidartinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
phenytoin and pexidartinib both increase Other (see comment). Avoid or Use Alternate Drug. Pexidartinib can cause hepatotoxicity. Avoid coadministration of pexidartinib with other products know to cause hepatoxicity. - pirtobrutinib
phenytoin will decrease the level or effect of pirtobrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- pomalidomide
phenytoin decreases levels of pomalidomide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- ponatinib
phenytoin 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.
- ponesimod
phenytoin will decrease the level or effect of ponesimod by Other (see comment). Avoid or Use Alternate Drug. Not recommended. Based on limited data, coadministration of strong CYP3A4 and UGT1A1 inducers (eg, rifampin, phenytoin, carbamazepine) may decrease systemic exposure of ponesimod. The clinical relevance is unclear.
- posaconazole
phenytoin will decrease the level or effect of posaconazole by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug.
- pralsetinib
phenytoin 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.
- pretomanid
phenytoin 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.
phenytoin, pretomanid. Either increases toxicity of the other by Other (see comment). Avoid or Use Alternate Drug. Comment: Pretomanid regimen associated with hepatotoxicity. Avoid alcohol and hepatotoxic agents, including herbal supplements and drugs other than bedaquiline and linezolid. - progesterone intravaginal gel
phenytoin will decrease the level or effect of progesterone intravaginal gel by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Use of nonhormonal contraceptives advised
- progesterone micronized
phenytoin will decrease the level or effect of progesterone micronized by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Use of nonhormonal contraceptives advised
- progesterone, natural
phenytoin will decrease the level or effect of progesterone, natural by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Use of nonhormonal contraceptives advised
- quizartinib
phenytoin will decrease the level or effect of quizartinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- rabeprazole
phenytoin will decrease the level or effect of rabeprazole by affecting hepatic enzyme CYP2C19 metabolism. Avoid or Use Alternate Drug. Consider alternative for one of the interacting drugs
- ranolazine
phenytoin will decrease the level or effect of ranolazine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.
- ribociclib
phenytoin 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
phenytoin will decrease the level or effect of rifabutin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- rimegepant
phenytoin will decrease the level or effect of rimegepant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- ripretinib
phenytoin 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.
- ritlecitinib
phenytoin will decrease the level or effect of ritlecitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration with strong CYP3A inducers may decrease ritlecitinib AUC and peak plasma concentration, which may result in loss of or reduced efficacy.
- rolapitant
phenytoin 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
phenytoin will decrease the level or effect of romidepsin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of romidepsin and phenytoin, a potent CYP3A4 inducer, as this may decrease romidepsin concentrations and efficacy.
- ropeginterferon alfa 2b
ropeginterferon alfa 2b and phenytoin 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.
- selpercatinib
phenytoin will decrease the level or effect of selpercatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- selumetinib
phenytoin will decrease the level or effect of selumetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- sildenafil
phenytoin 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
phenytoin will decrease the level or effect of silodosin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.
- simvastatin
phenytoin will decrease the level or effect of simvastatin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.
- siponimod
phenytoin 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
phenytoin will decrease the level or effect of sirolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.
- sodium oxybate
phenytoin, sodium oxybate. Either increases effects 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.
- sofosbuvir
phenytoin 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
phenytoin 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.
phenytoin 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.
phenytoin 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
phenytoin 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
phenytoin will decrease the level or effect of sorafenib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- sotagliflozin
phenytoin 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
phenytoin will decrease the level or effect of sotorasib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- sparsentan
phenytoin will decrease the level or effect of sparsentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- stiripentol
phenytoin 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.
phenytoin will decrease the level or effect of stiripentol by affecting hepatic enzyme CYP2C19 metabolism. Avoid or Use Alternate Drug. If unable to avoid coadministration of stiripentol with strong CYP1A2 inducers, increase stiripentol dose. - tamsulosin
phenytoin will decrease the level or effect of tamsulosin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- tazemetostat
phenytoin will decrease the level or effect of tazemetostat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- tetracycline
phenytoin will decrease the level or effect of tetracycline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- tezacaftor
phenytoin will decrease the level or effect of tezacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- tivozanib
phenytoin will decrease the level or effect of tivozanib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- tolvaptan
phenytoin will decrease the level or effect of tolvaptan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.
- trabectedin
phenytoin will decrease the level or effect of trabectedin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- trimipramine
phenytoin will decrease the level or effect of trimipramine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- tucatinib
phenytoin will decrease the level or effect of tucatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
phenytoin 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
phenytoin will decrease the level or effect of ubrogepant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- ulipristal
phenytoin will decrease the level or effect of ulipristal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- upadacitinib
phenytoin 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.
- valbenazine
phenytoin will decrease the level or effect of valbenazine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Concomitant use not recommended.
- velpatasvir
phenytoin will decrease the level or effect of velpatasvir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.
- vemurafenib
phenytoin decreases levels of vemurafenib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- venetoclax
phenytoin 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.
- voclosporin
phenytoin will decrease the level or effect of voclosporin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- vonoprazan
phenytoin will decrease the level or effect of vonoprazan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- vorapaxar
phenytoin decreases levels of vorapaxar by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- voriconazole
phenytoin will decrease the level or effect of voriconazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- vortioxetine
phenytoin will decrease the level or effect of vortioxetine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- voxelotor
phenytoin 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
phenytoin will decrease the level or effect of voxilaprevir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.
- zanubrutinib
phenytoin will decrease the level or effect of zanubrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
Monitor Closely (355)
- abiraterone
phenytoin 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.
- albendazole
phenytoin decreases levels of albendazole by increasing metabolism. Use Caution/Monitor. Phenytoin decreases levels of albendazole active metabolites; monitor for decreased efficacy.
- almotriptan
phenytoin will decrease the level or effect of almotriptan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- alpelisib
alpelisib will decrease the level or effect of phenytoin by pharmacodynamic synergism. Modify Therapy/Monitor Closely.
- alprazolam
phenytoin will decrease the level or effect of alprazolam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- amikacin
phenytoin will decrease the level or effect of amikacin by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- amiodarone
amiodarone will increase the level or effect of phenytoin by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor.
phenytoin will decrease the level or effect of amiodarone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. An increased risk of phenytoin toxicity (ataxia, hyperreflexa, nystagmus, tremor) and/or decreased amiodarone concentrations. Because of the long half-life of amiodarone, the full extent of this interaction may not be evident for several weeks; careful monitoring is required. - amitriptyline
phenytoin will decrease the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Monitor therapeutic efficacy of amitriptyline; an increased dose may be required. Serum phenytoin levels should be obtained when tricyclic antidepressant agents are added to therapy due to the potential for impaired phenytoin metabolism and decreased seizure threshold. Tricyclic antidepressants when given concomitantly with anticonvulsants can increase CNS depression.
phenytoin will decrease the level or effect of amitriptyline by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Monitor therapeutic efficacy of amitriptyline; an increased dose may be required. Serum phenytoin levels should be obtained when tricyclic antidepressant agents are added to therapy due to the potential for impaired phenytoin metabolism and decreased seizure threshold. Tricyclic antidepressants when given concomitantly with anticonvulsants can increase CNS depression. - amlodipine
amlodipine will increase the level or effect of phenytoin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely.
- amobarbital
amobarbital will decrease the level or effect of phenytoin by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor.
- antithrombin alfa
antithrombin alfa increases levels of phenytoin by unknown mechanism. Use Caution/Monitor.
phenytoin, antithrombin alfa. Other (see comment). Use Caution/Monitor. Comment: Hydantoin anticonvulsants increase anticoagulant effects at first, then decrease those effects with continued use (2+ wks). There are multiple mechanisms involved, including enzyme induction, plasma protein binding site competition, and additive effects on prothrombin time. - antithrombin III
antithrombin III increases levels of phenytoin by unknown mechanism. Use Caution/Monitor.
phenytoin, antithrombin III. Other (see comment). Use Caution/Monitor. Comment: Hydantoin anticonvulsants increase anticoagulant effects at first, then decrease those effects with continued use (2+ wks). There are multiple mechanisms involved, including enzyme induction, plasma protein binding site competition, and additive effects on prothrombin time. - apalutamide
apalutamide will decrease the level or effect of phenytoin by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor. Coadministration of apalutamide, a weak CYP2C9 inducer, with drugs that are CYP2C9 substrates can result in lower exposure to these medications. Evaluate for loss of therapeutic effect if medication must be coadministered.
- aprepitant
phenytoin will decrease the level or effect of aprepitant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- argatroban
argatroban increases levels of phenytoin by unknown mechanism. Use Caution/Monitor.
phenytoin, argatroban. Other (see comment). Use Caution/Monitor. Comment: Hydantoin anticonvulsants increase anticoagulant effects at first, then decrease those effects with continued use (2+ wks). There are multiple mechanisms involved, including enzyme induction, plasma protein binding site competition, and additive effects on prothrombin time. - aripiprazole
phenytoin will decrease the level or effect of aripiprazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- artesunate
phenytoin 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.
- atogepant
phenytoin 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
phenytoin will decrease the level or effect of atorvastatin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- avanafil
phenytoin 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.
- avatrombopag
phenytoin 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.
- bazedoxifene/conjugated estrogens
phenytoin will decrease the level or effect of bazedoxifene/conjugated estrogens by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
phenytoin will decrease the level or effect of bazedoxifene/conjugated estrogens by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. If the estrogen is being used for contraception then loss of contraception may occur.
phenytoin 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. - belumosudil
phenytoin 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
bemiparin increases levels of phenytoin by unknown mechanism. Use Caution/Monitor.
phenytoin, bemiparin. Other (see comment). Use Caution/Monitor. Comment: Hydantoin anticonvulsants increase anticoagulant effects at first, then decrease those effects with continued use (2+ wks). There are multiple mechanisms involved, including enzyme induction, plasma protein binding site competition, and additive effects on prothrombin time. - benzhydrocodone/acetaminophen
phenytoin 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.
- bexagliflozin
phenytoin 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
phenytoin will decrease the level or effect of bexarotene by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- bivalirudin
bivalirudin increases levels of phenytoin by unknown mechanism. Use Caution/Monitor.
phenytoin, bivalirudin. Other (see comment). Use Caution/Monitor. Comment: Hydantoin anticonvulsants increase anticoagulant effects at first, then decrease those effects with continued use (2+ wks). There are multiple mechanisms involved, including enzyme induction, plasma protein binding site competition, and additive effects on prothrombin time. - bleomycin
bleomycin decreases levels of phenytoin by increasing metabolism. Use Caution/Monitor.
- blinatumomab
blinatumomab increases levels of phenytoin 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
phenytoin will decrease the level or effect of bortezomib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- bosentan
bosentan will decrease the level or effect of phenytoin by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor.
- brentuximab vedotin
phenytoin decreases levels of brentuximab vedotin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- brexanolone
brexanolone, phenytoin. Either increases toxicity of the other by sedation. Use Caution/Monitor.
- brexpiprazole
phenytoin 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.
- brivaracetam
phenytoin will decrease the level or effect of brivaracetam by affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor. Brivaracetam plasma concentration decreased by 21%.
brivaracetam increases levels of phenytoin by decreasing metabolism. Use Caution/Monitor. Up to 20% increase in phenytoin plasma concentrations observed. Monitor phenytoin levels when brivaracetam is coadministered or discontinued from ongoing phenytoin therapy. . - brodalumab
brodalumab, phenytoin. 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
phenytoin will decrease the level or effect of bromocriptine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- budesonide
phenytoin will decrease the level or effect of budesonide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
phenytoin will decrease the level or effect of budesonide by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. - buprenorphine
phenytoin will decrease the level or effect of buprenorphine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- buprenorphine buccal
phenytoin will decrease the level or effect of buprenorphine buccal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- buprenorphine subdermal implant
phenytoin 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
phenytoin will decrease the level or effect of buprenorphine transdermal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- buprenorphine, long-acting injection
phenytoin 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.
- buspirone
phenytoin will decrease the level or effect of buspirone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- busulfan
phenytoin decreases levels of busulfan by increasing hepatic clearance. Use Caution/Monitor.
phenytoin will decrease the level or effect of busulfan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. - butabarbital
butabarbital will decrease the level or effect of phenytoin by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor.
- butalbital
butalbital will decrease the level or effect of phenytoin by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor.
- cabazitaxel
phenytoin 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.
- calcifediol
phenytoin, calcifediol. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Drugs that stimulate microsomal hydroxylation reduce the half-life of calcifediol.
- calcitriol
phenytoin will decrease the level or effect of calcitriol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely.
- canagliflozin
phenytoin 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
phenytoin 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 phenytoin 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.
cannabidiol will increase the level or effect of phenytoin by decreasing metabolism. Modify Therapy/Monitor Closely. Cannabidiol may potentially inhibit CYP2C9 activity. Consider reducing the dose when concomitantly using CYP2C9 substrates.Cannabidiol may potentially inhibit CYP2C9 activity. Consider reducing the dose when concomitantly using CYP2C9 substrates. - capecitabine
capecitabine increases levels of phenytoin by unknown mechanism. Use Caution/Monitor. Based on case reports.
- carbamazepine
carbamazepine will decrease the level or effect of phenytoin by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor.
phenytoin will decrease the level or effect of carbamazepine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. - carboplatin
carboplatin decreases levels of phenytoin by unknown mechanism. Use Caution/Monitor.
- carmustine
carmustine decreases levels of phenytoin by unknown mechanism. Use Caution/Monitor.
- cenobamate
cenobamate will increase the level or effect of phenytoin by unspecified interaction mechanism. Modify Therapy/Monitor Closely. Concomitant use of phenytoin with multiple doses of cenobamate 200 mg qDay increased phenytoin mean Cmax and AUC by 70% and 80. Gradually decrease phenytoin dosage by up to 50% when used concomitantly with cenobamate.
cenobamate will increase the level or effect of phenytoin 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, phenytoin. Either increases effects of the other by sedation. Use Caution/Monitor. - chloramphenicol
chloramphenicol increases levels of phenytoin by decreasing metabolism. Use Caution/Monitor.
- chlordiazepoxide
phenytoin will decrease the level or effect of chlordiazepoxide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely.
- chloroquine
phenytoin will decrease the level or effect of chloroquine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- cilostazol
phenytoin will decrease the level or effect of cilostazol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- cimetidine
cimetidine will increase the level or effect of phenytoin by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor.
- cinacalcet
phenytoin will decrease the level or effect of cinacalcet by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- ciprofloxacin
ciprofloxacin decreases effects of phenytoin by unknown mechanism. Use Caution/Monitor. Ciprofloxacin has been reported to both increase and decrease phenytoin concentrations. Additional clinical evidence is needed however; phenytoin serum concentrations should be monitored in patients.
- cisatracurium
phenytoin decreases effects of cisatracurium by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. Monitor closely for more rapid recovery from neuromuscular blockade than expected; infusion rate requirements may be higher.
- cisplatin
cisplatin decreases levels of phenytoin by unknown mechanism. Use Caution/Monitor.
- citalopram
phenytoin will decrease the level or effect of citalopram by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- clomipramine
phenytoin will decrease the level or effect of clomipramine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- clonazepam
phenytoin will decrease the level or effect of clonazepam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- clopidogrel
phenytoin 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
phenytoin will decrease the level or effect of clorazepate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- clozapine
phenytoin will decrease the level or effect of clozapine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. When adding phenytoin therapy to patients stabilized on clozapine, monitor patient closely for worsening of psychotic symptoms. If needed, increase the clozapine dose cautiously on basis of psychotic symptoms. Conversely, when phenytoin is discontinued, levels of clozapine may significantly increase.
- colchicine
phenytoin will decrease the level or effect of colchicine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- colesevelam
colesevelam will decrease the level or effect of phenytoin by Mechanism: inhibition of GI absorption. Applies only to oral form of both agents. Modify Therapy/Monitor Closely. Administer phenytoin at least 4 hr before colesevelam
- conivaptan
phenytoin will decrease the level or effect of conivaptan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- conjugated estrogens
phenytoin will decrease the level or effect of conjugated estrogens by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
phenytoin will decrease the level or effect of conjugated estrogens by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. If the estrogen is being used for contraception then loss of contraception may occur. - conjugated estrogens, vaginal
phenytoin will decrease the level or effect of conjugated estrogens, vaginal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
phenytoin will decrease the level or effect of conjugated estrogens, vaginal by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. If the estrogen is being used for contraception then loss of contraception may occur. - cortisone
phenytoin will decrease the level or effect of cortisone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
phenytoin will decrease the level or effect of cortisone by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. - crizotinib
phenytoin decreases levels of crizotinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Concomitant use of strong CYP3A inducers should be avoided. .
crizotinib increases levels of phenytoin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Coadministration of crizotinib with CYP3A substrates with narrow therapeutic indices should be avoided. - cyclosporine
phenytoin will decrease the level or effect of cyclosporine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
phenytoin will decrease the level or effect of cyclosporine by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. - dalteparin
dalteparin increases levels of phenytoin by unknown mechanism. Use Caution/Monitor.
phenytoin, dalteparin. Other (see comment). Use Caution/Monitor. Comment: Hydantoin anticonvulsants increase anticoagulant effects at first, then decrease those effects with continued use (2+ wks). There are multiple mechanisms involved, including enzyme induction, plasma protein binding site competition, and additive effects on prothrombin time. - daprodustat
phenytoin will decrease the level or effect of daprodustat by Other (see comment). Modify Therapy/Monitor Closely. CYP2C8 inducers may decrease daprodustat exposure, which may result in loss of efficacy. Monitor hemoglobin and adjust daprodustat dose when initiating or stopping therapy with CYP2C8 inducers during treatment
- dapsone topical
phenytoin increases toxicity of dapsone topical by altering metabolism. Modify Therapy/Monitor Closely. May induce methemoglobinemia.
- daridorexant
phenytoin 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
phenytoin will decrease the level or effect of darifenacin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- dasatinib
phenytoin will decrease the level or effect of dasatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Concomitant use will lead to decreased dasatinib plasma concentrations. Consider using alternative therapeutic agents with low enzyme induction potential for coadministration with dasatinib. However, if concomitant use with phenytoin is required, consider increasing the dasatinib dose and monitor the patient closely for dasatinib toxicity (myelosuppression, fluid retention, diarrhea, hemorrhage, or skin rash).
- deferasirox
phenytoin 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
phenytoin will decrease the level or effect of deflazacort by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- deutetrabenazine
phenytoin and deutetrabenazine both increase sedation. Use Caution/Monitor.
- dexamethasone
phenytoin will decrease the level or effect of dexamethasone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
phenytoin will decrease the level or effect of dexamethasone by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. - dexlansoprazole
phenytoin will decrease the level or effect of dexlansoprazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- diazepam
phenytoin will decrease the level or effect of diazepam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- diazepam intranasal
phenytoin will decrease the level or effect of diazepam intranasal by affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor. Strong or moderate CYP2C19 inducers may increase rate of diazepam elimination; therefore, efficacy of diazepam may be decreased.
phenytoin 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. - difelikefalin
difelikefalin and phenytoin both increase sedation. Use Caution/Monitor.
- digoxin
phenytoin will decrease the level or effect of digoxin by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- diltiazem
phenytoin will decrease the level or effect of diltiazem by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- disopyramide
phenytoin will decrease the level or effect of disopyramide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Phenytoin decreases the levels of disopyramide but can also increase the toxicity.
phenytoin increases toxicity of disopyramide by increasing metabolism. Use Caution/Monitor. Hydantoins decreases the level, but increases the toxicity, of disopyramide. - disulfiram
disulfiram will increase the level or effect of phenytoin by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor.
- docetaxel
phenytoin will decrease the level or effect of docetaxel by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
docetaxel decreases levels of phenytoin by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
docetaxel decreases levels of phenytoin by increasing metabolism. Use Caution/Monitor. - doxorubicin
phenytoin will decrease the level or effect of doxorubicin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
doxorubicin decreases levels of phenytoin by increasing metabolism. Use Caution/Monitor. - doxorubicin liposomal
phenytoin will decrease the level or effect of doxorubicin liposomal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
doxorubicin liposomal decreases levels of phenytoin by increasing metabolism. Use Caution/Monitor. - dronabinol
phenytoin will decrease the level or effect of dronabinol by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor. Dronabinol is a CYP2C9 substrate.
phenytoin will decrease the level or effect of dronabinol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Dronabinol is a CYP3A4 substrate.
dronabinol increases levels of phenytoin by plasma protein binding competition. Modify Therapy/Monitor Closely. Dronabinol is highly bound to plasma proteins and may displace and increase the free fraction of other concomitantly administered highly protein-bound drugs. This has not been confirmed in vivo. Caution with narrow therapeutic index drugs that are highly protein bound when initiating or increasing the dose of dronabinol. - dulaglutide
dulaglutide, phenytoin. 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, phenytoin. 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
phenytoin will decrease the level or effect of duvelisib by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- efavirenz
efavirenz will increase the level or effect of phenytoin by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor.
phenytoin will decrease the level or effect of efavirenz by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. When given together, periodic monitoring for reduced efavirenz efficacy and phenytoin plasma concentrations are recommended .
phenytoin will increase the level or effect of efavirenz by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor. - elagolix
elagolix will increase the level or effect of phenytoin by affecting hepatic enzyme CYP2C19 metabolism. Modify Therapy/Monitor Closely. Elagolix is a weak CYP2C19 inhibitor. Caution with sensitive CYP2C19 substrates.
phenytoin will decrease the level or effect of elagolix by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. - eletriptan
phenytoin will decrease the level or effect of eletriptan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- eliglustat
eliglustat increases levels of phenytoin by P-glycoprotein (MDR1) efflux transporter. Modify Therapy/Monitor Closely. Monitor therapeutic drug concentrations, as indicated, or consider reducing the dosage of the P-gp substrate and titrate to clinical effect.
- elranatamab
elranatamab will increase the level or effect of phenytoin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Elranatamab causes cytokine release syndrome (CRS) that may suppress activity of CYP enzymes, resulting in increased exposure of CYP substrates. This is more likely to occur from initiation of elranatamab step-up dosing up to 14 days after the first treatment dose and during and after CRS.
- elvitegravir/cobicistat/emtricitabine/tenofovir DF
elvitegravir/cobicistat/emtricitabine/tenofovir DF decreases levels of phenytoin by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor. Elvitegravir is a moderate CYP2C9 inducer.
- enfortumab vedotin
phenytoin will decrease the level or effect of enfortumab vedotin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- enoxaparin
enoxaparin increases levels of phenytoin by unknown mechanism. Use Caution/Monitor.
phenytoin, enoxaparin. Other (see comment). Use Caution/Monitor. Comment: Hydantoin anticonvulsants increase anticoagulant effects at first, then decrease those effects with continued use (2+ wks). There are multiple mechanisms involved, including enzyme induction, plasma protein binding site competition, and additive effects on prothrombin time. - epcoritamab
epcoritamab, phenytoin. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Epcoritamab causes release of cytokines that may suppress activity of CYP enzymes, resulting in increased exposure of CYP substrates. For certain CYP substrates, minimal changes in their concentration may lead to serious adverse reactions. If needed, modify therapy as recommended in the substrate's prescribing information. .
- erlotinib
phenytoin will decrease the level or effect of erlotinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Avoid concomitant use because there is a potential for decreased erlotinib exposure and efficacy. However, if concomitant use is clinically warranted, consider an increase in erlotinib dose as tolerated at 2 week intervals and monitor patient's safety. If the erlotinib dose is increased, reduce it immediately to the indicated starting dose upon discontinuation of phenytoin.
phenytoin will decrease the level or effect of erlotinib by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. - escitalopram
phenytoin will decrease the level or effect of escitalopram by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- esketamine intranasal
esketamine intranasal, phenytoin. Either increases toxicity of the other by sedation. Modify Therapy/Monitor Closely.
- eslicarbazepine acetate
phenytoin will decrease the level or effect of eslicarbazepine acetate by increasing metabolism. Use Caution/Monitor. Higher dosage of eslicarbazepine may be necessary and dose adjustment may be needed for phenytoin
eslicarbazepine acetate will increase the level or effect of phenytoin by affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor. - esomeprazole
esomeprazole will increase the level or effect of phenytoin by affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor.
phenytoin will decrease the level or effect of esomeprazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. - estradiol
phenytoin will decrease the level or effect of estradiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
phenytoin will decrease the level or effect of estradiol by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. - estradiol vaginal
phenytoin will decrease the level or effect of estradiol vaginal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- estrogens conjugated synthetic
phenytoin will decrease the level or effect of estrogens conjugated synthetic by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
phenytoin will decrease the level or effect of estrogens conjugated synthetic by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. If the estrogen is being used for contraception then loss of contraception may occur. - estrogens esterified
phenytoin will decrease the level or effect of estrogens esterified by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. If the estrogen is being used for contraception then loss of contraception may occur.
- estropipate
phenytoin will decrease the level or effect of estropipate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
phenytoin will decrease the level or effect of estropipate by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. If the estrogen is being used for contraception then loss of contraception may occur. - eszopiclone
phenytoin will decrease the level or effect of eszopiclone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- ethanol
ethanol decreases levels of phenytoin by increasing metabolism. Use Caution/Monitor. Decreased phenytoin levels may be seen with chronic alcohol ingestion.
ethanol increases levels of phenytoin by decreasing metabolism. Use Caution/Monitor. Increased phenytoin levels may be seen with acute alcohol ingestion. - ethosuximide
phenytoin, ethosuximide. Other (see comment). Use Caution/Monitor. Comment: Ethosuximide may enhance CNS depressant effects and may increase serum concentrations of phenytoin. Phenytoin, a CYP3A4 inducer, may decrease plasma levels of ethosuximide (a CYP3A4 substrate.).
- etonogestrel
phenytoin will decrease the level or effect of etonogestrel by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- etoposide
phenytoin will decrease the level or effect of etoposide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- exemestane
phenytoin 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.
- felbamate
felbamate will increase the level or effect of phenytoin by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor.
phenytoin will decrease the level or effect of felbamate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Felbamate may increase serum concentrations of phenytoin. Phenytoin, a CYP3A4 inducer, may decrease plasma levels of felbamate (a CYP3A4 substrate). - felodipine
phenytoin will decrease the level or effect of felodipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. When possible, avoid coadministration of these drugs and consider alternative therapy. When an alternative therapy is not possible, patients should be monitored for the desired cardiovascular effects such as heart rate, chest pain, or blood pressure.
phenytoin decreases levels of felodipine by increasing metabolism. Use Caution/Monitor. - fentanyl
phenytoin 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
phenytoin 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
phenytoin 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
phenytoin 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, phenytoin. 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
phenytoin 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 phenytoin by affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor.
- fleroxacin
fleroxacin decreases effects of phenytoin by unknown mechanism. Use Caution/Monitor. There are also case reports of quinolones increasing phenytoin levels.
- flibanserin
phenytoin 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.
- floxuridine
floxuridine increases levels of phenytoin by unknown mechanism. Use Caution/Monitor. Based on case reports.
- fluconazole
fluconazole will increase the level or effect of phenytoin by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor.
- fludrocortisone
phenytoin will decrease the level or effect of fludrocortisone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
phenytoin will decrease the level or effect of fludrocortisone by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. - fluorouracil
fluorouracil increases levels of phenytoin by unknown mechanism. Use Caution/Monitor. Based on case reports.
- fluoxetine
fluoxetine will increase the level or effect of phenytoin by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor.
- flurazepam
phenytoin will decrease the level or effect of flurazepam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- fluticasone furoate
phenytoin will decrease the level or effect of fluticasone furoate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- fluticasone inhaled
phenytoin will decrease the level or effect of fluticasone inhaled by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- fluvastatin
fluvastatin increases levels of phenytoin by decreasing metabolism. Use Caution/Monitor.
- fluvoxamine
fluvoxamine will increase the level or effect of phenytoin by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor.
- fondaparinux
fondaparinux increases levels of phenytoin by unknown mechanism. Use Caution/Monitor.
phenytoin, fondaparinux. Other (see comment). Use Caution/Monitor. Comment: Hydantoin anticonvulsants increase anticoagulant effects at first, then decrease those effects with continued use (2+ wks). There are multiple mechanisms involved, including enzyme induction, plasma protein binding site competition, and additive effects on prothrombin time. - fosamprenavir
phenytoin, fosamprenavir. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Coadministration of phenytoin and fosamprenavir alone may decrease the concentration of amprenavir, the active metabolite; when given with the combination of fosamprenavir and ritonavir an increased concentration of amprenavir is observed.
- fosaprepitant
phenytoin will decrease the level or effect of fosaprepitant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- gefitinib
phenytoin 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.
- gemifloxacin
gemifloxacin decreases effects of phenytoin by unknown mechanism. Use Caution/Monitor. There are also case reports of quinolones increasing phenytoin levels.
- gentamicin
phenytoin will decrease the level or effect of gentamicin by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- glofitamab
glofitamab, phenytoin. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Glofitamab causes release of cytokines that may suppress activity of CYP enzymes, resulting in increased exposure of CYP substrates. For certain CYP substrates, minimal changes in their concentration may lead to serious adverse reactions. If needed, modify therapy as recommended in the substrate's prescribing information. .
- glyburide
phenytoin decreases levels of glyburide by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor. Strong CYP2C9 inducers may increase glyburide metabolism.
- green tea
phenytoin decreases levels of green tea by increasing metabolism. Use Caution/Monitor. (Caffeine). Potential for decreased effects of caffeine in green tea. .
- guanfacine
phenytoin 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, phenytoin. 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.
- hawthorn
hawthorn increases effects of phenytoin by pharmacodynamic synergism. Use Caution/Monitor.
- heparin
heparin increases levels of phenytoin by unknown mechanism. Use Caution/Monitor.
phenytoin, heparin. Other (see comment). Use Caution/Monitor. Comment: Hydantoin anticonvulsants increase anticoagulant effects at first, then decrease those effects with continued use (2+ wks). There are multiple mechanisms involved, including enzyme induction, plasma protein binding site competition, and additive effects on prothrombin time. - hyaluronidase
hyaluronidase, phenytoin. Other (see comment). Use Caution/Monitor. Comment: Drug combination has been found to be incompatible.
- hydrocodone
phenytoin 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
phenytoin will decrease the level or effect of hydrocortisone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
phenytoin will decrease the level or effect of hydrocortisone by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. - hydroxyprogesterone caproate (DSC)
phenytoin will decrease the level or effect of hydroxyprogesterone caproate (DSC) by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- ifosfamide
phenytoin 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.
phenytoin 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
phenytoin will decrease the level or effect of iloperidone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- imatinib
imatinib will increase the level or effect of phenytoin by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor.
phenytoin will decrease the level or effect of imatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Alternatives to phenytoin, with less enzyme induction potential, should be considered. Combo may decrease imatinib levels and efficacy.
phenytoin will decrease the level or effect of imatinib by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. - imipramine
phenytoin will decrease the level or effect of imipramine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Consider phenytoin serum levels if a tricyclic antidepressant is added to therapy or if the patient begins to exhibit signs of toxicity; lower doses of phenytoin may be required. If phenytoin is added to tricyclic antidepressant therapy, monitor for clinical efficacy of the tricyclic agent. Tricyclic antidepressants when given concomitantly with anticonvulsants can increase CNS depression.
- indinavir
phenytoin will decrease the level or effect of indinavir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
phenytoin will decrease the level or effect of indinavir by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. - itraconazole
phenytoin will decrease the level or effect of itraconazole by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Antifungal failure may occur due to clinically significant decreases in itraconazole serum concentrations when given with phenytoin. Increased itraconazole dosage may be needed.
- ivermectin
phenytoin will decrease the level or effect of ivermectin by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- ixabepilone
phenytoin will decrease the level or effect of ixabepilone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- ixekizumab
ixekizumab, phenytoin. 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.
- ketoconazole
ketoconazole will increase the level or effect of phenytoin by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor.
- L-methylfolate
L-methylfolate decreases levels of phenytoin by unspecified interaction mechanism. Use Caution/Monitor.
- lacosamide
phenytoin increases toxicity of lacosamide by Other (see comment). Use Caution/Monitor. Comment: Coadministration of lacosamide with sodium channel-blocking antiseizure drugs may increase the risk for AV block, bradycardia, or ventricular tachyarrhythmias. Monitor ECG before beginning lacosamide and after lacosamide is titrated to steady-state.
- lamotrigine
phenytoin decreases levels of lamotrigine by increasing metabolism. Use Caution/Monitor.
- lapatinib
phenytoin will decrease the level or effect of lapatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
phenytoin will decrease the level or effect of lapatinib by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. A reduction in therapeutic effectiveness of lapatinib may occur. Concomitant use of phenytoin with dasatinib, nilotinib, lapatinib, or pazopanib should be avoided. - lasmiditan
lasmiditan, phenytoin. 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.
- leflunomide
leflunomide will increase the level or effect of phenytoin by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor.
- lemborexant
lemborexant, phenytoin. 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
phenytoin will decrease the level or effect of lesinurad by affecting hepatic enzyme CYP2C9/10 metabolism. Modify Therapy/Monitor Closely.
- letermovir
letermovir will decrease the level or effect of phenytoin by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor. Monitor phenytoin levels.
- levamlodipine
phenytoin 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.
- levodopa
phenytoin decreases effects of levodopa by unknown mechanism. Use Caution/Monitor.
- levofloxacin
levofloxacin decreases effects of phenytoin by unknown mechanism. Use Caution/Monitor. There are also case reports of quinolones increasing phenytoin levels.
- levoketoconazole
levoketoconazole will increase the level or effect of phenytoin by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor.
- levonorgestrel intrauterine
phenytoin decreases levels of levonorgestrel intrauterine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- levonorgestrel oral
phenytoin decreases levels of levonorgestrel oral by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- levonorgestrel oral/ethinylestradiol/ferrous bisglycinate
phenytoin will decrease the level or effect of levonorgestrel oral/ethinylestradiol/ferrous bisglycinate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. 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.
- linagliptin
phenytoin 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.
- lomustine
phenytoin will decrease the level or effect of lomustine by increasing metabolism. Use Caution/Monitor. Coadministration of enzyme inducing antiepileptics with lomustine may cause a decrease in plasma concentration and reduced efficacy of lomustine.
lomustine will increase the level or effect of phenytoin by decreasing metabolism. Use Caution/Monitor. Coadministration of lomustine with phenytoin may decrease of phenytoin levels and seizure control. - lonapegsomatropin
lonapegsomatropin will decrease the level or effect of phenytoin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Limited published data indicate that growth hormone treatment increases cytochrome P450 (CYP450)-mediated antipyrine clearance. Caution with sensitive CYP substrates
- loperamide
phenytoin will decrease the level or effect of loperamide by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- lopinavir
phenytoin will decrease the level or effect of lopinavir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- loratadine
phenytoin will decrease the level or effect of loratadine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- lumacaftor/ivacaftor
lumacaftor/ivacaftor, phenytoin. affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor. In vitro studies suggest that lumacaftor may induce and ivacaftor may inhibit CYP2C19 substrates. .
lumacaftor/ivacaftor, phenytoin. affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor. In vitro studies suggest that lumacaftor may induce and ivacaftor may inhibit CYP2C9 substrates. . - lurasidone
lurasidone, phenytoin. 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.
- maraviroc
phenytoin will decrease the level or effect of maraviroc by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
phenytoin will decrease the level or effect of maraviroc by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. The plasma concentrations and pharmacologic effects of maraviroc may be increased by phenytoin. Maraviroc dosage adjustment is recommended during concomitant therapy with phenytoin. Coadministration of maraviroc and phenytoin is contraindicated in patients with severe renal impairment. - marijuana
phenytoin will decrease the level or effect of marijuana by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- medroxyprogesterone
phenytoin will decrease the level or effect of medroxyprogesterone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Contraceptirve failure possible
- mestranol
phenytoin will decrease the level or effect of mestranol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
phenytoin will decrease the level or effect of mestranol by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
mestranol decreases effects of phenytoin by decreasing metabolism. Use Caution/Monitor. - metformin
phenytoin decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor. Patient should be closely observed for loss of blood glucose control; when drugs are withdrawn from a patient receiving metformin, patient should be observed closely for hypoglycemia.
- methadone
phenytoin will decrease the level or effect of methadone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- methotrexate
phenytoin increases toxicity of methotrexate by Other (see comment). Use Caution/Monitor. Comment: Methotrexate is partially bound to serum albumin, and toxicity may be increased because of displacement by certain drugs, such as phenytoin.
- methylphenidate
methylphenidate will increase the level or effect of phenytoin 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 phenytoin 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
phenytoin will decrease the level or effect of methylprednisolone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
phenytoin will decrease the level or effect of methylprednisolone by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. - metronidazole
metronidazole will increase the level or effect of phenytoin by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor.
- metyrapone
phenytoin decreases levels of metyrapone by increasing metabolism. Use Caution/Monitor.
- mexiletine
phenytoin decreases levels of mexiletine by increasing metabolism. Use Caution/Monitor.
- miconazole vaginal
miconazole vaginal will increase the level or effect of phenytoin by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor.
- midazolam
phenytoin will decrease the level or effect of midazolam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- midazolam intranasal
midazolam intranasal, phenytoin. 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.
- mifepristone
phenytoin 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, phenytoin. 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
phenytoin will decrease the level or effect of mirtazapine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- mitoxantrone
mitoxantrone decreases levels of phenytoin by increasing metabolism. Use Caution/Monitor.
- modafinil
phenytoin will decrease the level or effect of modafinil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- moxifloxacin
moxifloxacin decreases effects of phenytoin by unknown mechanism. Use Caution/Monitor. There are also case reports of quinolones increasing phenytoin levels.
- nateglinide
nateglinide will increase the level or effect of phenytoin by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor.
phenytoin will decrease the level or effect of nateglinide by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor. Inducers of CYP2C9 decrease levels of nateglinide by increasing its metabolism. Coadministration may reduce nateglinide's hypoglycemic action. - nefazodone
phenytoin will decrease the level or effect of nefazodone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- nelfinavir
phenytoin will decrease the level or effect of nelfinavir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
phenytoin will decrease the level or effect of nelfinavir by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. - neomycin PO
phenytoin will decrease the level or effect of neomycin PO by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- nevirapine
phenytoin will decrease the level or effect of nevirapine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- nicardipine
phenytoin will decrease the level or effect of nicardipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- nilotinib
nilotinib will increase the level or effect of phenytoin by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor. Avoid concomitant use of phenytoin with nilotinib.
phenytoin will decrease the level or effect of nilotinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
phenytoin will decrease the level or effect of nilotinib by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. A reduction in therapeutic effectiveness of nilotinib may occur. Concomitant use of phenytoin with lapatinib, nilotinib, lapatinib, or pazopanib should be avoided. - nilutamide
nilutamide will increase the level or effect of phenytoin by decreasing metabolism. Use Caution/Monitor.
- nisoldipine
phenytoin will decrease the level or effect of nisoldipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- nitisinone
nitisinone will increase the level or effect of phenytoin by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor. Nitisinone inhibits CYP2C9. Caution if CYP2C9 substrate coadministered, particularly those with a narrow therapeutic index.
- ofloxacin
ofloxacin decreases effects of phenytoin by unknown mechanism. Use Caution/Monitor. There are also case reports of quinolones increasing phenytoin levels.
- oliceridine
phenytoin 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.
- omeprazole
omeprazole will increase the level or effect of phenytoin by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor.
phenytoin will decrease the level or effect of omeprazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. - ondansetron
phenytoin 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.
- oritavancin
oritavancin will increase the level or effect of phenytoin 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 phenytoin by inhibition of GI absorption. Applies only to oral form of both agents. Modify Therapy/Monitor Closely. Risk of convulsions.
- osilodrostat
phenytoin 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.
- ospemifene
phenytoin decreases levels of ospemifene by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
phenytoin decreases levels of ospemifene by affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor.
phenytoin decreases levels of ospemifene by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor.
phenytoin, ospemifene. Either increases levels of the other by plasma protein binding competition. Modify Therapy/Monitor Closely. - oxaliplatin
oxaliplatin decreases levels of phenytoin by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
oxaliplatin decreases levels of phenytoin by increasing metabolism. Use Caution/Monitor.
oxaliplatin will decrease the level or effect of phenytoin by unknown mechanism. Use Caution/Monitor. Monitor phenytoin concentrations/effects during treatment with oxaliplatin. Adjust phenytoin/fosphenytoin dose as necessary to maintain concentrations in the desired range. - oxcarbazepine
oxcarbazepine increases levels of phenytoin by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor. Oxcarbazepine increases levels of phenytoin at doses >1200 mg/day; monitor phenytoin levels during oxcarbazepine titration period and dosage modification; may require a decrease in phenytoin dose.
- oxycodone
phenytoin decreases levels of oxycodone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- paclitaxel
paclitaxel decreases levels of phenytoin by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
paclitaxel decreases levels of phenytoin by increasing metabolism. Use Caution/Monitor.
phenytoin will decrease the level or effect of paclitaxel by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
phenytoin 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
paclitaxel protein bound decreases levels of phenytoin by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
paclitaxel protein bound decreases levels of phenytoin by increasing metabolism. Use Caution/Monitor.
phenytoin will decrease the level or effect of paclitaxel protein bound by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
phenytoin 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
phenytoin will decrease the level or effect of paliperidone by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- pancuronium
phenytoin decreases effects of pancuronium by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. Monitor closely for more rapid recovery from neuromuscular blockade than expected; infusion rate requirements may be higher.
- pantoprazole
phenytoin will decrease the level or effect of pantoprazole by affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor.
- paricalcitol
phenytoin will decrease the level or effect of paricalcitol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- paromomycin
phenytoin will decrease the level or effect of paromomycin by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- pazopanib
phenytoin will decrease the level or effect of pazopanib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- peginterferon alfa 2b
peginterferon alfa 2b decreases levels of phenytoin by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor. When patients are administered peginterferon alpha-2b with CYP2C9 substrates, the therapeutic effect of these drugs may be altered. .
- pentobarbital
pentobarbital will decrease the level or effect of phenytoin by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor.
- phenindione
phenindione increases levels of phenytoin by unknown mechanism. Use Caution/Monitor.
phenytoin, phenindione. Other (see comment). Use Caution/Monitor. Comment: Hydantoin anticonvulsants increase anticoagulant effects at first, then decrease those effects with continued use (2+ wks). There are multiple mechanisms involved, including enzyme induction, plasma protein binding site competition, and additive effects on prothrombin time. - phenobarbital
phenobarbital will decrease the level or effect of phenytoin by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor.
- pimavanserin
phenytoin 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.
- pitolisant
phenytoin 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
phenytoin 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
phenytoin decreases levels of posaconazole by increasing metabolism. Use Caution/Monitor.
- prednisolone
phenytoin will decrease the level or effect of prednisolone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
phenytoin will decrease the level or effect of prednisolone by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. - prednisone
phenytoin will decrease the level or effect of prednisone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
phenytoin will decrease the level or effect of prednisone by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. - primidone
primidone will decrease the level or effect of phenytoin by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor.
phenytoin increases effects of primidone by increasing metabolism. Use Caution/Monitor. Phenytoin enhances the conversion of primidone to phenobarbital. - protamine
protamine increases levels of phenytoin by unknown mechanism. Use Caution/Monitor.
phenytoin, protamine. Other (see comment). Use Caution/Monitor. Comment: Hydantoin anticonvulsants increase anticoagulant effects at first, then decrease those effects with continued use (2+ wks). There are multiple mechanisms involved, including enzyme induction, plasma protein binding site competition, and additive effects on prothrombin time. - quazepam
phenytoin will decrease the level or effect of quazepam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- quetiapine
phenytoin will decrease the level or effect of quetiapine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Increased doses of quetiapine may be required to maintain control of psychotic symptoms in patients receiving quetiapine and phenytoin. Caution should be taken if phenytoin is withdrawn from therapy or replaced with a non-inducing anticonvulsant.
- quinidine
phenytoin will decrease the level or effect of quinidine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
phenytoin decreases levels of quinidine by increasing metabolism. Use Caution/Monitor. - quinine
phenytoin will decrease the level or effect of quinine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Use caution when prescribing phenytoin and quinine together due to a decrease in quinine plasma concentrations and potential lack of efficacy.
- repaglinide
phenytoin will decrease the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- rifampin
rifampin will decrease the level or effect of phenytoin by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor.
- rifapentine
rifapentine will decrease the level or effect of phenytoin by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor.
- riociguat
phenytoin 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
phenytoin will decrease the level or effect of risperidone by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- ritlecitinib
ritlecitinib will increase the level or effect of phenytoin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Ritlecitinib inhibits CYP3A4 substrates; coadministration increases AUC and peak plasma concentration sensitive substrates, which may increase risk of adverse reactions. Additional monitoring and dosage adjustment may be needed in accordance with product labeling of CYP3A substrates.
- ritonavir
phenytoin will decrease the level or effect of ritonavir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
phenytoin will decrease the level or effect of ritonavir by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. - rivaroxaban
phenytoin decreases levels of rivaroxaban by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Avoid concomitant use of rivaroxaban with drugs that are combined P-gp and strong CYP3A4 inducers. Consider increasing the rivaroxaban dose if these drugs must be coadministered.
- rocuronium
phenytoin decreases effects of rocuronium by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. Monitor closely for more rapid recovery from neuromuscular blockade than expected; infusion rate requirements may be higher.
- rufinamide
rufinamide increases levels of phenytoin by decreasing renal clearance. Use Caution/Monitor.
phenytoin decreases levels of rufinamide by increasing metabolism. Use Caution/Monitor. - ruxolitinib
phenytoin will decrease the level or effect of ruxolitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- ruxolitinib topical
phenytoin will decrease the level or effect of ruxolitinib topical by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- saquinavir
phenytoin will decrease the level or effect of saquinavir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Clinicians may want to consider using alternative medication to phenytoin in patients on saquinavir therapy. However, if it becomes necessary to give these agents concurrently, upward adjustments in saquinavir dosing may be needed to maintain antiviral effectiveness.
phenytoin will decrease the level or effect of saquinavir by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. - sarilumab
sarilumab, phenytoin. 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.
- secobarbital
secobarbital will decrease the level or effect of phenytoin by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor.
- secukinumab
secukinumab, phenytoin. 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
phenytoin 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.
- sertraline
sertraline increases levels of phenytoin by decreasing metabolism. Use Caution/Monitor.
- sevelamer
sevelamer decreases levels of phenytoin by increasing elimination. Use Caution/Monitor.
- silodosin
phenytoin will decrease the level or effect of silodosin by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- sirolimus
phenytoin will decrease the level or effect of sirolimus by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- sodium sulfate/?magnesium sulfate/potassium chloride
sodium sulfate/?magnesium sulfate/potassium chloride increases toxicity of phenytoin by Other (see comment). Use Caution/Monitor. Comment: Coadministration with medications that cause fluid and electrolyte abnormalities may increase the risk of adverse events of seizure, arrhythmias, and renal impairment.
- sodium sulfate/potassium sulfate/magnesium sulfate
sodium sulfate/potassium sulfate/magnesium sulfate increases toxicity of phenytoin by Other (see comment). Use Caution/Monitor. Comment: Coadministration with medications that cause fluid and electrolyte abnormalities may increase the risk of adverse events of seizure, arrhythmias, and renal impairment.
- solifenacin
phenytoin will decrease the level or effect of solifenacin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- somapacitan
somapacitan will decrease the level or effect of phenytoin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Limited published data indicate that growth hormone treatment increases cytochrome P450 (CYP450)-mediated antipyrine clearance. Caution with sensitive CYP substrates
- somatrogon
somatrogon will decrease the level or effect of phenytoin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Limited published data indicate that growth hormone treatment increases cytochrome P450 (CYP450)-mediated antipyrine clearance. Caution with sensitive CYP substrates
- somatropin
somatropin will decrease the level or effect of phenytoin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Limited published data indicate that growth hormone treatment increases cytochrome P450 (CYP450)-mediated antipyrine clearance. Caution with sensitive CYP substrates
- sorafenib
phenytoin decreases levels of sorafenib by increasing metabolism. Use Caution/Monitor.
- sparsentan
sparsentan will decrease the level or effect of phenytoin by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor. Sparsentan (a CYP2C9 inducer) decreases exposure of CYP2C9 substrates and reduces efficacy related to these substrates.
sparsentan will decrease the level or effect of phenytoin 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 phenytoin 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.
stiripentol, phenytoin. Either increases effects of the other by sedation. Use Caution/Monitor. Concomitant use stiripentol with other CNS depressants, including alcohol, may increase the risk of sedation and somnolence. - streptomycin
phenytoin will decrease the level or effect of streptomycin by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- sufentanil SL
phenytoin 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.
- sulfamethoxazole
sulfamethoxazole will increase the level or effect of phenytoin by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor.
- sunitinib
phenytoin will decrease the level or effect of sunitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- suvorexant
phenytoin 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
phenytoin will decrease the level or effect of tacrolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
phenytoin will decrease the level or effect of tacrolimus by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Tacrolimus dosage requirements may be greater when administered concurrently with phenytoin. - tadalafil
phenytoin 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.
- talquetamab
talquetamab will increase the level or effect of phenytoin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Talquetamab causes cytokine release syndrome (CRS) that may suppress activity of CYP enzymes, resulting in increased exposure of CYP substrates. This is more likely to occur from initiation of talquetamab step-up dosing up to 14 days after the first treatment dose and during and after CRS.
- tamoxifen
phenytoin will decrease the level or effect of tamoxifen by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- tasimelteon
phenytoin 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 phenytoin 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 phenytoin 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.
- teduglutide
teduglutide increases levels of phenytoin by Other (see comment). Use Caution/Monitor. Comment: Teduglutide may increase absorption of concomitant PO medications; caution with with drugs requiring titration or those with a narrow therapeutic index; dose adjustment may be necessary.
- temsirolimus
phenytoin will decrease the level or effect of temsirolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- teniposide
phenytoin will decrease the level or effect of teniposide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- terbinafine
phenytoin will decrease the level or effect of terbinafine by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor.
phenytoin will decrease the level or effect of terbinafine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. - tesamorelin
tesamorelin will decrease the level or effect of phenytoin by altering metabolism. Modify Therapy/Monitor Closely. Monitor levels
- tetracaine
tetracaine, phenytoin. Other (see comment). Use Caution/Monitor. Comment: Monitor for signs of methemoglobinemia when methemoglobin-inducing drugs are coadministered.
- theophylline
phenytoin will decrease the level or effect of theophylline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- tiagabine
phenytoin will decrease the level or effect of tiagabine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- ticagrelor
phenytoin decreases levels of ticagrelor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Avoid use of ticagrelor with potent CYP3A inducers.
- ticlopidine
ticlopidine will increase the level or effect of phenytoin by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor.
- tinidazole
tinidazole will increase the level or effect of phenytoin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. During concurrent therapy, consider monitoring clinical response to tinidazole and signs/symptoms of phentyoin toxicity (eg, nystagmus, ataxis, dysarthria, and lethargy)
phenytoin will decrease the level or effect of tinidazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. - tipranavir
phenytoin will decrease the level or effect of tipranavir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- tobramycin
phenytoin will decrease the level or effect of tobramycin by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- tofacitinib
phenytoin 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
phenytoin will decrease the level or effect of tolterodine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- tolvaptan
phenytoin will decrease the level or effect of tolvaptan by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- topiramate
phenytoin decreases levels of topiramate by increasing metabolism. Use Caution/Monitor.
- toremifene
phenytoin 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
phenytoin 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
- treosulfan
treosulfan decreases levels of phenytoin by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
treosulfan decreases levels of phenytoin by increasing metabolism. Use Caution/Monitor. - triamcinolone acetonide injectable suspension
phenytoin will decrease the level or effect of triamcinolone acetonide injectable suspension by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- triazolam
phenytoin will decrease the level or effect of triazolam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- triclabendazole
triclabendazole will increase the level or effect of phenytoin 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.
- trofinetide
trofinetide will increase the level or effect of phenytoin 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).
- ustekinumab
ustekinumab, phenytoin. 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.
- valoctocogene roxaparvovec
phenytoin and valoctocogene roxaparvovec both increase Other (see comment). Use Caution/Monitor. Medications that may cause hepatotoxicity when combined with valoctogene roxaparvovec may potentiate the risk of elevated liver enzymes. Closely monitor these medications and consider alternative medications in case of potential drug interactions.
- valproic acid
valproic acid will increase the level or effect of phenytoin by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor.
- vardenafil
phenytoin will decrease the level or effect of vardenafil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- vecuronium
phenytoin decreases effects of vecuronium by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. Monitor closely for more rapid recovery from neuromuscular blockade than expected; infusion rate requirements may be higher.
- vemurafenib
phenytoin decreases levels of vemurafenib by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- verapamil
phenytoin will decrease the level or effect of verapamil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- vilanterol/fluticasone furoate inhaled
phenytoin will decrease the level or effect of vilanterol/fluticasone furoate inhaled by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- vilazodone
phenytoin 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
vinblastine decreases levels of phenytoin by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
vinblastine decreases levels of phenytoin by increasing metabolism. Use Caution/Monitor.
vinblastine will decrease the level or effect of phenytoin by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Concurrent use of vinblastine and phenytoin may reduce phenytoin plasma levels and increase seizure activity. - vincristine
vincristine decreases levels of phenytoin by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
vincristine decreases levels of phenytoin by increasing metabolism. Use Caution/Monitor. - vincristine liposomal
vincristine liposomal decreases levels of phenytoin by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
vincristine liposomal decreases levels of phenytoin by increasing metabolism. Use Caution/Monitor. - vindesine
vindesine decreases levels of phenytoin by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
vindesine decreases levels of phenytoin by increasing metabolism. Use Caution/Monitor. - vinorelbine
vinorelbine decreases levels of phenytoin by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
vinorelbine decreases levels of phenytoin by increasing metabolism. Use Caution/Monitor. - vitamin D
phenytoin 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.
- voriconazole
voriconazole will increase the level or effect of phenytoin by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor.
phenytoin decreases levels of voriconazole by increasing metabolism. Modify Therapy/Monitor Closely. - vortioxetine
phenytoin 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
phenytoin will decrease the level or effect of warfarin by affecting hepatic enzyme CYP2C9/10 metabolism. Modify Therapy/Monitor Closely.
- zafirlukast
zafirlukast will increase the level or effect of phenytoin by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor.
Minor (111)
- acetaminophen
phenytoin decreases levels of acetaminophen by increasing metabolism. Minor/Significance Unknown. Enhanced metabolism incr levels of hepatotoxic metabolites.
- acetaminophen IV
phenytoin decreases levels of acetaminophen IV by increasing metabolism. Minor/Significance Unknown. Enhanced metabolism incr levels of hepatotoxic metabolites.
- acetaminophen rectal
phenytoin decreases levels of acetaminophen rectal by increasing metabolism. Minor/Significance Unknown. Enhanced metabolism incr levels of hepatotoxic metabolites.
- acetazolamide
acetazolamide, phenytoin. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Increased risk of anticonvulsant induced osteomalacia.
- alfentanil
phenytoin will decrease the level or effect of alfentanil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- alfuzosin
phenytoin will decrease the level or effect of alfuzosin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- alosetron
phenytoin will decrease the level or effect of alosetron by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- alvimopan
phenytoin will decrease the level or effect of alvimopan by P-glycoprotein (MDR1) efflux transporter. Minor/Significance Unknown.
- ambrisentan
phenytoin will decrease the level or effect of ambrisentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- armodafinil
phenytoin will decrease the level or effect of armodafinil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
phenytoin will decrease the level or effect of armodafinil by P-glycoprotein (MDR1) efflux transporter. Minor/Significance Unknown. - atracurium
phenytoin decreases effects of atracurium by pharmacodynamic antagonism. Minor/Significance Unknown.
- auranofin
auranofin increases levels of phenytoin by unspecified interaction mechanism. Minor/Significance Unknown.
- biotin
phenytoin decreases levels of biotin by unspecified interaction mechanism. Minor/Significance Unknown. Biotin supplementation may be necessary.
- bosentan
phenytoin will decrease the level or effect of bosentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- brinzolamide
brinzolamide, phenytoin. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Increased risk of anticonvulsant induced osteomalacia.
- carbamazepine
carbamazepine, phenytoin. Mechanism: unspecified interaction mechanism. Minor/Significance Unknown. Carbamazepine may increase or decrease phenytoin levels.
- caspofungin
phenytoin decreases levels of caspofungin by increasing metabolism. Minor/Significance Unknown.
- cevimeline
phenytoin will decrease the level or effect of cevimeline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- clarithromycin
phenytoin will decrease the level or effect of clarithromycin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- clopidogrel
clopidogrel increases levels of phenytoin by decreasing metabolism. Minor/Significance Unknown.
- cyanocobalamin
phenytoin decreases levels of cyanocobalamin by inhibition of GI absorption. Applies only to oral form of both agents. Minor/Significance Unknown.
- dapsone
phenytoin will decrease the level or effect of dapsone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- dexmethylphenidate
dexmethylphenidate increases effects of phenytoin by decreasing metabolism. Minor/Significance Unknown.
- diazoxide
diazoxide decreases levels of phenytoin by increasing metabolism. Minor/Significance Unknown.
- disulfiram
disulfiram increases levels of phenytoin by decreasing metabolism. Minor/Significance Unknown.
- docetaxel
phenytoin will decrease the level or effect of docetaxel by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- donepezil
phenytoin will decrease the level or effect of donepezil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- doxycycline
phenytoin decreases levels of doxycycline by increasing metabolism. Minor/Significance Unknown.
- dutasteride
phenytoin will decrease the level or effect of dutasteride by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- eplerenone
phenytoin will decrease the level or effect of eplerenone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- ethosuximide
ethosuximide increases effects of phenytoin by pharmacodynamic synergism. Minor/Significance Unknown.
- eucalyptus
phenytoin will decrease the level or effect of eucalyptus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- ezogabine
phenytoin decreases levels of ezogabine by Mechanism: unknown. Minor/Significance Unknown. Upon discontinuation of phenytoin, ezogabine clearance decreased by approximately 30%. Consider an increase in the ezogabine dose during concurrent use.
- fexofenadine
phenytoin will decrease the level or effect of fexofenadine by P-glycoprotein (MDR1) efflux transporter. Minor/Significance Unknown.
- finasteride
phenytoin will decrease the level or effect of finasteride by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- folic acid
folic acid decreases levels of phenytoin by increasing metabolism. Minor/Significance Unknown. Large doses of folic acid (>10 mg/day).
- furosemide
phenytoin decreases levels of furosemide by inhibition of GI absorption. Applies only to oral form of both agents. Minor/Significance Unknown.
- galantamine
phenytoin will decrease the level or effect of galantamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- grapefruit
grapefruit, phenytoin. Other (see comment). Minor/Significance Unknown. Comment: Grapefruit juice has been determined to have no effect on the pharmacokinetics of phenytoin.
- immune globulin IM (IGIM)
phenytoin, immune globulin IM (IGIM). Mechanism: unknown. Minor/Significance Unknown. Risk of hypersensitivity myocarditis.
- immune globulin IV (IGIV)
phenytoin, immune globulin IV (IGIV). Mechanism: unknown. Minor/Significance Unknown. Risk of hypersensitivity myocarditis.
- immune globulin SC
phenytoin, immune globulin SC. Mechanism: unknown. Minor/Significance Unknown. Risk of hypersensitivity myocarditis (theoretical interaction, based on IM and IV immune globulin).
- influenza virus vaccine quadrivalent
influenza virus vaccine quadrivalent, phenytoin. Mechanism: unknown. Minor/Significance Unknown. Vaccine administration may incr or decr phenytoin levels.
- influenza virus vaccine quadrivalent, cell-cultured
influenza virus vaccine quadrivalent, cell-cultured, phenytoin. Mechanism: unknown. Minor/Significance Unknown. Vaccine administration may incr or decr phenytoin levels.
- influenza virus vaccine trivalent
influenza virus vaccine trivalent, phenytoin. Mechanism: unknown. Minor/Significance Unknown. Vaccine administration may incr or decr phenytoin levels.
- influenza virus vaccine trivalent, recombinant
influenza virus vaccine trivalent, recombinant, phenytoin. Mechanism: unknown. Minor/Significance Unknown. Vaccine administration may incr or decr phenytoin levels.
- isoniazid
isoniazid increases levels of phenytoin by decreasing metabolism. Minor/Significance Unknown.
- isradipine
phenytoin will decrease the level or effect of isradipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- itraconazole
phenytoin will decrease the level or effect of itraconazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- ketoconazole
phenytoin will decrease the level or effect of ketoconazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- L-methylfolate
L-methylfolate decreases levels of phenytoin by increasing metabolism. Minor/Significance Unknown.
- levocarnitine
phenytoin decreases levels of levocarnitine by unspecified interaction mechanism. Minor/Significance Unknown.
- levoketoconazole
phenytoin will decrease the level or effect of levoketoconazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- levothyroxine
phenytoin decreases levels of levothyroxine by increasing metabolism. Minor/Significance Unknown.
phenytoin decreases levels of levothyroxine by plasma protein binding competition. Minor/Significance Unknown. - lily of the valley
phenytoin, lily of the valley. Either increases toxicity of the other by pharmacodynamic synergism. Minor/Significance Unknown.
- liothyronine
phenytoin decreases levels of liothyronine by increasing metabolism. Minor/Significance Unknown.
phenytoin decreases levels of liothyronine by plasma protein binding competition. Minor/Significance Unknown. - lithium
phenytoin increases toxicity of lithium by unknown mechanism. Minor/Significance Unknown.
- loratadine
phenytoin will decrease the level or effect of loratadine by P-glycoprotein (MDR1) efflux transporter. Minor/Significance Unknown.
- meperidine
phenytoin decreases levels of meperidine by increasing metabolism. Minor/Significance Unknown.
- methazolamide
methazolamide, phenytoin. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Increased risk of anticonvulsant induced osteomalacia.
- methsuximide
methsuximide increases effects of phenytoin by pharmacodynamic synergism. Minor/Significance Unknown.
- montelukast
phenytoin will decrease the level or effect of montelukast by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- mycophenolate
mycophenolate increases effects of phenytoin by plasma protein binding competition. Minor/Significance Unknown. Mycophenolate decreased phenytoin protein binding from 90% to 87% in vitro. The clinical significance of this interaction is unknown. .
- nimodipine
phenytoin will decrease the level or effect of nimodipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- nitrendipine
phenytoin will decrease the level or effect of nitrendipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- onabotulinumtoxinA
phenytoin decreases effects of onabotulinumtoxinA by pharmacodynamic antagonism. Minor/Significance Unknown.
- oxcarbazepine
phenytoin decreases levels of oxcarbazepine by increasing metabolism. Minor/Significance Unknown.
- oxybutynin
phenytoin will decrease the level or effect of oxybutynin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- paclitaxel
phenytoin will decrease the level or effect of paclitaxel by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- paclitaxel protein bound
phenytoin will decrease the level or effect of paclitaxel protein bound by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- parecoxib
phenytoin will decrease the level or effect of parecoxib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- phenobarbital
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
phenytoin will decrease the level or effect of pimozide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- pioglitazone
phenytoin will decrease the level or effect of pioglitazone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- propafenone
phenytoin will decrease the level or effect of propafenone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- pyridoxine
pyridoxine decreases levels of phenytoin by increasing metabolism. Minor/Significance Unknown. High dose of pyridoxine (vitamin B6), >=200 mg/day.
- pyridoxine (Antidote)
pyridoxine (Antidote) decreases levels of phenytoin by increasing metabolism. Minor/Significance Unknown. High dose of pyridoxine (vitamin B6), >=200 mg/day.
- pyrimethamine
pyrimethamine decreases effects of phenytoin by pharmacodynamic antagonism. Minor/Significance Unknown.
- rabeprazole
phenytoin will decrease the level or effect of rabeprazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown. Consider alternative for one of the interacting drugs
- ramelteon
phenytoin will decrease the level or effect of ramelteon by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- rapacuronium
phenytoin decreases effects of rapacuronium by pharmacodynamic antagonism. Minor/Significance Unknown.
- rifabutin
rifabutin decreases levels of phenytoin by increasing metabolism. Minor/Significance Unknown.
- sage
sage decreases effects of phenytoin by pharmacodynamic antagonism. Minor/Significance Unknown. Theoretical interaction; some species of sage may cause convulsions.
- saxagliptin
phenytoin will decrease the level or effect of saxagliptin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- serdexmethylphenidate/dexmethylphenidate
serdexmethylphenidate/dexmethylphenidate increases effects of phenytoin by decreasing metabolism. Minor/Significance Unknown.
- succinylcholine
phenytoin decreases effects of succinylcholine by pharmacodynamic antagonism. Minor/Significance Unknown.
- sucralfate
sucralfate decreases levels of phenytoin by inhibition of GI absorption. Applies only to oral form of both agents. Minor/Significance Unknown.
- sufentanil
phenytoin will decrease the level or effect of sufentanil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- sulfadiazine
sulfadiazine increases levels of phenytoin by decreasing metabolism. Minor/Significance Unknown.
- sulfamethoxazole
sulfamethoxazole increases levels of phenytoin by decreasing metabolism. Minor/Significance Unknown.
- sulfisoxazole
sulfisoxazole increases levels of phenytoin by decreasing metabolism. Minor/Significance Unknown.
- thyroid desiccated
phenytoin decreases levels of thyroid desiccated by increasing metabolism. Minor/Significance Unknown.
phenytoin decreases levels of thyroid desiccated by plasma protein binding competition. Minor/Significance Unknown. - tiagabine
phenytoin decreases levels of tiagabine by increasing metabolism. Minor/Significance Unknown.
- tibolone
phenytoin decreases levels of tibolone by increasing metabolism. Minor/Significance Unknown. Theoretical interaction.
- tolazamide
tolazamide increases levels of phenytoin by plasma protein binding competition. Minor/Significance Unknown.
- tolbutamide
tolbutamide increases levels of phenytoin by plasma protein binding competition. Minor/Significance Unknown.
phenytoin decreases effects of tolbutamide by pharmacodynamic antagonism. Minor/Significance Unknown. - topiramate
topiramate increases levels of phenytoin by decreasing metabolism. Minor/Significance Unknown.
- toremifene
phenytoin decreases levels of toremifene by increasing metabolism. Minor/Significance Unknown.
- trazodone
trazodone increases levels of phenytoin by unspecified interaction mechanism. Minor/Significance Unknown.
- typhoid polysaccharide vaccine
phenytoin decreases levels of typhoid polysaccharide vaccine by increasing metabolism. Minor/Significance Unknown.
- typhoid vaccine live
phenytoin decreases levels of typhoid vaccine live by increasing metabolism. Minor/Significance Unknown.
- valproic acid
valproic acid, phenytoin. Mechanism: plasma protein binding competition. Minor/Significance Unknown. Valproic acid may increase or decrease phenytoin levels.
phenytoin decreases levels of valproic acid by increasing metabolism. Minor/Significance Unknown. - vigabatrin
vigabatrin decreases levels of phenytoin by unknown mechanism. Minor/Significance Unknown.
- vinblastine
phenytoin will decrease the level or effect of vinblastine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
phenytoin will decrease the level or effect of vinblastine by P-glycoprotein (MDR1) efflux transporter. Minor/Significance Unknown. Phenytoin may be less likely to interact with vinblastine. Careful monitoring of patients for seizure activity is recommended, as is monitoring of plasma phenytoin levels. - vincristine
phenytoin will decrease the level or effect of vincristine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
phenytoin will decrease the level or effect of vincristine by P-glycoprotein (MDR1) efflux transporter. Minor/Significance Unknown. Plasma concentrations and therapeutic effect of Phenytoin may be reduced by Vincristine. Frequency of seizures may be increased. - vincristine liposomal
phenytoin will decrease the level or effect of vincristine liposomal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
phenytoin will decrease the level or effect of vincristine liposomal by P-glycoprotein (MDR1) efflux transporter. Minor/Significance Unknown. Plasma concentrations and therapeutic effect of Phenytoin may be reduced by Vincristine. Frequency of seizures may be increased. - vinorelbine
phenytoin will decrease the level or effect of vinorelbine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- zaleplon
phenytoin will decrease the level or effect of zaleplon by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- ziprasidone
phenytoin will decrease the level or effect of ziprasidone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- zolpidem
phenytoin will decrease the level or effect of zolpidem by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- zonisamide
phenytoin will decrease the level or effect of zonisamide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
Adverse Effects
Frequency Not Defined
Drowsiness
Fatigue
Ataxia
Irritability
Headache
Restlessness
Slurred speech
Nervousness
Nystagmus
Dizziness
Vertigo
Dysarthria
Paresthesia
Rash
Pruritus
Gingival hyperplasia (pediatric patients)
Ataxia
Paradoxical seizure
Drug withdrawal seizure
Diplopia
Psychosis (high dose)
Toxic amblyopia
Encephalopathy
AV conduction disorder
Ventricular fibrillation
Nausea
Vomiting
Constipation
Diarrhea
Megaloblastic (folate-deficiency) anemia
Hypocalcemia
Hepatotoxicity
Hypertrichosis
Lymphadenopathy, including benign lymph node hyperplasia, pseudolymphoma, lymphoma, and Hodgkin’s disease
Purple glove syndrome
Rash
Allergic reactions in the form of rash or, rarely, more serious forms (drug reaction with eosinophilia and systemic symptoms, or DRESS) or anaphylaxis
Purpuric rash
Toxic epidermal necrolysis
Bullous, exfoliative, or purpuric dermatitis
Coarsening of facial features
Periarteritis nodosa
Immunoglobulin abnormalities
Altered taste sensation, including metallic taste
Peyronie disease
IV >50 mg/min
- CNS depression
- Cardiovascular collapse
- Hypotension
Rare
- Dyskinesia
- Ophthalmoplegia
- Nephrotoxicity
- Stevens-Johnson syndrome
- Lupus erythematosus
- Rickets
- Osteomalacia
Postmarketing Reports
Cerebellar atrophy
Angioedema
Generalized exanthematous pustulosis
Urticaria
Hematologic and lymphatic system: thrombocytopenia, leukopenia, granulocytopenia, agranulocytosis, pure red cell aplasia, and pancytopenia with or without bone marrow suppression
Warnings
Black Box Warnings
Cardiovascular risk associated with rapid infusion rates
- Risk of hypotension and arrhythmias with infusion rates that exceed 50 mg/min in adults and 1-3 mg/kg/min (or 50 mg/min, whichever is slower) for pediatric patients
- Careful cardiac monitoring is needed during and after IV administration
- These events have also been reported at or below 50 mg/min
- Reduce infusion rate or discontinuation may be needed
Contraindications
Hypersensitivity
Sinus bradycardia
Sinoatrial block
Second and third degree A-V block
Adams-Stokes syndrome
Concurrent use with delavirdine
History of prior acute hepatotoxicity attributable to phenytoin
Cautions
Erratically absorbed when administered IM, so this route should be used as a last resort
ONLY extended-release capsules should be used for once-daily dosing regimens
Decreased bone mineral density reported with chronic use
Rapid intravenous administration increases the risk of adverse cardiovascular reactions, including severe hypotension and cardiac arrhythmias; in pediatric patients, administer the drug at a rate not exceeding 1 to 3 mg/kg/min or 50 mg per minute, whichever is slower; although risk of cardiovascular toxicity increases with infusion rates above recommended infusion rate, these events have also been reported at or below recommended infusion rate
May cause fetal harm when administered to a pregnant woman
Phenytoin induces hepatic metabolizing enzymes, which may enhance metabolism of vitamin D and decrease vitamin D levels, leading to vitamin D deficiency, hypocalcemia, and hypophosphatemia; consideration should be given to screening with bone-related laboratory and radiological tests as appropriate and initiating treatment plans according to established guidelines
Use caution in cardiovascular disease, hypoalbuminemia, hepatic impairment, hypothyroidism, or seizures; because fraction of unbound phenytoin is increased in patients with renal or hepatic disease, or in those with hypoalbuminemia, the monitoring of phenytoin serum levels should be based on the unbound fraction in those patients
Associated with exacerbation of porphyria; exercise caution when used in patients with this disease
Extensively bound to serum plasma proteins and is prone to competitive displacement
Acute alcoholic intake may increase phenytoin serum levels, while chronic alcoholic use may decrease serum levels
Risk of hypotension and arrhythmias with infusion rates that exceed 50 mg/min in adults and 1-3 mg/kg/min (or 50 mg/min, whichever is slower) for pediatric patients
Hematologic effects reported with use including agranulocytosis, leukopenia, pancytopenia, neutropenia, thrombocytopenia, and anemias
Phenytoin is a potent inducer of hepatic drug-metabolizing enzymes
Increased risk of suicidal thoughts or behavior reported
May render OCPs ineffective because of induction of hepatic metabolism
Risk of gingival hyperplasia
Local toxicity (purple glove syndrome) that includes edema, discoloration, and pain distal to the site of injection has been reported following peripheral IV injection; may or may not be associated with extravasation; this syndrome may not develop for several days after injection
IV infusion not recommended by many due to poor solubility and risk of crystal formation; others state it is doable with right solvent and concentration
Good for automatic and reentrant arrhythmias, not PSVT's
Phenytoin was listed by the FDA as one of the drugs to monitor after having identified potential signs of serious risks or new safety information in the agency's Adverse Event Reporting System (AERS) database during the last 3 months of 2011
Drug interactions resulting in decreased effectiveness of nondepolarizing neuromuscular blocking agents have been reported
The FDA has not suggested that clinicians stop prescribing any drugs on the watch list or that patients stop taking them; it has, however, advised that patients with questions about watch-list drugs discuss them with their clinician
Antiepileptic drugs should not be abruptly discontinued because of the possibility of increased seizure frequency, including status epilepticus
Hyperglycemia, resulting from drug's inhibitory effect on insulin release reported; phenytoin may also raise serum glucose level in patients diabetes mellitus; use caution
Not indicated for seizures resulting from hypoglycemia or other metabolic causes; appropriate diagnostic procedures should be performed as indicated
Not effective for absence seizures; if tonic-clonic and absence seizures present, combined drug therapy needed
Sustained serum levels of phenytoin above optimal range may produce confusional states referred to as "delirium", "psychosis", or "encephalopathy", or rarely irreversible cerebellar dysfunction; accordingly, at the first sign of acute toxicity, plasma levels are recommended; dose reduction of phenytoin therapy is indicated if plasma levels are excessive; termination recommended if symptoms persist
The lethal dose in pediatric patients is not known; in adults, the lethal dose is estimated to be 2- 5 g; initial symptoms include nystagmus, ataxia, and dysarthria; other signs are tremor, hyperreflexia, lethargy, slurred speech, blurred vision, nausea, and vomiting; death is due to respiratory and circulatory depression
Phenytoin may decrease serum concentrations of thyroid hormone (T4 and T3), sometimes with an accompanying increase in thyroid-stimulating hormone (TSH), but usually in absence of clinical hypothyroidism
Cases of bradycardia and cardiac arrest reported, both at recommended phenytoin doses and levels, and in association with phenytoin toxicity; most reports of cardiac arrest occurred in patients with underlying cardiac disease
Angioedema reported with phenytoin and fosphenytoin; discontinue immediately if symptoms of angioedema (eg, facial, perioral, or upper airway swelling) occur
Metabolized by hepatic cytochrome P450 enzymes CYP2C9 and CYP2C19, and is particularly susceptible to inhibitory drug interactions because it is subject to saturable metabolism; if metabolism inhibited, may produce significant increases in circulating phenytoin concentrations and enhance the risk of drug toxicity
Concomitant administration of phenytoin and valproate associated with increased risk of valproate-associated hyperammonemia; patients treated concomitantly with these two drugs should be monitored for signs and symptoms of hyperammonemia
Patients with decreased CYP2C9 function
- Patients who are intermediate or poor metabolizers of CYP2C9 substrates (eg, *1/*3, *2/*2, *3/*3) may exhibit increased phenytoin serum concentrations compared to patients who are normal metabolizers (eg, *1/*1); patients who are known to be intermediate or poor metabolizers may ultimately require lower doses to maintain similar steady-state concentrations compared to normal metabolizers
- In patients who are known to be carriers of the decreased function CYP2C9*2 or *3 alleles (intermediate and poor metabolizers), consider starting at the low end of the dosage range and monitor serum concentrations to maintain total phenytoin concentrations of 10 to 20 mcg/mL; if early signs of dose-related central nervous system (CNS) toxicity develop, serum concentrations should be checked immediately
Severe cutaneous reactions
- Can cause severe cutaneous adverse reactions (SCARs), which may be fatal
- Reported reactions include toxic epidermal necrolysis (TEN), Stevens-Johnson syndrome (SJS), acute generalized exanthematous pustulosis (AGEP), and Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS)
- Onset is usually within 28 days, but can occur later
- Discontinue at the first sign of a rash, unless the rash is clearly not drug-related
- If signs or symptoms suggest a severe cutaneous adverse reaction, do not resume drug; consider alternant therapy
- Studies in patients of Chinese ancestry have found a strong association between risk of developing SJS/TEN and the presence of HLA-B*1502, an inherited allelic variant of the HLA B gene in patients taking carbamazepine
- Limited evidence suggests that HLA-B*1502 or CYP2C9*3 may also be a risk factor for the development of SJS/TEN in patients taking other antiepileptic drugs
-
DRESS
- DRESS, also known as multiorgan hypersensitivity, reported in patients taking antiepileptic drugs, including phenytoin and fosphenytoin
- Some of these events have been fatal or life-threatening
- DRESS typically, although not exclusively, presents with fever, rash, lymphadenopathy, and/or facial swelling, in association with other organ system involvement (eg, hepatitis, nephritis, hematological abnormalities, myocarditis, or myositis sometimes resembling an acute viral infection); eosinophilia is often present
- Early manifestations of hypersensitivity (eg, fever or lymphadenopathy) may be present even though rash is not evident
- If such signs or symptoms are present, evaluate patient immediately; discontinue drug if unable to confirm other etiology for the rash
Pregnancy & Lactation
Pregnancy: Pregnancy exposure registry that monitors pregnancy outcomes in women exposed to antiepileptic drugs (AEDs), such as phenytoin, during pregnancy is available; pregnant patients taking should enroll in the North American Antiepileptic Drug (NAAED) Pregnancy Registry by calling the toll free number 1-888-233-2334; it must be done by patients themselves; Information on the registry can also be found at the website http://www.aedpregnancyregistry.org/
An increased incidence of major malformations (such as orofacial clefts and cardiac defects) and abnormalities characteristic of fetal hydantoin syndrome (dysmorphic skull and facial features, nail and digit hypoplasia, growth abnormalities [including microcephaly], and cognitive deficits) reported among children born to epileptic women who took phenytoin alone or in combination with other antiepileptic drugs during pregnancy
An increase in seizure frequency may occur during pregnancy; periodic measurement of plasma phenytoin concentrations may be valuable to make appropriate dosage adjustments; postpartum restoration of original dosage will probably be indicated
Consider vitamin K supplementation for 1 month before birth
Lactation: Phenytoin is secreted in human milk; developmental and health benefits of breastfeeding should be considered along with mother’s clinical need for therapy and any potential adverse effects on breastfed infant from phenytoin or from underlying maternal condition
Pregnancy Categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk. C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done. D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk. X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist. NA: Information not available.Pharmacology
Mechanism of Action
Promotes Na+ efflux or decreases Na+ influx from membranes in motor cortex neurons; stabilizes neuronal membrane
Slows conduction velocity
Absorption
Bioavailability: May vary between different manufacturers; dependent on formulation
Onset: 1 week (PO); 2-24 hr (PO with loading dose); 0.5-1 hr (IV)
Peak plasma time: 1.5-3 hr (immediate-release); 4-12 hr (extended-release)
Distribution
Protein bound: 95% (adults); 85% (infants); 80% (neonates)
Vd: 0.6-0.7 L/kg (adults); 0.7 L/kg (children); 0.7-0.8 L/kg (infants); 0.8-0.9 L/kg (full-term neonate); 1-1.2 L/kg (premature neonate)
Metabolism
Metabolized by hepatic P450 enzyme CYP2C9
Metabolites: Inactive
Enzymes induced: CYP3A4
Elimination
Half-life: 22 hr (PO); 10-15 hr (IV)
Excretion: Urine
Pharmacogenomics
HLA variants
- Patients with HLA-B*1502 with are more likely to have a severe dermatologic reaction (eg, toxic epidermal necrolysis, Stevens-Johnson syndrome) when taking phenytoin
- This allele occurs almost exclusively in patients with ancestry across broad areas of Asia, including Han Chinese, Filipinos, Malaysians, South Asian Indians, and Thais
Epoxide genotypes
- Maternal epoxide (EPHX1) genotypes 113*H and 139*R are associated with risk of fetal hydantoin syndrome among pregnant women taking phenytoin
- Increased levels of the reactive epoxide metabolites by either inhibiting the detoxification of these metabolites by epoxide hydrolase or by increasing conversion to epoxide metabolites by inducing CYP3A4, 2C9, or 2C19
Genetic testing laboratories (for HLA variants)
- Kashi Clinical Laboratories (www.kashilab.com)
- LabCorp (http://www.labcorp.com/)
- Specialty Laboratories (http://www.specialtylabs.com)
- Quest (http://www.questdiagnostics.com)
Administration
IV Incompatibilities
Solution
- D5/NS
- D5W
- LR
- 1/2NS
- NS(?)
Additive
- Amikacin
- Bretylium
- Dobutamine
- Hydroxyzine
- Insulin (regular)
- Levorphanol, lidocaine, lincomycin
- Meperidine, metaraminol, morphine sulfate
- Nitroglycerin, norepinephrine
- Pentobarbital, procaine
- Streptomycin
Syringe
- Hydromorphone
- Sufentanil
Y-site
- Ampho B cholesteryl sulfate, ciprofloxacin, clarithromycin, diltiazem, enalaprilat, fenoldopam, fentanyl, gatifloxacin, heparin, heparin/hydrocortisone, hydromorphone, linezolid, methadone, morphine sulfate, KCl, propofol, sufentanil, theophylline, vitamins B/C
IV Compatibilities
Additive
- Verapamil
Y-site
- Esmolol
- Famotidine
- Fluconazole
- Foscarnet
- Tacrolimus
IV Preparation
Load IV in 250 mL NS; monitor BP
Further dilution of IV infusion solution is controversial, and no consensus exists as to optimal concentration and length of stability
Stability is concentration and pH dependent
Based on limited clinical consensus, NS and LR are recommended diluents; dilutions of 1-10 mg/mL have been used and should be administered ASAP after preparation
IV/IM Administration
Administer slowly; no more than 50 mg/min in adults and no more than 1-3 mg/kg/min in pediatric patients
IM: Although approved for IM use, IM administration is not recommended, due to erratic absorption and pain on injection; fosphenytoin may be considered
IV: IV infusion not recommended
Storage
Store intact vials at room temperature; protect from freezing
If refrigerated, ppt forms, but dissolves on standing at room temp; OK for use
Images
BRAND | FORM. | UNIT PRICE | PILL IMAGE |
---|---|---|---|
phenytoin oral - | 100 mg/4 mL suspension | ![]() | |
phenytoin oral - | 50 mg chewable tablet | ![]() | |
phenytoin oral - | 125 mg/5 mL suspension | ![]() | |
phenytoin oral - | 125 mg/5 mL suspension | ![]() | |
phenytoin oral - | 50 mg chewable tablet | ![]() | |
phenytoin oral - | 50 mg chewable tablet | ![]() | |
phenytoin oral - | 100 mg/4 mL suspension | ![]() | |
Dilantin Infatabs oral - | 50 mg chewable tablet | ![]() | |
Dilantin-125 oral - | 125 mg/5 mL suspension | ![]() |
Copyright © 2010 First DataBank, Inc.
Patient Handout
phenytoin oral
PHENYTOIN CHEWABLE TABLET - ORAL
(FEN-i-toyn)
COMMON BRAND NAME(S): Dilantin
USES: Phenytoin is used to prevent and control seizures (also called an anticonvulsant or antiepileptic drug). It works by reducing the spread of seizure activity in the brain.
HOW TO USE: Read the Medication Guide provided by your pharmacist before you start taking phenytoin and each time you get a refill. If you have any questions, ask your doctor or pharmacist.The tablets may be chewed thoroughly before swallowing or swallowed whole.Take this medication by mouth as directed by your doctor, usually 2 or 3 times a day. This product is not recommended for use once a day. You may take it with food if stomach upset occurs. Take this medication with a full glass (8 ounces or 240 milliliters) of water unless your doctor directs you otherwise.Use this medication regularly in order to get the most benefit from it. It is important to take all doses on time to keep the amount of medicine in your body at a constant level. Remember to use it at the same times each day. The dosage is based on your medical condition, lab tests, and response to treatment. For children, the dosage is also based on weight.Antacids and nutritional tube-feeding (enteral) products may decrease the absorption of phenytoin. Do not take these products at the same time as your phenytoin dose. Separate liquid nutritional products at least 1 hour before and 1 hour after your phenytoin dose, or as directed by your doctor.Do not stop taking this medication without consulting your doctor. Seizures may become worse when the drug is suddenly stopped. Your dose may need to be gradually decreased.Tell your doctor if your condition does not improve or if it gets worse.
SIDE EFFECTS: Headache, nausea, vomiting, constipation, dizziness, feeling of spinning, drowsiness, trouble sleeping, or nervousness may occur. If any of these effects last or get worse, tell your doctor or pharmacist promptly.Phenytoin may cause swelling and bleeding of the gums. Massage your gums and brush and floss your teeth regularly to minimize this problem. See your dentist regularly.Remember that this medication has been prescribed because your doctor has judged that the benefit to you is greater than the risk of side effects. Many people using this medication do not have serious side effects.Tell your doctor right away if you have any serious side effects, including: slow heartbeat, unusual eye movements, loss of coordination, trouble speaking, confusion, muscle twitching, double/blurred vision, tingling of the hands/feet, facial changes (such as swollen lips, butterfly-shaped rash around the nose/cheeks), excessive hair growth, increased thirst/urination, unusual tiredness, bone/joint pain, easily broken bones.A small number of people who take anticonvulsants for any condition (such as seizure, bipolar disorder, pain) may experience depression, suicidal thoughts/attempts, or other mental/mood problems. Tell your doctor right away if you or your family/caregiver notice any unusual/sudden changes in your mood, thoughts, or behavior including signs of depression, suicidal thoughts/attempts, thoughts about harming yourself.Rarely, males may have a painful or prolonged erection lasting 4 or more hours. If this occurs, stop using this drug and get medical help right away, or permanent problems could occur.Get medical help right away if you have any very serious side effects, including: uncontrolled muscle movements, signs of liver problems (such as nausea/vomiting that doesn't stop, stomach/abdominal pain, yellowing eyes/skin, dark urine), easy bruising/bleeding.A very serious allergic reaction to this drug is rare. However, get medical help right away if you notice any symptoms of a serious allergic reaction, including: fever, swollen lymph nodes, rash, itching/swelling (especially of the face/tongue/throat), severe dizziness, trouble breathing.This is not a complete list of possible side effects. If you notice other effects not listed above, contact your doctor or pharmacist.In the US -Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088 or at www.fda.gov/medwatch.In Canada - Call your doctor for medical advice about side effects. You may report side effects to Health Canada at 1-866-234-2345.
PRECAUTIONS: Before taking phenytoin, tell your doctor or pharmacist if you are allergic to it; or to other anti-seizure medications (such as carbamazepine, ethosuximide, ethotoin, fosphenytoin, oxcarbazepine, phenobarbital, primidone, trimethadione); or if you have any other allergies. This product may contain inactive ingredients, which can cause allergic reactions or other problems. Talk to your pharmacist for more details.Before using this medication, tell your doctor or pharmacist your medical history, especially of: alcohol use, certain blood conditions (porphyria), diabetes, liver disease (including liver disease caused by past phenytoin use), lupus, folate or vitamin B-12 deficiency (megaloblastic anemia).This drug may make you dizzy or drowsy. Alcohol or marijuana (cannabis) can make you more dizzy or drowsy. Do not drive, use machinery, or do anything that needs alertness until you can do it safely. Limit alcoholic beverages. Talk to your doctor if you are using marijuana (cannabis). Alcohol may also affect your blood levels of this drug.Before having surgery, tell your doctor or dentist about all the products you use (including prescription drugs, nonprescription drugs, and herbal products).If you have diabetes, this product may make it harder to control your blood sugar. Check your blood sugar regularly as directed and share the results with your doctor. Your doctor may need to adjust your diabetes medication, exercise program, or diet.Vitamin D supplements may be necessary to prevent weakening of the bones (osteomalacia). Discuss this with your doctor.During pregnancy, this medication should be used only when clearly needed. It may harm an unborn baby. However, since untreated seizures are a serious condition that can harm both a pregnant woman and her unborn baby, do not stop taking this medication unless directed by your doctor. If you are planning pregnancy, become pregnant, or think you may be pregnant, immediately talk to your doctor about the benefits and risks of using this medication during pregnancy. Since birth control pills, patches, implants, and injections may not work if taken with this medication (see also Drug Interactions section), discuss reliable forms of birth control with your doctor.Phenytoin passes into breast milk. Consult your doctor before breast-feeding.
DRUG INTERACTIONS: See also How to Use section.Drug interactions may change how your medications work or increase your risk for serious side effects. This document does not contain all possible drug interactions. Keep a list of all the products you use (including prescription/nonprescription drugs and herbal products) and share it with your doctor and pharmacist. Do not start, stop, or change the dosage of any medicines without your doctor's approval.Some products that may interact with this drug include: colesevelam, orlistat, sucralfate.Other medications can affect the removal of phenytoin from your body, which may affect how phenytoin works. Examples include amiodarone, azapropazone, azole antifungals (such as itraconazole), macrolide antibiotics (such as erythromycin), estrogens, isoniazid, rifamycins (such as rifabutin), St. John's wort, among others.Phenytoin can speed up the removal of other medications from your body, which may affect how they work. Examples of affected drugs include atazanavir, some drugs to treat cancer (such as imatinib, irinotecan), cobicistat, corticosteroids (such as prednisone), doravirine, etravirine, felodipine, nisoldipine, quetiapine, quinidine, rilpivirine, suvorexant, telithromycin, theophylline, vitamin D, among others.This medication may decrease the effectiveness of hormonal birth control such as pills, patch, or ring. This could cause pregnancy. Discuss with your doctor or pharmacist if you should use additional reliable birth control methods while using this medication. Also tell your doctor if you have any new spotting or breakthrough bleeding, because these may be signs that your birth control is not working well.This medication may interfere with certain lab tests, possibly causing false test results. Make sure lab personnel and all your doctors know you use this drug.
OVERDOSE: If someone has overdosed and has serious symptoms such as passing out or trouble breathing, call 911. Otherwise, call a poison control center right away. US residents can call their local poison control center at 1-800-222-1222. Canada residents can call a provincial poison control center. Symptoms of overdose may include: severe mental/mood changes, severe drowsiness, loss of consciousness, slowed breathing.
NOTES: Do not share this medication with others.Lab and/or medical tests (such as phenytoin blood levels, liver function, complete blood count) should be done while you are taking this medication. Keep all medical and lab appointments. Consult your doctor for more details.Do not change from one brand of this product to another, or to another dose form of this drug (such as capsules) without consulting your doctor or pharmacist. Your dosage may have to be adjusted.
MISSED DOSE: If you miss a dose, take it as soon as you remember unless it is within 4 hours of the next dose. In that case, skip the missed dose. Take your next dose at the regular time. Check with your doctor if you miss doses for more than 2 days in a row. Do not double the dose to catch up.
STORAGE: Store at room temperature away from light and moisture. Do not store in the bathroom. Keep all medications away from children and pets.Do not flush medications down the toilet or pour them into a drain unless instructed to do so. Properly discard this product when it is expired or no longer needed. Consult your pharmacist or local waste disposal company.
MEDICAL ALERT: Your condition can cause complications in a medical emergency. For information about enrolling in MedicAlert, call 1-888-633-4298 (US) or 1-800-668-1507 (Canada).
Information last revised August 2023. Copyright(c) 2023 First Databank, Inc.
IMPORTANT: HOW TO USE THIS INFORMATION: This is a summary and does NOT have all possible information about this product. This information does not assure that this product is safe, effective, or appropriate for you. This information is not individual medical advice and does not substitute for the advice of your health care professional. Always ask your health care professional for complete information about this product and your specific health needs.
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