Dosing & Uses
Dosage Forms & Strengths
codeine/acetaminophen/butalbital/caffeine
capsule: Schedule III
- 30mg/325mg/50mg/40mg
- 30mg/300mg/50mg/40mg
Tension Headache
1-2 tab/cap PO q4hr; not to exceed 6 tab/cap per day
To discontinue therapy, decrease dose by 25% to 50% every 2-4 days; monitor for symptoms/signs of withdrawal; if withdrawal symptoms occur, raise dose to the previous level and taper more slowly, either by increasing the interval between decreases, decreasing the amount of change in dose, or both; do not abruptly discontinue therapy in a physically dependent patient
Dosing Considerations
Use lowest effective dosage for shortest duration consistent with individual patient treatment goals
Initiate dosing regimen for each patient individually, taking into account patient's severity of pain, patient response, prior analgesic treatment experience, and risk factors for addiction, abuse, and misuse
Evidence supporting efficacy and safety of drug in treatment of multiple recurrent headaches is unavailable
Limitation of Use
- Because of the risks of addiction, abuse, and misuse with opioids and butalbital, even at recommended doses, reserve therapy for use in patients for whom alternative treatment options [e.g., non-opioid, non-barbiturate analgesics] have not been tolerated, or are not expected to be tolerated, have not provided adequate analgesia, or are not expected to provide adequate analgesia
Access to naloxone for opioid overdose
- Assess need for naloxone upon initiating and renewing treatment
-
Consider prescribing naloxone
- Based on patient’s risk factors for overdose (eg, concomitant use of CNS depressants, a history of opioid use disorder, prior opioid overdose); presence of risk factors should not prevent proper pain management
- Household members (including children) or other close contacts at risk for accidental ingestion or overdose
-
Consult patients and caregivers on the following:
- Availability of naloxone for emergency treatment of opioid overdose
- Ways differ on how to obtain naloxone as permitted by individual state dispensing and prescribing requirements or guidelines (eg, by prescription, directly from a pharmacist, as part of a community-based program)
Dosage Forms & Strengths
codeine/acetaminophen/butalbital/caffeine
capsule: Schedule III
- 30mg/325mg/50mg/40mg
- 30mg/300/mg/50mg/40mg
The FDA has recommended that codeine not be used in children <12 years and all pediatric patients undergoing tonsillectomy and/or adenoidectomy
Tension Headache (Off-label)
<12 years: Safety and efficacy not established
≥12 years: 1-2 tab/cap PO q4hr; not to exceed 6 tab/cap per day (not to exceed acetaminophen 4 g/day); to discontinue therapy, decrease dose by 25% to 50% every 2-4 days; monitor for symptoms/signs of withdrawal; if withdrawal symptoms occur, raise the dose to the previous level and taper more slowly, either by increasing the interval between decreases, decreasing the amount of change in dose, or both; do not abruptly discontinue therapy in a physically dependent patient
Interactions
Interaction Checker
No Results

Contraindicated
Serious - Use Alternative
Significant - Monitor Closely
Minor

Contraindicated (3)
- alvimopan
alvimopan, codeine. receptor binding competition. Contraindicated. Alvimopan is contraindicated in opioid tolerant patients (ie, those who have taken therapeutic doses of opioids for >7 consecutive days immediately prior to taking alvimopan). Patients recently exposed to opioids are expected to be more sensitive to the effects of alvimopan and therefore may experience abdominal pain, nausea and vomiting, and diarrhea. No significant interaction is expected with concurrent use of opioid analgesics and alvimopan in patients who received opioid analgesics for 7 or fewer consecutive days prior to alvimopan.
- doravirine
butalbital 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.
- fezolinetant
caffeine will increase the level or effect of fezolinetant by affecting hepatic enzyme CYP1A2 metabolism. Contraindicated. Fezolinetant AUC and peak plasma concentration are increased if coadministered with drugs that are weak, moderate, or strong CYP1A2 inhibitors
Serious - Use Alternative (99)
- abemaciclib
butalbital 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.
- acrivastine
acrivastine and codeine both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate
- alosetron
butalbital will decrease the level or effect of alosetron by affecting hepatic enzyme CYP1A2 metabolism. Avoid or Use Alternate Drug.
- alpelisib
butalbital will decrease the level or effect of alpelisib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of alpelisib (CYP3A4 substrate) with strong CYP3A4 inducers.
- amisulpride
amisulpride and codeine both increase sedation. Avoid or Use Alternate Drug.
- antithrombin alfa
butalbital decreases effects of antithrombin alfa by increasing metabolism. Avoid or Use Alternate Drug.
- antithrombin III
butalbital decreases effects of antithrombin III by increasing metabolism. Avoid or Use Alternate Drug.
- argatroban
butalbital decreases effects of argatroban by increasing metabolism. Avoid or Use Alternate Drug.
- asenapine
asenapine and codeine both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate
- asenapine transdermal
asenapine transdermal and codeine both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate
- avapritinib
avapritinib and codeine both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate
butalbital will decrease the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. - bemiparin
butalbital decreases effects of bemiparin by increasing metabolism. Avoid or Use Alternate Drug.
- benzhydrocodone/acetaminophen
benzhydrocodone/acetaminophen, codeine. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.
benzhydrocodone/acetaminophen and codeine both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate - benzhydrocodone/acetaminophen
benzhydrocodone/acetaminophen, butalbital. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.
benzhydrocodone/acetaminophen and butalbital both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate - bivalirudin
butalbital decreases effects of bivalirudin by increasing metabolism. Avoid or Use Alternate Drug.
- bremelanotide
bremelanotide will decrease the level or effect of codeine 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.
- brexpiprazole
brexpiprazole and butalbital both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate
- brigatinib
butalbital will decrease the level or effect of brigatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration with strong CYP3A4 inducers may decrease brigatinib efficacy.
- brimonidine
brimonidine and codeine both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate
- buprenorphine
buprenorphine, codeine. Other (see comment). Avoid or Use Alternate Drug. Comment: Mixed opiate agonist/antagonists usually produce additive sedation with narcotics; however, in narcotic addicted pts., the antagonist activity may provoke withdrawal Sx.
- buprenorphine buccal
buprenorphine buccal, codeine. Other (see comment). Avoid or Use Alternate Drug. Comment: Mixed opiate agonist/antagonists usually produce additive sedation with narcotics; however, in narcotic addicted pts., the antagonist activity may provoke withdrawal Sx.
- buprenorphine subdermal implant
buprenorphine subdermal implant and butalbital both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate
buprenorphine subdermal implant and codeine both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate - buprenorphine transdermal
buprenorphine transdermal and codeine both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate
buprenorphine transdermal and butalbital both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate - buprenorphine, long-acting injection
buprenorphine, long-acting injection and codeine both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate
buprenorphine, long-acting injection and butalbital both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate - bupropion
caffeine increases toxicity of bupropion by unspecified interaction mechanism. Avoid or Use Alternate Drug. May lower seizure threshold; keep bupropion dose as low as possible.
- butorphanol
butorphanol, codeine. Other (see comment). Avoid or Use Alternate Drug. Comment: Mixed opiate agonist/antagonists usually produce additive sedation with narcotics; however, in narcotic addicted pts., the antagonist activity may provoke withdrawal Sx.
- calcium/magnesium/potassium/sodium oxybates
butalbital, 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.
- calcium/magnesium/potassium/sodium oxybates
codeine, 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.
- clonidine
clonidine, codeine. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration enhances CNS depressant effects.
- copanlisib
butalbital 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.
- dacomitinib
dacomitinib will increase the level or effect of codeine by affecting hepatic enzyme CYP2D6 metabolism. Avoid or Use Alternate Drug. Avoid use with CYP2D6 substrates where minimal increases in concentration of the CYP2D6 substrate may lead to serious or life-threatening toxicities.
- dalteparin
butalbital decreases effects of dalteparin by increasing metabolism. Avoid or Use Alternate Drug.
- daridorexant
butalbital will decrease the level or effect of daridorexant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- deflazacort
butalbital 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.
- diazepam intranasal
diazepam intranasal, codeine. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.
- dihydroergotamine
butalbital will decrease the level or effect of dihydroergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- dihydroergotamine intranasal
butalbital will decrease the level or effect of dihydroergotamine intranasal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- dipyridamole
caffeine decreases effects of dipyridamole by pharmacodynamic antagonism. Contraindicated.
butalbital decreases levels of dipyridamole by increasing metabolism. Contraindicated. - dronedarone
butalbital will decrease the level or effect of dronedarone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- givosiran
givosiran will increase the level or effect of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of sensitive CYP1A2 substrates with givosiran. If unavoidable, decrease the CYP1A2 substrate dosage in accordance with approved product labeling.
- duloxetine
butalbital will decrease the level or effect of duloxetine by affecting hepatic enzyme CYP1A2 metabolism. Avoid or Use Alternate Drug.
- duvelisib
butalbital will increase 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.
- elacestrant
butalbital will decrease the level or effect of elacestrant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- eluxadoline
codeine, eluxadoline. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Avoid coadministration with other drugs that cause constipation. Increases risk for constipation related serious adverse reactions. .
- enoxaparin
butalbital decreases effects of enoxaparin by increasing metabolism. Avoid or Use Alternate Drug.
- erdafitinib
butalbital will decrease the level or effect of erdafitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- ergotamine
butalbital will decrease the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- erythromycin base
butalbital will decrease the level or effect of erythromycin base by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- erythromycin ethylsuccinate
butalbital will decrease the level or effect of erythromycin ethylsuccinate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- erythromycin lactobionate
butalbital will decrease the level or effect of erythromycin lactobionate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- erythromycin stearate
butalbital will decrease the level or effect of erythromycin stearate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- everolimus
butalbital will decrease the level or effect of everolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- fedratinib
butalbital 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.
- fentanyl
fentanyl, butalbital. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration with other CNS depressants, such as skeletal muscle relaxants, may cause respiratory depression, hypotension, profound sedation, coma, and/or death. Consider dose reduction of either or both agents to avoid serious adverse effects. Monitor for hypotension, respiratory depression, and profound sedation.
fentanyl, codeine. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration with other CNS depressants, such as skeletal muscle relaxants, may cause respiratory depression, hypotension, profound sedation, coma, and/or death. Consider dose reduction of either or both agents to avoid serious adverse effects. Monitor for hypotension, respiratory depression, and profound sedation. - fentanyl intranasal
fentanyl intranasal, codeine. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration with other CNS depressants, such as skeletal muscle relaxants, may cause respiratory depression, hypotension, profound sedation, coma, and/or death. Consider dose reduction of either or both agents to avoid serious adverse effects. Monitor for hypotension, respiratory depression, and profound sedation.
fentanyl intranasal, butalbital. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration with other CNS depressants, such as skeletal muscle relaxants, may cause respiratory depression, hypotension, profound sedation, coma, and/or death. Consider dose reduction of either or both agents to avoid serious adverse effects. Monitor for hypotension, respiratory depression, and profound sedation. - fentanyl transdermal
fentanyl transdermal, butalbital. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration with other CNS depressants, such as skeletal muscle relaxants, may cause respiratory depression, hypotension, profound sedation, coma, and/or death. Consider dose reduction of either or both agents to avoid serious adverse effects. Monitor for hypotension, respiratory depression, and profound sedation.
fentanyl transdermal, codeine. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration with other CNS depressants, such as skeletal muscle relaxants, may cause respiratory depression, hypotension, profound sedation, coma, and/or death. Consider dose reduction of either or both agents to avoid serious adverse effects. Monitor for hypotension, respiratory depression, and profound sedation. - fentanyl transmucosal
fentanyl transmucosal, codeine. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration with other CNS depressants, such as skeletal muscle relaxants, may cause respiratory depression, hypotension, profound sedation, coma, and/or death. Consider dose reduction of either or both agents to avoid serious adverse effects. Monitor for hypotension, respiratory depression, and profound sedation.
fentanyl transmucosal, butalbital. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration with other CNS depressants, such as skeletal muscle relaxants, may cause respiratory depression, hypotension, profound sedation, coma, and/or death. Consider dose reduction of either or both agents to avoid serious adverse effects. Monitor for hypotension, respiratory depression, and profound sedation. - fexinidazole
butalbital 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.
- givosiran
givosiran will increase the level or effect of codeine by affecting hepatic enzyme CYP2D6 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of sensitive CYP2D6 substrates with givosiran. If unavoidable, decrease the CYP2D6 substrate dosage in accordance with approved product labeling.
- finerenone
butalbital will decrease the level or effect of finerenone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- fondaparinux
butalbital decreases effects of fondaparinux by increasing metabolism. Avoid or Use Alternate Drug.
- fostamatinib
butalbital will decrease the level or effect of fostamatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- ganaxolone
butalbital 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.
- glasdegib
butalbital will decrease the level or effect of glasdegib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of glasdegib with strong CYP3A inducers.
- heparin
butalbital decreases effects of heparin by increasing metabolism. Avoid or Use Alternate Drug.
- hydrocodone
hydrocodone, butalbital. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.
hydrocodone, codeine. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation. - infigratinib
butalbital will decrease the level or effect of infigratinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- iobenguane I 131
caffeine will decrease the level or effect of iobenguane I 131 by Other (see comment). Avoid or Use Alternate Drug. Based on the mechanism of action of iobenguane, drugs that reduce catecholamine uptake or that deplete catecholamine stores may interfere with iobenguane uptake into cells, and thus, reduce iobenguane efficacy. Discontinue interfering drugs for at least 5 half-lives before administration of either the dosimetry or an iobenguane dose. Do not administer these drugs until at least 7 days after each iobenguane dose.
- isocarboxazid
isocarboxazid increases toxicity of codeine by unknown mechanism. Avoid or Use Alternate Drug. Risk of hypotension, hyperpyrexia, somnolence, or death; separate by 14 d.
- isocarboxazid
isocarboxazid, butalbital. Other (see comment). Contraindicated. Comment: CNS depressants such as barbiturates should not be used in combination with isocarboxazid.
- istradefylline
butalbital 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.
- ivosidenib
butalbital 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.
- larotrectinib
butalbital 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
butalbital 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
butalbital will decrease the level or effect of lemborexant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
lemborexant, butalbital. Either increases effects of the other by sedation. Avoid or Use Alternate Drug. Use of lemborexant with other drugs to treat insomnia is not recommended. - lenacapavir
butalbital will decrease the level or effect of lenacapavir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of lenacapavir with moderate CYP3A4 inducers.
- leniolisib
butalbital will decrease the level or effect of leniolisib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- linezolid
linezolid increases toxicity of codeine by unknown mechanism. Avoid or Use Alternate Drug. Risk of hypotension, hyperpyrexia, somnolence, or death; separate by 14 d.
- lonafarnib
acetaminophen will increase the level or effect of lonafarnib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration of lonafarnib (a sensitive CYP3A substrate) with weak CYP3A inhibitors is unavoidable, reduce to, or continue lonafarnib at starting dose. Closely monitor for arrhythmias and events (eg, syncope, heart palpitations) since lonafarnib effect on QT interval is unknown.
- lovastatin
butalbital will decrease the level or effect of lovastatin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- lumateperone
butalbital will decrease the level or effect of lumateperone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- lurbinectedin
butalbital will decrease the level or effect of lurbinectedin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- macimorelin
butalbital 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.
- mestranol
butalbital decreases levels of mestranol by increasing metabolism. Avoid or Use Alternate Drug. May result in contraceptive failure.
- methoxyflurane
butalbital increases toxicity of methoxyflurane by increasing metabolism. Contraindicated. Increased metabolism of methoxyflurane to nephrotoxic compounds.
- methylene blue
methylene blue and codeine both increase serotonin levels. Avoid or Use Alternate Drug. If drug combination must be administered, monitor for evidence of serotonergic or opioid-related toxicities
methylene blue and butalbital both increase serotonin levels. Avoid or Use Alternate Drug. If drug combination must be administered, monitor for evidence of serotonergic or opioid-related toxicities - metoclopramide intranasal
codeine, 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.
butalbital, 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
butalbital 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.
- nalbuphine
nalbuphine, codeine. Other (see comment). Avoid or Use Alternate Drug. Comment: Mixed opiate agonist/antagonists usually produce additive sedation with narcotics; however, in narcotic addicted pts., the antagonist activity may provoke withdrawal Sx.
- mobocertinib
butalbital will decrease the level or effect of mobocertinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- naldemedine
butalbital 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
butalbital 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.
- olopatadine intranasal
codeine 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.
butalbital 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
butalbital 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.
- ozanimod
ozanimod and codeine both increase sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Avoid or Use Alternate Drug. Because the active metabolite of ozanimod inhibits MAO-B in vitro, there is a potential for serious adverse reactions, including hypertensive crisis. Therefore, coadministration of ozanimod with drugs that can increase norepinephrine or serotonin is not recommended. Monitor for hypertension with concomitant use.
ozanimod increases toxicity of caffeine by sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Avoid or Use Alternate Drug. Because the active metabolite of ozanimod inhibits MAO-B in vitro, there is a potential for serious adverse reactions, including hypertensive crisis. Therefore, coadministration of ozanimod with drugs that can increase norepinephrine or serotonin is not recommended. Monitor for hypertension with concomitant use. - omaveloxolone
butalbital will decrease the level or effect of omaveloxolone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- pexidartinib
acetaminophen 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.
- pretomanid
acetaminophen, 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.
- regadenoson
caffeine decreases effects of regadenoson by pharmacodynamic antagonism. Avoid or Use Alternate Drug. Avoid methylxanthines for 12 hours before regadenoson administration.
Monitor Closely (467)
- abiraterone
abiraterone increases levels of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Avoid coadministration of abiraterone with substrates of CYP2D6. If alternative therapy cannot be used, exercise caution and consider a dose reduction of the CYP2D6 substrate.
butalbital will decrease the level or effect of abiraterone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. - acalabrutinib
butalbital will decrease the level or effect of acalabrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- albuterol
codeine increases and albuterol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
albuterol and caffeine both decrease sedation. Use Caution/Monitor. - acebutolol
butalbital decreases levels of acebutolol by increasing metabolism. Use Caution/Monitor. Consider a higher beta-blocker dose during coadministration of butalbital. Atenolol, sotalol, nadolol less likely to be affected than other beta blockers.
- alfentanil
alfentanil increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
- acrivastine
acrivastine and butalbital both increase sedation. Use Caution/Monitor.
- albuterol
butalbital increases and albuterol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
- alfentanil
alfentanil and codeine both increase sedation. Use Caution/Monitor.
butalbital and alfentanil both increase sedation. Use Caution/Monitor. - almotriptan
butalbital will decrease the level or effect of almotriptan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- alprazolam
alprazolam and codeine both increase sedation. Use Caution/Monitor.
alprazolam increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor. - alprazolam
butalbital will decrease the level or effect of alprazolam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
butalbital and alprazolam both increase sedation. Use Caution/Monitor. - amitriptyline
amitriptyline increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
- amiodarone
butalbital will decrease the level or effect of amiodarone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
amiodarone will increase the level or effect of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Prevents conversion of codeine to its active metabolite morphine. - amisulpride
amisulpride and butalbital both increase sedation. Use Caution/Monitor.
- amitriptyline
codeine and amitriptyline both increase sedation. Use Caution/Monitor.
- amitriptyline
butalbital will decrease the level or effect of amitriptyline by affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor.
butalbital will decrease the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely.
butalbital and amitriptyline both increase sedation. Use Caution/Monitor. - amlodipine
butalbital will decrease the level or effect of amlodipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- amobarbital
amobarbital increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
amobarbital and codeine both increase sedation. Use Caution/Monitor.
amobarbital and butalbital both increase sedation. Use Caution/Monitor. - amoxapine
amoxapine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
butalbital and amoxapine both increase sedation. Use Caution/Monitor.
codeine and amoxapine both increase sedation. Use Caution/Monitor. - apalutamide
apalutamide will decrease the level or effect of acetaminophen by increasing elimination. Use Caution/Monitor. Apalutamide induces UGT and may decrease systemic exposure of drugs that are UGT substrates.
- apomorphine
butalbital and apomorphine both increase sedation. Use Caution/Monitor.
codeine and apomorphine both increase sedation. Use Caution/Monitor. - arformoterol
arformoterol and caffeine both decrease sedation. Use Caution/Monitor.
- aprepitant
butalbital will decrease the level or effect of aprepitant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- arformoterol
codeine increases and arformoterol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
- arformoterol
butalbital increases and arformoterol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
- aripiprazole
aripiprazole increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
codeine and aripiprazole both increase sedation. Use Caution/Monitor.
butalbital and aripiprazole both increase sedation. Use Caution/Monitor.
butalbital will decrease the level or effect of aripiprazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. - armodafinil
butalbital increases and armodafinil decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
codeine increases and armodafinil decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
armodafinil and caffeine both decrease sedation. Use Caution/Monitor. - artemether/lumefantrine
artemether/lumefantrine will increase the level or effect of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.
butalbital will decrease the level or effect of artemether/lumefantrine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. - atogepant
acetaminophen will increase the level or effect of atogepant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- avapritinib
acetaminophen will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- axitinib
acetaminophen increases levels of axitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- azelastine
azelastine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
- asenapine
asenapine and butalbital both increase sedation. Use Caution/Monitor.
- azelastine
azelastine and codeine both increase sedation. Use Caution/Monitor.
- asenapine transdermal
asenapine transdermal and butalbital both increase sedation. Use Caution/Monitor.
- atenolol
butalbital decreases levels of atenolol by increasing metabolism. Use Caution/Monitor. Consider a higher beta-blocker dose during coadministration of butalbital. Atenolol, sotalol, nadolol less likely to be affected than other beta blockers.
- atogepant
butalbital 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
butalbital will decrease the level or effect of atorvastatin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- avanafil
butalbital will decrease the level or effect of avanafil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. For patients with ED, monitor response carefully because of potential for decreased effectiveness
- avapritinib
avapritinib and butalbital both increase sedation. Use Caution/Monitor.
- azelastine
azelastine and butalbital both increase sedation. Use Caution/Monitor.
- baclofen
baclofen and codeine both increase sedation. Use Caution/Monitor.
butalbital and baclofen both increase sedation. Use Caution/Monitor. - bazedoxifene/conjugated estrogens
butalbital will decrease the level or effect of bazedoxifene/conjugated estrogens by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- belladonna and opium
codeine and belladonna and opium both increase sedation. Use Caution/Monitor.
belladonna and opium increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor. - belladonna and opium
butalbital and belladonna and opium both increase sedation. Use Caution/Monitor.
- benperidol
benperidol increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
- belumosudil
butalbital 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.
- benazepril
butalbital increases toxicity of benazepril by unspecified interaction mechanism. Use Caution/Monitor.
- benperidol
codeine and benperidol both increase sedation. Use Caution/Monitor.
butalbital and benperidol both increase sedation. Use Caution/Monitor. - benzphetamine
caffeine and benzphetamine both decrease sedation. Use Caution/Monitor.
butalbital increases and benzphetamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
codeine increases and benzphetamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor. - betaxolol
butalbital decreases levels of betaxolol by increasing metabolism. Use Caution/Monitor. Consider a higher beta-blocker dose during coadministration of butalbital. Atenolol, sotalol, nadolol less likely to be affected than other beta blockers.
- brompheniramine
brompheniramine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
- brexanolone
brexanolone, codeine. Either increases toxicity of the other by sedation. Use Caution/Monitor.
- bisoprolol
butalbital decreases levels of bisoprolol by increasing metabolism. Use Caution/Monitor. Consider a higher beta-blocker dose during coadministration of butalbital. Atenolol, sotalol, nadolol less likely to be affected than other beta blockers.
- bortezomib
butalbital will decrease the level or effect of bortezomib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- brexanolone
brexanolone, butalbital. Either increases toxicity of the other by sedation. Use Caution/Monitor.
- brexpiprazole
brexpiprazole and codeine both increase sedation. Use Caution/Monitor.
- brimonidine
brimonidine and butalbital both increase sedation. Use Caution/Monitor.
- brivaracetam
brivaracetam and codeine both increase sedation. Use Caution/Monitor.
brivaracetam and butalbital both increase sedation. Use Caution/Monitor. - brompheniramine
brompheniramine and butalbital both increase sedation. Use Caution/Monitor.
brompheniramine and codeine both increase sedation. Use Caution/Monitor. - budesonide
butalbital will decrease the level or effect of budesonide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- bupivacaine implant
acetaminophen, bupivacaine implant. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: Local anesthetics may increase the risk of developing methemoglobinemia when concurrently exposed to drugs that also cause methemoglobinemia.
- buprenorphine
buprenorphine and codeine both increase sedation. Use Caution/Monitor.
- buprenorphine
butalbital and buprenorphine both increase sedation. Use Caution/Monitor.
- buprenorphine buccal
buprenorphine buccal and codeine both increase sedation. Use Caution/Monitor.
butalbital and buprenorphine buccal both increase sedation. Use Caution/Monitor.
buprenorphine buccal increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor. - buprenorphine, long-acting injection
butalbital increases toxicity of buprenorphine, long-acting injection by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Coadministration of buprenorphine and benzodiazepines or other CNS depressants increases risk of adverse reactions including overdose, respiratory depression, and death. Cessation of benzodiazepines or other CNS depressants is preferred in most cases. In some cases, monitoring at a higher level of care for tapering CNS depressants may be appropriate. In others, gradually tapering a patient off of a prescribed benzodiazepine or other CNS depressant or decreasing to the lowest effective dose may be appropriate.
codeine increases toxicity of buprenorphine, long-acting injection by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Coadministration of buprenorphine and benzodiazepines or other CNS depressants increases risk of adverse reactions including overdose, respiratory depression, and death. Cessation of benzodiazepines or other CNS depressants is preferred in most cases. In some cases, monitoring at a higher level of care for tapering CNS depressants may be appropriate. In others, gradually tapering a patient off of a prescribed benzodiazepine or other CNS depressant or decreasing to the lowest effective dose may be appropriate.
butalbital 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. - busulfan
acetaminophen increases levels of busulfan by decreasing metabolism. Use Caution/Monitor. Use of acetaminophen prior to (< 72 hours) or concurrently with busulfan may result in decreased clearance of busulfan due to acetaminophen-induced decreases in glutathione levels.
- butabarbital
butabarbital increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
- bupropion
butalbital, bupropion. increasing metabolism. Use Caution/Monitor. Decr levels of bupropion, but incr levels of active metabolites. .
bupropion will decrease the level or effect of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Prevents the conversion of codeine to its active metabolite morphine. - buspirone
butalbital will decrease the level or effect of buspirone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- butabarbital
butabarbital and codeine both increase sedation. Use Caution/Monitor.
- butabarbital
butabarbital and butalbital both increase sedation. Use Caution/Monitor.
- butalbital
butalbital and codeine both increase sedation. Use Caution/Monitor.
butalbital increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor. - butorphanol
butorphanol and codeine both increase sedation. Use Caution/Monitor.
butalbital and butorphanol both increase sedation. Use Caution/Monitor.
butorphanol increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor. - caffeine
butalbital increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
codeine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor. - carbinoxamine
carbinoxamine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
- cannabidiol
butalbital 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.
- carbinoxamine
carbinoxamine and codeine both increase sedation. Use Caution/Monitor.
- captopril
butalbital, captopril. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Enhanced hypotensive effects.
- carbamazepine
butalbital will decrease the level or effect of carbamazepine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- carbinoxamine
carbinoxamine and butalbital both increase sedation. Use Caution/Monitor.
- carisoprodol
carisoprodol and codeine both increase sedation. Use Caution/Monitor.
butalbital and carisoprodol both increase sedation. Use Caution/Monitor. - carvedilol
butalbital will decrease the level or effect of carvedilol by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor.
butalbital decreases levels of carvedilol by increasing metabolism. Use Caution/Monitor. Consider a higher beta-blocker dose during coadministration of butalbital. Atenolol, sotalol, nadolol less likely to be affected than other beta blockers. - celecoxib
celecoxib decreases effects of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Prevents conversion of codeine to its active metabolite morphine.
- celiprolol
butalbital decreases levels of celiprolol by increasing metabolism. Use Caution/Monitor. Atenolol, sotalol, nadolol less likely to be affected than other beta blockers.
- cenobamate
cenobamate, butalbital. Either increases effects of the other by sedation. Use Caution/Monitor.
cenobamate, codeine. Either increases effects of the other by sedation. Use Caution/Monitor. - chloral hydrate
chloral hydrate and codeine both increase sedation. Use Caution/Monitor.
chloral hydrate increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
butalbital and chloral hydrate both increase sedation. Use Caution/Monitor. - chlordiazepoxide
chlordiazepoxide and codeine both increase sedation. Use Caution/Monitor.
butalbital and chlordiazepoxide both increase sedation. Use Caution/Monitor.
chlordiazepoxide increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor. - chloroquine
chloroquine will increase the level or effect of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Prevents conversion of codeine to its active metabolite morphine.
- chlorpheniramine
chlorpheniramine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
- chlorpheniramine
chlorpheniramine and butalbital both increase sedation. Use Caution/Monitor.
- chlorpheniramine
chlorpheniramine and codeine both increase sedation. Use Caution/Monitor.
- chlorpromazine
chlorpromazine will decrease the level or effect of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Prevents conversion of codeine to its active metabolite morphine
codeine and chlorpromazine both increase sedation. Use Caution/Monitor.
butalbital and chlorpromazine both increase sedation. Use Caution/Monitor.
chlorpromazine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor. - chlorzoxazone
chlorzoxazone and codeine both increase sedation. Use Caution/Monitor.
butalbital and chlorzoxazone both increase sedation. Use Caution/Monitor. - cinnarizine
cinnarizine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
- cilostazol
butalbital 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 codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Prevents conversion of codeine to its active metabolite morphine.
- cinacalcet
cinacalcet decreases effects of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Prevents conversion of codeine to its active metabolite morphine.
butalbital will decrease the level or effect of cinacalcet by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. - cinnarizine
cinnarizine and butalbital both increase sedation. Use Caution/Monitor.
cinnarizine and codeine both increase sedation. Use Caution/Monitor. - ciprofloxacin
ciprofloxacin will increase the level or effect of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor. The hepatic metabolism of caffeine may be decreased by ciprofloxacin; pharmacologic effects of caffeine may be increased.
- clemastine
clemastine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
clemastine and butalbital both increase sedation. Use Caution/Monitor.
clemastine and codeine both increase sedation. Use Caution/Monitor. - clobazam
codeine, clobazam. Other (see comment). Use Caution/Monitor. Comment: Concomitant administration can increase the potential for CNS effects (e.g., increased sedation or respiratory depression).
clobazam decreases effects of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Prevents conversion of codeine to its active metabolite morphine. - clomipramine
clomipramine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
- clomipramine
butalbital will decrease the level or effect of clomipramine by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.
butalbital will decrease the level or effect of clomipramine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely.
butalbital and clomipramine both increase sedation. Use Caution/Monitor. - clomipramine
codeine and clomipramine both increase sedation. Use Caution/Monitor.
clomipramine decreases effects of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Prevents conversion of codeine to its active metabolite morphine. - clonazepam
butalbital and clonazepam both increase sedation. Use Caution/Monitor.
clonazepam increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
clonazepam and codeine both increase sedation. Use Caution/Monitor. - clopidogrel
butalbital 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
clorazepate increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
- clorazepate
clorazepate and codeine both increase sedation. Use Caution/Monitor.
- clorazepate
butalbital and clorazepate both increase sedation. Use Caution/Monitor.
- clozapine
clozapine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
codeine and clozapine both increase sedation. Use Caution/Monitor.
butalbital will decrease the level or effect of clozapine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
butalbital and clozapine both increase sedation. Use Caution/Monitor.
butalbital will decrease the level or effect of clozapine by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.
clozapine decreases effects of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Prevents conversion of codeine to its active metabolite morphine. - cocaine topical
cocaine topical decreases effects of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Prevents conversion of codeine to its active metabolite morphine.
- codeine
codeine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
- codeine
butalbital and codeine both increase sedation. Use Caution/Monitor.
- colchicine
butalbital will decrease the level or effect of colchicine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- conivaptan
butalbital will decrease the level or effect of conivaptan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- conjugated estrogens
butalbital will decrease the level or effect of conjugated estrogens by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- conjugated estrogens, vaginal
butalbital will decrease the level or effect of conjugated estrogens, vaginal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- cortisone
butalbital will decrease the level or effect of cortisone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- cyclizine
cyclizine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
cyclizine and codeine both increase sedation. Use Caution/Monitor.
cyclizine and butalbital both increase sedation. Use Caution/Monitor. - cyclobenzaprine
butalbital and cyclobenzaprine both increase sedation. Use Caution/Monitor.
cyclobenzaprine and codeine both increase sedation. Use Caution/Monitor. - cyproheptadine
cyproheptadine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
- cyclosporine
butalbital will decrease the level or effect of cyclosporine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- cyproheptadine
cyproheptadine and codeine both increase sedation. Use Caution/Monitor.
- cyproheptadine
cyproheptadine and butalbital both increase sedation. Use Caution/Monitor.
- dantrolene
dantrolene and codeine both increase sedation. Use Caution/Monitor.
butalbital and dantrolene both increase sedation. Use Caution/Monitor. - dapsone topical
acetaminophen increases toxicity of dapsone topical by altering metabolism. Modify Therapy/Monitor Closely. May induce methemoglobinemia .
- daridorexant
butalbital 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.
codeine 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
darifenacin decreases effects of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Prevents conversion of codeine to its active metabolite morphine.
butalbital will decrease the level or effect of darifenacin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. - darunavir
butalbital will decrease the level or effect of darunavir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- deferasirox
deferasirox increases levels of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.
- desflurane
desflurane and codeine both increase sedation. Use Caution/Monitor. Opioids may decrease MAC requirements, less inhalation anesthetic may be required.
- dasatinib
butalbital will decrease the level or effect of dasatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- desipramine
codeine and desipramine both increase sedation. Use Caution/Monitor.
butalbital and desipramine both increase sedation. Use Caution/Monitor.
desipramine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
desipramine decreases effects of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Prevents conversion of codeine to its active metabolite morphine. - desvenlafaxine
desvenlafaxine will increase the level or effect of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Desvenlafaxine inhibits CYP2D6; with higher desvenlafaxine doses (ie, 400 mg) decrease the CYP2D6 substrate dose by up to 50%; no dosage adjustment needed with desvenlafaxine doses <100 mg
- dexchlorpheniramine
dexchlorpheniramine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
- deutetrabenazine
butalbital and deutetrabenazine both increase sedation. Use Caution/Monitor.
- deutetrabenazine
codeine and deutetrabenazine both increase sedation. Use Caution/Monitor.
- dexamethasone
butalbital will decrease the level or effect of dexamethasone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- dexchlorpheniramine
dexchlorpheniramine and codeine both increase sedation. Use Caution/Monitor.
dexchlorpheniramine and butalbital both increase sedation. Use Caution/Monitor. - dexfenfluramine
caffeine and dexfenfluramine both decrease sedation. Use Caution/Monitor.
butalbital increases and dexfenfluramine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
codeine increases and dexfenfluramine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor. - dexmedetomidine
dexmedetomidine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
dexmedetomidine and codeine both increase sedation. Use Caution/Monitor.
butalbital and dexmedetomidine both increase sedation. Use Caution/Monitor. - dexmethylphenidate
butalbital increases and dexmethylphenidate decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
codeine increases and dexmethylphenidate decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
caffeine and dexmethylphenidate both decrease sedation. Use Caution/Monitor. - dextroamphetamine
butalbital increases and dextroamphetamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
codeine increases and dextroamphetamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
caffeine and dextroamphetamine both decrease sedation. Use Caution/Monitor. - dextromoramide
butalbital and dextromoramide both increase sedation. Use Caution/Monitor.
codeine and dextromoramide both increase sedation. Use Caution/Monitor.
dextromoramide increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor. - diamorphine
butalbital and diamorphine both increase sedation. Use Caution/Monitor.
codeine and diamorphine both increase sedation. Use Caution/Monitor.
diamorphine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor. - diazepam
diazepam and codeine both increase sedation. Use Caution/Monitor.
butalbital will decrease the level or effect of diazepam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
butalbital and diazepam both increase sedation. Use Caution/Monitor. - diethylpropion
caffeine and diethylpropion both decrease sedation. Use Caution/Monitor.
- diazepam intranasal
butalbital will decrease the level or effect of diazepam intranasal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Strong or moderate CYP3A4 inducers may increase rate of diazepam elimination; therefore, efficacy of diazepam may be decreased.
diazepam intranasal, butalbital. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Coadministration may potentiate the CNS-depressant effects of each drug. - diethylpropion
codeine increases and diethylpropion decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
- diethylpropion
butalbital increases and diethylpropion decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
- difelikefalin
difelikefalin and codeine both increase sedation. Use Caution/Monitor.
difelikefalin and butalbital both increase sedation. Use Caution/Monitor. - difenoxin hcl
difenoxin hcl increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
butalbital and difenoxin hcl both increase sedation. Use Caution/Monitor.
codeine and difenoxin hcl both increase sedation. Use Caution/Monitor. - diltiazem
butalbital will decrease the level or effect of diltiazem by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- dimenhydrinate
dimenhydrinate increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
- dimenhydrinate
dimenhydrinate and codeine both increase sedation. Use Caution/Monitor.
- dimenhydrinate
dimenhydrinate and butalbital both increase sedation. Use Caution/Monitor.
- diphenhydramine
diphenhydramine decreases effects of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Prevents conversion of codeine to its active metabolite morphine.
diphenhydramine and codeine both increase sedation. Use Caution/Monitor.
diphenhydramine and butalbital both increase sedation. Use Caution/Monitor.
diphenhydramine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor. - diphenoxylate hcl
butalbital and diphenoxylate hcl both increase sedation. Use Caution/Monitor.
codeine and diphenoxylate hcl both increase sedation. Use Caution/Monitor.
diphenoxylate hcl increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor. - dipipanone
butalbital and dipipanone both increase sedation. Use Caution/Monitor.
codeine and dipipanone both increase sedation. Use Caution/Monitor.
dipipanone increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor. - dobutamine
butalbital increases and dobutamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
codeine increases and dobutamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
dobutamine and caffeine both decrease sedation. Use Caution/Monitor. - dopamine
butalbital increases and dopamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
codeine increases and dopamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
caffeine and dopamine both decrease sedation. Use Caution/Monitor. - dopexamine
butalbital increases and dopexamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
codeine increases and dopexamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
dopexamine and caffeine both decrease sedation. Use Caution/Monitor. - dosulepin
butalbital and dosulepin both increase sedation. Use Caution/Monitor.
codeine and dosulepin both increase sedation. Use Caution/Monitor. - doxepin
doxepin increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
- doxepin
butalbital and doxepin both increase sedation. Use Caution/Monitor.
codeine and doxepin both increase sedation. Use Caution/Monitor. - doxycycline
butalbital decreases levels of doxycycline by increasing metabolism. Use Caution/Monitor.
- doxylamine
doxylamine and codeine both increase sedation. Use Caution/Monitor.
- doxylamine
butalbital and doxylamine both increase sedation. Use Caution/Monitor.
- dronabinol
butalbital will increase the level or effect of dronabinol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Dronabinol is a CYP3A4 substrate.
- dronedarone
dronedarone decreases effects of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Prevents conversion of codeine to its active metabolite morphine.
- droperidol
codeine and droperidol both increase sedation. Use Caution/Monitor.
butalbital and droperidol both increase sedation. Use Caution/Monitor.
droperidol increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor. - droxidopa
caffeine and droxidopa both increase sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Use Caution/Monitor. May increase risk for supine hypertension
- duloxetine
duloxetine decreases effects of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Prevents conversion of codeine to its active metabolite morphine.
- elagolix
butalbital will decrease the level or effect of elagolix by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- eletriptan
butalbital will decrease the level or effect of eletriptan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- eltrombopag
eltrombopag increases levels of acetaminophen by decreasing metabolism. Use Caution/Monitor. UGT inhibition; significance of interaction unclear.
butalbital will decrease the level or effect of eltrombopag by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor.
butalbital will decrease the level or effect of eltrombopag by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor. - elvitegravir/cobicistat/emtricitabine/tenofovir DF
elvitegravir/cobicistat/emtricitabine/tenofovir DF increases levels of codeine by affecting hepatic enzyme CYP2D6 metabolism. Modify Therapy/Monitor Closely. Cobicistat is a CYP2D6 inhibitor; caution with CYP2D6 substrates for which elevated plasma concentrations are associated with serious and/or life-threatening events.
- exenatide injectable solution
exenatide injectable solution will decrease the level or effect of acetaminophen by unspecified interaction mechanism. Use Caution/Monitor. To avoid potential interaction, give acetaminophen at least 1 hour before or 4 hours after exenatide injection.
- ephedrine
ephedrine and caffeine both decrease sedation. Use Caution/Monitor.
codeine increases and ephedrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
butalbital increases and ephedrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor. - epinephrine
epinephrine and caffeine both decrease sedation. Use Caution/Monitor.
butalbital increases and epinephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
codeine increases and epinephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor. - epinephrine inhaled
caffeine, epinephrine inhaled. Either increases effects of the other by sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Use Caution/Monitor.
- epinephrine racemic
butalbital increases and epinephrine racemic decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
codeine increases and epinephrine racemic decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor. - epinephrine racemic
epinephrine racemic and caffeine both decrease sedation. Use Caution/Monitor.
- erlotinib
butalbital will decrease the level or effect of erlotinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- esketamine intranasal
esketamine intranasal, codeine. Either increases toxicity of the other by sedation. Modify Therapy/Monitor Closely.
esketamine intranasal, caffeine. Either increases toxicity of the other by sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Use Caution/Monitor. Closely monitor blood pressure with concomitant use of esketamine nasal with stimulants. . - escitalopram
butalbital will decrease the level or effect of escitalopram by affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor.
- estazolam
estazolam increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
- esketamine intranasal
esketamine intranasal, butalbital. Either increases toxicity of the other by sedation. Modify Therapy/Monitor Closely.
- esmolol
butalbital decreases levels of esmolol by increasing metabolism. Use Caution/Monitor. Consider a higher beta-blocker dose during coadministration of butalbital. Atenolol, sotalol, nadolol less likely to be affected than other beta blockers.
- estazolam
estazolam and codeine both increase sedation. Use Caution/Monitor.
butalbital and estazolam both increase sedation. Use Caution/Monitor. - estradiol
butalbital will decrease the level or effect of estradiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- ethanol
ethanol increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
codeine and ethanol both increase sedation. Use Caution/Monitor. - estradiol vaginal
butalbital will decrease the level or effect of estradiol vaginal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- ethinylestradiol
ethinylestradiol will increase the level or effect of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.
- estrogens conjugated synthetic
butalbital will decrease the level or effect of estrogens conjugated synthetic by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- estropipate
butalbital will decrease the level or effect of estropipate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- ethanol
butalbital and ethanol both increase sedation. Use Caution/Monitor.
- ethotoin
butalbital will decrease the level or effect of ethotoin by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor.
- etomidate
etomidate and codeine both increase sedation. Use Caution/Monitor.
etomidate and butalbital both increase sedation. Use Caution/Monitor. - etonogestrel
butalbital will decrease the level or effect of etonogestrel by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- exenatide injectable suspension
exenatide injectable suspension will decrease the level or effect of acetaminophen by unspecified interaction mechanism. Use Caution/Monitor. To avoid potential interaction, give acetaminophen at least 1 hour before or 4 hours after exenatide injection.
- fedratinib
fedratinib will increase the level or effect of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP2D6 substrates as necessary.
- etravirine
butalbital will decrease the level or effect of etravirine by affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor.
butalbital will decrease the level or effect of etravirine by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor.
butalbital will decrease the level or effect of etravirine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. - felodipine
butalbital will decrease the level or effect of felodipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- fenfluramine
caffeine and fenfluramine both decrease sedation. Use Caution/Monitor.
codeine increases and fenfluramine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
butalbital increases and fenfluramine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor. - fesoterodine
butalbital 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 caffeine by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.
- finerenone
acetaminophen will increase the level or effect of finerenone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Monitor serum potassium during initiation and dosage adjustment of either finererone or moderate CYP3A4 inhibitors. Adjust finererone dosage as needed.
- flibanserin
codeine and flibanserin both increase sedation. Modify Therapy/Monitor Closely. Risk for sedation increased if flibanserin is coadministration with other CNS depressants.
acetaminophen will increase the level or effect of flibanserin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Increased flibanserin adverse effects may occur if coadministered with multiple weak CYP3A4 inhibitors. - flibanserin
butalbital and flibanserin both increase sedation. Modify Therapy/Monitor Closely. Risk for sedation increased if flibanserin is coadministration with other CNS depressants.
- imatinib
imatinib decreases levels of acetaminophen by decreasing hepatic clearance. Modify Therapy/Monitor Closely. In vitro, imatinib was found to inhibit acetaminophen O-glucuronidation (Ki value of 58.5 micro-M) at therapeutic levels; avoid chronic acetaminophen therapy with imatinib; if occasional acetaminophen administered, do not exceed 1300 mg/day.
- fludrocortisone
butalbital will decrease the level or effect of fludrocortisone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- fluoxetine
fluoxetine will decrease the level or effect of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Prevents conversion of codeine to its active metabolite morphine
- fluphenazine
fluphenazine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
codeine and fluphenazine both increase sedation. Use Caution/Monitor.
butalbital and fluphenazine both increase sedation. Use Caution/Monitor. - flurazepam
butalbital and flurazepam both increase sedation. Use Caution/Monitor.
flurazepam and codeine both increase sedation. Use Caution/Monitor.
flurazepam increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor. - fluvoxamine
fluvoxamine will increase the level or effect of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.
- formoterol
butalbital increases and formoterol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
codeine increases and formoterol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor. - formoterol
formoterol and caffeine both decrease sedation. Use Caution/Monitor.
- fosamprenavir
butalbital will decrease the level or effect of fosamprenavir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- gabapentin
gabapentin, codeine. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Coadministration of CNS depressants can result in serious, life-threatening, and fatal respiratory depression. Use lowest dose possible and monitor for respiratory depression and sedation.
- fosaprepitant
butalbital will decrease the level or effect of fosaprepitant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- fosphenytoin
butalbital will decrease the level or effect of fosphenytoin by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor.
- gabapentin
gabapentin, butalbital. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Coadministration of CNS depressants can result in serious, life-threatening, and fatal respiratory depression. Use lowest dose possible and monitor for respiratory depression and sedation.
- gabapentin enacarbil
gabapentin enacarbil, codeine. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Coadministration of CNS depressants can result in serious, life-threatening, and fatal respiratory depression. Use lowest dose possible and monitor for respiratory depression and sedation.
gabapentin enacarbil, butalbital. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Coadministration of CNS depressants can result in serious, life-threatening, and fatal respiratory depression. Use lowest dose possible and monitor for respiratory depression and sedation. - ganaxolone
butalbital and ganaxolone both increase sedation. Use Caution/Monitor.
codeine and ganaxolone both increase sedation. Use Caution/Monitor. - glecaprevir/pibrentasvir
butalbital will decrease the level or effect of glecaprevir/pibrentasvir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Coadministration of drugs that induce CYP3A4 with glecaprevir/pibrentasvir may decrease glecaprevir/pibrentasvir plasma concentrations. Potential for loss of therapeutic effect.
- green tea
green tea increases effects of caffeine by Other (see comment). Use Caution/Monitor. Comment: Potential for increased risk of CNS stimulation due to caffeine component of green tea. Caution advised.
- guselkumab
guselkumab, caffeine. Other (see comment). Use Caution/Monitor. Comment: Formation of CYP450 enzymes can be altered by increased levels of certain cytokines during chronic inflammation; thus, normalizing the formation of CYP450 enzymes. Upon initiation or discontinuation of guselkumab in patients who are receiving concomitant CYP450 substrates, particularly those with a narrow therapeutic index, consider monitoring for therapeutic effect.
- haloperidol
haloperidol increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
codeine and haloperidol both increase sedation. Use Caution/Monitor.
haloperidol decreases effects of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Prevents conversion of codeine to its active metabolite morphine. - gotu kola
gotu kola increases effects of butalbital by pharmacodynamic synergism. Use Caution/Monitor. May enhance CNS depression.
- hydromorphone
hydromorphone increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
- guanfacine
butalbital 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.
- haloperidol
butalbital and haloperidol both increase sedation. Use Caution/Monitor.
- hawthorn
hawthorn increases effects of butalbital by pharmacodynamic synergism. Use Caution/Monitor. May enhance CNS depression.
- hemin
butalbital decreases effects of hemin by pharmacodynamic antagonism. Use Caution/Monitor. Drugs that increase delta-aminolevulinic acid synthetase may decrease hemin effect.
- hops
hops increases effects of butalbital by pharmacodynamic synergism. Use Caution/Monitor. May enhance CNS depression.
- hydrocortisone
butalbital will decrease the level or effect of hydrocortisone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- hydromorphone
codeine and hydromorphone both increase sedation. Use Caution/Monitor.
butalbital and hydromorphone both increase sedation. Use Caution/Monitor. - hydroxyprogesterone caproate (DSC)
butalbital will decrease the level or effect of hydroxyprogesterone caproate (DSC) by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- hydroxyzine
hydroxyzine and codeine both increase sedation. Use Caution/Monitor.
hydroxyzine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor. - hydroxyzine
hydroxyzine and butalbital both increase sedation. Use Caution/Monitor.
- iloperidone
iloperidone increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
- ifosfamide
butalbital 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.
butalbital increases effects 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
butalbital will decrease the level or effect of iloperidone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
codeine and iloperidone both increase sedation. Use Caution/Monitor.
butalbital and iloperidone both increase sedation. Use Caution/Monitor. - imipramine
butalbital will decrease the level or effect of imipramine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely.
butalbital and imipramine both increase sedation. Use Caution/Monitor.
codeine and imipramine both increase sedation. Use Caution/Monitor.
imipramine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
imipramine decreases effects of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Prevents conversion of codeine to its active metabolite morphine.
butalbital will decrease the level or effect of imipramine by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.
butalbital will decrease the level or effect of imipramine by affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor. - indinavir
butalbital will decrease the level or effect of indinavir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- isavuconazonium sulfate
acetaminophen will increase the level or effect of isavuconazonium sulfate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- isoniazid
isoniazid will increase the level or effect of acetaminophen by affecting hepatic enzyme CYP2E1 metabolism. Use Caution/Monitor.
- isoproterenol
isoproterenol and caffeine both decrease sedation. Use Caution/Monitor.
- isoniazid
isoniazid decreases effects of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Prevents conversion of codeine to its active metabolite morphine.
- isoproterenol
codeine increases and isoproterenol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
butalbital increases and isoproterenol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor. - ivacaftor
acetaminophen increases levels of ivacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Monitor when coadministered with weak CYP3A4 inhibitors .
- ixabepilone
butalbital will decrease the level or effect of ixabepilone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- ketamine
ketamine and codeine both increase sedation. Use Caution/Monitor.
- kava
kava increases effects of butalbital by pharmacodynamic synergism. Use Caution/Monitor. May enhance CNS depression.
- ketamine
ketamine and butalbital both increase sedation. Use Caution/Monitor.
- ketoconazole
ketoconazole decreases effects of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Prevents conversion of codeine to its active metabolite morphine.
- ketotifen, ophthalmic
codeine and ketotifen, ophthalmic both increase sedation. Use Caution/Monitor.
butalbital and ketotifen, ophthalmic both increase sedation. Use Caution/Monitor.
ketotifen, ophthalmic increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor. - labetalol
butalbital decreases levels of labetalol by increasing metabolism. Use Caution/Monitor. Consider a higher beta-blocker dose during coadministration of butalbital. Atenolol, sotalol, nadolol less likely to be affected than other beta blockers.
- lemborexant
acetaminophen will increase the level or effect of lemborexant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Lower nightly dose of lemborexant recommended if coadministered with weak CYP3A4 inhibitors. See drug monograph for specific dosage modification.
- letermovir
letermovir increases levels of caffeine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- lasmiditan
lasmiditan, codeine. 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.
- lapatinib
butalbital will decrease the level or effect of lapatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- lasmiditan
lasmiditan, butalbital. Either increases effects of the other by sedation. Use Caution/Monitor. Coadministration of lasmiditan and other CNS depressant drugs, including alcohol have not been evaluated in clinical studies. Lasmiditan may cause sedation, as well as other cognitive and/or neuropsychiatric adverse reactions.
- lemborexant
lemborexant, codeine. 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.
- letermovir
letermovir increases levels of codeine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- levalbuterol
levalbuterol and caffeine both decrease sedation. Use Caution/Monitor.
codeine increases and levalbuterol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
butalbital increases and levalbuterol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor. - levamlodipine
butalbital will decrease the level or effect of levamlodipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. No information is available on the quantitative effects of CYP3A4 inducers on amlodipine. Closely monitor blood pressure when amlodipine is coadministered with CYP3A4 inducers.
- levonorgestrel oral/ethinylestradiol/ferrous bisglycinate
levonorgestrel oral/ethinylestradiol/ferrous bisglycinate will decrease the level or effect of acetaminophen by unknown mechanism. Use Caution/Monitor.
acetaminophen increases levels of levonorgestrel oral/ethinylestradiol/ferrous bisglycinate by decreasing hepatic clearance. Use Caution/Monitor. Coadministration of ascorbic acid and certain combined hormonal contraceptives (CHCs) containing EE may increase plasma EE concentrations, possibly by inhibition of conjugation. - levorphanol
levorphanol increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
- levoketoconazole
levoketoconazole decreases effects of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Prevents conversion of codeine to its active metabolite morphine.
- levonorgestrel oral/ethinylestradiol/ferrous bisglycinate
butalbital 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.
- levorphanol
codeine and levorphanol both increase sedation. Use Caution/Monitor.
butalbital and levorphanol both increase sedation. Use Caution/Monitor. - levothyroxine
caffeine decreases levels of levothyroxine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor. Caffeine (a sympathomimetic) concomitantly used with oral levothyroxine may increase the effects of sympathomimetics or thyroid hormone. Thyroid hormones may increase the risk of coronary insufficiency when sympathomimetic agents are administered to patients with coronary artery disease.
- lidocaine
butalbital will decrease the level or effect of lidocaine by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.
- lisdexamfetamine
caffeine and lisdexamfetamine both decrease sedation. Use Caution/Monitor.
codeine increases and lisdexamfetamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor. - lisdexamfetamine
butalbital increases and lisdexamfetamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
- lixisenatide (DSC)
lixisenatide (DSC) will decrease the level or effect of acetaminophen by inhibition of GI absorption. Applies only to oral form of both agents. Modify Therapy/Monitor Closely. GLP1 agonists delay gastric emptying, which may affect absorption of concomitantly administered oral medications. No effects on acetaminophen Cmax and Tmax were observed when acetaminophen was administered 1 hr before lixisenatide. When administered 1 or 4 hr after lixisenatide, acetaminophen Cmax was decreased by 29% and 31% respectively and median Tmax was delayed by 2 and 1.75 hr, respectively.
- lofepramine
lofepramine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
- lofepramine
codeine and lofepramine both increase sedation. Use Caution/Monitor.
butalbital and lofepramine both increase sedation. Use Caution/Monitor. - lofexidine
butalbital and lofexidine both increase sedation. Use Caution/Monitor.
codeine and lofexidine both increase sedation. Use Caution/Monitor.
lofexidine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor. - lomitapide
acetaminophen increases levels of lomitapide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Lomitapide dose should not exceed 30 mg/day.
- lopinavir
lopinavir decreases effects of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Prevents conversion of codeine to its active metabolite morphine.
butalbital will decrease the level or effect of lopinavir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. - loprazolam
loprazolam increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
- loprazolam
butalbital and loprazolam both increase sedation. Use Caution/Monitor.
loprazolam and codeine both increase sedation. Use Caution/Monitor. - loratadine
butalbital will decrease the level or effect of loratadine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- lorazepam
lorazepam increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
lorazepam and codeine both increase sedation. Use Caution/Monitor. - lorazepam
butalbital and lorazepam both increase sedation. Use Caution/Monitor.
- lormetazepam
lormetazepam increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
- lorcaserin
lorcaserin will increase the level or effect of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Prevents conversion of codeine to its active metabolite morphine.
- lormetazepam
lormetazepam and codeine both increase sedation. Use Caution/Monitor.
butalbital and lormetazepam both increase sedation. Use Caution/Monitor. - loxapine
butalbital and loxapine both increase sedation. Use Caution/Monitor.
codeine and loxapine both increase sedation. Use Caution/Monitor.
loxapine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor. - loxapine inhaled
loxapine inhaled increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
codeine and loxapine inhaled both increase sedation. Use Caution/Monitor.
butalbital and loxapine inhaled both increase sedation. Use Caution/Monitor. - lumefantrine
butalbital will decrease the level or effect of lumefantrine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
lumefantrine will increase the level or effect of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. - maprotiline
maprotiline increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
- lurasidone
lurasidone, butalbital. 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.
lurasidone, codeine. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: Potential for increased CNS depressant effects when used concurrently; monitor for increased adverse effects and toxicity. - maprotiline
butalbital and maprotiline both increase sedation. Use Caution/Monitor.
codeine and maprotiline both increase sedation. Use Caution/Monitor. - maraviroc
butalbital will decrease the level or effect of maraviroc by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- marijuana
marijuana increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
codeine and marijuana both increase sedation. Use Caution/Monitor. - marijuana
butalbital and marijuana both increase sedation. Use Caution/Monitor.
- melatonin
melatonin increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
- melatonin
codeine and melatonin both increase sedation. Use Caution/Monitor.
butalbital and melatonin both increase sedation. Use Caution/Monitor. - meperidine
butalbital and meperidine both increase sedation. Use Caution/Monitor.
codeine and meperidine both increase sedation. Use Caution/Monitor.
meperidine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor. - meprobamate
meprobamate increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
butalbital and meprobamate both increase sedation. Use Caution/Monitor.
codeine and meprobamate both increase sedation. Use Caution/Monitor. - mestranol
butalbital will decrease the level or effect of mestranol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- metaproterenol
metaproterenol and caffeine both decrease sedation. Use Caution/Monitor.
- metaproterenol
codeine increases and metaproterenol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
- metaproterenol
butalbital increases and metaproterenol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
- metaxalone
butalbital and metaxalone both increase sedation. Use Caution/Monitor.
metaxalone and codeine both increase sedation. Use Caution/Monitor. - methadone
butalbital will decrease the level or effect of methadone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
butalbital and methadone both increase sedation. Use Caution/Monitor.
codeine and methadone both increase sedation. Use Caution/Monitor.
methadone increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor. - methamphetamine
butalbital increases and methamphetamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
codeine increases and methamphetamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
caffeine and methamphetamine both decrease sedation. Use Caution/Monitor. - methocarbamol
butalbital and methocarbamol both increase sedation. Use Caution/Monitor.
methocarbamol and codeine both increase sedation. Use Caution/Monitor. - methotrexate
caffeine decreases effects of methotrexate by pharmacodynamic antagonism. Use Caution/Monitor.
- methylenedioxymethamphetamine
caffeine and methylenedioxymethamphetamine both decrease sedation. Use Caution/Monitor.
butalbital increases and methylenedioxymethamphetamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
codeine increases and methylenedioxymethamphetamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor. - methylphenidate
caffeine increases effects of methylphenidate by pharmacodynamic synergism. Use Caution/Monitor. Risk of acute hypertensive episode.
- methylprednisolone
butalbital will decrease the level or effect of methylprednisolone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- midazolam
midazolam increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
midazolam and codeine both increase sedation. Use Caution/Monitor. - metoprolol
butalbital decreases levels of metoprolol by increasing metabolism. Use Caution/Monitor. Consider a higher beta-blocker dose during coadministration of butalbital. Atenolol, sotalol, nadolol less likely to be affected than other beta blockers.
- midazolam intranasal
acetaminophen will increase the level or effect of midazolam intranasal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Coadministration of mild CYP3A4 inhibitors with midazolam intranasal may cause higher midazolam systemic exposure, which may prolong sedation.
- midodrine
caffeine and midodrine both decrease sedation. Use Caution/Monitor.
- mexiletine
butalbital will decrease the level or effect of mexiletine by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.
- midazolam
butalbital will decrease the level or effect of midazolam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
butalbital and midazolam both increase sedation. Use Caution/Monitor. - midazolam intranasal
midazolam intranasal, codeine. Either increases effects 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.
midazolam intranasal, butalbital. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Concomitant use of barbiturates, alcohol, or other CNS depressants may increase the risk of hypoventilation, airway obstruction, desaturation, or apnea and may contribute to profound and/or prolonged drug effect. - midodrine
butalbital increases and midodrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
codeine increases and midodrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor. - mipomersen
mipomersen, acetaminophen. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: Both drugs have potential to increase hepatic enzymes; monitor LFTs.
- mirabegron
mirabegron will increase the level or effect of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.
- mirtazapine
butalbital and mirtazapine both increase sedation. Use Caution/Monitor.
mirtazapine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor. - mirtazapine
codeine and mirtazapine both increase sedation. Use Caution/Monitor.
- modafinil
caffeine and modafinil both decrease sedation. Use Caution/Monitor.
- modafinil
codeine increases and modafinil decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
butalbital increases and modafinil decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor. - morphine
butalbital and morphine both increase sedation. Use Caution/Monitor.
codeine and morphine both increase sedation. Use Caution/Monitor.
morphine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor. - motherwort
butalbital and motherwort both increase sedation. Use Caution/Monitor.
codeine and motherwort both increase sedation. Use Caution/Monitor.
motherwort increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor. - moxonidine
butalbital and moxonidine both increase sedation. Use Caution/Monitor.
codeine and moxonidine both increase sedation. Use Caution/Monitor.
moxonidine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor. - nabilone
butalbital and nabilone both increase sedation. Use Caution/Monitor.
codeine and nabilone both increase sedation. Use Caution/Monitor.
nabilone increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor. - nadolol
butalbital decreases levels of nadolol by increasing metabolism. Use Caution/Monitor. Consider a higher beta-blocker dose during coadministration of butalbital. Atenolol, sotalol, nadolol less likely to be affected than other beta blockers.
- nalbuphine
nalbuphine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
- nalbuphine
codeine and nalbuphine both increase sedation. Use Caution/Monitor.
- nalbuphine
butalbital and nalbuphine both increase sedation. Use Caution/Monitor.
- nateglinide
butalbital will decrease the level or effect of nateglinide by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor.
- nebivolol
butalbital decreases levels of nebivolol by increasing metabolism. Use Caution/Monitor. Consider a higher beta-blocker dose during coadministration of butalbital. Atenolol, sotalol, nadolol less likely to be affected than other beta blockers.
- nelfinavir
butalbital will decrease the level or effect of nelfinavir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- nicardipine
butalbital will decrease the level or effect of nicardipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- nilotinib
butalbital will decrease the level or effect of nilotinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- nisoldipine
butalbital will decrease the level or effect of nisoldipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- norepinephrine
norepinephrine and caffeine both decrease sedation. Use Caution/Monitor.
codeine increases and norepinephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
butalbital increases and norepinephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor. - norgestrel
butalbital will decrease the level or effect of norgestrel by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Moderate CYP3A4 inducers may decrease progestin concentration; consider use of additional barrier methods
- nortriptyline
nortriptyline increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
- nortriptyline
codeine and nortriptyline both increase sedation. Use Caution/Monitor.
- nortriptyline
butalbital and nortriptyline both increase sedation. Use Caution/Monitor.
- olanzapine
butalbital will decrease the level or effect of olanzapine by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.
codeine and olanzapine both increase sedation. Use Caution/Monitor.
butalbital and olanzapine both increase sedation. Use Caution/Monitor.
olanzapine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor. - oliceridine
oliceridine, butalbital. Either increases toxicity of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. 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.
butalbital 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.
oliceridine, codeine. Either increases toxicity of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. 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. - opium tincture
opium tincture increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
- omeprazole
butalbital will decrease the level or effect of omeprazole by affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor.
- opium tincture
codeine and opium tincture both increase sedation. Use Caution/Monitor.
- opium tincture
butalbital and opium tincture both increase sedation. Use Caution/Monitor.
- orphenadrine
orphenadrine and codeine both increase sedation. Use Caution/Monitor.
butalbital and orphenadrine both increase sedation. Use Caution/Monitor. - osilodrostat
butalbital will decrease the level or effect of osilodrostat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Monitor cortisol concentration and patient?s signs and symptoms during coadministration or discontinuation with strong CYP3A4 inducers. Adjust dose of osilodrostat if necessary.
- oxazepam
oxazepam and codeine both increase sedation. Use Caution/Monitor.
oxazepam increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor. - oxazepam
butalbital and oxazepam both increase sedation. Use Caution/Monitor.
- oxycodone
oxycodone increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
- oxycodone
codeine and oxycodone both increase sedation. Use Caution/Monitor.
butalbital and oxycodone both increase sedation. Use Caution/Monitor. - oxymorphone
oxymorphone increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
butalbital and oxymorphone both increase sedation. Use Caution/Monitor.
codeine and oxymorphone both increase sedation. Use Caution/Monitor. - paliperidone
butalbital and paliperidone both increase sedation. Use Caution/Monitor.
codeine and paliperidone both increase sedation. Use Caution/Monitor.
paliperidone increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor. - papaveretum
butalbital and papaveretum both increase sedation. Use Caution/Monitor.
codeine and papaveretum both increase sedation. Use Caution/Monitor.
papaveretum increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor. - papaverine
butalbital and papaverine both increase sedation. Use Caution/Monitor.
codeine and papaverine both increase sedation. Use Caution/Monitor. - pefloxacin
pefloxacin will increase the level or effect of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.
- parecoxib
butalbital will decrease the level or effect of parecoxib by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor.
- paroxetine
paroxetine will decrease the level or effect of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Prevents conversion of codeine to its active metabolite morphine.
- passion flower
passion flower increases effects of butalbital by pharmacodynamic synergism. Use Caution/Monitor. May enhance CNS depression.
- pazopanib
butalbital will decrease the level or effect of pazopanib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- peginterferon alfa 2b
peginterferon alfa 2b, codeine. Other (see comment). Use Caution/Monitor. Comment: When patients are administered peginterferon alpha-2b with CYP2D6 substrates, the therapeutic effect of these drugs may be altered. Peginterferon alpha-2b may increase or decrease levels of CYP2D6 substrate.
- pegvisomant
codeine decreases effects of pegvisomant by unknown mechanism. Use Caution/Monitor.
- penbutolol
butalbital decreases levels of penbutolol by increasing metabolism. Use Caution/Monitor. Consider a higher beta-blocker dose during coadministration of butalbital. Atenolol, sotalol, nadolol less likely to be affected than other beta blockers.
- pentazocine
codeine and pentazocine both increase sedation. Use Caution/Monitor.
butalbital and pentazocine both increase sedation. Use Caution/Monitor.
pentazocine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor. - pentobarbital
butalbital and pentobarbital both increase sedation. Use Caution/Monitor.
pentobarbital increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
pentobarbital and codeine both increase sedation. Use Caution/Monitor. - perampanel
perampanel and codeine both increase sedation. Use Caution/Monitor.
- perphenazine
perphenazine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
- perphenazine
butalbital and perphenazine both increase sedation. Use Caution/Monitor.
- perphenazine
codeine and perphenazine both increase sedation. Use Caution/Monitor.
- phendimetrazine
caffeine and phendimetrazine both decrease sedation. Use Caution/Monitor.
codeine increases and phendimetrazine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
butalbital increases and phendimetrazine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor. - phenobarbital
phenobarbital and codeine both increase sedation. Use Caution/Monitor.
butalbital and phenobarbital both increase sedation. Use Caution/Monitor.
phenobarbital increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor. - phentermine
butalbital increases and phentermine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
codeine increases and phentermine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
caffeine and phentermine both decrease sedation. Use Caution/Monitor. - phenylephrine
butalbital increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
codeine increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
caffeine and phenylephrine both decrease sedation. Use Caution/Monitor. - phenylephrine PO
codeine increases and phenylephrine PO decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor. .
caffeine and phenylephrine PO both decrease sedation. Use Caution/Monitor.
butalbital increases and phenylephrine PO decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor. . - phenytoin
butalbital will decrease the level or effect of phenytoin by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor.
- pholcodine
pholcodine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
- pholcodine
codeine and pholcodine both increase sedation. Use Caution/Monitor.
- pholcodine
butalbital and pholcodine both increase sedation. Use Caution/Monitor.
- pimozide
codeine and pimozide both increase sedation. Use Caution/Monitor.
butalbital and pimozide both increase sedation. Use Caution/Monitor.
pimozide increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor. - pindolol
butalbital decreases levels of pindolol by increasing metabolism. Use Caution/Monitor. Consider a higher beta-blocker dose during coadministration of butalbital. Atenolol, sotalol, nadolol less likely to be affected than other beta blockers.
- pirbuterol
pirbuterol and caffeine both decrease sedation. Use Caution/Monitor.
- pirbuterol
codeine increases and pirbuterol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
- pirbuterol
butalbital increases and pirbuterol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
- pitolisant
butalbital 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
butalbital 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.
- prednisolone
butalbital will decrease the level or effect of prednisolone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- prednisone
butalbital will decrease the level or effect of prednisone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- pregabalin
pregabalin, codeine. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Coadministration of CNS depressants can result in serious, life-threatening, and fatal respiratory depression. Use lowest dose possible and monitor for respiratory depression and sedation.
pregabalin, butalbital. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Coadministration of CNS depressants can result in serious, life-threatening, and fatal respiratory depression. Use lowest dose possible and monitor for respiratory depression and sedation. - primidone
primidone increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
primidone and codeine both increase sedation. Use Caution/Monitor.
butalbital and primidone both increase sedation. Use Caution/Monitor. - prochlorperazine
butalbital and prochlorperazine both increase sedation. Use Caution/Monitor.
codeine and prochlorperazine both increase sedation. Use Caution/Monitor.
prochlorperazine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor. - promethazine
promethazine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
promethazine and butalbital both increase sedation. Use Caution/Monitor.
promethazine and codeine both increase sedation. Use Caution/Monitor. - propafenone
butalbital decreases levels of propafenone by increasing metabolism. Use Caution/Monitor.
- propylhexedrine
caffeine and propylhexedrine both decrease sedation. Use Caution/Monitor.
- propofol
propofol and codeine both increase sedation. Use Caution/Monitor.
- propofol
propofol and butalbital both increase sedation. Use Caution/Monitor.
- propranolol
butalbital decreases levels of propranolol by increasing metabolism. Use Caution/Monitor. Consider a higher beta-blocker dose during coadministration of butalbital. Atenolol, sotalol, nadolol less likely to be affected than other beta blockers.
- propylhexedrine
codeine increases and propylhexedrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
butalbital increases and propylhexedrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor. - protriptyline
butalbital and protriptyline both increase sedation. Use Caution/Monitor.
codeine and protriptyline both increase sedation. Use Caution/Monitor.
protriptyline increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor. - quazepam
quazepam and codeine both increase sedation. Use Caution/Monitor.
butalbital and quazepam both increase sedation. Use Caution/Monitor.
quazepam increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor. - quetiapine
butalbital and quetiapine both increase sedation. Use Caution/Monitor.
codeine and quetiapine both increase sedation. Use Caution/Monitor.
quetiapine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
butalbital will decrease the level or effect of quetiapine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. - quinidine
quinidine will decrease the level or effect of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Prevents conversion of codeine to its active metabolite morphine.
butalbital will decrease the level or effect of quinidine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. - rasagiline
rasagiline increases effects of caffeine by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Risk of acute hypertensive episode.
- ramelteon
butalbital and ramelteon both increase sedation. Use Caution/Monitor.
codeine and ramelteon both increase sedation. Use Caution/Monitor.
butalbital will decrease the level or effect of ramelteon by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor. - remimazolam
remimazolam, codeine. Either increases toxicity of the other by sedation. Modify Therapy/Monitor Closely. Coadministration may result in profound sedation, respiratory depression, coma, and/or death. Continuously monitor vital signs during sedation and recovery period if coadministered. Carefully titrate remimazolam dose if administered with opioid analgesics and/or sedative/hypnotics.
remimazolam, butalbital. Either increases toxicity of the other by sedation. Modify Therapy/Monitor Closely. Coadministration may result in profound sedation, respiratory depression, coma, and/or death. Continuously monitor vital signs during sedation and recovery period if coadministered. Carefully titrate remimazolam dose if administered with opioid analgesics and/or sedative/hypnotics. - repaglinide
butalbital will decrease the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- ribociclib
ribociclib will increase the level or effect of codeine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- rifampin
rifampin decreases levels of butalbital by increasing metabolism. Use Caution/Monitor.
- risperidone
codeine and risperidone both increase sedation. Use Caution/Monitor.
butalbital and risperidone both increase sedation. Use Caution/Monitor.
risperidone increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor. - ritonavir
ritonavir will decrease the level or effect of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Prevents conversion of codeine to its active metabolite morphine.
butalbital will decrease the level or effect of ritonavir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. - rucaparib
rucaparib will increase the level or effect of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Modify Therapy/Monitor Closely. Adjust dosage of CYP1A2 substrates, if clinically indicated.
- rolapitant
rolapitant will increase the level or effect of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Rolapitant may increase plasma concentrations of CYP2D6 substrates for at least 28 days following rolapitant administration.
- salmeterol
butalbital increases and salmeterol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
salmeterol and caffeine both decrease sedation. Use Caution/Monitor. - salmeterol
codeine increases and salmeterol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
- scullcap
scullcap increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
- saquinavir
butalbital will decrease the level or effect of saquinavir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- scullcap
codeine and scullcap both increase sedation. Use Caution/Monitor.
butalbital and scullcap both increase sedation. Use Caution/Monitor. - secobarbital
secobarbital increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
butalbital and secobarbital both increase sedation. Use Caution/Monitor.
secobarbital and codeine both increase sedation. Use Caution/Monitor. - selegiline
selegiline increases effects of caffeine by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Risk of acute hypertensive episode.
selegiline increases toxicity of codeine by unknown mechanism. Modify Therapy/Monitor Closely. Potential for increased CNS depression, drowsiness, dizziness or hypotension, so use with any MAOI should be cautious. - shepherd's purse
butalbital and shepherd's purse both increase sedation. Use Caution/Monitor.
shepherd's purse increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor. - sertraline
sertraline decreases effects of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Prevents conversion of codeine to its active metabolite morphine.
- solriamfetol
caffeine and solriamfetol both increase sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Use Caution/Monitor.
- sevoflurane
sevoflurane and codeine both increase sedation. Use Caution/Monitor.
- shepherd's purse
codeine and shepherd's purse both increase sedation. Use Caution/Monitor.
- sildenafil
butalbital will decrease the level or effect of sildenafil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- solifenacin
butalbital will decrease the level or effect of solifenacin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- sorafenib
butalbital decreases levels of sorafenib by increasing metabolism. Use Caution/Monitor.
- sotalol
butalbital decreases levels of sotalol by increasing metabolism. Use Caution/Monitor. Consider a higher beta-blocker dose during coadministration of butalbital. Atenolol, sotalol, nadolol less likely to be affected than other beta blockers.
- stiripentol
stiripentol, codeine. 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.
stiripentol, caffeine. affecting hepatic enzyme CYP1A2 metabolism. Modify Therapy/Monitor Closely. Stiripentol is a CYP1A2 inhibitor and inducer. Monitor CYP1A2 substrates coadministered with stiripentol for increased or decreased effects. CYP1A2 substrates may require dosage adjustment. - sufentanil
codeine and sufentanil both increase sedation. Use Caution/Monitor.
butalbital and sufentanil both increase sedation. Use Caution/Monitor.
sufentanil increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor. - sufentanil SL
butalbital 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.
- tapentadol
tapentadol increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
- suvorexant
suvorexant and codeine both increase sedation. Modify Therapy/Monitor Closely. Dosage adjustments of suvorexant and concomitant CNS depressants may be necessary
- sunitinib
butalbital will decrease the level or effect of sunitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- tacrolimus
butalbital will decrease the level or effect of tacrolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- tadalafil
butalbital will decrease the level or effect of tadalafil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- tapentadol
codeine and tapentadol both increase sedation. Use Caution/Monitor.
butalbital and tapentadol both increase sedation. Use Caution/Monitor. - tazemetostat
acetaminophen will increase the level or effect of tazemetostat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- temazepam
temazepam increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
butalbital and temazepam both increase sedation. Use Caution/Monitor.
temazepam and codeine both increase sedation. Use Caution/Monitor. - temsirolimus
butalbital will decrease the level or effect of temsirolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- terbutaline
terbutaline and caffeine both decrease sedation. Use Caution/Monitor.
- terbinafine
terbinafine will increase the level or effect of codeine by affecting hepatic enzyme CYP2D6 metabolism. Modify Therapy/Monitor Closely. Assess need to reduce dose of CYP2D6-metabolized drug.
- terbinafine
butalbital will decrease the level or effect of terbinafine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- terbutaline
codeine increases and terbutaline decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
butalbital increases and terbutaline decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor. - teriflunomide
teriflunomide decreases levels of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.
- tetracaine
tetracaine, acetaminophen. Other (see comment). Use Caution/Monitor. Comment: Monitor for signs of methemoglobinemia when methemoglobin-inducing drugs are coadministered.
- thalidomide
thalidomide increases effects of butalbital by unspecified interaction mechanism. Use Caution/Monitor. Increased sedative effects.
- thioridazine
thioridazine decreases effects of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Prevents conversion of codeine to its active metabolite morphine.
codeine and thioridazine both increase sedation. Use Caution/Monitor.
thioridazine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor. - theophylline
butalbital will decrease the level or effect of theophylline by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.
butalbital will decrease the level or effect of theophylline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. - thiothixene
thiothixene increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
- thioridazine
butalbital and thioridazine both increase sedation. Use Caution/Monitor.
- thiothixene
codeine and thiothixene both increase sedation. Use Caution/Monitor.
butalbital and thiothixene both increase sedation. Use Caution/Monitor. - ticlopidine
ticlopidine decreases effects of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Prevents conversion of codeine to its active metabolite morphine.
- timolol
butalbital decreases levels of timolol by increasing metabolism. Use Caution/Monitor. Consider a higher beta-blocker dose during coadministration of butalbital. Atenolol, sotalol, nadolol less likely to be affected than other beta blockers.
- tinidazole
butalbital will decrease the level or effect of tinidazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
acetaminophen will increase the level or effect of tinidazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. - tipranavir
butalbital will decrease the level or effect of tipranavir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- warfarin
acetaminophen increases effects of warfarin by anticoagulation. Use Caution/Monitor.
Minor (204)
- acetazolamide
acetazolamide decreases levels of acetaminophen by increasing metabolism. Minor/Significance Unknown. Enhanced metabolism incr levels of hepatotoxic metabolites.
acetazolamide, butalbital. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Increased risk of anticonvulsant induced osteomalacia. - adenosine
caffeine decreases effects of adenosine by pharmacodynamic antagonism. Minor/Significance Unknown.
- albiglutide
albiglutide decreases levels of acetaminophen by unspecified interaction mechanism. Minor/Significance Unknown.
- alfentanil
butalbital will decrease the level or effect of alfentanil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- alfuzosin
butalbital will decrease the level or effect of alfuzosin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- alosetron
butalbital will decrease the level or effect of alosetron by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.
butalbital will decrease the level or effect of alosetron by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown. - amantadine
amantadine, caffeine. Either increases effects of the other by pharmacodynamic synergism. Minor/Significance Unknown. Potential for additive CNS stimulation.
- American ginseng
American ginseng increases effects of caffeine by pharmacodynamic synergism. Minor/Significance Unknown.
- amitriptyline
butalbital, amitriptyline. Other (see comment). Minor/Significance Unknown. Comment: Barbiturates may increase adverse effects, including respiratory depression, produced by toxic doses of TCAs. With therapeutic doses of TCAs, barbiturates increase metabolism and decrease blood concentrations of TCAs.
- amobarbital
amobarbital will decrease the level or effect of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.
- amoxapine
butalbital, amoxapine. Other (see comment). Minor/Significance Unknown. Comment: Barbiturates may increase adverse effects, including respiratory depression, produced by toxic doses of TCAs. With therapeutic doses of TCAs, barbiturates increase metabolism and decrease blood concentrations of TCAs.
- amphotericin B deoxycholate
butalbital decreases levels of amphotericin B deoxycholate by inhibition of GI absorption. Applies only to oral form of both agents. Minor/Significance Unknown.
- antipyrine
butalbital will decrease the level or effect of antipyrine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.
- antithrombin alfa
acetaminophen increases effects of antithrombin alfa by unknown mechanism. Minor/Significance Unknown.
- antithrombin III
acetaminophen increases effects of antithrombin III by unknown mechanism. Minor/Significance Unknown.
- argatroban
acetaminophen increases effects of argatroban by unknown mechanism. Minor/Significance Unknown.
- armodafinil
butalbital will decrease the level or effect of armodafinil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
armodafinil will decrease the level or effect of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown. - ascorbic acid
butalbital decreases levels of ascorbic acid by increasing elimination. Minor/Significance Unknown.
- bemiparin
acetaminophen increases effects of bemiparin by unknown mechanism. Minor/Significance Unknown.
- bivalirudin
acetaminophen increases effects of bivalirudin by unknown mechanism. Minor/Significance Unknown.
- butabarbital
butabarbital will decrease the level or effect of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.
- asenapine
butalbital will decrease the level or effect of asenapine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.
asenapine will increase the level or effect of codeine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown. - ashwagandha
ashwagandha increases effects of butalbital by pharmacodynamic synergism. Minor/Significance Unknown. May enhance CNS depression.
- brimonidine
brimonidine increases effects of codeine by pharmacodynamic synergism. Minor/Significance Unknown. Increased CNS depression.
- atazanavir
butalbital will decrease the level or effect of atazanavir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- bosentan
butalbital will decrease the level or effect of bosentan by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.
butalbital will decrease the level or effect of bosentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown. - brimonidine
brimonidine increases effects of butalbital by pharmacodynamic synergism. Minor/Significance Unknown. Increased CNS depression.
- brinzolamide
brinzolamide, butalbital. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Increased risk of anticonvulsant induced osteomalacia.
- buprenorphine subdermal implant
butalbital will decrease the level or effect of buprenorphine subdermal implant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown. 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 inhibitor 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.
- butalbital
butalbital will decrease the level or effect of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.
- caffeine
butalbital will decrease the level or effect of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.
- calcium acetate
caffeine decreases levels of calcium acetate by increasing renal clearance. Minor/Significance Unknown.
- calcium carbonate
caffeine decreases levels of calcium carbonate by increasing renal clearance. Minor/Significance Unknown.
- calcium chloride
caffeine decreases levels of calcium chloride by increasing renal clearance. Minor/Significance Unknown.
- calcium citrate
caffeine decreases levels of calcium citrate by increasing renal clearance. Minor/Significance Unknown.
- calcium gluconate
caffeine decreases levels of calcium gluconate by increasing renal clearance. Minor/Significance Unknown.
- carbamazepine
carbamazepine will decrease the level or effect of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.
carbamazepine decreases levels of acetaminophen by increasing metabolism. Minor/Significance Unknown. Enhanced metabolism incr levels of hepatotoxic metabolites. - celecoxib
butalbital will decrease the level or effect of celecoxib by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.
- cholestyramine
cholestyramine decreases levels of acetaminophen by inhibition of GI absorption. Applies only to oral form of both agents. Minor/Significance Unknown.
- cevimeline
butalbital will decrease the level or effect of cevimeline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- chloramphenicol
chloramphenicol increases levels of butalbital by decreasing metabolism. Minor/Significance Unknown.
butalbital decreases levels of chloramphenicol by increasing metabolism. Minor/Significance Unknown. - chlorpromazine
butalbital decreases levels of chlorpromazine by increasing metabolism. Minor/Significance Unknown.
- cigarette smoking
cigarette smoking will decrease the level or effect of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.
- cimetidine
cimetidine will increase the level or effect of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.
butalbital will decrease the level or effect of cimetidine by affecting hepatic enzyme CYP2C19 metabolism. Minor/Significance Unknown. - clarithromycin
butalbital will decrease the level or effect of clarithromycin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
butalbital decreases levels of clarithromycin by increasing elimination. Minor/Significance Unknown. - clonazepam
clonazepam decreases levels of acetaminophen by increasing metabolism. Minor/Significance Unknown. Enhanced metabolism incr levels of hepatotoxic metabolites.
- clotrimazole
clotrimazole increases levels of caffeine by decreasing metabolism. Minor/Significance Unknown.
- clomipramine
butalbital, clomipramine. Other (see comment). Minor/Significance Unknown. Comment: Barbiturates may increase adverse effects, including respiratory depression, produced by toxic doses of TCAs. With therapeutic doses of TCAs, barbiturates increase metabolism and decrease blood concentrations of TCAs.
- clotrimazole
butalbital decreases levels of clotrimazole by inhibition of GI absorption. Applies only to oral form of both agents. Minor/Significance Unknown.
- cocaine topical
butalbital will decrease the level or effect of cocaine topical by affecting hepatic enzyme CYP2B6 metabolism. Minor/Significance Unknown.
- colestipol
colestipol decreases levels of acetaminophen by inhibition of GI absorption. Applies only to oral form of both agents. Minor/Significance Unknown.
- dalteparin
acetaminophen increases effects of dalteparin by unknown mechanism. Minor/Significance Unknown.
- dapsone
butalbital will decrease the level or effect of dapsone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- desipramine
butalbital, desipramine. Other (see comment). Minor/Significance Unknown. Comment: Barbiturates may increase adverse effects, including respiratory depression, produced by toxic doses of TCAs. With therapeutic doses of TCAs, barbiturates increase metabolism and decrease blood concentrations of TCAs.
- dextroamphetamine
dextroamphetamine increases effects of codeine by unspecified interaction mechanism. Minor/Significance Unknown.
- diazepam
diazepam decreases levels of acetaminophen by increasing metabolism. Minor/Significance Unknown. Enhanced metabolism incr levels of hepatotoxic metabolites.
- diclofenac
butalbital will decrease the level or effect of diclofenac by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.
- disopyramide
butalbital will decrease the level or effect of disopyramide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- disulfiram
disulfiram will increase the level or effect of acetaminophen by affecting hepatic enzyme CYP2E1 metabolism. Minor/Significance Unknown.
- docetaxel
butalbital will decrease the level or effect of docetaxel by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- donepezil
butalbital will decrease the level or effect of donepezil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- dosulepin
butalbital, dosulepin. Other (see comment). Minor/Significance Unknown. Comment: Barbiturates may increase adverse effects, including respiratory depression, produced by toxic doses of TCAs. With therapeutic doses of TCAs, barbiturates increase metabolism and decrease blood concentrations of TCAs.
- doxepin
butalbital, doxepin. Other (see comment). Minor/Significance Unknown. Comment: Barbiturates may increase adverse effects, including respiratory depression, produced by toxic doses of TCAs. With therapeutic doses of TCAs, barbiturates increase metabolism and decrease blood concentrations of TCAs.
- dutasteride
butalbital will decrease the level or effect of dutasteride by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- efavirenz
butalbital will decrease the level or effect of efavirenz by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- enoxaparin
acetaminophen increases effects of enoxaparin by unknown mechanism. Minor/Significance Unknown.
- eplerenone
butalbital will decrease the level or effect of eplerenone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- erythromycin base
erythromycin base will increase the level or effect of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.
butalbital decreases levels of erythromycin base by increasing elimination. Minor/Significance Unknown. - erythromycin ethylsuccinate
butalbital decreases levels of erythromycin ethylsuccinate by increasing elimination. Minor/Significance Unknown.
erythromycin ethylsuccinate will increase the level or effect of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown. - erythromycin lactobionate
butalbital decreases levels of erythromycin lactobionate by increasing elimination. Minor/Significance Unknown.
erythromycin lactobionate will increase the level or effect of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown. - erythromycin stearate
butalbital decreases levels of erythromycin stearate by increasing elimination. Minor/Significance Unknown.
erythromycin stearate will increase the level or effect of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown. - ethanol
ethanol will decrease the level or effect of acetaminophen by affecting hepatic enzyme CYP2E1 metabolism. Minor/Significance Unknown.
ethanol increases toxicity of acetaminophen by decreasing metabolism. Minor/Significance Unknown. - ethosuximide
ethosuximide decreases levels of acetaminophen by increasing metabolism. Minor/Significance Unknown. Enhanced metabolism incr levels of hepatotoxic metabolites.
ethosuximide decreases effects of butalbital by pharmacodynamic antagonism. Minor/Significance Unknown. - eucalyptus
eucalyptus increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Minor/Significance Unknown.
- felbamate
felbamate decreases levels of acetaminophen by increasing metabolism. Minor/Significance Unknown. Enhanced metabolism incr levels of hepatotoxic metabolites.
- eucalyptus
butalbital will decrease the level or effect of eucalyptus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
codeine and eucalyptus both increase sedation. Minor/Significance Unknown.
butalbital and eucalyptus both increase sedation. Minor/Significance Unknown. - finasteride
butalbital will decrease the level or effect of finasteride by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- fluconazole
fluconazole increases levels of caffeine by decreasing metabolism. Minor/Significance Unknown.
- fluoxetine
fluoxetine decreases effects of codeine by decreasing metabolism. Minor/Significance Unknown. Decreased conversion of codeine to active metabolite morphine.
- fluconazole
butalbital decreases levels of fluconazole by inhibition of GI absorption. Applies only to oral form of both agents. Minor/Significance Unknown.
- flurbiprofen
butalbital will decrease the level or effect of flurbiprofen by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.
- fondaparinux
acetaminophen increases effects of fondaparinux by unknown mechanism. Minor/Significance Unknown.
- fosphenytoin
fosphenytoin decreases levels of acetaminophen by increasing metabolism. Minor/Significance Unknown. Enhanced metabolism incr levels of hepatotoxic metabolites.
- frovatriptan
butalbital will decrease the level or effect of frovatriptan by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.
- galantamine
butalbital will decrease the level or effect of galantamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- grapefruit
grapefruit increases levels of caffeine by decreasing metabolism. Minor/Significance Unknown.
- green tea
green tea increases effects of acetaminophen by pharmacodynamic synergism. Minor/Significance Unknown. (Theoretical, due to caffeine content).
- griseofulvin
butalbital decreases levels of griseofulvin by inhibition of GI absorption. Applies only to oral form of both agents. Minor/Significance Unknown.
- guarana
guarana increases effects of caffeine by pharmacodynamic synergism. Minor/Significance Unknown.
- haloperidol
haloperidol, butalbital. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Risk of hyperthermia if haloperidol admin. during barbiturate withdrawal.
- heparin
acetaminophen increases effects of heparin by unknown mechanism. Minor/Significance Unknown.
- ibuprofen
butalbital will decrease the level or effect of ibuprofen by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.
- ibuprofen IV
butalbital will decrease the level or effect of ibuprofen IV by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.
- imatinib
imatinib decreases effects of codeine by decreasing metabolism. Minor/Significance Unknown. Decreased conversion of codeine to active metabolite morphine.
butalbital will decrease the level or effect of imatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
imatinib will increase the level or effect of codeine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown. - imipramine
butalbital, imipramine. Other (see comment). Minor/Significance Unknown. Comment: Barbiturates may increase adverse effects, including respiratory depression, produced by toxic doses of TCAs. With therapeutic doses of TCAs, barbiturates increase metabolism and decrease blood concentrations of TCAs.
- isoniazid
isoniazid will increase the level or effect of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.
isoniazid increases toxicity of acetaminophen by unknown mechanism. Minor/Significance Unknown. - itraconazole
itraconazole increases levels of caffeine by decreasing metabolism. Minor/Significance Unknown.
- lacosamide
lacosamide decreases levels of acetaminophen by increasing metabolism. Minor/Significance Unknown. Enhanced metabolism incr levels of hepatotoxic metabolites.
- ketoconazole
ketoconazole increases levels of caffeine by decreasing metabolism. Minor/Significance Unknown.
- lamotrigine
lamotrigine decreases levels of acetaminophen by increasing metabolism. Minor/Significance Unknown. Enhanced metabolism incr levels of hepatotoxic metabolites.
- levetiracetam
levetiracetam decreases levels of acetaminophen by increasing metabolism. Minor/Significance Unknown. Enhanced metabolism incr levels of hepatotoxic metabolites.
- levoketoconazole
levoketoconazole increases levels of caffeine by decreasing metabolism. Minor/Significance Unknown.
- lidocaine
lidocaine increases toxicity of codeine by pharmacodynamic synergism. Minor/Significance Unknown. Risk of increased CNS depression.
- isocarboxazid
isocarboxazid increases levels of butalbital by decreasing metabolism. Minor/Significance Unknown. Theoretical interaction.
- isradipine
butalbital will decrease the level or effect of isradipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- ketoconazole
butalbital will decrease the level or effect of ketoconazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
butalbital decreases levels of ketoconazole by inhibition of GI absorption. Applies only to oral form of both agents. Minor/Significance Unknown. - lansoprazole
butalbital will decrease the level or effect of lansoprazole by affecting hepatic enzyme CYP2C19 metabolism. Minor/Significance Unknown.
- levoketoconazole
butalbital will decrease the level or effect of levoketoconazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
butalbital decreases levels of levoketoconazole by inhibition of GI absorption. Applies only to oral form of both agents. Minor/Significance Unknown. - levothyroxine
butalbital decreases levels of levothyroxine by increasing metabolism. Minor/Significance Unknown.
- linezolid
linezolid increases levels of butalbital by decreasing metabolism. Minor/Significance Unknown. Theoretical interaction.
- liothyronine
butalbital decreases levels of liothyronine by increasing metabolism. Minor/Significance Unknown.
- liraglutide
liraglutide decreases levels of acetaminophen by unspecified interaction mechanism. Minor/Significance Unknown.
- lofepramine
butalbital, lofepramine. Other (see comment). Minor/Significance Unknown. Comment: Barbiturates may increase adverse effects, including respiratory depression, produced by toxic doses of TCAs. With therapeutic doses of TCAs, barbiturates increase metabolism and decrease blood concentrations of TCAs.
- lorazepam
lorazepam decreases levels of acetaminophen by increasing metabolism. Minor/Significance Unknown. Enhanced metabolism incr levels of hepatotoxic metabolites.
- losartan
butalbital will decrease the level or effect of losartan by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.
- maprotiline
butalbital, maprotiline. Other (see comment). Minor/Significance Unknown. Comment: Barbiturates may increase adverse effects, including respiratory depression, produced by toxic doses of TCAs. With therapeutic doses of TCAs, barbiturates increase metabolism and decrease blood concentrations of TCAs.
- maraviroc
maraviroc will increase the level or effect of codeine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.
- marijuana
marijuana will increase the level or effect of codeine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.
- meloxicam
butalbital will decrease the level or effect of meloxicam by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.
- methazolamide
methazolamide, butalbital. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Increased risk of anticonvulsant induced osteomalacia.
- methsuximide
methsuximide decreases levels of acetaminophen by increasing metabolism. Minor/Significance Unknown. Enhanced metabolism incr levels of hepatotoxic metabolites.
methsuximide decreases effects of butalbital by pharmacodynamic antagonism. Minor/Significance Unknown. - metoclopramide
metoclopramide increases levels of acetaminophen by enhancing GI absorption. Applies only to oral form of both agents. Minor/Significance Unknown.
- mexiletine
mexiletine will increase the level or effect of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.
- metronidazole
metronidazole will increase the level or effect of acetaminophen by affecting hepatic enzyme CYP2E1 metabolism. Minor/Significance Unknown.
- miconazole vaginal
butalbital decreases levels of miconazole vaginal by inhibition of GI absorption. Applies only to oral form of both agents. Minor/Significance Unknown.
miconazole vaginal increases levels of caffeine by decreasing metabolism. Minor/Significance Unknown. - modafinil
modafinil will decrease the level or effect of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.
- montelukast
butalbital will decrease the level or effect of montelukast by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- nettle
nettle increases effects of butalbital by pharmacodynamic synergism. Minor/Significance Unknown. (High dose nettle; theoretical interaction) May enhance CNS depression.
- nifedipine
butalbital will decrease the level or effect of nifedipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- nilotinib
nilotinib will increase the level or effect of codeine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.
- nimodipine
butalbital will decrease the level or effect of nimodipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- nitrendipine
butalbital will decrease the level or effect of nitrendipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- nortriptyline
butalbital, nortriptyline. Other (see comment). Minor/Significance Unknown. Comment: Barbiturates may increase adverse effects, including respiratory depression, produced by toxic doses of TCAs. With therapeutic doses of TCAs, barbiturates increase metabolism and decrease blood concentrations of TCAs.
- oxcarbazepine
oxcarbazepine decreases levels of acetaminophen by increasing metabolism. Minor/Significance Unknown. Enhanced metabolism incr levels of hepatotoxic metabolites.
- oxybutynin
oxybutynin decreases levels of acetaminophen by unspecified interaction mechanism. Minor/Significance Unknown.
butalbital will decrease the level or effect of oxybutynin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown. - oxybutynin topical
oxybutynin topical decreases levels of acetaminophen by unspecified interaction mechanism. Minor/Significance Unknown.
- paclitaxel
butalbital will decrease the level or effect of paclitaxel by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- oxybutynin transdermal
oxybutynin transdermal decreases levels of acetaminophen by unspecified interaction mechanism. Minor/Significance Unknown.
- paclitaxel protein bound
butalbital will decrease the level or effect of paclitaxel protein bound by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- parecoxib
parecoxib will increase the level or effect of codeine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.
butalbital will decrease the level or effect of parecoxib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown. - peginterferon alfa 2a
peginterferon alfa 2a will increase the level or effect of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.
- pentobarbital
pentobarbital will decrease the level or effect of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.
- perphenazine
perphenazine will increase the level or effect of codeine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.
perphenazine decreases effects of codeine by decreasing metabolism. Minor/Significance Unknown. Decreased conversion of codeine to active metabolite morphine. - phenelzine
phenelzine increases levels of butalbital by decreasing metabolism. Minor/Significance Unknown. Theoretical interaction.
- phenindione
acetaminophen increases effects of phenindione by unknown mechanism. Minor/Significance Unknown.
- phenobarbital
phenobarbital decreases levels of acetaminophen by increasing metabolism. Minor/Significance Unknown. Enhanced metabolism incr levels of hepatotoxic metabolites.
phenobarbital will decrease the level or effect of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown. - phenytoin
phenytoin decreases levels of acetaminophen by increasing metabolism. Minor/Significance Unknown. Enhanced metabolism incr levels of hepatotoxic metabolites.
- pimozide
butalbital will decrease the level or effect of pimozide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- pioglitazone
butalbital will decrease the level or effect of pioglitazone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- pipemidic acid
pipemidic acid will increase the level or effect of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.
- piroxicam
butalbital will decrease the level or effect of piroxicam by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.
- posaconazole
butalbital decreases levels of posaconazole by inhibition of GI absorption. Applies only to oral form of both agents. Minor/Significance Unknown.
posaconazole increases levels of caffeine by decreasing metabolism. Minor/Significance Unknown. - primidone
primidone decreases levels of acetaminophen by increasing metabolism. Minor/Significance Unknown. Enhanced metabolism incr levels of hepatotoxic metabolites.
primidone will decrease the level or effect of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown. - propafenone
propafenone will increase the level or effect of codeine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.
butalbital will decrease the level or effect of propafenone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
propafenone decreases effects of codeine by decreasing metabolism. Minor/Significance Unknown. Decreased conversion of codeine to active metabolite morphine. - protamine
acetaminophen increases effects of protamine by unknown mechanism. Minor/Significance Unknown.
- protriptyline
butalbital, protriptyline. Other (see comment). Minor/Significance Unknown. Comment: Barbiturates may increase adverse effects, including respiratory depression, produced by toxic doses of TCAs. With therapeutic doses of TCAs, barbiturates increase metabolism and decrease blood concentrations of TCAs.
- quinacrine
quinacrine will increase the level or effect of codeine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.
quinacrine decreases effects of codeine by decreasing metabolism. Minor/Significance Unknown. Decreased conversion of codeine to active metabolite morphine. - quinine
butalbital will decrease the level or effect of quinine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- rabeprazole
butalbital will decrease the level or effect of rabeprazole by affecting hepatic enzyme CYP2C19 metabolism. Minor/Significance Unknown.
butalbital will decrease the level or effect of rabeprazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown. - ramelteon
butalbital will decrease the level or effect of ramelteon by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.
butalbital will decrease the level or effect of ramelteon by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown. - ranolazine
ranolazine will increase the level or effect of codeine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.
- rifabutin
rifabutin decreases levels of acetaminophen by increasing metabolism. Minor/Significance Unknown. Enhanced metabolism incr levels of hepatotoxic metabolites.
- rifampin
rifampin will decrease the level or effect of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.
rifampin decreases levels of acetaminophen by increasing metabolism. Minor/Significance Unknown. Enhanced metabolism incr levels of hepatotoxic metabolites. - riluzole
butalbital will decrease the level or effect of riluzole by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.
- rufinamide
rufinamide decreases levels of acetaminophen by increasing metabolism. Minor/Significance Unknown. Enhanced metabolism incr levels of hepatotoxic metabolites.
- rose hips
butalbital decreases levels of rose hips by increasing elimination. Minor/Significance Unknown.
- ruxolitinib
acetaminophen will increase the level or effect of ruxolitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- ruxolitinib topical
acetaminophen will increase the level or effect of ruxolitinib topical by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- sage
sage increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Minor/Significance Unknown.
codeine and sage both increase sedation. Minor/Significance Unknown.
butalbital and sage both increase sedation. Minor/Significance Unknown. - saxagliptin
butalbital will decrease the level or effect of saxagliptin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- secobarbital
secobarbital will decrease the level or effect of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.
- sertraline
sertraline decreases effects of codeine by decreasing metabolism. Minor/Significance Unknown. Decreased conversion of codeine to active metabolite morphine.
- selegiline transdermal
selegiline transdermal increases levels of butalbital by decreasing metabolism. Minor/Significance Unknown. Theoretical interaction.
- Siberian ginseng
Siberian ginseng increases effects of butalbital by pharmacodynamic synergism. Minor/Significance Unknown. May enhance CNS depression.
- smoking
smoking will decrease the level or effect of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.
- sufentanil
butalbital will decrease the level or effect of sufentanil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- sulfamethoxazole
butalbital will decrease the level or effect of sulfamethoxazole by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.
- tamoxifen
butalbital will decrease the level or effect of tamoxifen by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- thiamine
caffeine decreases levels of thiamine by inhibition of GI absorption. Applies only to oral form of both agents. Minor/Significance Unknown. Coffee, tea are high in anti-thiamine factors.
- thioridazine
thioridazine decreases effects of codeine by decreasing metabolism. Minor/Significance Unknown. Decreased conversion of codeine to active metabolite morphine.
thioridazine decreases levels of butalbital by unspecified interaction mechanism. Minor/Significance Unknown. - thyroid desiccated
butalbital decreases levels of thyroid desiccated by increasing metabolism. Minor/Significance Unknown.
- tiagabine
tiagabine decreases levels of acetaminophen by increasing metabolism. Minor/Significance Unknown. Enhanced metabolism incr levels of hepatotoxic metabolites.
- tipranavir
tipranavir will increase the level or effect of codeine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.
- tibolone
butalbital decreases levels of tibolone by increasing metabolism. Minor/Significance Unknown. Theoretical interaction.
- tobacco use
tobacco use will decrease the level or effect of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.
- tolbutamide
butalbital will decrease the level or effect of tolbutamide by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.
- topiramate
topiramate decreases levels of acetaminophen by increasing metabolism. Minor/Significance Unknown. Enhanced metabolism incr levels of hepatotoxic metabolites.
butalbital decreases levels of topiramate by increasing metabolism. Minor/Significance Unknown. - tranylcypromine
tranylcypromine increases levels of butalbital by decreasing metabolism. Minor/Significance Unknown. Theoretical interaction.
- valproic acid
valproic acid decreases levels of acetaminophen by increasing metabolism. Minor/Significance Unknown. Enhanced metabolism incr levels of hepatotoxic metabolites.
- trazodone
butalbital, trazodone. Other (see comment). Minor/Significance Unknown. Comment: Barbiturates may increase adverse effects, including respiratory depression, produced by toxic doses of TCAs. With therapeutic doses of TCAs, barbiturates increase metabolism and decrease blood concentrations of TCAs.
- trimipramine
butalbital, trimipramine. Other (see comment). Minor/Significance Unknown. Comment: Barbiturates may increase adverse effects, including respiratory depression, produced by toxic doses of TCAs. With therapeutic doses of TCAs, barbiturates increase metabolism and decrease blood concentrations of TCAs.
- venlafaxine
venlafaxine decreases effects of codeine by decreasing metabolism. Minor/Significance Unknown. Decreased conversion of codeine to active metabolite morphine.
- verapamil
verapamil will increase the level or effect of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.
- vinblastine
butalbital will decrease the level or effect of vinblastine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- vincristine
butalbital will decrease the level or effect of vincristine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- vincristine liposomal
butalbital will decrease the level or effect of vincristine liposomal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- vinorelbine
butalbital will decrease the level or effect of vinorelbine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- voriconazole
butalbital will decrease the level or effect of voriconazole by affecting hepatic enzyme CYP2C19 metabolism. Minor/Significance Unknown.
voriconazole increases levels of caffeine by decreasing metabolism. Minor/Significance Unknown.
butalbital will decrease the level or effect of voriconazole by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown. - yerba mate
yerba mate increases effects of caffeine by pharmacodynamic synergism. Minor/Significance Unknown.
- zaleplon
butalbital will decrease the level or effect of zaleplon by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- ziconotide
ziconotide, codeine. Mechanism: unspecified interaction mechanism. Minor/Significance Unknown. Additive decreased GI motility. Additive analgesia. Ziconotide does NOT potentiate opioid induced respiratory depression.
- zileuton
zileuton will increase the level or effect of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.
- ziprasidone
butalbital will decrease the level or effect of ziprasidone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- zonisamide
zonisamide decreases levels of acetaminophen by increasing metabolism. Minor/Significance Unknown. Enhanced metabolism increase levels of hepatotoxic metabolites.
Adverse Effects
>10%
Codeine
- Drowsiness
- Constipation
1-10%
Codeine
- Bradycardia, hypotension, tachycardia
- Confusion, dizziness, false feeling of well being, headache, lightheadedness, malaise, paradoxical CNS stimulation, restlessness, weakness
- Rash, urticaria
- Anorexia, nausea, vomiting, xerostomia
- LFT's increased
- Ureteral spasm, urination decreased
- Dyspnea
- Burning at injection site, blurred vision, histamine release
Frequency Not Defined
Acetaminophen
- Angioedema, laryngeal edema
- Pruritic maculopapular rash, urticaria
- Agranulocytosis, leukopenia, neutropenia, pancytopenia, thrombocytopenia, thrombocytopenic purpura
- Hepatotoxicity
- Anaphylactoid reaction
Butalbital
- Drowsiness, dizziness, intoxicated feeling, lightheadedness, sedation
- Abdominal pain, nausea, vomiting
- Shortness of breath
Caffeine
- Tachycardia, palpitations (dose dependent)
- Insomnia, irritability restlessness, nervousness, tremor, tinnitus
- Diarrhea, nausea, vomiting
- Diuresis
Warnings
Black Box Warnings
Hepatotoxicity may occur with acetaminophen doses that exceed 4 g/day; take into account all acetaminophen-containing products that the patient is taking, including PRN doses and OTC products
Acetaminophen has been associated with cases of acute liver failure, at times resulting in liver transplantation or death
New dosage limit allows no more than 325 mg/dosage unit for prescription medications that contain acetaminophen
Healthcare professionals can direct patients to take 1 or 2 tablets, capsules, or other dosage units of a prescription product containing 325 mg of acetaminophen up to 6 times a day (12 dosage units) and still not exceed the maximum daily dose of acetaminophen of 4 g/day
Accidental ingestion of butalbital, acetaminophen, caffeine, and codeine phosphate capsules, especially by children, can result in fatal overdose; keep out of reach of children
Opioid analgesic risk evaluation and mitigation strategy (REMS)
- To ensure that benefits of opioid analgesics outweigh risks of addiction, abuse, and misuse, the Food and Drug Administration (FDA) has required a REMS for these products; under requirements of the REMS, drug companies with approved opioid analgesic products must make REMS-compliant education programs available to healthcare providers
-
Healthcare providers are strongly encouraged to:
- Complete a REMS-compliant education program
- Counsel patients and/or their caregivers, with every prescription, on safe use, serious risks, storage, and disposal of these products
- Emphasize to patients and their caregivers the importance of reading the Medication Guide every time it is provided by their pharmacist
- Consider other tools to improve patient, household, and community safety
Addiction, abuse, and misuse
- Risk of opioid addiction, abuse, and misuse, which can lead to overdose and death; assess each patient’s risk prior to prescribing and monitor all patients regularly for the development of these behaviors or conditions
Life-threatening respiratory depression
- Serious, life-threatening, or fatal respiratory depression may occur
- Monitor for respiratory depression, especially during initiation or following a dose increase
Accidental ingestion
- Accidental ingestion of even 1 dose, especially by children, can result in a fatal overdose
Neonatal opioid withdrawal syndrome
- Prolonged use during pregnancy can result in neonatal opioid withdrawal syndrome, which may be life-threatening if not recognized and treated, and requires management according to protocols developed by neonatology experts
- If opioid use is required for a prolonged period in a pregnant woman, advise the patient of the risk of neonatal opioid withdrawal syndrome and ensure that appropriate treatment will be available
Ultra-rapid metabolism of codeine and other risk factors for life-threatening respiratory depression in children
- Respiratory depression and death reported in children who received codeine following tonsillectomy and/or adenoidectomy that were also ultra-rapid metabolizers of codeine due to CYP2D6 polymorphism
- Contraindicated in children <12 years and in children <18 years following tonsillectomy and/or adenoidectomy; avoid use in adolescents 12-18 years who have risk factors that may increase sensitivity to respiratory depressant effects of codeine
Interactions with drugs affecting cytochrome P450 isoenzymes
- Use of cytochrome P450 3A4 inducers, 3A4 inhibitors, or 2D6 inhibitors requires careful consideration of the effects on parent drug, codeine, and active metabolite, morphine
Risks from concomitant use with benzodiazepines or other CNS depressants
- Concomitant use of opioids with benzodiazepines or other central nervous system (CNS) depressants, including alcohol, may result in profound sedation, respiratory depression, coma, and death
- Reserve concomitant prescribing of codeine sulfate tablets and benzodiazepines or other CNS depressants for use in patients for whom alternative treatment options are inadequate
- Limit dosages and durations to minimum required
- Follow patients for signs and symptoms of respiratory depression and sedation
Contraindications
Hypersensitivity to drug or components
Hepatitis or severe hepatic/renal impairment
Repeated administration in patients with anemia, cardiovascular, pulmonary, or renal disease porphyria
Children <12 years
Postoperative management in children <18 years following tonsillectomy and/or adenoidectomy (see Black Box Warnings)
Acute or severe bronchial asthma in an unmonitored setting or in the absence of resuscitative equipment
Concurrent use of monoamine oxidase inhibitors (MAOIs) or use of MAOIs within the last 14 days
Significant respiratory depression
Known or suspected gastrointestinal obstruction, including paralytic ileus
Cautions
As Butalbital, acetaminophen, caffeine, and codeine phosphate capsules contain butalbital and codeine, they expose users to the risks of addiction, abuse, and misuse; assess each patient’s risk for addiction, abuse, or misuse prior to prescribing therapy, and monitor all patients receiving drug for development of addiction behaviors and conditions
Opioids and barbiturates are sought by drug abusers and people with addiction disorders and are subject to criminal diversion; consider these risks when prescribing or dispensing this medication; strategies to reduce these risks include prescribing drug in smallest appropriate quantity and advising patient on proper disposal of unused drug; contact local state professional licensing board or state controlled substances authority for information on how to prevent and detect abuse or diversion of this product
Acetaminophen associated with cases of acute liver failure, at times resulting in liver transplant and death; risk increases in individuals with underlying liver disease, alcohol ingestion, and/or use of more than 1 acetaminophen-containing product (see Black Box Warnings)
Acetaminophen may cause rare serious skin reactions (eg, acute generalized exanthematous pustulosis, Stevens-Johnson Syndrome, toxic epidermal necrolysis), which can be fatal; discontinued at the first appearance of skin rash
Use caution in patients withG6PD deficiency
Avoid driving car or operating machinery
May increase respiratory depressant effects; caution with head injury, COPD, or other conditions with decreased respiratory drive
Codeine may cause tolerance/dependency
Life-threatening respiratory depression and death have occurred in children who received codeine; codeine is subject to variability in metabolism based upon CYP2D6 genotype, which can lead to an increased exposure to active metabolite morphine; children < 12 years appear to be more susceptible to respiratory depressant effects of codeine, particularly if there are risk factors for respiratory depression; many reported cases of death occurred in postoperative period following tonsillectomy and/or adenoidectomy, and many of children had evidence of being ultra-rapid metabolizers of codeine
Opioids can cause sleep-related breathing disorders including central sleep apnea (CSA) and sleep-related hypoxemia; opioid use increases risk of CSA in a dose-dependent fashion; in patients who present with CSA, consider decreasing opioid dosage using best practices for opioid taper
Avoid use of capsules in adolescents 12-18 years of age who have other risk factors that may increase sensitivity to respiratory depressant effects of codeine unless benefits outweigh risks; risk factors include conditions associated with hypoventilation, such as postoperative status, obstructive sleep apnea, obesity, severe pulmonary disease, neuromuscular disease, and concomitant use of other medications that cause respiratory depression; when prescribing codeine for adolescents, healthcare providers should choose lowest effective dose for shortest period of time and inform patients and caregivers about risks and the signs of morphine overdose
Concomitant use of opioids with benzodiazepines or another central nervous system (CNS) depressants, including alcohol or muscle relaxant, may result in profound sedation, respiratory depression, coma, and death; if concomitant use with benzodiazepine warranted, consider prescribing naloxone for emergency treatment of opioid overdose
Accidental ingestion of butalbital, acetaminophen, caffeine, and codeine phosphate capsules, especially by children, can result in fatal overdose; keep out of reach of children
Serious, life-threatening, or fatal respiratory depression may occur; monitor closely, especially upon initiation or following a dose increase
Do not abruptly discontinue therapy in a patient physically dependent on opioids; when discontinuing therapy, in a physically dependent patient, gradually taper the dosage; rapid tapering in a patient physically dependent on opioids may lead to a withdrawal syndrome and return of pain
Adrenal Insufficiency may occur; if diagnosed, treat with physiologic replacement of corticosteroids, and wean patient off of the opioid
In patients who may be susceptible to intracranial effects of CO2 retention (e.g., those with evidence of increased intracranial pressure or brain tumors), butalbital, acetaminophen, caffeine, and codeine phosphate capsules may reduce respiratory drive, and resultant CO2 retention can further increase intracranial pressure; monitor for sedation and respiratory depression; carbon dioxide (CO2 ) retention from opioid-induced respiratory depression can exacerbate sedating effects of opioids
Opioids may obscure clinical course in patient with a head injury; avoid use of butalbital, acetaminophen, caffeine, and codeine phosphate capsules in patients with impaired consciousness or coma
Butalbital, acetaminophen, caffeine, and codeine phosphate capsules may cause severe hypotension including orthostatic hypotension and syncope in ambulatory patients; there is increased risk in patients whose ability to maintain blood pressure has already been compromised by a reduced blood volume or concurrent administration of certain CNS depressant drugs; monitor these patients for signs of hypotension after initiating or titrating dosage
The codeine in butalbital, acetaminophen, caffeine, and codeine phosphate capsules may increase frequency of seizures in patients with seizure disorders and may increase risk of seizures occurring in other clinical settings associated with seizures; monitor patients with a history of seizure disorders for worsened seizure control during butalbital, acetaminophen, caffeine, and codeine phosphate capsules
Rarely, acetaminophen may cause serious skin reactions such as acute generalized exanthematous pustulosis (AGEP), Stevens-Johnson Syndrome (SJS), and toxic epidermal necrolysis (TEN), which can be fatal; patients should be informed about signs of serious skin reactions, and use of drug should be discontinued at first appearance of skin rash or any other sign of hypersensitivity
Life-threatening respiratory depression is more likely to occur in elderly, cachectic, or debilitated patients because they may have altered pharmacokinetics or altered clearance compared to younger, healthier patients; monitor patients closely for respiratory depression, especially within first 24-72 hr of initiating therapy with and following dosage increases of this drug
To reduce risk of respiratory depression, proper dosing and titration are essential; overestimating dosage when converting patients from another opioid product can result in a fatal overdose with first dose
Management of respiratory depression may include close observation, supportive measures, and use of opioid antagonists,depending on the patient’s clinical status
Patient access to naloxone for emergency treatment of opioid overdose
- Presence of risk factors for overdose should not prevent proper management of pain in any given patient; also consider prescribing naloxone if patient has household members (including children) or other close contacts at risk for accidental ingestion or overdose
- Assess potential need for naloxone; consider prescribing for emergency treatment of opioid overdose
- Consult on availability and ways to obtain naloxone as permitted by individual state naloxone dispensing and prescribing requirements or guidelines
- Educate patients regarding the signs and symptoms of respiratory depression and to call 911 or seek immediate emergency medical help in the event of a known or suspected overdose
Drug interaction overview
- Concomitant use of serotonergic drugs may result in serotonin syndrome; discontinue therapy if serotonin syndrome is suspected
- Avoid coadministration with mixed agonist/antagonist and partial agonist opioid analgesics
- Effects of concomitant use or discontinuation of cytochrome P450 3A4 inducers, 3A4 inhibitors, or 2D6 inhibitors with codeine are complex; use of cytochrome P450 3A4 inducers, 3A4 inhibitors, or 2D6 inhibitors with Butalbital, Acetaminophen, Caffeine, and Codeine Phosphate Capsules require careful consideration of effects on codeine and active metabolite, morphine
Pregnancy & Lactation
Pregnancy
Prolonged use of opioid analgesics during pregnancy may cause neonatal opioid withdrawal syndrome; available data in pregnant women are insufficient to inform a drug-associated risk for major birth defects and miscarriage
Labor and delivery
- Use of codeine during labor may lead to respiratory depression in the neonate; opioids cross the placenta and may produce respiratory depression and psycho-physiologic effects in neonates; an opioid antagonist, such as naloxone, must be available for reversal of opioid-induced respiratory depression in the neonate; use is not recommended in pregnant women during or immediately prior to labor, when other analgesic techniques are more appropriate; opioid analgesics, can prolong labor through actions which temporarily reduce the strength, duration, and frequency of uterine contractions; however, this effect is not consistent and may be offset by increased rate of cervical dilation, which tends to shorten labor; monitor neonates exposed to opioid analgesics during labor for signs of excess sedation and respiratory depression
Lactation
Codeine and its active metabolite, morphine, are present in human milk; there are published studies and cases that have reported excessive sedation, respiratory depression, and death in infants exposed to codeine via breast milk; women who are ultra-rapid metabolizers of codeine achieve higher than expected serum levels of morphine, potentially leading to higher levels of morphine in breast milk that can be dangerous in their breastfed infants; in women with normal codeine metabolism (normal CYP2D6 activity), the amount of codeine secreted into human milk is low and dose-dependent
There is no information on effects of codeine milk production; because of potential for serious adverse reactions, including excess sedation, respiratory depression, and death in a breastfed infant, breastfeeding is not recommended during treatment
Withdrawal seizures in newborns whose mothers had taken butalbital-containing drug during pregnancy reported
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
Codeine: Opioid agonist; analgesia
Acetaminophen: Acts on hypothalamus to produce analgesia and antipyresis
Butalbital: Barbiturate; elicits generalized CNS depressant effects
Caffeine: Vasoconstrictive properties of cerebral blood vessels may be helpful when treating headaches
Pharmacogenomics
10% of codeine is metabolized to morphine by CYP2D6; the active morphine metabolite has a higher affinity for opioid receptors
CYP2D6 poor metabolizers may not achieve adequate analgesia
Ultra-rapid metabolizers (up to 7% of Caucasians and up to 30% of Asian and African populations) may have increased toxicity due to rapid conversion
Images
Formulary
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