Version July 2025
Serious and sometimes fatal dermatologic reactions, including toxic epidermal necrolysis (TEN) and Stevens-Johnson syndrome, have been reported during treatment with carbamazepine. These reactions are estimated to occur in 1 to 6 per 10,000 new users in countries with mainly Caucasian populations, but the risk in some Asian countries is estimated to be about 10 times higher. Studies in patients of Chinese ancestry have found a strong association between the risk of developing Stevens-Johnson syndrome/TEN and the presence of HLA-B*1502, an inherited allelic variant of the HLA-B gene. HLA-B*1502 is found almost exclusively in patients with ancestry across broad areas of Asia. Patients with ancestry in genetically at-risk populations should be screened for the presence of HLA-B*1502 prior to initiating treatment with carbamazepine. Patients testing positive for the allele should not be treated with carbamazepine unless the benefit clearly outweighs the risk.
Aplastic anemia and agranulocytosis have been reported in association with the use of carbamazepine. Data from a population-based case-control study demonstrate that the risk of developing these reactions is 5 to 8 times greater than in the general population. However, the overall risk of these reactions in the untreated general population is low, approximately 6 patients per 1 million population per year for agranulocytosis and 2 patients per 1 million population per year for aplastic anemia.
Although reports of transient or persistent decreased platelet or white blood cell counts (WBCs) are not uncommon in association with the use of carbamazepine, data are not available to accurately estimate their incidence or outcome. However, the vast majority of the cases of leukopenia have not progressed to the more serious conditions of aplastic anemia or agranulocytosis.
Because of the very low incidence of agranulocytosis and aplastic anemia, the vast majority of minor hematological changes observed in monitoring of patients on carbamazepine are unlikely to signal the occurrence of either abnormality. Nonetheless, complete pretreatment hematological testing should be obtained as a baseline. If a patient in the course of treatment exhibits low or decreased white blood cell or platelet counts, the patient should be monitored closely. Discontinuation of the drug should be considered if any evidence of significant bone marrow depression develops.
Dosage guidance:
Safety: Prior to initiating carbamazepine therapy, test for HLA-B*15:02 allele in patients with increased risk for this genetic variant (eg, Han Chinese, Thai, Malaysian, Indian, or Vietnamese descent); this is associated with a significantly increased risk of Stevens-Johnson syndrome and/or toxic epidermal necrolysis; do NOT initiate in patients with a positive result (Ref). Although testing recommendations are not well established, consider testing for HLA-A*31:01 and HLA-A*24:02 allele. These alleles are found in a broader range of ethnic groups and also increase the risk for hypersensitivity reactions (Ref). A negative genetic test does not entirely rule out the possibility of a hypersensitivity or cutaneous reaction, and patients should be monitored throughout therapy.
Dosing: Dosing recommendations are expressed as the total daily dose (ie, per 24 hours) unless stated otherwise. Total daily oral dose is given in 2 to 4 divided doses per day depending on the type of preparation. Immediate release (suspension, tablet, chewable tablet) (usually dosed 2 to 4 times daily) and 12-hour ER (dosed twice daily) preparations are available.
Bipolar disorder, hypomania and mild to moderate mania or episodes with mixed features (alternative agent) and bipolar major depression (alternative agent) (Ref):
Acute treatment (monotherapy): Oral: Initial: 100 to 400 mg/day in 2 to 4 divided doses based on chosen formulation; may increase dose based on response and tolerability in increments of 200 mg/day every 1 to 4 days; usual dose range: 600 mg/day to 1.2 g/day in 2 to 4 divided doses based on chosen formulation; maximum dose: 1.6 g/day (Ref). Doses up to 1.8 g/day may be necessary in some patients for optimal response (Ref). Also see “Dosing” above.
Maintenance (monotherapy) (off-label use): Oral: Continue dose that was used to achieve control of the acute episode (Ref).
Focal (partial) onset seizures and generalized onset seizures (monotherapy or adjunctive therapy):
Note: Avoid use in nonmotor (absence) seizures.
Oral: Initial 2 to 3 mg/kg/day (100 to 200 mg/day) in 2 to 4 divided doses based on chosen formulation or up to 400 mg/day in 2 to 4 divided doses based on chosen formulation (according to manufacturer's labeling), which may not be as well tolerated; may gradually increase dose based on seizure control, tolerability, and serum concentrations every ≥5 days in increments of ≤200 mg/day to a usual maintenance dose of ~10 mg/kg/day (800 mg/day to 1.2 g/day) in 2 to 4 divided doses based on chosen formulation. Serum concentrations may decrease due to hepatic enzyme autoinduction and dose may need to be further increased after 2 to 3 months of treatment to 15 to 20 mg/kg/day in 2 to 4 divided doses based on chosen formulation; doses up to ~2 g/day may be needed in some patients for optimal effect (Ref). Also see “Dosing” above.
Neuropathic pain:
Note: For use in trigeminal or glossopharyngeal neuralgia. May also be used in critically ill patients with neuropathic pain as a component of multimodal pain control (alternative agent) (Ref).
Oral: Initial: 200 to 400 mg/day in 2 to 4 divided doses based on chosen formulation, gradually increasing (eg, over several weeks) in increments of 200 mg/day as needed. Usual maintenance dose: 600 to 800 mg/day in 2 to 4 divided doses based on chosen formulation; maximum dose: 1.2 g/day (Ref). Also see “Dosing” above.
Discontinuation of therapy: In chronic therapy, withdraw gradually over 2 to 6 months to minimize the potential of increased seizure frequency (in patients with epilepsy) and other withdrawal symptoms (eg, dysphoria, hallucinations, headache, insomnia, tremor) unless safety concerns require more rapid withdrawal (Ref). In patients discontinuing therapy for treatment of bipolar disorder, close monitoring for several weeks to months for reemergence of mania/hypomania is recommended (Ref).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
The renal dosing recommendations are based upon the best available evidence and clinical expertise. Senior Editorial Team: Bruce Mueller, PharmD, FCCP, FASN, FNKF; Jason A. Roberts, PhD, BPharm (Hons), B App Sc, FSHP, FISAC; Michael Heung, MD, MS.
Note: In moderate to severe kidney dysfunction, serum 10,11-carbamazepine epoxide levels may be increased. Consider measuring serum 10,11-carbamazepine epoxide levels in instances where toxicity is suspected, but serum carbamazepine levels are within normal range (Ref).
Mild to severe impairment: Initial: No dosage adjustment necessary (Ref). Subsequent dose adjustments should be based on patient response, tolerability, and serum concentrations.
Hemodialysis: Initial: No dosage adjustment necessary. Dose may be administered without regard to timing of dialysis on dialysis days (Ref). Subsequent dose adjustments should be based on patient response, tolerability, and serum concentrations.
Peritoneal dialysis: Initial: No dosage adjustment necessary (Ref). Subsequent dose adjustments should be based on patient response, tolerability, and serum concentrations.
CRRT: Initial: No dosage adjustment necessary (Ref). Subsequent dose adjustments should be based on patient response, tolerability, and serum concentrations.
The liver dosing recommendations are based upon the best available evidence and clinical expertise. Senior Editorial Team: Matt Harris, PharmD, MHS, BCPS, FAST; Jeong Park, PharmD, MS, BCPS, FCCP, FAST; Arun Jesudian, MD, Sasan Sakiani, MD.
Note: Carbamazepine undergoes extensive hepatic metabolism with conversion to active metabolites (Ref). There are no pharmacokinetic data in patients with end-stage liver disease; however, significant accumulation is expected in patients with severe liver impairment (Ref).
Liver impairment prior to treatment initiation:
Initial or dose titration in patients with preexisting liver cirrhosis:
Child-Turcotte-Pugh class A: Oral: Initial: Start with lowest indication-specific dose and frequency; use with caution. If necessary, may adjust dose based on response, tolerability, and total carbamazepine serum concentrations; dose adjustments should be done no more frequently than the usual indication-specific intervals and maximum doses should not exceed the usual indication-specific maximum recommended doses. May consider obtaining 10,11-epoxide metabolite serum concentrations and/or free carbamazepine serum concentrations to assess risk of toxicity (Ref).
Child-Turcotte-Pugh Class B to C: Avoid use (Ref).
Liver impairment developing in patient already receiving carbamazepine:
Chronic disease progression (eg, outpatient):
Progression from baseline to Child-Turcotte-Pugh class A to B: Oral: Continue current dose; monitor total carbamazepine serum concentrations and assess for response and tolerability (eg, excessive sedation) and consider 10,11-epoxide metabolite serum concentrations and/or free carbamazepine serum concentrations to assess risk of toxicity; adjust dose if necessary (Ref).
Child-Turcotte-Pugh Class C: Consider switching to an alternative agent (Ref).
Carbamazepine-induced liver injury: Permanently discontinue use if carbamazepine-induced liver injury is confirmed and laboratory abnormalities cannot be explained by other etiologies (eg, alcohol, active viral hepatitis) (Ref).
Refer to adult dosing.
(For additional information see "Carbamazepine: Pediatric drug information")
Dosage guidance:
Safety: Prior to initiating carbamazepine therapy, test for HLA-B*15:02 allele in patients with increased risk for this genetic variant (eg, Han Chinese, Thai, Malaysian, Indian, or Vietnamese descent); this is associated with a significantly increased risk of Stevens-Johnson syndrome and/or toxic epidermal necrolysis; do NOT initiate in patients with a positive result (Ref). Although testing recommendations are not well established, consider testing for HLA-A*31:01 and HLA-A*24:02 allele. These alleles are found in a broader range of ethnic groups and also increase the risk for hypersensitivity reactions (Ref). A negative genetic test does not entirely rule out the possibility of a hypersensitivity or cutaneous reaction, and patients should be monitored throughout therapy.
Dosage form information: Concentration of oral suspensions may vary between commercially available preparations (20 mg/mL) and extemporaneously compounded formulations (eg, 40 mg/mL); precautions should be taken to verify and avoid confusion between the different concentrations; dose should be clearly presented as mg.
Bipolar disorder; mild to moderate mania or episodes with mixed features, monotherapy: Limited data available:
Immediate-release formulations:
Children ≥6 years and Adolescents: Oral: Initial: 10 to 20 mg/kg/day in divided doses 2 or 3 times daily for 1 week; evaluate serum concentration and titrate dose to target range: 7 to 12 mcg/mL (Ref). Maximum dose in trials with the immediate-release product not reported; in bipolar pediatric trials with the extended-release formulation, the maximum daily dose was 1,200 mg/day, not to exceed 35 mg/kg/day (Ref).
Dosing based on two open-labeled comparative (lithium and/or valproic acid derivatives) trials (n=109; carbamazepine treatment group, n=33); both trials showed positive efficacy results based on scoring assessments; target serum levels reached in 2.53 ± 1.45 weeks; serum concentrations were monitored weekly and concomitant as-needed parenteral benzodiazepine (eg, lorazepam) or antipsychotic (eg, haloperidol or chlorpromazine) therapy was allowed during the early acute phase (Ref).
Extended-release formulations:
Children ≥9 years and Adolescents: Oral: Initial: 200 mg once daily at bedtime; increase dose in 100 to 200 mg/day increments using twice-daily dosing at 3- to 7-day intervals up to a maximum daily dose: 1,200 mg/day; not to exceed 35 mg/kg/day or a serum concentration of 12 mcg/mL (Ref). The largest trial was open-labeled (n=157, age range: 10 to 17 years) and included patients in a mixed or manic state; ~57% of subjects responded to carbamazepine therapy; mean duration of therapy was 109.6 ± 70.2 days; final daily dose range: 200 to 1,200 mg/day; however, the maximum daily dose of 1,200 mg was most common (final dose in 32% of children and 25% of adolescents) (Ref).
Seizures; monotherapy or adjunctive therapy, generalized tonic-clonic, focal (partial) onset seizures, mixed focal (partial) or generalized seizure:
Note: Dosage must be adjusted according to patient's response and serum concentrations.
Oral:
Infants and Children <6 years:
Immediate-release formulations:
Tablets: Oral: Initial: 10 to 20 mg/kg/day in divided doses twice or 3 times daily; titrate at weekly intervals until optimal response; maintenance doses administered 3 or 4 times daily; maximum daily dose: 35 mg/kg/day.
Suspension: Oral: Initial: 10 to 20 mg/kg/day in divided doses 4 times daily; titrate at weekly intervals until optimal response; maintenance doses administered 3 or 4 times daily; maximum daily dose: 35 mg/kg/day.
Children ≥6 to 12 years:
Immediate-release formulations:
Tablets: Oral: Initial: 100 mg twice daily, titrate by up to 100 mg/day at weekly intervals. Usual maintenance dose range: 400 to 800 mg/day in 3 to 4 divided doses. Maximum daily dose: 1,000 mg/day.
Suspension: Oral: Initial: 50 mg 4 times daily, titrate by up to 100 mg/day at weekly intervals. Usual maintenance daily dose range: 400 to 800 mg/day in 3 to 4 divided doses. Maximum daily dose: 1,000 mg/day.
Extended-release formulations: Capsules, tablets: Oral: Initial: 100 mg twice daily, titrate by up to 100 mg/day at weekly intervals. Usual maintenance daily dose range: 400 to 800 mg/day in divided doses twice daily. Maximum daily dose: 1,000 mg/day.
Adolescents:
Immediate-release formulations:
Tablets: Oral: Initial: 200 mg twice daily, titrate by up to 200 mg/day increments at weekly intervals. Usual maintenance daily dose range: 800 to 1,200 mg/day in divided doses 3 or 4 times daily.
Suspension: Oral: Initial: 100 mg 4 times daily, titrate by up to 200 mg/day increments at weekly intervals. Usual maintenance daily dose range: 800 to 1,200 mg/day in divided doses 3 or 4 times daily.
Extended-release formulations: Capsule, tablet: Oral: Initial: 200 mg twice daily, titrate by up to 200 mg/day increments at weekly intervals. Usual maintenance daily dose range: 800 to 1,200 mg/day in divided doses twice daily.
Maximum daily doses:
Adolescents ≤15 years: 1,000 mg/day.
Adolescents >15 years: 1,200 mg/day.
Rectal: Limited data available: Infants, Children, and Adolescents: Rectal: Maintenance dose: Administer the same total daily dose as small, diluted doses administered more frequently than the oral; dilute the oral suspension with an equal volume of water; if defecation occurs within the first 2 hours, repeat the dose (Ref).
Dosing conversions: Close monitoring and possible dosage adjustment may be necessary during any dosage form conversions due to pharmacokinetics differences amongst immediate-release dosage forms (ie, suspension formulation produces higher peak concentrations compared to the tablet) and between the immediate- and extended-release formulations.
Conversion from immediate-release solid dosage form to suspension: Use the same daily dose and divide into 3 daily doses; monitor serum concentrations.
Conversion from immediate-release tablets to extended-release formulations: Use the same daily dose and divide into 2 daily doses; monitor serum concentrations.
Discontinuation of therapy: Discontinuation of treatment for epilepsy is dependent on several factors to minimize chance of seizure relapse. Favorable factors include: childhood onset, normal EEG at time of discontinuation, idiopathic generalized epilepsy, low seizure frequency before and during treatment, seizure type, normal neurologic exam, and normal intellectual development. Withdrawal of therapy is typically evaluated if patient has been seizure free for 2 years. Abrupt discontinuation is not recommended. Gradual tapers have ranged from 6 weeks to 9 months. The slow discontinuation should be tailored to the patient's preference and needs. Other considerations include the drug pharmacokinetic properties, dosage at the start of withdrawal, dosage forms, and need for follow-up serum concentration monitoring (Ref).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Altered kidney function:
Infants, Children, and Adolescents: Oral:
Note: Consider measuring serum 10,11-carbamazepine epoxide levels in instances where toxicity is suspected, but serum carbamazepine levels are within normal range. Based on experience in adult patients, serum 10,11-carbamazepine epoxide levels may be increased with moderate to severe kidney dysfunction; clearance of parent drug and the 10,11-carbamazepine epoxide metabolite are urine flow dependent (Ref).
Mild to severe impairment: Initial: No dosage adjustment necessary. Monitor closely and adjust dose based on clinical response, tolerability (eg, adverse drug reactions), and serum concentrations of carbamazepine and its active metabolite (Ref).
Hemodialysis, intermittent: There are no dosing adjustments in the manufacturer's labeling; based on pharmacokinetic profile of carbamazepine (ie, lipophilicity, high protein binding, minimal renal clearance), no dose adjustments to initial doses necessary; monitor closely and adjust dose based on clinical response, tolerability, and serum concentrations (Ref).
Peritoneal dialysis: Initial: There are no dosing adjustments in the manufacturer's labeling; based on pharmacokinetic profile of carbamazepine (ie, lipophilicity, high protein binding, minimal renal clearance), no dose adjustments to initial doses necessary; monitor closely and adjust dose based on clinical response, tolerability, and serum concentrations (Ref).
CRRT: There are no pediatric-specific recommendations for dosing in patients receiving CRRT; based on adult experience, dose adjustments should be based on clinical response, tolerability, and serum concentrations (Ref).
Infants, Children, and Adolescents: There are no dosage adjustments provided in the manufacturer's labeling. Use with caution in hepatic impairment and consider dose reduction; metabolized primarily in the liver.
Hematologic effects with carbamazepine can be divided into bone marrow suppressive and proliferative effects (Ref). Bone marrow suppression-related hematological effects present as anemia, aplastic anemia, leukopenia, neutropenia, or thrombocytopenia. Proliferative effects can cause eosinophilia, leukocytosis, lymphocytosis, or macrocytosis (Ref). True incidence of hematological effects associated with carbamazepine is not known but appears to be low overall. One study determined an incidence of 0.14% for severe neutropenia and 0.03% for thrombocytopenia (as combined treatment) (Ref). Most cases of aplastic anemia had confounding variables, such as coincidental disease or concurrent medications (Ref). Leukopenia often reverses, even with continued treatment; rarely persistent and if so, typically clinically insignificant. Thrombocytopenia is reversible with discontinuation (Ref).
Mechanism: Unknown; hematologic effects may occur due to immune-mediated or toxic mechanisms (Ref).
Onset: Varied. Based on case reports: Agranulocytosis: 6 to 1,100 days (most cases within 4 months of initiation); aplastic anemia: 4 to >1,500 days; thrombocytopenia: 6 to 300 days. Leukopenia generally develops more slowly, typically within the first 3 months of treatment (Ref).
Risk factors:
• General:
- Concurrent mediations with additive hematologic effects (Ref)
- First year of treatment (Ref)
- History of adverse hematologic reaction to any drug
• Leukopenia/neutropenia:
- Low-normal or below-normal baseline WBC and neutrophil counts (Ref)
Carbamazepine has been reported to increase the risk of heart failure (Ref). Sinus tachycardia may occur, especially in younger patients without preexisting heart disease in the setting of overdose. Bradyarrhythmia or atrioventricular (AV) conduction delay may also occur, especially in older females with long-term therapy at therapeutic or modestly elevated doses; reversible with discontinuation (Ref).
Mechanism: Carbamazepine blocks sodium channels, causing QRS interval prolongation, predisposing patients to hypotension and ventricular arrhythmias. May also unmask latent AV conduction defect in older patients (Ref). Additionally, carbamazepine may have negative chronotropic and dromotropic effects (Ref).
Onset: Varied; acute in younger patients with supratherapeutic levels (tachyarrhythmia) and chronic in older patients (bradyarrhythmia) (Ref).
Risk factors:
• Preexisting AV conduction delay (Ref)
• Predisposition to conduction abnormalities (Ref)
• Concurrent use of medications with AV-blocking effects (Ref)
• Older females on chronic therapy are at higher risk of bradyarrhythmia (Ref)
• Younger patients with overdose are at higher risk of tachyarrhythmia (Ref)
Carbamazepine is associated with transient, asymptomatic increased serum transaminases (Ref); increased gamma-glutamyl transferase (GGT) levels and increased serum alkaline phosphatase (ALP) due to the enzyme-inducing properties of carbamazepine, rather than cell damage, have also been reported (Ref). Hepatotoxicity (hepatocellular hepatitis, cholestatic hepatitis or hepatitis [mixed]) can occur, often as part of drug rash eosinophilia with systemic symptoms (DRESS) (Ref). Intrahepatic cholestasis (vanishing bile duct syndrome [also known as ductopenic syndrome]) and granulomatous hepatitis have also been reported (Ref). Hepatotoxicity is generally reversible upon discontinuation of therapy, with improvements observed over a period of days and normalization of serum liver enzymes within 4 weeks (Ref).
Mechanism: Unknown; acute liver injury may be caused by immune-mediated mechanisms triggered by arene oxide metabolite formation (Ref).
Onset: Varied; duration of therapy prior to hepatotoxicity usually ranges from 6 to 12 weeks (Ref); although can be several months (Ref). Elevated liver enzyme tests most often occur within the first 2 months of initiation (Ref).
Risk factors:
• HLA-A*3101 may increase susceptibility to hepatotoxicity (Ref)
• Longer duration of therapy (median duration: 30 weeks) may be associated with a poor outcome (Ref)
• Concurrent therapy with other hepatotoxic drugs or drugs that increase carbamazepine levels (Ref)
• High degree of cross-reactivity exists between aromatic antiseizure medications, including phenytoin, carbamazepine, phenobarbital, primidone, and oxcarbazepine (Ref)
• An increased risk of severe injury has been noted in pediatric patients <10 years of age with hepatocellular injury (Ref)
A variety of delayed hypersensitivity reactions, ranging from mild with maculopapular rash (also known as morbilliform rash) to severe cutaneous adverse reactions (SCARs), including Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN), drug reaction with eosinophilia and systemic symptoms (DRESS), and acute generalized exanthematous pustulosis (AGEP) have been reported (Ref).
Mechanism: Non–dose-related; immunologic. Delayed hypersensitivity reactions, including maculopapular eruptions and SCARs are T-cell-mediated (Ref).
Onset: Delayed hypersensitivity reactions: Varied. Maculopapular rash usually occurs 3 to 20 days after start of therapy (Ref). SCARs usually occur 1 to 12 weeks after initiation (Ref); reexposure may lead to more rapid onset (usually with 1 to 4 days) (Ref).
Risk factors:
• General:
- HLA-A*3101 has been identified as potential risk factor for SJS/TEN, DRESS and maculopapular eruption induced by carbamazepine in European, Japanese, and Korean patients (Ref)
- High degree of cross-reactivity exists between aromatic antiseizure medications, including phenytoin, carbamazepine, phenobarbital, primidone, and oxcarbazepine; lamotrigine may also show cross-sensitivity with carbamazepine (Ref)
- Very young patients and older patients may be at risk for severe SCARs associated with aromatic antiseizure medications, including carbamazepine (Ref)
• DRESS:
- Family history of DRESS (Ref)
- Viral reactivation, in particular human herpesvirus 6 (HHV-6) reactivation may be associated with a prolonged and more severe course of DRESS (Ref)
• SJS/TEN:
- HLA-B*1502 allele increases risk of SJS/TEN in South-East Asian populations (Ref)
- Cranial irradiation may increase the risk of SJS/TEN (Ref)
Carbamazepine may cause syndrome of inappropriate antidiuretic hormone secretion (SIADH) and hyponatremia. Incidence varies from 1.8% to 40%. Most cases reported in the literature are asymptomatic or mild. It is also rare that carbamazepine monotherapy can contribute to clinically significant hyponatremia (Ref).
Mechanism : Dose-related; carbamazepine may increase the sensitivity of osmoreceptors to ADH in the distal convoluted tubules and collecting ducts (Ref).
Onset: Varied; one case reported onset within 24 hours in the setting of high doses/serum drug concentrations (Ref). Another case reported onset within 2 months (Ref).
Risk factors:
• High doses/serum drug concentrations (Ref)
• Females (Ref)
• Age >40 years (Ref)
• Low baseline serum sodium levels (Ref)
• Psychiatric illness (Ref)
• Surgery (Ref)
• Hypothyroidism (Ref)
• Concurrent medications that cause SIADH (eg, selective serotonin reuptake inhibitors) (Ref)
• Concurrent diuretic use (Ref)
Carbamazepine may cause CNS effects, such as ataxia, dizziness, and drowsiness (Ref), as well as psychiatric effects such as anxiety and depression (Ref). The depression risk with carbamazepine may be lower than other conventional antiseizure medications (Ref). Rare reports of psychosis have been associated with polydipsia after taking carbamazepine, which resolved following correction of hyponatremia (Ref).
Mechanism: Dose-related; related to the pharmacologic action. Hyponatremia may contribute to psychosis (Ref).
Risk factors:
• Higher doses and concentrations of carbamazepine and its active metabolite (Ref)
• Older patients
Antiseizure medications have been associated with suicidal ideation and suicidal tendencies. However, the FDA meta-analysis has been criticized due to several important limitations (Ref). The risk of suicide is increased in epilepsy (Ref), but the occurrence of suicidal ideation/tendencies in epilepsy is multifactorial. While some antiseizure medications (but not all) have been associated with treatment-emergent psychiatric effects such as anxiety and depression, other factors such as post-ictal suicidal behavior and pertinent patient history must also be evaluated to provide an accurate assessment of risk for any individual drug (Ref). Due to the tricyclic structure of carbamazepine, the depression risk may be lower than with other conventional antiseizure medications (Ref). Carbamazepine has been associated with a lower incidence of suicidal behavior compared to barbiturates (Ref).
Onset: Varied; peak incidence of suicidality across antiseizure medications (not specific to individual agents) has been noted to occur between 1 and 12 weeks of therapy (Ref). A review of clinical trials noted that risk extended from 1 week to 24 weeks of therapy, corresponding to the duration of most trials.
Risk factors:
• History of depression (Ref)
• Use in conditions other than epilepsy or bipolar disorder (Ref)
• In patients with bipolar disorder, risk for repeat suicide attempt was increased in patients with alcohol/substance abuse disorder, rapid cycling, and earlier age at onset of first manic episode (Ref)
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.
>10%:
Gastrointestinal: Nausea (29%), vomiting (18%)
Nervous system: Ataxia (15%) (table 1), dizziness (44%) (table 2), drowsiness (32%) (table 3)
|
Drug (Carbamazepine) |
Placebo |
Population |
Dose |
Dosage Form |
Indication |
Number of Patients (Carbamazepine) |
Number of Patients (Placebo) |
|---|---|---|---|---|---|---|---|
|
15% |
0.4% |
Adults |
400 to 1,600 mg/day |
Extended-release capsules |
Acute mania associated with bipolar I disorder |
251 |
248 |
|
Drug (Carbamazepine) |
Placebo |
Population |
Dose |
Dosage Form |
Indication |
Number of Patients (Carbamazepine) |
Number of Patients (Placebo) |
|---|---|---|---|---|---|---|---|
|
44% |
12% |
Adults |
400 to 1,600 mg/day |
Extended-release capsules |
Acute mania associated with bipolar I disorder |
251 |
248 |
|
Drug (Carbamazepine) |
Placebo |
Population |
Dose |
Dosage Form |
Indication |
Number of Patients (Carbamazepine) |
Number of Patients (Placebo) |
|---|---|---|---|---|---|---|---|
|
32% |
13% |
Adults |
400 to 1,600 mg/day |
Extended-release capsules |
Acute mania associated with bipolar I disorder |
251 |
248 |
1% to 10%:
Cardiovascular: Hypertension (3%; including exacerbation of hypertension)
Dermatologic: Pruritus (8%), skin rash (7%)
Gastrointestinal: Constipation (10%), xerostomia (8%)
Nervous system: Abnormality in thinking (2%), asthenia (8%), paresthesia (2%), speech disturbance (6%), tremor (3%), twitching (2%), vertigo (2%)
Ophthalmic: Blurred vision (6%)
Frequency not defined: Nervous system: Suicidal tendencies
Postmarketing:
Cardiovascular: Arterial insufficiency (cerebral artery), atrioventricular block (including second-degree atrioventricular block and complete atrioventricular block) (Ref), cardiac arrhythmia, collapse, coronary artery disease (aggravation), edema, heart failure, hypotension, pulmonary embolism, sinus tachycardia (Ref), syncope, thromboembolism, thrombophlebitis
Dermatologic: Acute generalized exanthematous pustulosis (Ref), alopecia (Ref), diaphoresis, dyschromia, erythema multiforme (Ref), erythema nodosum, erythematous rash, exfoliative dermatitis, maculopapular rash (Ref), onychomadesis, pruritic rash, skin photosensitivity, Stevens-Johnson syndrome (Ref), toxic epidermal necrolysis (Ref), urticaria, vitiligo (Ref)
Endocrine & metabolic: Acute intermittent porphyria (Ref), albuminuria, decreased serum calcium, decreased thyroid hormones, hirsutism, hyperammonemia (Ref), hyperlipidemia (Ref), hyponatremia (Ref), porphyria (variegate) (Ref), porphyria cutanea tarda (Ref), SIADH (Ref)
Gastrointestinal: Abdominal pain, anorexia, diarrhea, dysgeusia (Ref), gastric distress, glossitis, glottis edema, pancreatitis (Ref), stomatitis
Genitourinary: Acute urinary retention (Ref), azotemia, defective spermatogenesis, glycosuria, impotence, microscopic urine deposits, oliguria, reduced fertility (male), urinary frequency
Hematologic & oncologic: Adenopathy, agranulocytosis (Ref), aplastic anemia (Ref), bone marrow depression (Ref), eosinophilia (Ref), hypogammaglobulinemia, leukocytosis (Ref), leukopenia (Ref), lymphadenopathy (Ref), neutropenia (Ref), pancytopenia (Ref), purpuric disease, thrombocytopenia (Ref)
Hepatic: Cholestatic hepatitis (Ref), granulomatous hepatitis (Ref), hepatic failure (Ref), hepatitis (mixed), hepatocellular hepatitis, hepatotoxicity (idiosyncratic) (Ref), increased gamma-glutamyl transferase (Ref), increased serum alkaline phosphatase (Ref), increased serum transaminases, intrahepatic cholestasis (vanishing bile duct syndrome), jaundice (Ref)
Hypersensitivity: Anaphylaxis, angioedema (Ref), drug reaction with eosinophilia and systemic symptoms (Ref), lip edema
Nervous system: Agitation, anxiety (Ref), aseptic meningitis (Ref), asterixis (Ref), chills, confusion, depression (Ref), fatigue, headache, hyperacusis, involuntary body movements, neuroleptic malignant syndrome (Ref), peripheral neuritis, psychosis (Ref), talkativeness, unsteadiness, visual hallucination
Neuromuscular & skeletal: Arthralgia (Ref), exacerbation of systemic lupus erythematosus, lower limb cramp, lupus-like syndrome (Ref), myalgia, osteoporosis
Ophthalmic: Conjunctivitis, diplopia, eye movement disorder, eyelid edema, increased intraocular pressure (Ref), nystagmus disorder (Ref), punctate cataract
Otic: Tinnitus
Renal: Acute kidney injury (Ref)
Respiratory: Dry throat, laryngeal edema, pulmonary hypersensitivity reaction (Ref)
Miscellaneous: Fever (Ref)
Hypersensitivity to carbamazepine, tricyclic antidepressants, or any component of the formulation; bone marrow depression; with or within 14 days of MAO inhibitor use; concomitant use of nefazodone, delavirdine, or other non-nucleoside reverse transcriptase inhibitors that are substrate of CYP3A4.
Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Canadian labeling: Additional contraindications (not in US labeling): Atrioventricular (AV) heart block; hepatic disease; history of hepatic porphyria (acute intermittent porphyria, variegate porphyria, porphyria cutanea tarda); serious blood disorder; concurrent use with itraconazole and voriconazole.
Concerns related to adverse effects:
• Blood dyscrasias: [US Boxed Warning]: The risk of developing anemia or agranulocytosis is increased during treatment. Complete pretreatment hematological testing should be obtained prior to use; monitor patient closely if white blood cells or platelet counts decrease during therapy; discontinue if significant bone marrow suppression occurs. A spectrum of hematologic effects has been reported with use (eg, agranulocytosis, aplastic anemia, neutropenia, leukopenia, thrombocytopenia, pancytopenia, and anemias); patients with a previous history of adverse hematologic reaction to any drug may be at increased risk. Early detection of hematologic change is important; advise patients of early signs and symptoms including fever, sore throat, mouth ulcers, infections, easy bruising, and petechial or purpuric hemorrhage.
• CNS depression: May cause CNS depression, which may impair physical or mental abilities; patients must be cautioned about performing tasks which require mental alertness (eg, operating machinery or driving).
• Dermatologic toxicity: [US Boxed Warning]: Severe and sometimes fatal dermatologic reactions, including toxic epidermal necrolysis (TEN) and Stevens-Johnson syndrome (SJS), may occur during therapy. The risk is increased in patients with the variant HLA-B*1502 allele, found most often in patients of Asian ancestry. Patients with an increased likelihood of carrying this allele should be screened prior to initiating therapy. Avoid use in patients testing positive for the allele; discontinue therapy in patients who have a serious dermatologic reaction. The risk of SJS or TEN may also be increased if carbamazepine is used in combination with other antiseizure drugs associated with these reactions. Presence of the HLA-B*1502 allele has not been found to predict the risk of less serious dermatologic reactions such as antiseizure hypersensitivity syndrome or nonserious rash.
• Hepatotoxicity: Hepatotoxicity ranging from slight elevations in liver enzymes to rare hepatic failure has been reported and may occur concomitantly with other immunoallergenic syndromes such as multiorgan hypersensitivity (DRESS syndrome) and serious dermatologic reactions including SJS; monitor baseline and periodic liver function, particularly in patients with a history of liver disease; discontinue carbamazepine immediately in cases of aggravated liver dysfunction. In some cases, hepatic effects may progress despite discontinuation of carbamazepine. Rare cases of a hepatic failure and vanishing bile duct syndrome involving destruction and disappearance of the intrahepatic bile ducts have been reported. Clinical courses of vanishing bile duct syndrome have been variable ranging from fulminant to indolent.
• Hypersensitivity reactions: The risk of developing a hypersensitivity reaction may be increased in patients with the variant HLA-A*3101 allele. These hypersensitivity reactions include SJS/TEN, maculopapular eruptions, and drug reaction with eosinophilia and systemic symptoms (DRESS/multiorgan hypersensitivity). The HLA-A*3101 allele may occur more frequently in patients of African-American, Asian, European, Indian, Arabic, Latin American, and Native American ancestry. Hypersensitivity has also been reported in patients experiencing reactions to other antiseizure medications; the history of hypersensitivity reactions in the patient or their immediate family members should be reviewed. Approximately 25% to 30% of patients allergic to carbamazepine will also have reactions with oxcarbazepine. Also, rare cases of anaphylaxis and angioedema have been reported; may occur after first dose or subsequent doses. Discontinue therapy if symptoms occur. Do not rechallenge patients if such reactions occur; initiate alternative treatment.
• Hyponatremia: Hyponatremia may occur and is often caused by the syndrome of inappropriate antidiuretic hormone secretion (SIADH). Risk of SIADH appears to be dose-related. Elderly or patients taking diuretics are at increased risk for hyponatremia. Consider discontinuing therapy in patients with symptomatic hyponatremia.
• Multiorgan hypersensitivity reactions: Potentially serious, sometimes fatal multiorgan hypersensitivity reactions (also known as drug reaction with eosinophilia and systemic symptoms [DRESS]) have been reported with some antiseizure drugs; including carbamazepine; monitor for signs and symptoms of possible disparate manifestations associated with lymphatic, hepatic, renal, and/or hematologic organ systems; gradual discontinuation and conversion to alternate therapy may be required.
• Psychiatric effects: May activate latent psychosis and/or cause confusion or agitation; elderly patients may be at an increased risk for psychiatric effects.
• Renal toxicity: Renal toxicity has been reported; monitor renal function at baseline and periodically thereafter.
• Suicidal ideation: Pooled analysis of trials involving various antiseizure medications (regardless of indication) showed an increased risk of suicidal thoughts/behavior (incidence rate: 0.43% treated patients compared to 0.24% of patients receiving placebo); risk observed as early as 1 week after initiation and continued through duration of trials (most trials ≤24 weeks). Monitor all patients for notable changes in behavior that might indicate suicidal thoughts or depression; notify healthcare provider immediately if symptoms occur.
Disease-related concerns:
• Anticholinergic sensitivity: Has mild anticholinergic activity; use with caution in patients with sensitivity to anticholinergic effects (urinary retention, increased intraocular pressure, constipation).
• Bariatric surgery: Presurgical assessment of the indication for use, symptoms, and goals of therapy should be documented to enable post-surgical assessment. Two small retrospective case series describe wide interpatient variability in postsurgery drug levels for persons receiving ER formulations, including loss of efficacy and toxicities, were reported (Porat 2022; Triplett 2021). Perform pre- and postsurgical therapeutic drug monitoring, especially in persons with seizure disorders, and monitor for continued efficacy as an alternate formulation (eg, immediate release) may be needed (Porat 2022; Triplett 2021).
• Cardiovascular disease: May cause conduction abnormalities, including AV heart block; use caution in patients with underlying ECG abnormalities, preexisting cardiac damage, or patients who are at risk for conduction abnormalities. In a scientific statement from the American Heart Association, carbamazepine has been determined to be an agent that may exacerbate underlying myocardial dysfunction (magnitude: major) in patients with heart failure (AHA [Page 2016]).
• Hepatic impairment: Use with caution in patients with hepatic impairment; avoid use in patients with hepatic porphyria (eg, acute intermittent porphyria, variegate porphyria, porphyria cutanea tarda).
• Myasthenia gravis: Use with caution in patients with myasthenia gravis; may exacerbate condition (Mehrizi 2012).
• Renal impairment: Use with caution in patients with renal impairment.
Special populations:
• Asian ancestry: [US Boxed Warning]: Patients with an increased likelihood of carrying the HLA-B*1502 allele, such as those of Asian descent, should be screened for the variant HLA-B*1502 allele prior to initiating therapy. This genetic variant has been associated with a significantly increased risk of developing Stevens-Johnson syndrome and/or toxic epidermal necrolysis. Patients with a positive result should not be started on carbamazepine.
• Older adult: May activate latent psychosis, confusion, or agitation.
• Pediatric: Exacerbation of certain seizure types have been seen after initiation of therapy in children with epileptic encephalopathies such as Lennox-Gastaut syndrome and Dravet syndrome. This risk is also increased in children with idiopathic generalized epilepsies such as absence epilepsy and juvenile myoclonic epilepsy.
Dosage form specific issues:
• Sorbitol: The suspension may contain sorbitol; avoid use in patents with hereditary fructose intolerance.
• Suspension: Administration of the suspension will yield higher peak and lower trough serum levels than an equal dose of the tablet form; consider a lower starting dose given more frequently (same total daily dose) when using the suspension.
Other warnings/precautions:
• Appropriate use: Not effective in absence, myoclonic, or akinetic seizures; carbamazepine administration may increase the frequency of seizures in patients with these types of seizures.
• Withdrawal: Antiseizure medications should not be discontinued abruptly because of the possibility of increasing seizure frequency; therapy should be withdrawn gradually to minimize the potential of increased seizure frequency, unless safety concerns require a more rapid withdrawal.
Substitution of different carbamazepine products may result in changes in serum concentrations; closely monitor serum concentrations when a change in product is required.
Some dosage forms may contain propylene glycol; in neonates large amounts of propylene glycol delivered orally, intravenously (eg, >3,000 mg/day), or topically have been associated with potentially fatal toxicities which can include metabolic acidosis, seizures, renal failure, and CNS depression; toxicities have also been reported in children and adults including hyperosmolality, lactic acidosis, seizures and respiratory depression; use caution (AAP 1997; Shehab 2009).
Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Capsule Extended Release 12 Hour, Oral:
Carbatrol: 100 mg [contains fd&c blue #2 (indigotine,indigo carmine)]
Carbatrol: 200 mg, 300 mg
Equetro: 100 mg, 200 mg, 300 mg [contains fd&c blue #2 (indigotine,indigo carmine)]
Generic: 100 mg, 200 mg, 300 mg
Suspension, Oral:
TEGretol: 100 mg/5 mL (450 mL) [contains fd&c yellow #6 (sunset yellow), propylene glycol; citrus-vanilla flavor]
Generic: 100 mg/5 mL (5 mL, 10 mL [DSC], 450 mL); 200 mg/10 mL (10 mL)
Tablet, Oral:
Epitol: 200 mg [scored]
TEGretol: 200 mg [scored; contains fd&c red #40 (allura red ac dye)]
Generic: 200 mg
Tablet Chewable, Oral:
Generic: 100 mg, 200 mg
Tablet Extended Release 12 Hour, Oral:
TEGretol-XR: 100 mg, 200 mg, 400 mg
Generic: 100 mg, 200 mg, 400 mg
Yes
Capsule, 12-hour (carBAMazepine ER Oral)
100 mg (per each): $1.91 - $1.96
200 mg (per each): $1.91 - $1.96
300 mg (per each): $1.91 - $1.96
Capsule, 12-hour (Carbatrol Oral)
100 mg (per each): $2.13
200 mg (per each): $2.13
300 mg (per each): $2.13
Capsule, 12-hour (Equetro Oral)
100 mg (per each): $4.63
200 mg (per each): $5.23
300 mg (per each): $5.87
Chewable (carBAMazepine Oral)
100 mg (per each): $0.64 - $0.69
200 mg (per each): $1.80
Suspension (carBAMazepine Oral)
100 mg/5 mL (per mL): $0.17 - $1.33
Suspension (TEGretol Oral)
100 mg/5 mL (per mL): $0.53
Tablet, 12-hour (carBAMazepine ER Oral)
100 mg (per each): $1.10 - $1.15
200 mg (per each): $1.61 - $2.08
400 mg (per each): $3.23 - $4.16
Tablet, 12-hour (TEGretol-XR Oral)
100 mg (per each): $1.98
200 mg (per each): $3.96
400 mg (per each): $7.91
Tablets (carBAMazepine Oral)
200 mg (per each): $1.12 - $1.68
Tablets (Epitol Oral)
200 mg (per each): $1.60
Tablets (TEGretol Oral)
200 mg (per each): $3.70
Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Suspension, Oral:
TEGretol: 100 mg/5 mL (450 mL) [contains fd&c yellow #6 (sunset yellow), propylene glycol]
Generic: 100 mg/5 mL (450 mL)
Tablet, Oral:
TEGretol: 200 mg
Generic: 200 mg
Tablet Chewable, Oral:
Generic: 100 mg, 200 mg
Tablet Extended Release 12 Hour, Oral:
TEGretol CR: 200 mg, 400 mg
Generic: 200 mg, 400 mg
Oral:
Chewable or IR tablets: Administer with food.
Suspension: Shake well before administration. Must be given on a 3 to 4 times/day schedule versus tablets, which can be given 2 to 4 times/day. Because a given dose of suspension will produce higher peak and lower trough levels than the same dose given as the tablet form, patients given the suspension should be started on lower doses given more frequently (same total daily dose) and increased slowly to avoid unwanted side effects. When carbamazepine suspension has been combined with chlorpromazine or thioridazine solutions, a precipitate forms, which may result in loss of effect. Therefore, it is recommended that the carbamazepine suspension dosage form not be administered at the same time with other liquid medicinal agents or diluents. Should be administered with meals.
Extended-release formulations :
ER capsule (Carbatrol, Equetro): Consists of three different types of beads: immediate release, extended release, and enteric release. The bead types are combined in a ratio to allow twice daily dosing. May be opened and contents sprinkled over food such as a teaspoon of applesauce; may be administered with or without food; do not crush or chew capsule or beads inside capsule.
ER tablet: Should be inspected for damage. Damaged ER tablets (without release portal) should not be administered. Should be administered with meals; swallow whole, do not crush or chew.
Bariatric surgery: Carbamazepine is available as an ER formulation and the release characteristics may be significantly altered in an unknown manner in patients who have undergone bariatric surgery; providers should determine if the condition being treated can be safely monitored (including therapeutic drug monitoring if appropriate) or if a switch to an alternate formulation is necessary (Ref). With IR formulations, it is important to note that oral suspensions may contain nonabsorbable sugars (eg, mannitol, sorbitol, xylitol) that can cause dumping syndrome after bariatric surgery; refer to package labeling and monitor for tolerability with use (Ref).
Oral:
Immediate release:
Chewable and conventional tablets: Administer with food 2 to 3 times daily.
Oral suspension: Shake well before use; administer with food 3 to 4 times daily. Since a dose of suspension will produce higher peak and lower trough levels than the same dose given as the tablet form, patients given the suspension should be started on lower doses given more frequently (same total daily dose) and increased slowly to avoid unwanted side effects. When carbamazepine suspension has been combined with chlorpromazine or thioridazine solutions, a precipitate forms which may result in loss of effect. Therefore, it is recommended that the carbamazepine suspension dosage form not be administered at the same time with other liquid medicinal agents or diluents.
Extended release:
Capsules (Carbatrol, Equetro): Consists of 3 different types of beads: Immediate release, extended release, and enteric release. The bead types are combined in a ratio to allow twice daily dosing. Capsules may be opened and contents sprinkled over food such as a teaspoon of applesauce; do not store medication/food mixture for later use; drink fluids after dose to make sure mixture is completely swallowed; may be administered with or without food; do not crush or chew.
Tablet (Tegretol-XR): Administer with food twice daily; examine XR tablets for cracks or chips or other damage; do not use damaged extended-release tablets without release portal. Swallow tablet whole; do not crush or chew.
Rectal: Dilute the oral suspension with an equal volume of water prior to administration; if defecation occurs within the first 2 hours, repeat the dose (Ref).
Hazardous agent (NIOSH 2016 [group 2]).
Use appropriate precautions for receiving, handling, storage, preparation, dispensing, transporting, administration, and disposal. Follow NIOSH and USP 800 recommendations and institution-specific policies/procedures for appropriate containment strategy (NIOSH 2016; USP-NF 2020).
Note: Facilities may perform risk assessment of some hazardous drugs to determine if appropriate for alternative handling and containment strategies (USP-NF 2020). Refer to institution-specific handling policies/procedures.
An FDA-approved patient medication guide, which is available with the product information and as follows, must be dispensed with this medication:
Carbatrol: https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/020712s038lbl.pdf#page=23
Equetro: https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/021710s018lbl.pdf#page=27
TEGretol, TEGretol-XR: https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/016608s121_018927s60_020234s054lbl.pdf#page=19
Bipolar disorder: Monotherapy in the acute treatment of hypomania and mild to moderate mania or episodes with mixed features associated with bipolar disorder.
Focal (partial) onset seizures and generalized onset seizures: Monotherapy and adjunctive therapy in the treatment of patients with focal onset seizures and generalized onset seizures.
Limitations of use: Carbamazepine is not indicated for the treatment of nonmotor (absence) seizures; it has been associated with increased frequency of generalized convulsions in these patients.
Neuropathic pain: Treatment of trigeminal or glossopharyngeal neuralgia.
Bipolar major depression; Maintenance treatment for bipolar disorder
CarBAMazepine may be confused with OXcarbazepine
Epitol may be confused with Epinal
Tegretol, Tegretol-XR may be confused with Toprol-XL, Toradol, Trental
The Institute for Safe Medication Practices (ISMP) includes this medication among its list of drugs which have a heightened risk of causing significant patient harm when used in error (High-Alert Medications in Community/Ambulatory Care Settings).
Beers Criteria: Carbamazepine is identified in the Beers Criteria as a potentially inappropriate medication to be used with caution in patients 65 years and older due to the potential to cause or exacerbate syndrome of inappropriate antidiuretic hormone secretion (SIADH) or hyponatremia; monitor sodium concentration closely when initiating or adjusting the dose in older adults (Beers Criteria [AGS 2023]).
Carbamazepine is identified in the Screening Tool of Older Person's Prescriptions (STOPP) criteria as a potentially inappropriate medication in older adults (≥65 years of age) with a history of recurrent falls due to an increased risk of falls (O’Mahony 2023).
Substrate of CYP1A2 (Minor), CYP2C8 (Minor), CYP3A4 (Major); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential; Induces BCRP, CYP1A2 (Weak), CYP2B6 (Moderate), CYP3A4 (Strong), OATP1B1/1B3, P-glycoprotein, UGT1A1;
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the drug interactions program by clicking on the “Launch drug interactions program” link above.
Abemaciclib: CYP3A4 Inducers (Strong) may decrease serum concentration of Abemaciclib. Risk X: Avoid
Abiraterone Acetate: CYP3A4 Inducers (Strong) may decrease serum concentration of Abiraterone Acetate. Management: Avoid coadministration with strong CYP3A4 inducers. For patients treated with single-agent abiraterone who require therapy with a strong CYP3A4 inducers, abiraterone frequency may increased to twice daily. See full mono for details. Risk D: Consider Therapy Modification
Acalabrutinib: CYP3A4 Inducers (Strong) may decrease serum concentration of Acalabrutinib. Management: Avoid co-administration of strong CYP3A inducers in patients taking acalabrutinib. If strong CYP3A inducers cannot be avoided, increase the dose of acalabrutinib to 200 mg twice daily. Risk D: Consider Therapy Modification
Acetaminophen: CarBAMazepine may increase metabolism of Acetaminophen. This may 1) diminish the effect of acetaminophen; and 2) increase the risk of liver damage. Risk C: Monitor
Acoramidis: UGT1A1 Inducers may decrease serum concentration of Acoramidis. Risk X: Avoid
Adagrasib: CYP3A4 Inducers (Strong) may decrease serum concentration of Adagrasib. Risk X: Avoid
Adenosine: CarBAMazepine may increase adverse/toxic effects of Adenosine. Specifically, the risk of higher degree heart block may be increased. Management: Monitor for increased degrees of heart block and bradycardia when these agents are combined. Consider using a lower initial dose of adenosine (3 mg) for the treatment of supraventricular tachycardia in patients who are receiving carbamazepine. Risk C: Monitor
Afatinib: P-glycoprotein/ABCB1 Inducers may decrease serum concentration of Afatinib. Management: Increase the afatinib dose by 10 mg as tolerated in patients requiring chronic coadministration of P-gp inducers with afatinib. Reduce afatinib dose back to the original afatinib dose 2 to 3 days after discontinuation of the P-gp inducer. Risk D: Consider Therapy Modification
Albendazole: CarBAMazepine may decrease active metabolite exposure of Albendazole. Risk C: Monitor
Aldesleukin: May increase serum concentration of CYP Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors). Risk C: Monitor
Alfacalcidol: CYP3A4 Inducers (Strong) may decrease serum concentration of Alfacalcidol. Risk C: Monitor
ALfentanil: CYP3A4 Inducers (Strong) may decrease serum concentration of ALfentanil. Management: If concomitant use of alfentanil and strong CYP3A4 inducers is necessary, consider dosage increase of alfentanil until stable drug effects are achieved. Monitor patients for signs of opioid withdrawal. Risk D: Consider Therapy Modification
Aliskiren: P-glycoprotein/ABCB1 Inducers may decrease serum concentration of Aliskiren. Risk C: Monitor
Alpelisib: CYP3A4 Inducers (Strong) may decrease serum concentration of Alpelisib. Risk X: Avoid
ALPRAZolam: CYP3A4 Inducers (Strong) may decrease serum concentration of ALPRAZolam. Risk C: Monitor
Amiodarone: May increase serum concentration of CarBAMazepine. CarBAMazepine may decrease serum concentration of Amiodarone. CarBAMazepine may decrease active metabolite exposure of Amiodarone. Risk C: Monitor
AmLODIPine: CYP3A4 Inducers (Strong) may decrease serum concentration of AmLODIPine. Risk C: Monitor
Antihepaciviral Combination Products: CYP3A4 Inducers (Strong) may decrease serum concentration of Antihepaciviral Combination Products. Risk X: Avoid
Apixaban: Inducers of CYP3A4 (Strong) and P-glycoprotein may decrease serum concentration of Apixaban. Risk X: Avoid
Apremilast: CYP3A4 Inducers (Strong) may decrease serum concentration of Apremilast. Risk X: Avoid
Aprepitant: CYP3A4 Inducers (Strong) may decrease serum concentration of Aprepitant. Risk X: Avoid
ARIPiprazole Lauroxil: CYP3A4 Inducers (Strong) may decrease active metabolite exposure of ARIPiprazole Lauroxil. Management: Patients taking the 441 mg dose of aripiprazole lauroxil increase their dose to 662 mg if used with a strong CYP3A4 inducer for more than 14 days. No dose adjustment is necessary for patients using the higher doses of aripiprazole lauroxil. Risk D: Consider Therapy Modification
ARIPiprazole: CYP3A4 Inducers (Strong) may decrease serum concentration of ARIPiprazole. Management: For indications other than major depressive disorder: double the oral aripiprazole dose over 1 to 2 weeks and closely monitor. Avoid use of strong CYP3A4 inducers for more than 14 days with extended-release injectable aripiprazole. Risk D: Consider Therapy Modification
Armodafinil: CarBAMazepine may decrease serum concentration of Armodafinil. Armodafinil may decrease serum concentration of CarBAMazepine. Risk C: Monitor
Artemether and Lumefantrine: CYP3A4 Inducers (Strong) may decrease serum concentration of Artemether and Lumefantrine. CYP3A4 Inducers (Strong) may decrease active metabolite exposure of Artemether and Lumefantrine. Specifically, concentrations of dihydroartemisinin (DHA), the active metabolite of artemether may be decreased. Risk X: Avoid
Artesunate: CarBAMazepine may decrease active metabolite exposure of Artesunate. Risk C: Monitor
Atazanavir: CarBAMazepine may decrease serum concentration of Atazanavir. Atazanavir may increase serum concentration of CarBAMazepine. Risk X: Avoid
Atogepant: CYP3A4 Inducers (Strong) may decrease serum concentration of Atogepant. Management: For treatment of episodic migraine, the recommended dose of atogepant is 30 mg once daily or 60 mg once daily when combined with CYP3A4 inducers. When used for treatment of chronic migraine, use of atogepant with CYP3A4 inducers should be avoided. Risk D: Consider Therapy Modification
Atorvastatin: CYP3A4 Inducers (Strong) may decrease serum concentration of Atorvastatin. Risk C: Monitor
Atrasentan: CYP3A4 Inducers (Strong) may decrease serum concentration of Atrasentan. Risk X: Avoid
Avacopan: CarBAMazepine may decrease serum concentration of Avacopan. Avacopan may increase serum concentration of CarBAMazepine. Risk X: Avoid
Avanafil: CYP3A4 Inducers (Strong) may decrease serum concentration of Avanafil. Risk X: Avoid
Avapritinib: CYP3A4 Inducers (Strong) may decrease serum concentration of Avapritinib. Risk X: Avoid
Axitinib: CYP3A4 Inducers (Strong) may decrease serum concentration of Axitinib. Risk X: Avoid
Barnidipine: CYP3A4 Inducers (Strong) may decrease serum concentration of Barnidipine. Risk C: Monitor
Bazedoxifene: CarBAMazepine may decrease serum concentration of Bazedoxifene. This may lead to loss of efficacy or, if bazedoxifene is combined with estrogen therapy, an increased risk of endometrial hyperplasia. Risk C: Monitor
Bedaquiline: CYP3A4 Inducers (Strong) may decrease serum concentration of Bedaquiline. CYP3A4 Inducers (Strong) may decrease active metabolite exposure of Bedaquiline. Risk X: Avoid
Belumosudil: CYP3A4 Inducers (Strong) may decrease serum concentration of Belumosudil. Management: Increase the dose of belumosudil to 200 mg twice daily when coadministered with strong CYP3A4 inducers. Risk D: Consider Therapy Modification
Benidipine: CYP3A4 Inducers (Strong) may decrease serum concentration of Benidipine. Risk C: Monitor
Benperidol: CYP3A4 Inducers (Strong) may decrease serum concentration of Benperidol. Risk C: Monitor
Benzhydrocodone: CYP3A4 Inducers (Strong) may decrease serum concentration of Benzhydrocodone. Specifically, the serum concentrations of hydrocodone may be reduced. Risk C: Monitor
Berotralstat: P-glycoprotein/ABCB1 Inducers may decrease serum concentration of Berotralstat. Risk X: Avoid
Beta-Acetyldigoxin: P-glycoprotein/ABCB1 Inducers may decrease serum concentration of Beta-Acetyldigoxin. Risk C: Monitor
Betamethasone (Systemic): CYP3A4 Inducers (Strong) may decrease serum concentration of Betamethasone (Systemic). Risk C: Monitor
Bictegravir: CarBAMazepine may decrease serum concentration of Bictegravir. Management: When possible consider using an alternative antiseizure drug with concurrent bictegravir, emtricitabine, and tenofovir alafenamide. If the combination must be used, monitor closely for evidence of reduced antiviral effectiveness. Risk D: Consider Therapy Modification
Bisoprolol: CYP3A4 Inducers (Strong) may decrease serum concentration of Bisoprolol. Risk C: Monitor
Blonanserin: CYP3A4 Inducers (Strong) may decrease serum concentration of Blonanserin. Risk C: Monitor
Bortezomib: CYP3A4 Inducers (Strong) may decrease serum concentration of Bortezomib. Risk X: Avoid
Bosutinib: CYP3A4 Inducers (Strong) may decrease serum concentration of Bosutinib. Risk X: Avoid
Brentuximab Vedotin: CYP3A4 Inducers (Strong) may decrease serum concentration of Brentuximab Vedotin. Specifically, concentrations of the active monomethyl auristatin E (MMAE) component may be decreased. Risk C: Monitor
Brexpiprazole: CYP3A4 Inducers (Strong) may decrease serum concentration of Brexpiprazole. Management: If brexpiprazole is used together with a strong CYP3A4 inducer, the brexpiprazole dose should gradually be doubled over the course of 1 to 2 weeks. Decrease brexpiprazole to original dose over 1 to 2 weeks if the strong CYP3A4 inducer is discontinued. Risk D: Consider Therapy Modification
Brigatinib: CYP3A4 Inducers (Strong) may decrease serum concentration of Brigatinib. Risk X: Avoid
Brivaracetam: CarBAMazepine may decrease serum concentration of Brivaracetam. Brivaracetam may increase active metabolite exposure of CarBAMazepine. Risk C: Monitor
Bromocriptine: CYP3A4 Inducers (Strong) may decrease serum concentration of Bromocriptine. Risk C: Monitor
Bromperidol: CYP3A4 Inducers (Strong) may decrease serum concentration of Bromperidol. Risk C: Monitor
Brotizolam: CYP3A4 Inducers (Strong) may decrease serum concentration of Brotizolam. Risk C: Monitor
Bulevirtide: May increase serum concentration of CYP3A4 Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors). Risk C: Monitor
Buprenorphine: CYP3A4 Inducers (Strong) may decrease serum concentration of Buprenorphine. Risk C: Monitor
BuPROPion: CYP2B6 Inducers (Moderate) may decrease serum concentration of BuPROPion. Risk C: Monitor
BusPIRone: CYP3A4 Inducers (Strong) may decrease serum concentration of BusPIRone. Management: Consider alternatives to this combination. If coadministration of these agents is deemed necessary, monitor patients for reduced buspirone effects and increase buspirone doses as needed. Risk D: Consider Therapy Modification
Butorphanol: CYP3A4 Inducers (Strong) may decrease serum concentration of Butorphanol. Risk C: Monitor
Cabazitaxel: CYP3A4 Inducers (Strong) may decrease serum concentration of Cabazitaxel. Risk C: Monitor
Cabotegravir: UGT1A1 Inducers may decrease serum concentration of Cabotegravir. Risk X: Avoid
Cabozantinib: CYP3A4 Inducers (Strong) may decrease serum concentration of Cabozantinib. Management: Avoid use of strong CYP3A4 inducers with cabozantinib if possible. If combined, increase cabozantinib capsules (Cometriq) by 40 mg from previous dose, max 180 mg daily. Increase cabozantinib tablets (Cabometyx) by 20 mg from previous dose, max 80 mg daily Risk D: Consider Therapy Modification
Calcifediol: CYP3A4 Inducers (Strong) may increase serum concentration of Calcifediol. Risk C: Monitor
Calcitriol (Systemic): CYP3A4 Inducers (Strong) may decrease serum concentration of Calcitriol (Systemic). Risk C: Monitor
Calcium Channel Blockers (Nondihydropyridine): May increase serum concentration of CarBAMazepine. CarBAMazepine may decrease serum concentration of Calcium Channel Blockers (Nondihydropyridine). Management: Consider alternatives to this combination when possible. If combined, monitor for increased carbamazepine concentrations and toxicities and monitor for decreased calcium channel blocker efficacy. Risk D: Consider Therapy Modification
Cannabidiol: CYP3A4 Inducers (Strong) may decrease serum concentration of Cannabidiol. CYP3A4 Inducers (Strong) may decrease active metabolite exposure of Cannabidiol. Risk C: Monitor
Cannabis: May increase serum concentration of CarBAMazepine. CarBAMazepine may decrease serum concentration of Cannabis. More specifically, tetrahydrocannabinol and cannabidiol serum concentrations may be decreased. Risk C: Monitor
Capivasertib: CYP3A4 Inducers (Strong) may decrease serum concentration of Capivasertib. Risk X: Avoid
Capmatinib: CYP3A4 Inducers (Strong) may decrease serum concentration of Capmatinib. Risk X: Avoid
Cariprazine: CYP3A4 Inducers (Strong) may decrease serum concentration of Cariprazine. Risk X: Avoid
Caspofungin: Inducers of Drug Clearance may decrease serum concentration of Caspofungin. Management: Consider using an increased caspofungin dose of 70 mg daily in adults (or 70 mg/m2, up to a maximum of 70 mg, daily in pediatric patients) when coadministered with known inducers of drug clearance. Risk D: Consider Therapy Modification
Celiprolol: P-glycoprotein/ABCB1 Inducers may decrease serum concentration of Celiprolol. Risk C: Monitor
Cenobamate: May decrease serum concentration of CarBAMazepine. Risk C: Monitor
Ceritinib: CYP3A4 Inducers (Strong) may decrease serum concentration of Ceritinib. Risk X: Avoid
Chlormethiazole: CarBAMazepine may decrease serum concentration of Chlormethiazole. Risk C: Monitor
ChlorproPAMIDE: CYP3A4 Inducers (Strong) may decrease serum concentration of ChlorproPAMIDE. Risk C: Monitor
Cilnidipine: CYP3A4 Inducers (Strong) may decrease serum concentration of Cilnidipine. Risk C: Monitor
Citalopram: CYP3A4 Inducers (Strong) may decrease serum concentration of Citalopram. Risk C: Monitor
Cladribine: BCRP/ABCG2 Inducers may decrease serum concentration of Cladribine. Risk C: Monitor
Cladribine: P-glycoprotein/ABCB1 Inducers may decrease serum concentration of Cladribine. Risk C: Monitor
Clarithromycin: May increase serum concentration of CarBAMazepine. CarBAMazepine may decrease serum concentration of Clarithromycin. CarBAMazepine may increase active metabolite exposure of Clarithromycin. Management: Consider alternatives to this combination when possible. If combined, monitor for increased carbamazepine effects/toxicities and for reduced clarithromycin efficacy. Risk D: Consider Therapy Modification
Clindamycin (Systemic): CYP3A4 Inducers (Strong) may decrease serum concentration of Clindamycin (Systemic). Risk C: Monitor
Clofazimine: May increase serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk C: Monitor
ClomiPRAMINE: CarBAMazepine may decrease serum concentration of ClomiPRAMINE. Risk C: Monitor
ClonazePAM: CYP3A4 Inducers (Strong) may decrease serum concentration of ClonazePAM. Risk C: Monitor
CloZAPine: CarBAMazepine may increase myelosuppressive effects of CloZAPine. More specifically, the risk of bone marrow suppression with this combination may be increased due to the independent myelosuppressive effects of the drugs. CarBAMazepine may decrease serum concentration of CloZAPine. Management: Avoid use with strong CYP3A4 inducers when possible. If combined, monitor patients closely and consider clozapine dose increases. Consider increased monitoring for neutropenia Risk D: Consider Therapy Modification
Cobicistat: May increase serum concentration of CarBAMazepine. CarBAMazepine may decrease serum concentration of Cobicistat. Risk X: Avoid
Cobimetinib: CYP3A4 Inducers (Strong) may decrease serum concentration of Cobimetinib. Risk X: Avoid
Codeine: CYP3A4 Inducers (Strong) may decrease active metabolite exposure of Codeine. Risk C: Monitor
Cola-Containing Drinks: May increase serum concentration of CarBAMazepine. Risk C: Monitor
Colchicine: CYP3A4 Inducers (Strong) may decrease serum concentration of Colchicine. Risk C: Monitor
Copanlisib: CYP3A4 Inducers (Strong) may decrease serum concentration of Copanlisib. Risk X: Avoid
Crinecerfont: CYP3A4 Inducers (Strong) may decrease serum concentration of Crinecerfont. Management: Double the morning and evening doses of crinecerfont during coadministration with strong CYP3A4 inducers. See full interaction monograph for details. Risk D: Consider Therapy Modification
Crizotinib: CYP3A4 Inducers (Strong) may decrease serum concentration of Crizotinib. Risk X: Avoid
CycloPHOSphamide: CYP2B6 Inducers (Moderate) may increase active metabolite exposure of CycloPHOSphamide. Risk C: Monitor
CycloSPORINE (Systemic): CYP3A4 Inducers (Strong) may decrease serum concentration of CycloSPORINE (Systemic). Management: Monitor closely for reduced cyclosporine concentrations when combined with strong CYP3A4 inducers. Cyclosporine dose increases will likely be required to maintain adequate serum concentrations. Risk D: Consider Therapy Modification
CYP3A4 Inducers (Moderate): May decrease serum concentration of CarBAMazepine. Risk C: Monitor
CYP3A4 Inducers (Strong): May decrease serum concentration of CarBAMazepine. Risk C: Monitor
CYP3A4 Inducers (Weak): May decrease serum concentration of CarBAMazepine. Risk C: Monitor
CYP3A4 Inhibitors (Moderate): May increase serum concentration of CarBAMazepine. Risk C: Monitor
CYP3A4 Inhibitors (Strong): May increase serum concentration of CarBAMazepine. CYP3A4 Inhibitors (Strong) may increase active metabolite exposure of CarBAMazepine. Risk C: Monitor
CYP3A4 Inhibitors (Weak): May increase serum concentration of CarBAMazepine. Risk C: Monitor
Cyproterone: CYP3A4 Inducers (Strong) may decrease serum concentration of Cyproterone. Risk C: Monitor
Dabigatran Etexilate: P-glycoprotein/ABCB1 Inducers may decrease serum concentration of Dabigatran Etexilate. Management: Avoid concurrent use of dabigatran with P-glycoprotein inducers whenever possible. Risk X: Avoid
Dabrafenib: May decrease serum concentration of CarBAMazepine. CarBAMazepine may decrease serum concentration of Dabrafenib. Risk C: Monitor
Daclatasvir: CYP3A4 Inducers (Strong) may decrease serum concentration of Daclatasvir. Risk X: Avoid
Dapsone (Systemic): May increase adverse/toxic effects of CYP3A4 Inducers (Strong). CYP3A4 Inducers (Strong) may decrease serum concentration of Dapsone (Systemic). Management: Consider alternatives to this combination when possible. Monitor for decreased dapsone efficacy if combined with strong CYP3A4 inducers. Risk D: Consider Therapy Modification
Daridorexant: CYP3A4 Inducers (Strong) may decrease serum concentration of Daridorexant. Risk X: Avoid
Darolutamide: Inducers of CYP3A4 (Strong) and P-glycoprotein may decrease serum concentration of Darolutamide. Risk X: Avoid
Darunavir: CarBAMazepine may decrease serum concentration of Darunavir. Darunavir may increase serum concentration of CarBAMazepine. Risk C: Monitor
Dasabuvir: CYP3A4 Inducers (Strong) may decrease serum concentration of Dasabuvir. Risk X: Avoid
Dasatinib: CYP3A4 Inducers (Strong) may decrease serum concentration of Dasatinib. Management: Avoid concurrent use of dasatinib with strong CYP3A4 inducers when possible. If such a combination cannot be avoided, consider increasing dasatinib dose and monitor clinical response and toxicity closely. Risk D: Consider Therapy Modification
Deferasirox: UGT1A1 Inducers may decrease serum concentration of Deferasirox. Management: Avoid concomitant use of deferasirox and UGT1A1 inducers when possible. If combined, consider a 50% increase in the initial deferasirox dose, with monitoring of serum ferritin concentrations and clinical response to guide further dosing. Risk D: Consider Therapy Modification
Deflazacort: CYP3A4 Inducers (Strong) may decrease active metabolite exposure of Deflazacort. Risk X: Avoid
Delamanid: CYP3A4 Inducers (Strong) may decrease serum concentration of Delamanid. Risk X: Avoid
Desmopressin: Hyponatremia-Associated Agents may increase hyponatremic effects of Desmopressin. Risk C: Monitor
Deuruxolitinib: CYP3A4 Inducers (Strong) may decrease serum concentration of Deuruxolitinib. Risk X: Avoid
DexAMETHasone (Systemic): CYP3A4 Inducers (Strong) may decrease serum concentration of DexAMETHasone (Systemic). Management: Avoid coadministration of dexamethasone and strong CYP3A4 inducers. If concomitant use cannot be avoided, consider dexamethasone dose increases. Risk D: Consider Therapy Modification
DiazePAM: CYP3A4 Inducers (Strong) may decrease serum concentration of DiazePAM. Risk C: Monitor
Dienogest: CYP3A4 Inducers (Strong) may decrease serum concentration of Dienogest. Risk C: Monitor
Digitoxin: CYP3A4 Inducers (Strong) may decrease serum concentration of Digitoxin. Risk C: Monitor
Digitoxin: P-glycoprotein/ABCB1 Inducers may decrease serum concentration of Digitoxin. Risk C: Monitor
Digoxin: P-glycoprotein/ABCB1 Inducers may decrease serum concentration of Digoxin. Risk C: Monitor
Dinutuximab Beta: May increase serum concentration of CYP Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors). Risk C: Monitor
Disopyramide: CYP3A4 Inducers (Strong) may decrease serum concentration of Disopyramide. Risk C: Monitor
DOCEtaxel: CYP3A4 Inducers (Strong) may decrease serum concentration of DOCEtaxel. Risk C: Monitor
Dolutegravir: CarBAMazepine may decrease serum concentration of Dolutegravir. Management: Increase dolutegravir to 50 mg twice/day in adults. Increase weight-based dose to twice daily in pediatric patients. Specific recommendations vary for combination products; see interaction monograph for details. Risk D: Consider Therapy Modification
Domperidone: CYP3A4 Inducers (Strong) may decrease serum concentration of Domperidone. Risk C: Monitor
Doravirine: CYP3A4 Inducers (Strong) may decrease serum concentration of Doravirine. Risk X: Avoid
Doxercalciferol: CYP3A4 Inducers (Strong) may increase active metabolite exposure of Doxercalciferol. Risk C: Monitor
DOXOrubicin (Conventional): CarBAMazepine may decrease serum concentration of DOXOrubicin (Conventional). DOXOrubicin (Conventional) may decrease serum concentration of CarBAMazepine. Risk X: Avoid
Doxycycline: CarBAMazepine may decrease serum concentration of Doxycycline. Risk C: Monitor
DroNABinol: CYP3A4 Inducers (Strong) may decrease serum concentration of DroNABinol. Risk C: Monitor
Dronedarone: CYP3A4 Inducers (Strong) may decrease serum concentration of Dronedarone. Risk X: Avoid
Duvelisib: CYP3A4 Inducers (Strong) may decrease serum concentration of Duvelisib. Risk X: Avoid
Dydrogesterone: CYP3A4 Inducers (Strong) may decrease serum concentration of Dydrogesterone. Risk C: Monitor
Ebastine: CYP3A4 Inducers (Strong) may decrease serum concentration of Ebastine. CYP3A4 Inducers (Strong) may decrease active metabolite exposure of Ebastine. Risk C: Monitor
Edoxaban: P-glycoprotein/ABCB1 Inducers may decrease serum concentration of Edoxaban. Management: Avoid coadministration of edoxaban and P-glycoprotein (P-gp) inducers if possible. If concomitant use is required, be aware the edoxaban efficacy may be decreased. Risk D: Consider Therapy Modification
Efavirenz: CarBAMazepine may decrease serum concentration of Efavirenz. Efavirenz may decrease serum concentration of CarBAMazepine. Risk X: Avoid
Elacestrant: CYP3A4 Inducers (Strong) may decrease serum concentration of Elacestrant. Risk X: Avoid
Elagolix, Estradiol, and Norethindrone: CYP3A4 Inducers (Strong) may decrease serum concentration of Elagolix, Estradiol, and Norethindrone. Risk C: Monitor
Elagolix: CYP3A4 Inducers (Strong) may decrease serum concentration of Elagolix. Risk C: Monitor
Elbasvir and Grazoprevir: CYP3A4 Inducers (Strong) may decrease serum concentration of Elbasvir and Grazoprevir. Risk X: Avoid
Elexacaftor, Tezacaftor, and Ivacaftor: CYP3A4 Inducers (Strong) may decrease serum concentration of Elexacaftor, Tezacaftor, and Ivacaftor. Risk X: Avoid
Eliglustat: CYP3A4 Inducers (Strong) may decrease serum concentration of Eliglustat. Risk X: Avoid
Elranatamab: May increase serum concentration of CYP Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors). Risk C: Monitor
Encorafenib: CYP3A4 Inducers (Strong) may decrease serum concentration of Encorafenib. Risk X: Avoid
Enfortumab Vedotin: CYP3A4 Inducers (Strong) may decrease serum concentration of Enfortumab Vedotin. Specifically, concentrations of the active monomethyl auristatin E (MMAE) component may be decreased. Risk C: Monitor
Ensartinib: CYP3A4 Inducers (Strong) may decrease serum concentration of Ensartinib. Risk X: Avoid
Entrectinib: CYP3A4 Inducers (Strong) may decrease serum concentration of Entrectinib. Risk X: Avoid
Enzalutamide: CYP3A4 Inducers (Strong) may decrease serum concentration of Enzalutamide. CYP3A4 Inducers (Strong) may decrease active metabolite exposure of Enzalutamide. Management: Consider using an alternative agent that has no or minimal CYP3A4 induction potential when possible. If this combination cannot be avoided, increase the dose of enzalutamide from 160 mg daily to 240 mg daily. Risk D: Consider Therapy Modification
Epcoritamab: May increase serum concentration of CYP Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors). Risk C: Monitor
Eplerenone: CYP3A4 Inducers (Strong) may decrease serum concentration of Eplerenone. Risk C: Monitor
Eravacycline: CYP3A4 Inducers (Strong) may decrease serum concentration of Eravacycline. Management: Increase the eravacycline dose to 1.5 mg/kg every 12 hours when combined with strong CYP3A4 inducers. Risk D: Consider Therapy Modification
Erdafitinib: CYP3A4 Inducers (Strong) may decrease serum concentration of Erdafitinib. Risk X: Avoid
Erlotinib: CYP3A4 Inducers (Strong) may decrease serum concentration of Erlotinib. Management: Avoid the combination of erlotinib and strong CYP3A4 inducers whenever possible. If this combination must be used, increase erlotinib dose by 50 mg increments every 2 weeks as tolerated, to a maximum of 450 mg/day. Risk D: Consider Therapy Modification
Escitalopram: CYP3A4 Inducers (Strong) may decrease serum concentration of Escitalopram. Risk C: Monitor
Esketamine (Injection): CYP3A4 Inducers (Strong) may decrease serum concentration of Esketamine (Injection). Risk C: Monitor
Eslicarbazepine: CarBAMazepine may increase adverse/toxic effects of Eslicarbazepine. CarBAMazepine may decrease serum concentration of Eslicarbazepine. Risk C: Monitor
Estazolam: CYP3A4 Inducers (Strong) may decrease serum concentration of Estazolam. Risk C: Monitor
Estrogen Derivatives: CYP3A4 Inducers (Strong) may decrease serum concentration of Estrogen Derivatives. Risk C: Monitor
Eszopiclone: CYP3A4 Inducers (Strong) may decrease serum concentration of Eszopiclone. Risk C: Monitor
Ethosuximide: CYP3A4 Inducers (Strong) may decrease serum concentration of Ethosuximide. Risk C: Monitor
Etizolam: CYP3A4 Inducers (Strong) may decrease serum concentration of Etizolam. Risk C: Monitor
Etoposide Phosphate: CYP3A4 Inducers (Strong) may decrease serum concentration of Etoposide Phosphate. Management: When possible, seek alternatives to strong CYP3A4-inducing medications in patients receiving etoposide phosphate. If these combinations cannot be avoided, monitor patients closely for diminished etoposide phosphate response. Risk D: Consider Therapy Modification
Etoposide: CYP3A4 Inducers (Strong) may decrease serum concentration of Etoposide. Management: When possible, seek alternatives to strong CYP3A4-inducing medications in patients receiving etoposide. If combined, monitor patients closely for diminished etoposide response and need for etoposide dose increases. Risk D: Consider Therapy Modification
Etoricoxib: CYP3A4 Inducers (Strong) may decrease serum concentration of Etoricoxib. Risk C: Monitor
Etravirine: CYP3A4 Inducers (Strong) may decrease serum concentration of Etravirine. Risk X: Avoid
Everolimus: Inducers of CYP3A4 (Strong) and P-glycoprotein may decrease serum concentration of Everolimus. Management: Afinitor: Double the everolimus daily dose, using increments of 5 mg or less, with careful monitoring; multiple increments may be necessary. Zortress: Avoid if possible and monitor for decreased everolimus concentrations if combined. Risk D: Consider Therapy Modification
Evogliptin: CYP3A4 Inducers (Strong) may decrease serum concentration of Evogliptin. Risk C: Monitor
Exemestane: CYP3A4 Inducers (Strong) may decrease serum concentration of Exemestane. Management: Increase the exemestane dose to 50 mg once daily in patients receiving concurrent strong CYP3A4 inducers. Monitor patients closely for evidence of toxicity or inadequate clinical response. Risk D: Consider Therapy Modification
Fedratinib: CYP3A4 Inducers (Strong) may decrease serum concentration of Fedratinib. Risk X: Avoid
Felbamate: CarBAMazepine may decrease serum concentration of Felbamate. Felbamate may decrease serum concentration of CarBAMazepine. Felbamate may increase active metabolite exposure of CarBAMazepine. Specifically, concentrations of the carbamazepine epoxide metabolite may be increased. Management: Initiate felbamate at typical doses (1,200 mg/day in 3 or 4 divided doses for adults and children 14 years of age or older; 15 mg/kg/day in 3 or 4 divided doses in children 2 to 14 years of age) while reducing the carbamazepine dose by 20%. Risk D: Consider Therapy Modification
Felodipine: CYP3A4 Inducers (Strong) may decrease serum concentration of Felodipine. Management: Consider alternatives to this combination when possible. If combined, monitor for reduced felodipine efficacy and the need for felodipine dose increases. Risk D: Consider Therapy Modification
Fenfluramine: CYP3A4 Inducers (Strong) may decrease serum concentration of Fenfluramine. Management: Avoid concurrent use of strong CYP3A4 inducers with fenfluramine when possible. If combined use cannot be avoided, consider increasing the fenfluramine dose, but do not exceed the fenfluramine maximum daily dose. Risk D: Consider Therapy Modification
FentaNYL: CYP3A4 Inducers (Strong) may decrease serum concentration of FentaNYL. Risk C: Monitor
Fesoterodine: CYP3A4 Inducers (Strong) may decrease active metabolite exposure of Fesoterodine. Risk C: Monitor
Fexinidazole: CYP3A4 Inducers (Strong) may increase active metabolite exposure of Fexinidazole. Risk X: Avoid
Fexofenadine: P-glycoprotein/ABCB1 Inducers may decrease serum concentration of Fexofenadine. Risk C: Monitor
Finerenone: CYP3A4 Inducers (Strong) may decrease serum concentration of Finerenone. Risk X: Avoid
Fingolimod: CarBAMazepine may decrease serum concentration of Fingolimod. CarBAMazepine may decrease active metabolite exposure of Fingolimod. Risk C: Monitor
Flibanserin: CYP3A4 Inducers (Strong) may decrease serum concentration of Flibanserin. Risk X: Avoid
Fludrocortisone: CYP3A4 Inducers (Strong) may decrease serum concentration of Fludrocortisone. Risk C: Monitor
Flunarizine: CarBAMazepine may decrease serum concentration of Flunarizine. Risk C: Monitor
FLUoxetine: May increase serum concentration of CarBAMazepine. Risk C: Monitor
Fosamprenavir: CYP3A4 Inducers (Strong) may decrease active metabolite exposure of Fosamprenavir. Risk C: Monitor
Fosaprepitant: CYP3A4 Inducers (Strong) may decrease serum concentration of Fosaprepitant. Specifically, CYP3A4 Inducers (Strong) may decrease serum concentrations of the active metabolite aprepitant. Risk X: Avoid
Fosnetupitant: CYP3A4 Inducers (Strong) may decrease active metabolite exposure of Fosnetupitant. Risk X: Avoid
Fosphenytoin-Phenytoin: May decrease serum concentration of CarBAMazepine. CarBAMazepine may decrease serum concentration of Fosphenytoin-Phenytoin. CarBAMazepine may increase serum concentration of Fosphenytoin-Phenytoin. Risk C: Monitor
Fostamatinib: CYP3A4 Inducers (Strong) may decrease active metabolite exposure of Fostamatinib. Risk X: Avoid
Fostemsavir: CYP3A4 Inducers (Strong) may decrease active metabolite exposure of Fostemsavir. Risk X: Avoid
Fruquintinib: CYP3A4 Inducers (Strong) may decrease serum concentration of Fruquintinib. Risk X: Avoid
Fusidic Acid (Systemic): May increase serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Management: Consider avoiding this combination if possible. If required, monitor patients closely for increased adverse effects of the CYP3A4 substrate. Risk D: Consider Therapy Modification
Futibatinib: Inducers of CYP3A4 (Strong) and P-glycoprotein may decrease serum concentration of Futibatinib. Risk X: Avoid
Ganaxolone: CYP3A4 Inducers (Strong) may decrease serum concentration of Ganaxolone. Management: Avoid concomitant use of ganaxolone and strong CYP3A4 inducers whenever possible. If combined, consider increasing the dose of ganaxolone, but do not exceed the maximum recommended daily dose. Risk D: Consider Therapy Modification
Gefitinib: CYP3A4 Inducers (Strong) may decrease serum concentration of Gefitinib. Management: In the absence of severe adverse reactions, increase the gefitinib dose to 500 mg daily in patients receiving strong CYP3A4 inducers; resume 250 mg dose 7 days after discontinuation of the strong inducer. Carefully monitor clinical response. Risk D: Consider Therapy Modification
Gemigliptin: CYP3A4 Inducers (Strong) may decrease serum concentration of Gemigliptin. CYP3A4 Inducers (Strong) may decrease active metabolite exposure of Gemigliptin. Risk X: Avoid
Gepirone: CYP3A4 Inducers (Strong) may decrease serum concentration of Gepirone. Risk X: Avoid
Gepotidacin: CYP3A4 Inducers (Strong) may decrease serum concentration of Gepotidacin. Risk X: Avoid
Gepotidacin: May increase serum concentration of CYP3A4 Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors). Risk X: Avoid
Gestrinone: CarBAMazepine may decrease serum concentration of Gestrinone. Risk C: Monitor
Gilteritinib: Inducers of CYP3A4 (Strong) and P-glycoprotein may decrease serum concentration of Gilteritinib. Risk X: Avoid
Givinostat: May increase serum concentration of CYP3A4 Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors). Risk C: Monitor
Glasdegib: CYP3A4 Inducers (Strong) may decrease serum concentration of Glasdegib. Risk X: Avoid
Glecaprevir and Pibrentasvir: CarBAMazepine may decrease serum concentration of Glecaprevir and Pibrentasvir. Risk X: Avoid
Glofitamab: May increase serum concentration of CYP Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors). Risk C: Monitor
Grapefruit Juice: May increase serum concentration of CarBAMazepine. Risk C: Monitor
GuanFACINE: CYP3A4 Inducers (Strong) may decrease serum concentration of GuanFACINE. Management: Increase extended-release guanfacine dose by up to double when initiating guanfacine in patients taking CYP3A4 inducers or if initiating a CYP3A4 inducer in a patient already taking extended-release guanfacine. Monitor for reduced guanfacine efficacy. Risk D: Consider Therapy Modification
Haloperidol: CarBAMazepine may decrease serum concentration of Haloperidol. Risk C: Monitor
Hormonal Contraceptives: CYP3A4 Inducers (Strong) may decrease serum concentration of Hormonal Contraceptives. Management: Advise patients to use an alternative method of contraception or a back-up method during coadministration, and to continue back-up contraception for 28 days after discontinuing a strong CYP3A4 inducer to ensure contraceptive reliability. Risk D: Consider Therapy Modification
HYDROcodone: CYP3A4 Inducers (Strong) may decrease serum concentration of HYDROcodone. Risk C: Monitor
Hydrocortisone (Systemic): CYP3A4 Inducers (Strong) may decrease serum concentration of Hydrocortisone (Systemic). Risk C: Monitor
Ibrexafungerp: CYP3A4 Inducers (Strong) may decrease serum concentration of Ibrexafungerp. Risk X: Avoid
Ibrutinib: CYP3A4 Inducers (Strong) may decrease serum concentration of Ibrutinib. Risk X: Avoid
Idelalisib: CYP3A4 Inducers (Strong) may decrease serum concentration of Idelalisib. Risk X: Avoid
Ifosfamide: CYP3A4 Inducers (Strong) may increase active metabolite exposure of Ifosfamide. CYP3A4 Inducers (Strong) may decrease active metabolite exposure of Ifosfamide. Risk C: Monitor
Imatinib: CYP3A4 Inducers (Strong) may decrease serum concentration of Imatinib. Management: Avoid use of imatinib and strong CYP3A4 inducers when possible. If such a combination must be used, increase imatinib dose by at least 50% and monitor the patient's clinical response closely. Doses up to 1200 mg/day (600 mg twice daily) have been used. Risk D: Consider Therapy Modification
Indinavir: CYP3A4 Inducers (Strong) may decrease serum concentration of Indinavir. Management: Consider avoiding the combination of indinavir and strong CYP3A4 inducers whenever possible due to the risk for decreased indinavir concentrations, reduced efficacy, and development of resistance. If combined, monitor for indinavir treatment failure Risk D: Consider Therapy Modification
Irinotecan Products: CYP3A4 Inducers (Strong) may decrease serum concentration of Irinotecan Products. CYP3A4 Inducers (Strong) may decrease active metabolite exposure of Irinotecan Products. Specifically, serum concentrations of SN-38 may be reduced. Management: Avoid administration of strong CYP3A4 inducers during irinotecan treatment, and substitute non-CYP3A4 inducing agents at least 2 weeks prior to irinotecan initiation, whenever possible. If combined, monitor for reduced irinotecan efficacy. Risk D: Consider Therapy Modification
Isavuconazonium Sulfate: CYP3A4 Inducers (Strong) may decrease active metabolite exposure of Isavuconazonium Sulfate. Specifically, CYP3A4 Inducers (Strong) may decrease isavuconazole serum concentrations. Risk X: Avoid
Isoniazid: CarBAMazepine may increase hepatotoxic effects of Isoniazid. Isoniazid may increase serum concentration of CarBAMazepine. Risk C: Monitor
Isradipine: CYP3A4 Inducers (Strong) may decrease serum concentration of Isradipine. Risk C: Monitor
Istradefylline: CYP3A4 Inducers (Strong) may decrease serum concentration of Istradefylline. Risk X: Avoid
Itraconazole: CYP3A4 Inducers (Strong) may decrease serum concentration of Itraconazole. CYP3A4 Inducers (Strong) may decrease active metabolite exposure of Itraconazole. Risk X: Avoid
Ivabradine: CYP3A4 Inducers (Strong) may decrease serum concentration of Ivabradine. Risk X: Avoid
Ivacaftor: CYP3A4 Inducers (Strong) may decrease serum concentration of Ivacaftor. Risk X: Avoid
Ivosidenib: CYP3A4 Inducers (Strong) may decrease serum concentration of Ivosidenib. Risk X: Avoid
Ixabepilone: CYP3A4 Inducers (Strong) may decrease serum concentration of Ixabepilone. Management: Avoid this combination whenever possible. If this combination must be used, a gradual increase in ixabepilone dose from 40 mg/m2 to 60 mg/m2 (given as a 4-hour infusion), as tolerated, should be considered. Risk D: Consider Therapy Modification
Ixazomib: CYP3A4 Inducers (Strong) may decrease serum concentration of Ixazomib. Risk X: Avoid
Ketamine: CYP3A4 Inducers (Strong) may decrease serum concentration of Ketamine. Risk C: Monitor
Ketoconazole (Systemic): CYP3A4 Inducers (Strong) may decrease serum concentration of Ketoconazole (Systemic). Management: The use of ketoconazole concurrently with or within 2 weeks of a strong CYP3A4 inducer is not recommended. If such a combination cannot be avoided, monitor patients closely for evidence of diminished clinical response to ketoconazole. Risk D: Consider Therapy Modification
Lacidipine: CYP3A4 Inducers (Strong) may decrease serum concentration of Lacidipine. Risk C: Monitor
Lacosamide: Antiseizure Agents (Sodium Channel Blockers) may increase adverse/toxic effects of Lacosamide. Specifically the risk for bradycardia, ventricular tachyarrhythmias, or a prolonged PR interval may be increased. Risk C: Monitor
LamoTRIgine: CarBAMazepine may increase adverse/toxic effects of LamoTRIgine. Specifically, the risk for hematologic toxicities may be increased. CarBAMazepine may increase arrhythmogenic effects of LamoTRIgine. CarBAMazepine may decrease serum concentration of LamoTRIgine. Management: Consider the risk of serious arrhythmias or death versus benefit of this combination. For patients taking carbamazepine without valproate, lamotrigine dose adjustments are recommended for lamotrigine initiation. See full interact monograph for details. Risk D: Consider Therapy Modification
Lapatinib: CYP3A4 Inducers (Strong) may decrease serum concentration of Lapatinib. Management: If concomitant use cannot be avoided, titrate lapatinib gradually from 1,250 mg/day up to 4,500 mg/day (HER2 positive metastatic breast cancer) or 1,500 mg/day up to 5,500 mg/day (hormone receptor/HER2 positive breast cancer) as tolerated. Risk D: Consider Therapy Modification
Larotrectinib: CYP3A4 Inducers (Strong) may decrease serum concentration of Larotrectinib. Management: Avoid use of strong CYP3A4 inducers with larotrectinib. If this combination cannot be avoided, double the larotrectinib dose. Reduced to previous dose after stopping the inducer after a period of 3 to 5 times the inducer's half-life. Risk D: Consider Therapy Modification
Lazertinib: CYP3A4 Inducers (Strong) may decrease serum concentration of Lazertinib. Risk X: Avoid
Ledipasvir: P-glycoprotein/ABCB1 Inducers may decrease serum concentration of Ledipasvir. Risk X: Avoid
Lefamulin (Intravenous): CYP3A4 Inducers (Strong) may decrease serum concentration of Lefamulin (Intravenous). Management: Avoid concomitant use of lefamulin intravenous infusion with strong CYP3A4 inducers unless the benefits outweigh the risks. Risk D: Consider Therapy Modification
Lefamulin (Intravenous): P-glycoprotein/ABCB1 Inducers may decrease serum concentration of Lefamulin (Intravenous). Management: Avoid concomitant use of lefamulin (intravenous) with P-glycoprotein/ABCB1 inducers unless the benefits outweigh the risks. Risk D: Consider Therapy Modification
Lefamulin: CYP3A4 Inducers (Strong) may decrease serum concentration of Lefamulin. Management: Avoid concomitant use of lefamulin with strong CYP3A4 inducers unless the benefits outweigh the risks. Risk D: Consider Therapy Modification
Lefamulin: P-glycoprotein/ABCB1 Inducers may decrease serum concentration of Lefamulin. Management: Avoid concomitant use of lefamulin with P-glycoprotein/ABCB1 inducers unless the benefits outweigh the risks. Risk D: Consider Therapy Modification
Lemborexant: CYP3A4 Inducers (Strong) may decrease serum concentration of Lemborexant. Risk X: Avoid
Lenacapavir: CYP3A4 Inducers (Strong) may decrease serum concentration of Lenacapavir. Risk X: Avoid
Leniolisib: CYP3A4 Inducers (Strong) may decrease serum concentration of Leniolisib. Risk X: Avoid
Lercanidipine: CYP3A4 Inducers (Strong) may decrease serum concentration of Lercanidipine. Risk C: Monitor
Letermovir: P-glycoprotein/ABCB1 Inducers may decrease serum concentration of Letermovir. Risk X: Avoid
Letermovir: UGT1A1 Inducers may decrease serum concentration of Letermovir. Risk X: Avoid
Leuprolide and Norethindrone: CYP3A4 Inducers (Strong) may decrease serum concentration of Leuprolide and Norethindrone. Specifically, norethindrone concentrations may be decreased. Risk C: Monitor
Levamlodipine: CYP3A4 Inducers (Strong) may decrease serum concentration of Levamlodipine. Risk C: Monitor
LevETIRAcetam: May increase adverse/toxic effects of CarBAMazepine. CarBAMazepine may decrease serum concentration of LevETIRAcetam. Risk C: Monitor
Levoketoconazole: CYP3A4 Inducers (Strong) may decrease serum concentration of Levoketoconazole. Risk X: Avoid
Levomethadone: CYP3A4 Inducers (Strong) may decrease serum concentration of Levomethadone. Risk C: Monitor
Levonorgestrel (IUD): CYP3A4 Inducers (Strong) may decrease therapeutic effects of Levonorgestrel (IUD). CYP3A4 Inducers (Strong) may decrease serum concentration of Levonorgestrel (IUD). Risk C: Monitor
Lidocaine (Systemic): CYP3A4 Inducers (Strong) may decrease serum concentration of Lidocaine (Systemic). Risk C: Monitor
LinaGLIPtin: CYP3A4 Inducers (Strong) may decrease serum concentration of LinaGLIPtin. Management: Strongly consider using an alternative to any strong CYP3A4 inducer in patients who are being treated with linagliptin. If this combination is used, monitor patients closely for evidence of reduced linagliptin effectiveness. Risk D: Consider Therapy Modification
LinaGLIPtin: P-glycoprotein/ABCB1 Inducers may decrease serum concentration of LinaGLIPtin. Management: Strongly consider using an alternative to any P-glycoprotein inducer in patients who are being treated with linagliptin. If this combination is used, monitor patients closely for evidence of reduced linagliptin effectiveness. Risk D: Consider Therapy Modification
Lithium: CarBAMazepine may increase adverse/toxic effects of Lithium. Risk C: Monitor
Lonafarnib: CYP3A4 Inducers (Strong) may decrease serum concentration of Lonafarnib. Risk X: Avoid
Lopinavir: CarBAMazepine may decrease serum concentration of Lopinavir. Lopinavir may increase serum concentration of CarBAMazepine. Management: Do not use a once daily lopinavir/ritonavir regimen together with carbamazepine. If used with a twice daily lopinavir/ritonavir regimen, monitor for reduced lopinavir/ritonavir effectiveness. Also monitor for increased carbamazepine effects/toxicities. Risk D: Consider Therapy Modification
Lorlatinib: CYP3A4 Inducers (Strong) may increase hepatotoxic effects of Lorlatinib. CYP3A4 Inducers (Strong) may decrease serum concentration of Lorlatinib. Risk X: Avoid
Lovastatin: CYP3A4 Inducers (Strong) may decrease serum concentration of Lovastatin. Risk C: Monitor
Loxapine: May increase active metabolite exposure of CarBAMazepine. Specifically, concentrations of carbamazepine epoxide (CBZE) may be increased. Risk C: Monitor
Lumacaftor and Ivacaftor: CYP3A4 Inducers (Strong) may decrease serum concentration of Lumacaftor and Ivacaftor. Specifically, the serum concentration of ivacaftor may be decreased. Risk X: Avoid
Lumateperone: CYP3A4 Inducers (Strong) may decrease serum concentration of Lumateperone. Risk X: Avoid
Lurasidone: CYP3A4 Inducers (Strong) may decrease serum concentration of Lurasidone. Risk X: Avoid
Lurbinectedin: CYP3A4 Inducers (Strong) may decrease serum concentration of Lurbinectedin. Risk X: Avoid
Macimorelin: CYP3A4 Inducers (Strong) may decrease serum concentration of Macimorelin. Risk X: Avoid
Macitentan: CYP3A4 Inducers (Strong) may decrease serum concentration of Macitentan. Risk X: Avoid
Manidipine: CYP3A4 Inducers (Strong) may decrease serum concentration of Manidipine. Management: Consider avoiding concomitant use of manidipine and strong CYP3A4 inducers. If combined, monitor closely for decreased manidipine effects and loss of efficacy. Increased manidipine doses may be required. Risk D: Consider Therapy Modification
Maraviroc: CYP3A4 Inducers (Strong) may decrease serum concentration of Maraviroc. Management: Increase maraviroc adult dose to 600 mg twice/day, but only if not receiving a strong CYP3A4 inhibitor. Not recommended for pediatric patients not also receiving a strong CYP3A4 inhibitor. Contraindicated in patients with CrCl less than 30 mL/min. Risk D: Consider Therapy Modification
Maribavir: CarBAMazepine may decrease serum concentration of Maribavir. Management: Increase the dose of maribavir to 800 mg twice daily when combined with carbamazepine. Risk D: Consider Therapy Modification
Mavacamten: CYP3A4 Inducers (Strong) may decrease serum concentration of Mavacamten. Risk X: Avoid
Mavorixafor: CYP3A4 Inducers (Strong) may decrease serum concentration of Mavorixafor. Risk X: Avoid
Mebendazole: CarBAMazepine may decrease serum concentration of Mebendazole. Risk C: Monitor
Mefloquine: May decrease therapeutic effects of CarBAMazepine. CarBAMazepine may decrease serum concentration of Mefloquine. Mefloquine may decrease serum concentration of CarBAMazepine. Management: Mefloquine is contraindicated for malaria prophylaxis in persons with a history of seizures. If carbamazepine is being used for another indication, monitor for decreased concentrations and efficacy of both carbamazepine and mefloquine. Risk D: Consider Therapy Modification
Meperidine: CYP3A4 Inducers (Strong) may decrease serum concentration of Meperidine. CYP3A4 Inducers (Strong) may increase active metabolite exposure of Meperidine. Specifically, concentrations of normeperidine, the CNS stimulating metabolite, may be increased. Risk C: Monitor
Methadone: CYP3A4 Inducers (Strong) may decrease serum concentration of Methadone. Risk C: Monitor
Methoxyflurane: CYP2B6 Inducers (Moderate) may increase metabolism of Methoxyflurane. Specifically, this increased metabolism may lead to increased production of nephrotoxic metabolites. Risk X: Avoid
Methylergonovine: CYP3A4 Inducers (Strong) may decrease serum concentration of Methylergonovine. Risk C: Monitor
MethylPREDNISolone: CYP3A4 Inducers (Strong) may decrease serum concentration of MethylPREDNISolone. Management: Consider methylprednisolone dose increases in patients receiving strong CYP3A4 inducers and monitor closely for reduced steroid efficacy. Risk D: Consider Therapy Modification
MetyraPONE: Coadministration of Antiseizure Agents and MetyraPONE may alter diagnostic results. Management: Consider alternatives to the use of the metyrapone test in patients taking antiseizure agents. Risk D: Consider Therapy Modification
Mianserin: May decrease therapeutic effects of CarBAMazepine. CarBAMazepine may decrease serum concentration of Mianserin. Risk C: Monitor
Midazolam: CYP3A4 Inducers (Strong) may decrease serum concentration of Midazolam. Risk C: Monitor
Midostaurin: CYP3A4 Inducers (Strong) may decrease serum concentration of Midostaurin. Risk X: Avoid
MiFEPRIStone: CYP3A4 Inducers (Strong) may decrease serum concentration of MiFEPRIStone. Management: Avoid combined use in patients treated for Cushing's disease. When used for pregnancy termination, mifepristone efficacy may be reduced and an alternative pregnancy termination procedure may be warranted. Ensure a follow-up assessment after combined use. Risk D: Consider Therapy Modification
Mirabegron: CYP3A4 Inducers (Strong) may decrease serum concentration of Mirabegron. Risk C: Monitor
Mirodenafil: CYP3A4 Inducers (Strong) may decrease serum concentration of Mirodenafil. Management: Consider avoiding the concomitant use of mirodenafil and strong CYP3A4 inducers. If combined, monitor for decreased mirodenafil effects. Mirodenafil dose increases may be required to achieve desired effects. Risk D: Consider Therapy Modification
Mirtazapine: CYP3A4 Inducers (Strong) may decrease serum concentration of Mirtazapine. Risk C: Monitor
Mitapivat: CYP3A4 Inducers (Strong) may decrease serum concentration of Mitapivat. Risk X: Avoid
Mobocertinib: CYP3A4 Inducers (Strong) may decrease serum concentration of Mobocertinib. CYP3A4 Inducers (Strong) may decrease active metabolite exposure of Mobocertinib. Risk X: Avoid
Monoamine Oxidase Inhibitors: CarBAMazepine may increase adverse/toxic effects of Monoamine Oxidase Inhibitors. Management: Do not use carbamazepine during, or within 14 days of discontinuing, treatment with a monoamine oxidase inhibitor. Risk X: Avoid
Montelukast: CYP3A4 Inducers (Strong) may decrease serum concentration of Montelukast. Risk C: Monitor
Mosunetuzumab: May increase serum concentration of CYP Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors). Risk C: Monitor
Naldemedine: CYP3A4 Inducers (Strong) may decrease serum concentration of Naldemedine. Risk X: Avoid
Naloxegol: CYP3A4 Inducers (Strong) may decrease serum concentration of Naloxegol. Risk X: Avoid
Nateglinide: CYP3A4 Inducers (Strong) may decrease serum concentration of Nateglinide. Risk C: Monitor
Nefazodone: May increase serum concentration of CarBAMazepine. Also, concentrations of the active CarBAMazepine epoxide metabolite may be reduced. CarBAMazepine may decrease serum concentration of Nefazodone. Concentrations of active Nefazodone metabolites may also be reduced. Risk X: Avoid
Nelfinavir: CYP3A4 Inducers (Strong) may decrease serum concentration of Nelfinavir. Risk C: Monitor
Neratinib: CYP3A4 Inducers (Strong) may decrease serum concentration of Neratinib. Risk X: Avoid
Netupitant: CYP3A4 Inducers (Strong) may decrease serum concentration of Netupitant. Risk X: Avoid
Neuromuscular-Blocking Agents (Nondepolarizing): CarBAMazepine may decrease serum concentration of Neuromuscular-Blocking Agents (Nondepolarizing). Risk C: Monitor
Nevirapine: CarBAMazepine may decrease serum concentration of Nevirapine. Risk X: Avoid
NiCARdipine: CYP3A4 Inducers (Strong) may decrease serum concentration of NiCARdipine. Risk C: Monitor
NIFEdipine (Topical): CYP3A4 Inducers (Strong) may decrease serum concentration of NIFEdipine (Topical). Risk C: Monitor
NIFEdipine: CYP3A4 Inducers (Strong) may decrease serum concentration of NIFEdipine. Management: Avoid coadministration of nifedipine with strong CYP3A4 inducers when possible and if combined, monitor patients closely for clinical signs of diminished nifedipine response. Risk D: Consider Therapy Modification
Nilotinib: CYP3A4 Inducers (Strong) may decrease serum concentration of Nilotinib. Risk X: Avoid
Nilvadipine: CYP3A4 Inducers (Strong) may decrease serum concentration of Nilvadipine. Risk C: Monitor
NiMODipine: CYP3A4 Inducers (Strong) may decrease serum concentration of NiMODipine. Risk X: Avoid
Nintedanib: Inducers of CYP3A4 (Strong) and P-glycoprotein may decrease serum concentration of Nintedanib. Risk X: Avoid
Nirmatrelvir and Ritonavir: May increase serum concentration of CarBAMazepine. CarBAMazepine may decrease serum concentration of Nirmatrelvir and Ritonavir. Risk X: Avoid
Nirogacestat: CYP3A4 Inducers (Strong) may decrease serum concentration of Nirogacestat. Risk X: Avoid
Nisoldipine: CYP3A4 Inducers (Strong) may decrease serum concentration of Nisoldipine. Risk X: Avoid
Nitrazepam: CYP3A4 Inducers (Strong) may decrease serum concentration of Nitrazepam. Risk C: Monitor
OLANZapine: CarBAMazepine may decrease serum concentration of OLANZapine. Risk C: Monitor
Olaparib: CYP3A4 Inducers (Strong) may decrease serum concentration of Olaparib. Risk X: Avoid
Oliceridine: CYP3A4 Inducers (Strong) may decrease serum concentration of Oliceridine. Risk C: Monitor
Olmutinib: CYP3A4 Inducers (Strong) may decrease serum concentration of Olmutinib. Risk C: Monitor
Olutasidenib: CYP3A4 Inducers (Strong) may decrease serum concentration of Olutasidenib. Risk X: Avoid
Omaveloxolone: CYP3A4 Inducers (Strong) may decrease serum concentration of Omaveloxolone. Risk X: Avoid
Omeprazole: CarBAMazepine may decrease serum concentration of Omeprazole. Omeprazole may increase serum concentration of CarBAMazepine. Risk C: Monitor
Ondansetron: CYP3A4 Inducers (Strong) may decrease serum concentration of Ondansetron. Risk C: Monitor
Opipramol: Antiseizure Agents may decrease serum concentration of Opipramol. Risk C: Monitor
Orlistat: May decrease serum concentration of Antiseizure Agents. Risk C: Monitor
Osilodrostat: CYP3A4 Inducers (Strong) may decrease serum concentration of Osilodrostat. Risk C: Monitor
Osimertinib: CYP3A4 Inducers (Strong) may decrease serum concentration of Osimertinib. Management: Avoid coadministration of osimertinib and strong CYP3A4 inducers if possible. If coadministration is unavoidable, increase osimertinib to 160 mg daily. Reduce osimertinib to 80 mg daily 3 weeks after discontinuation of the strong CYP3A4 inducer. Risk D: Consider Therapy Modification
OXcarbazepine: CYP3A4 Inducers (Strong) may decrease serum concentration of OXcarbazepine. Specifically, the concentrations of the 10-monohydroxy active metabolite of oxcarbazepine may be decreased. Risk C: Monitor
OxyCODONE: CYP3A4 Inducers (Strong) may decrease serum concentration of OxyCODONE. Risk C: Monitor
PACLitaxel (Conventional): CYP3A4 Inducers (Strong) may decrease serum concentration of PACLitaxel (Conventional). Risk C: Monitor
PACLitaxel (Protein Bound): CYP3A4 Inducers (Strong) may decrease serum concentration of PACLitaxel (Protein Bound). Risk C: Monitor
Pacritinib: CYP3A4 Inducers (Strong) may decrease serum concentration of Pacritinib. Risk X: Avoid
Palbociclib: CYP3A4 Inducers (Strong) may decrease serum concentration of Palbociclib. Risk X: Avoid
Paliperidone: P-glycoprotein/ABCB1 Inducers may decrease serum concentration of Paliperidone. Management: Avoid coadministration of extended-release injectable paliperidone and P-gp inducers. If coadministration is required, consider use of paliperidone extended-release tablets, monitor for reduced paliperidone effects, and increase the dose as needed. Risk D: Consider Therapy Modification
Palovarotene: CYP3A4 Inducers (Strong) may decrease serum concentration of Palovarotene. Risk X: Avoid
Panobinostat: CYP3A4 Inducers (Strong) may decrease serum concentration of Panobinostat. Risk X: Avoid
PAZOPanib: CYP3A4 Inducers (Strong) may decrease serum concentration of PAZOPanib. Risk X: Avoid
Pemigatinib: CYP3A4 Inducers (Strong) may decrease serum concentration of Pemigatinib. Risk X: Avoid
Perampanel: CYP3A4 Inducers (Strong) may decrease serum concentration of Perampanel. Management: Increase perampanel starting dose to 4 mg/day if used with strong CYP3A4 inducers. Increase perampanel dose by 2 mg/day no more than once weekly based on response and tolerability. Dose adjustments may be needed if the inducer is discontinued. Risk D: Consider Therapy Modification
Perazine: CYP3A4 Inducers (Strong) may decrease serum concentration of Perazine. Risk C: Monitor
Pexidartinib: CYP3A4 Inducers (Strong) may decrease serum concentration of Pexidartinib. Risk X: Avoid
Pimavanserin: CYP3A4 Inducers (Strong) may decrease serum concentration of Pimavanserin. Risk X: Avoid
Piperaquine: CYP3A4 Inducers (Strong) may decrease serum concentration of Piperaquine. Risk X: Avoid
Pirtobrutinib: CYP3A4 Inducers (Strong) may decrease serum concentration of Pirtobrutinib. Risk X: Avoid
Pitolisant: CYP3A4 Inducers (Strong) may decrease serum concentration of Pitolisant. Management: If on a stable pitolisant dose of 8.9 mg or 17.8 mg/day and starting a strong CYP3A4 inducer, double the pitolisant dose over 7 days (ie, to either 17.8 mg/day or 35.6 mg/day, respectively). Reduce pitolisant dose by 50% when the inducer is discontinued. Risk D: Consider Therapy Modification
Polatuzumab Vedotin: CYP3A4 Inducers (Strong) may decrease serum concentration of Polatuzumab Vedotin. Exposure to unconjugated MMAE, the cytotoxic small molecule component of polatuzumab vedotin, may be decreased. Risk C: Monitor
PONATinib: CYP3A4 Inducers (Strong) may decrease serum concentration of PONATinib. Management: Avoid coadministration of ponatinib with strong CYP3A4 inducers unless the potential benefit of concomitant treatment outweighs the risk of reduced ponatinib exposure. Monitor patients for reduced ponatinib efficacy if combined. Risk D: Consider Therapy Modification
Pralsetinib: CYP3A4 Inducers (Strong) may decrease serum concentration of Pralsetinib. Management: Avoid concomitant use of pralsetinib with strong CYP3A4 inducers when possible. If combined, increase the starting dose of pralsetinib to double the current pralsetinib dosage starting on day 7 of coadministration. Risk D: Consider Therapy Modification
Pravastatin: CarBAMazepine may decrease serum concentration of Pravastatin. Risk C: Monitor
Praziquantel: CYP3A4 Inducers (Strong) may decrease serum concentration of Praziquantel. Risk X: Avoid
PrednisoLONE (Systemic): CYP3A4 Inducers (Strong) may decrease serum concentration of PrednisoLONE (Systemic). Risk C: Monitor
PredniSONE: CYP3A4 Inducers (Strong) may decrease serum concentration of PredniSONE. Risk C: Monitor
Pretomanid: CYP3A4 Inducers (Strong) may decrease serum concentration of Pretomanid. Risk X: Avoid
Propacetamol: CarBAMazepine may increase metabolism of Propacetamol. This may 1) diminish the desired effects of propacetamol; and 2) increase the risk of liver damage. Risk C: Monitor
Propafenone: CYP3A4 Inducers (Strong) may decrease serum concentration of Propafenone. Risk C: Monitor
Pyrimethamine: CYP3A4 Inducers (Strong) may decrease serum concentration of Pyrimethamine. Risk C: Monitor
QUEtiapine: CarBAMazepine may decrease serum concentration of QUEtiapine. QUEtiapine may increase active metabolite exposure of CarBAMazepine. Management: Quetiapine dose increases to as much as 5 times the regular dose may be required to maintain therapeutic benefit. Reduce the quetiapine dose back to the previous/regular dose within 7 to 14 days of discontinuing carbamazepine. Risk D: Consider Therapy Modification
QuiNIDine: CYP3A4 Inducers (Strong) may decrease serum concentration of QuiNIDine. Risk C: Monitor
QuiNINE: CarBAMazepine may decrease serum concentration of QuiNINE. QuiNINE may increase serum concentration of CarBAMazepine. Management: Consider alternatives to this combination when possible. If coadministration of carbamazepine and quinine cannot be avoided, monitor for reduced quinine efficacy and for increased carbamazepine serum concentrations and toxicities. Risk D: Consider Therapy Modification
Quizartinib: CYP3A4 Inducers (Strong) may decrease serum concentration of Quizartinib. Risk X: Avoid
Radotinib: CYP3A4 Inducers (Strong) may decrease serum concentration of Radotinib. Management: Consider alternatives to this combination when possible as the risk of radotinib treatment failure may be increased. Risk D: Consider Therapy Modification
Ramelteon: CYP3A4 Inducers (Strong) may decrease serum concentration of Ramelteon. Risk C: Monitor
Ranolazine: CYP3A4 Inducers (Strong) may decrease serum concentration of Ranolazine. Risk X: Avoid
Reboxetine: CYP3A4 Inducers (Strong) may decrease serum concentration of Reboxetine. Risk C: Monitor
Regorafenib: CYP3A4 Inducers (Strong) may decrease serum concentration of Regorafenib. CYP3A4 Inducers (Strong) may increase active metabolite exposure of Regorafenib. Risk X: Avoid
Relugolix, Estradiol, and Norethindrone: Inducers of CYP3A4 (Strong) and P-glycoprotein may decrease serum concentration of Relugolix, Estradiol, and Norethindrone. Risk X: Avoid
Relugolix: Inducers of CYP3A4 (Strong) and P-glycoprotein may decrease serum concentration of Relugolix. Management: Avoid use of relugolix with drugs that are both strong CYP3A4 and P-glycoprotein (P-gp) inducer. If combined, increase the dose of relugolix to 240 mg once daily. Reduce back to 120 mg daily once the combined inducer is discontinued. Risk D: Consider Therapy Modification
Repaglinide: CYP3A4 Inducers (Strong) may decrease serum concentration of Repaglinide. Risk C: Monitor
Repotrectinib: CYP3A4 Inducers (Strong) may decrease serum concentration of Repotrectinib. Risk X: Avoid
Revumenib: CYP3A4 Inducers (Strong) may decrease serum concentration of Revumenib. Risk X: Avoid
Ribociclib: CYP3A4 Inducers (Strong) may decrease serum concentration of Ribociclib. Risk X: Avoid
Rifabutin: CYP3A4 Inducers (Strong) may decrease serum concentration of Rifabutin. Risk C: Monitor
Rilpivirine: CarBAMazepine may decrease serum concentration of Rilpivirine. Risk X: Avoid
Rimegepant: CYP3A4 Inducers (Strong) may decrease serum concentration of Rimegepant. Risk X: Avoid
Riociguat: CYP3A4 Inducers (Strong) may decrease serum concentration of Riociguat. Risk C: Monitor
Ripretinib: CYP3A4 Inducers (Strong) may decrease serum concentration of Ripretinib. Risk X: Avoid
RisperiDONE: CYP3A4 Inducers (Strong) may decrease serum concentration of RisperiDONE. CYP3A4 Inducers (Strong) may decrease active metabolite exposure of RisperiDONE. Management: Careful monitoring for reduced risperidone efficacy and possible dose adjustment are recommended when combined with strong CYP3A4 inducers. See full interaction monograph for details. Risk D: Consider Therapy Modification
Ritlecitinib: CYP3A4 Inducers (Strong) may decrease serum concentration of Ritlecitinib. Risk X: Avoid
Ritonavir: CarBAMazepine may decrease serum concentration of Ritonavir. Ritonavir may increase serum concentration of CarBAMazepine. Management: Consider avoiding this combination due to the potential for decreased ritonavir concentrations and the possible development of resistance. If combined, monitor for increased carbamazepine concentrations and effects and decreased ritonavir effects. Risk D: Consider Therapy Modification
Rivaroxaban: Inducers of CYP3A4 (Strong) and P-glycoprotein may decrease serum concentration of Rivaroxaban. Risk X: Avoid
Roflumilast (Systemic): CYP3A4 Inducers (Strong) may decrease serum concentration of Roflumilast (Systemic). CYP3A4 Inducers (Strong) may decrease active metabolite exposure of Roflumilast (Systemic). Risk X: Avoid
Rolapitant: CYP3A4 Inducers (Strong) may decrease serum concentration of Rolapitant. Risk X: Avoid
RomiDEPsin: CYP3A4 Inducers (Strong) may decrease serum concentration of RomiDEPsin. Risk X: Avoid
Rosuvastatin: CarBAMazepine may decrease serum concentration of Rosuvastatin. Risk C: Monitor
Rufinamide: May decrease serum concentration of CarBAMazepine. CarBAMazepine may decrease serum concentration of Rufinamide. Risk C: Monitor
Ruxolitinib (Systemic): CYP3A4 Inducers (Strong) may decrease serum concentration of Ruxolitinib (Systemic). CYP3A4 Inducers (Strong) may increase active metabolite exposure of Ruxolitinib (Systemic). Risk C: Monitor
Sacituzumab Govitecan: UGT1A1 Inducers may decrease active metabolite exposure of Sacituzumab Govitecan. Specifically, concentrations of SN-38 may be decreased. Risk X: Avoid
Samidorphan: CYP3A4 Inducers (Strong) may decrease serum concentration of Samidorphan. Risk X: Avoid
Saquinavir: CarBAMazepine may decrease serum concentration of Saquinavir. Risk X: Avoid
SAXagliptin: CYP3A4 Inducers (Strong) may decrease serum concentration of SAXagliptin. Risk C: Monitor
Seladelpar: CarBAMazepine may decrease serum concentration of Seladelpar. Risk C: Monitor
Selpercatinib: CYP3A4 Inducers (Strong) may decrease serum concentration of Selpercatinib. Risk X: Avoid
Selumetinib: CYP3A4 Inducers (Strong) may decrease serum concentration of Selumetinib. Risk X: Avoid
Sertindole: CYP3A4 Inducers (Strong) may decrease serum concentration of Sertindole. Risk C: Monitor
Sertraline: CarBAMazepine may decrease serum concentration of Sertraline. Risk C: Monitor
Sildenafil: CYP3A4 Inducers (Strong) may decrease serum concentration of Sildenafil. Risk C: Monitor
Simeprevir: CYP3A4 Inducers (Strong) may decrease serum concentration of Simeprevir. Risk X: Avoid
Simvastatin: CYP3A4 Inducers (Strong) may decrease serum concentration of Simvastatin. Risk C: Monitor
Siponimod: CarBAMazepine may decrease serum concentration of Siponimod. Risk X: Avoid
Sirolimus (Conventional): CYP3A4 Inducers (Strong) may decrease serum concentration of Sirolimus (Conventional). Management: Avoid concomitant use of strong CYP3A4 inducers and sirolimus if possible. If combined, monitor for reduced serum sirolimus concentrations. Sirolimus dose increases will likely be necessary to prevent subtherapeutic sirolimus levels. Risk D: Consider Therapy Modification
Sirolimus (Protein Bound): CYP3A4 Inducers (Strong) may decrease serum concentration of Sirolimus (Protein Bound). Risk X: Avoid
Sofosbuvir: P-glycoprotein/ABCB1 Inducers may decrease serum concentration of Sofosbuvir. Risk X: Avoid
Solifenacin: CYP3A4 Inducers (Strong) may decrease serum concentration of Solifenacin. Risk C: Monitor
Sonidegib: CYP3A4 Inducers (Strong) may decrease serum concentration of Sonidegib. Risk X: Avoid
SORAfenib: CYP3A4 Inducers (Strong) may decrease serum concentration of SORAfenib. Risk X: Avoid
Sotorasib: CYP3A4 Inducers (Strong) may decrease serum concentration of Sotorasib. Risk X: Avoid
Sparsentan: CYP3A4 Inducers (Strong) may decrease serum concentration of Sparsentan. Risk X: Avoid
Spironolactone: May increase serum concentration of CYP3A4 Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors). Risk C: Monitor
Stiripentol: CarBAMazepine may decrease serum concentration of Stiripentol. Stiripentol may increase serum concentration of CarBAMazepine. Management: Avoid the use of stiripentol and carbamazepine when possible. If combined, monitor for both reduced stiripentol efficacy and increased carbamazepine concentrations and toxicities. Dose adjustments of both drugs may be needed. Risk D: Consider Therapy Modification
SUFentanil: CYP3A4 Inducers (Strong) may decrease serum concentration of SUFentanil. Management: If a strong CYP3A4 inducer is initiated in a patient on sufentanil, consider a sufentanil dose increase and monitor for decreased sufentanil effects and opioid withdrawal symptoms. Risk D: Consider Therapy Modification
Sulthiame: CarBAMazepine may decrease serum concentration of Sulthiame. Risk C: Monitor
SUNItinib: CYP3A4 Inducers (Strong) may decrease serum concentration of SUNItinib. Management: Avoid when possible. If combined, increase sunitinib dose to a max of 87.5 mg daily when treating GIST or RCC. Increase sunitinib dose to a max of 62.5 mg daily when treating PNET. Monitor patients for both reduced efficacy and increased toxicities. Risk D: Consider Therapy Modification
Suvorexant: CYP3A4 Inducers (Strong) may decrease serum concentration of Suvorexant. Risk C: Monitor
Suzetrigine: CYP3A4 Inducers (Strong) may decrease serum concentration of Suzetrigine. Risk X: Avoid
Tacrolimus (Systemic): CYP3A4 Inducers (Strong) may decrease serum concentration of Tacrolimus (Systemic). Management: Tacrolimus dose increases will likely be needed during concomitant use with strong CYP3A4 inducers. Monitor more closely and frequently for decreased tacrolimus concentrations and effects when combined. Risk D: Consider Therapy Modification
Tadalafil: CYP3A4 Inducers (Strong) may decrease serum concentration of Tadalafil. Management: Erectile dysfunction or benign prostatic hypertrophy: monitor for decreased effectiveness - no standard dose adjustment is recommended. Avoid use of tadalafil for pulmonary arterial hypertension in patients receiving a strong CYP3A4 inducer. Risk D: Consider Therapy Modification
Talquetamab: May increase serum concentration of CYP Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors). Risk C: Monitor
Tamoxifen: CYP3A4 Inducers (Strong) may decrease serum concentration of Tamoxifen. CYP3A4 Inducers (Strong) may decrease active metabolite exposure of Tamoxifen. Risk X: Avoid
Tarlatamab: May increase serum concentration of CYP Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors). Risk C: Monitor
Tasimelteon: CYP3A4 Inducers (Strong) may decrease serum concentration of Tasimelteon. Risk X: Avoid
Taurursodiol: CYP3A4 Inducers (Strong) may decrease serum concentration of Taurursodiol. Specifically, the concentrations of phenylbutyrate may be decreased. Risk C: Monitor
Tazemetostat: CYP3A4 Inducers (Strong) may decrease serum concentration of Tazemetostat. Risk X: Avoid
Teclistamab: May increase serum concentration of CYP Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors). Risk C: Monitor
Temsirolimus: CYP3A4 Inducers (Strong) may decrease serum concentration of Temsirolimus. CYP3A4 Inducers (Strong) may decrease active metabolite exposure of Temsirolimus. Specifically, concentrations of sirolimus may be decreased. Management: Avoid concomitant use of temsirolimus and strong CYP3A4 inducers. If coadministration is unavoidable, increase temsirolimus dose to 50 mg per week. Resume previous temsirolimus dose after discontinuation of the strong CYP3A4 inducer. Risk D: Consider Therapy Modification
Teniposide: CYP3A4 Inducers (Strong) may decrease serum concentration of Teniposide. Risk C: Monitor
Tenofovir Alafenamide: CarBAMazepine may decrease serum concentration of Tenofovir Alafenamide. Risk X: Avoid
Tetrahydrocannabinol and Cannabidiol: CYP3A4 Inducers (Strong) may decrease serum concentration of Tetrahydrocannabinol and Cannabidiol. Management: Avoid use of the tetrahydrocannabinol/cannabidiol oromucosal spray and strong CYP3A4 inducers when possible. If combined use is necessary, careful titration is recommended, notably within the two weeks following discontinuation of the inducer. Risk D: Consider Therapy Modification
Tetrahydrocannabinol: CYP3A4 Inducers (Strong) may decrease serum concentration of Tetrahydrocannabinol. Risk C: Monitor
Tezacaftor and Ivacaftor: CYP3A4 Inducers (Strong) may decrease serum concentration of Tezacaftor and Ivacaftor. Risk X: Avoid
Theophylline Derivatives: CarBAMazepine may decrease serum concentration of Theophylline Derivatives. Theophylline Derivatives may decrease serum concentration of CarBAMazepine. Management: Seek alternatives to this combination when possible. If these agents are used together, monitor closely for decreased serum concentrations/therapeutic effects of both medications. Risk D: Consider Therapy Modification
Thiotepa: CYP3A4 Inducers (Strong) may increase active metabolite exposure of Thiotepa. CYP3A4 Inducers (Strong) may decrease serum concentration of Thiotepa. Management: Thiotepa prescribing information recommends avoiding concomitant use of thiotepa and strong CYP3A4 inducers. If concomitant use is unavoidable, monitor for adverse effects. Risk D: Consider Therapy Modification
Thiothixene: CarBAMazepine may decrease serum concentration of Thiothixene. Risk C: Monitor
Thyroid Products: CarBAMazepine may decrease serum concentration of Thyroid Products. Risk C: Monitor
TiaGABine: CYP3A4 Inducers (Strong) may decrease serum concentration of TiaGABine. Risk C: Monitor
Ticagrelor: CYP3A4 Inducers (Strong) may decrease serum concentration of Ticagrelor. CYP3A4 Inducers (Strong) may decrease active metabolite exposure of Ticagrelor. Risk X: Avoid
Tipranavir: CYP3A4 Inducers (Strong) may decrease serum concentration of Tipranavir. Risk C: Monitor
Tivozanib: CYP3A4 Inducers (Strong) may decrease serum concentration of Tivozanib. Risk X: Avoid
Tofacitinib: CYP3A4 Inducers (Strong) may decrease serum concentration of Tofacitinib. Risk X: Avoid
Tolvaptan: CYP3A4 Inducers (Strong) may decrease serum concentration of Tolvaptan. Risk X: Avoid
Topiramate: May increase CNS depressant effects of CarBAMazepine. CarBAMazepine may decrease serum concentration of Topiramate. Risk C: Monitor
Toremifene: CYP3A4 Inducers (Strong) may decrease serum concentration of Toremifene. CYP3A4 Inducers (Strong) may decrease active metabolite exposure of Toremifene. Risk X: Avoid
Trabectedin: CYP3A4 Inducers (Strong) may decrease serum concentration of Trabectedin. Risk X: Avoid
TraMADol: May decrease therapeutic effects of CarBAMazepine. TraMADol may increase CNS depressant effects of CarBAMazepine. CarBAMazepine may decrease serum concentration of TraMADol. Risk X: Avoid
TraZODone: CarBAMazepine may decrease serum concentration of TraZODone. TraZODone may increase serum concentration of CarBAMazepine. Management: Consider increasing the trazodone dose during coadministration with strong CYP3A4 inducers, such as carbamazepine. In addition, monitor for increased carbamazepine concentrations and effects during coadministration with trazodone. Risk D: Consider Therapy Modification
Treosulfan: May increase serum concentration of CYP3A4 Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors). Risk C: Monitor
Tretinoin (Systemic): CYP3A4 Inducers (Strong) may decrease serum concentration of Tretinoin (Systemic). Management: Avoid use of tretinoin and strong CYP3A4 inducers when possible. If combined, monitor for reduced tretinoin concentrations and efficacy. Risk D: Consider Therapy Modification
Triamcinolone (Systemic): CYP3A4 Inducers (Strong) may decrease serum concentration of Triamcinolone (Systemic). Risk C: Monitor
Triazolam: CYP3A4 Inducers (Strong) may decrease serum concentration of Triazolam. Management: Consider alternatives to this combination when possible. If combined, monitor for reduced triazolam efficacy. Substantial triazolam dose increases will likely be required. Risk D: Consider Therapy Modification
Tricyclic Antidepressants: CarBAMazepine may decrease serum concentration of Tricyclic Antidepressants. Risk C: Monitor
Trofinetide: May increase serum concentration of CYP3A4 Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors). Risk C: Monitor
Tropisetron: CYP3A4 Inducers (Strong) may decrease serum concentration of Tropisetron. Risk C: Monitor
Tucatinib: CYP3A4 Inducers (Strong) may decrease serum concentration of Tucatinib. Risk X: Avoid
Ubrogepant: CYP3A4 Inducers (Strong) may decrease serum concentration of Ubrogepant. Risk X: Avoid
Udenafil: CYP3A4 Inducers (Strong) may decrease serum concentration of Udenafil. Risk C: Monitor
Ulipristal: CYP3A4 Inducers (Strong) may decrease serum concentration of Ulipristal. Risk X: Avoid
Upadacitinib: CYP3A4 Inducers (Strong) may decrease serum concentration of Upadacitinib. Risk X: Avoid
Valbenazine: CYP3A4 Inducers (Strong) may decrease serum concentration of Valbenazine. CYP3A4 Inducers (Strong) may decrease active metabolite exposure of Valbenazine. Risk X: Avoid
Valproic Acid and Derivatives: CarBAMazepine may decrease serum concentration of Valproic Acid and Derivatives. Valproic Acid and Derivatives may increase active metabolite exposure of CarBAMazepine. Parent carbamazepine concentrations may be increased, decreased, or unchanged. Risk C: Monitor
Vandetanib: CYP3A4 Inducers (Strong) may decrease serum concentration of Vandetanib. CYP3A4 Inducers (Strong) may increase active metabolite exposure of Vandetanib. Risk X: Avoid
Vanzacaftor, Tezacaftor, and Deutivacaftor: CYP3A4 Inducers (Strong) may decrease serum concentration of Vanzacaftor, Tezacaftor, and Deutivacaftor. Risk X: Avoid
Vecuronium: CarBAMazepine may decrease serum concentration of Vecuronium. Risk C: Monitor
Velpatasvir: CYP2B6 Inducers (Moderate) may decrease serum concentration of Velpatasvir. Risk X: Avoid
Velpatasvir: CYP3A4 Inducers (Strong) may decrease serum concentration of Velpatasvir. Risk X: Avoid
Vemurafenib: CYP3A4 Inducers (Strong) may decrease serum concentration of Vemurafenib. Management: Avoid coadministration of vemurafenib and strong CYP3A4 inducers if possible. If coadministration is unavoidable, increase the vemurafenib dose by 240 mg as tolerated. Resume prior vemurafenib dose 2 weeks after discontinuation of strong CYP3A4 inducer. Risk D: Consider Therapy Modification
Venetoclax: CYP3A4 Inducers (Strong) may decrease serum concentration of Venetoclax. Risk X: Avoid
Vilazodone: CYP3A4 Inducers (Strong) may decrease serum concentration of Vilazodone. Management: Consider increasing vilazodone dose by as much as 2-fold (do not exceed 80 mg/day), based on response, in patients receiving strong CYP3A4 inducers for > 14 days. Reduce to the original vilazodone dose over 1 to 2 weeks after inducer discontinuation. Risk D: Consider Therapy Modification
VinCRIStine: CYP3A4 Inducers (Strong) may decrease serum concentration of VinCRIStine. Risk X: Avoid
Vinflunine: CYP3A4 Inducers (Strong) may decrease serum concentration of Vinflunine. Risk X: Avoid
Vinorelbine: CYP3A4 Inducers (Strong) may decrease serum concentration of Vinorelbine. Risk C: Monitor
Vitamin K Antagonists: CarBAMazepine may decrease serum concentration of Vitamin K Antagonists. Management: Monitor for decreased INR and effects of vitamin K antagonists if carbamazepine is initiated/dose increased, or increased INR and effects if carbamazepine is discontinued/dose decreased. Vitamin K antagonist dose adjustments will likely be required. Risk D: Consider Therapy Modification
Voclosporin: CYP3A4 Inducers (Strong) may decrease serum concentration of Voclosporin. Risk X: Avoid
Vonoprazan: CYP3A4 Inducers (Strong) may decrease serum concentration of Vonoprazan. Risk X: Avoid
Vorapaxar: CYP3A4 Inducers (Strong) may decrease serum concentration of Vorapaxar. Risk X: Avoid
Voriconazole: CarBAMazepine may decrease serum concentration of Voriconazole. Risk X: Avoid
Vortioxetine: CYP3A4 Inducers (Strong) may decrease serum concentration of Vortioxetine. Management: Consider increasing the vortioxetine dose to no more than 3 times the original dose when used with a strong drug metabolism inducer for more than 14 days. The vortioxetine dose should be returned to normal within 14 days of stopping the strong inducer. Risk D: Consider Therapy Modification
Voxelotor: CYP3A4 Inducers (Strong) may decrease serum concentration of Voxelotor. Management: Avoid concomitant use of voxelotor and strong CYP3A4 inducers. If unavoidable, increase the voxelotor dose to 2,500 mg once daily. For children ages 4 to less than 12 years, weight-based dose adjustments are required. See full monograph for details. Risk D: Consider Therapy Modification
Voxilaprevir: CYP3A4 Inducers (Strong) may decrease serum concentration of Voxilaprevir. Risk X: Avoid
Xanomeline: May increase serum concentration of CYP3A4 Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors). Risk C: Monitor
Zaleplon: CYP3A4 Inducers (Strong) may decrease serum concentration of Zaleplon. Management: Consider the use of an alternative hypnotic that is not metabolized by CYP3A4 in patients receiving strong CYP3A4 inducers. If zaleplon is combined with a strong CYP3A4 inducer, monitor for decreased effectiveness of zaleplon. Risk D: Consider Therapy Modification
Zanubrutinib: CYP3A4 Inducers (Strong) may decrease serum concentration of Zanubrutinib. Risk X: Avoid
Zavegepant: OATP1B1/1B3 (SLCO1B1/1B3) Inducers may decrease serum concentration of Zavegepant. Risk X: Avoid
Ziprasidone: CYP3A4 Inducers (Strong) may decrease serum concentration of Ziprasidone. Risk C: Monitor
Zolpidem: CYP3A4 Inducers (Strong) may decrease serum concentration of Zolpidem. Risk C: Monitor
Zonisamide: CYP3A4 Inducers (Strong) may decrease serum concentration of Zonisamide. Risk C: Monitor
Zopiclone: CarBAMazepine may increase CNS depressant effects of Zopiclone. CarBAMazepine may decrease serum concentration of Zopiclone. Risk C: Monitor
Zuclopenthixol: CYP3A4 Inducers (Strong) may decrease serum concentration of Zuclopenthixol. Risk C: Monitor
Zuranolone: CYP3A4 Inducers (Strong) may decrease serum concentration of Zuranolone. Risk X: Avoid
Carbamazepine serum levels may be increased if taken with food and/or grapefruit juice. Management: Monitor for increased toxic effects with concurrent ingestion of grapefruit juice. Maintain adequate hydration, unless instructed to restrict fluid intake.
Carbamazepine can increase the metabolism of hormonal contraceptives, decreasing their plasma concentrations and effectiveness. A barrier method of contraception is recommended in addition to the combination hormonal contraceptive when an enzyme-inducing antiseizure medication such as carbamazepine is used in patients who could become pregnant (ACOG 2020). Consult drug interactions database for more detailed information related to the use of carbamazepine and specific contraceptives.
Agents other than carbamazepine should be considered to treat people with epilepsy of childbearing potential (Pack 2024). Manage epilepsy in patients who could become pregnant based on a shared decision-making process that optimizes seizure control and considers the possibility of pregnancy during treatment (Pack 2024). Regularly discuss age-specific and developmental needs, including pregnancy planning and contraceptive options during the patient’s reproductive lifespan (ACOG 2020; NICE 2022). Obtain baseline concentrations of carbamazepine and the active metabolite twice prior to pregnancy while the patient has stable seizure control and is on a minimal dose (Arfman 2020).
Evaluate pregnancy status and provide preconception counseling prior to initiating treatment for bipolar disorder in patients who could become pregnant (BAP [McAllister-Williams 2017]; CANMAT [Yatham 2018]). Patients effectively treated may continue their current medication when planning a pregnancy unless contraindications exist (ACOG 2023; BAP [McAllister-Williams 2017]); the lowest effective dose and avoidance of polytherapy is recommended (CANMAT [Yatham 2018]). Carbamazepine should not be initiated for the first time in a patient planning to become pregnant; consider transitioning to another agent prior to pregnancy in patients already taking carbamazepine for bipolar disorder (ACOG 2023; BAP [McAllister-Williams 2017]). Manage mental health conditions in patients who could become pregnant based on a shared decision-making process that considers the possibility of pregnancy during treatment and the risks of discontinuing therapy (ACOG 2023; BAP [McAllister-Williams 2017]; CANMAT [Yatham 2018]).
Carbamazepine crosses the placenta (Schmidt 2023). Umbilical cord concentrations of carbamazepine and the active epoxide metabolite are highly variable but correlate with maternal serum concentrations (Kacirova 2016).
Carbamazepine may be associated with an increased risk of major congenital malformations compared to some other antiseizure medications (Battino 2024; Bromley 2023; Cohen 2023; Pack 2024). Teratogenic events associated with carbamazepine include spina bifida, craniofacial defects, and cardiovascular malformations. Children exposed in utero to carbamazepine monotherapy likely have a lower prevalence of autism spectrum disorder compared to some other antiseizure medications (Dreier 2023; Pack 2024). Screen for major congenital malformations and monitor fetal growth when antiseizure medications are used during pregnancy. Conduct age-appropriate developmental screening in children who had in utero exposure to antiseizure medications (Pack 2024).
Due to pregnancy-induced physiologic changes, some pharmacokinetic properties of carbamazepine may be altered; however, it is not clear if changes are clinically significant (Arfman 2020; Pennell 2022; Schoretsanitis 2024). Based on available data, some recommendations suggest adjusting the dose of carbamazepine based on clinical features, seizure risk, and previous doses (Arfman 2020). Guidelines recommend monitoring concentrations of antiseizure medications during pregnancy and adjusting doses based on decreasing concentrations and seizure control (Pack 2024). Formulate a plan to return to prepregnancy doses after delivery (NICE 2022)
Epilepsy is associated with adverse maternal and fetal outcomes (Kuang 2024; Mazzone 2023). Convulsive seizures should be minimized to reduce risks to the fetus and pregnant patient. Use caution if removing or replacing an effective seizure medication in patients who become pregnant during therapy. Folic acid supplementation prior to and during pregnancy minimizes the risk of congenital malformations and poor neurodevelopment (Pack 2024).
Untreated bipolar disorder is associated with fetal growth restriction, preterm birth, adverse neurodevelopment, and may increase the risk of postpartum psychosis, worsening mood, and postpartum hospitalization. Discontinuing effective medications during pregnancy increases the risk of symptom relapse. Patients effectively treated for bipolar disorder prepregnancy may use the same medication during pregnancy unless contraindications exist. Management of mental health conditions should be made as part of a shared decision-making process. Treatment should not be withheld or discontinued based only on pregnancy status. When medications are used, the lowest effective dose of a single agent is recommended. Optimize dosing prior to changing a medication or adding additional agents whenever possible. Close monitoring for symptom improvement with a validated screening tool during pregnancy is recommended. Manage side effects as needed (ACOG 2023). Agents other than carbamazepine are preferred if treatment for bipolar disorder is initiated during pregnancy (BAP [McAllister-Williams 2017]). Data collection to monitor pregnancy outcomes following exposure to antiepileptic drugs is ongoing. Encourage patients to enroll in the North American Antiepileptic Drug (NAAED) Pregnancy Registry (1-888-233-2334 or https://www.aedpregnancyregistry.org).
Carbamazepine and its active epoxide metabolite are present in breast milk.
Data related to the presence of carbamazepine and the active metabolite, carbamazepine epoxide, in breast milk are available from multiple reports summarized in review articles (Schmidt 2023; Shawahna 2022). Carbamazepine can also be detected in the serum of breastfed infants (Schmidt 2023).
• 2 studies evaluated carbamazepine and carbamazepine epoxide concentrations in breast milk, maternal serum, and newborn serum of breastfed infants at a center following requests for therapeutic drug monitoring. In both studies, the median dose of carbamazepine was 600 mg/day and sampling generally occurred prior to the morning dose:
– Carbamazepine and carbamazepine epoxide concentrations were evaluated between 1 and 5 days postpartum in one study, which included 162 mothers and 135 breastfed newborns. A complete set of carbamazepine breast milk (colostrum) and maternal, infant serum concentrations were available from 123 mother infant pairs. Carbamazepine epoxide concentrations were also measured in 122 women and 97 newborns. Median carbamazepine concentrations were 4.6 mg/L (maternal serum), 2.2 mg/L (breast milk), 0.5 mg/L (infant serum). Median carbamazepine epoxide concentrations were 4.4 mg/L (maternal serum), 0.7 mg/L (breast milk), and 0.3 mg/L (infant serum) (Kacirova 2022).
– The second study evaluated carbamazepine epoxide concentrations between 6 and 29 days postpartum (median 7 days). This study included 66 mothers and 63 breastfed newborns. Median carbamazepine concentrations were 4.5 mg/L (maternal serum), 2.1 mg/L (breast milk), 0.5 mg/L (infant serum). Median carbamazepine epoxide concentrations were 0.9 mg/L (maternal serum), 0.5 mg/L (breast milk), and 0.3 mg/L (infant serum) (Kacirova 2021).
• In both studies, breast milk concentrations of carbamazepine and carbamazepine epoxide were significantly correlated to maternal serum concentrations. Infant serum concentrations of carbamazepine were lower than the limit of quantification (<1 mg/L) in 53% of infants in the study conducted immediately postpartum and 65% of infants in the second study. Maternal serum concentrations of carbamazepine were decreased with concomitant use of enzyme inducing antiseizure medications as expected. Authors of the studies concluded that routine monitoring of infant serum following exposure to carbamazepine via breast milk would not be needed unless signs of carbamazepine toxicity are observed (Kacirova 2021; Kacirova 2022).
• Maternal and infant serum concentrations were evaluated in a study of patients taking carbamazepine for epilepsy during pregnancy and postpartum. The median maternal dose of carbamazepine was 600 mg/day (range 400 to 1,100 mg/day), and sampling occurred in 11 mothers and their breastfed infants between 6 and 17 weeks' postpartum (median 12 weeks). The median carbamazepine concentrations were 6.7 mg/L (maternal serum), 0.35 mg/L (infant serum) and median carbamazepine epoxide concentrations were 1.3 mg/L (maternal serum) and 0.05 mg/L (infant serum). Breast milk was not sampled in this study (Birnbaum 2020).
• Carbamazepine has also been detected in a breastfed infant following maternal use during the postpartum period only. 3 months postpartum, while taking carbamazepine 200 mg in the morning and 300 mg in the evening, carbamazepine serum concentrations (14 hours after a dose) were 4.7 mg/L (mother) and 0.7 mg/L (infant) (Wisner 1998).
Product labeling notes hepatitis, poor weight gain, regurgitation, and vomiting have been reported in infants exposed to carbamazepine via breast milk; however, the relationship between these adverse events and carbamazepine exposure are not clear (Tomson 2022).
Based on available data, poorer developmental outcomes have not been observed in breastfed children exposed to carbamazepine (Tomson 2022).
• Exposure to antiseizure medications via breast milk was not found to impair long term cognitive development in a prospective observational study that included 181 children of 177 mothers who took carbamazepine, lamotrigine, phenytoin, or valproate monotherapy during pregnancy. Cognitive outcomes in children at 6 years of age who were breastfed (n=78) were compared to those who were not (n=103). In the carbamazepine group, 23 infants were breastfed and 24 were not; the mean duration of breastfeeding was 6.9 months. The average maternal dose of carbamazepine during pregnancy was 750 mg in patients who breastfed and 851 mg in patients who did not. The study found no adverse cognitive outcomes in breastfed children at 6 years of age across all antiseizure medications (mean IQ score breastfed: 108; not breastfed 104; p= 0.04). The mean IQ scores for children in the carbamazepine group were 107 (breastfed) and 105 (not breastfed; p= 0.61) (Meador 2014).
• These results are similar to those of another study with a different cohort at age 3 years (Veiby 2013).
According to the manufacturer, the decision to breastfeed during therapy should consider the risk of infant exposure, the benefits of breastfeeding to the infant, and the benefits of treatment to the mother. Monitor infants exposed to antiseizure medications for sedation, signs of poor sucking, proper weight gain, abnormal platelet counts, abnormal liver function, and achievement of developmental milestones (Shawahna 2022; Tomson 2022). Measure antiseizure medication serum concentrations in the infant if symptoms of toxicity occur (Tomson 2022).
Formulate a plan to return to prepregnancy doses if the dose of carbamazepine was changed during pregnancy; gradual dose adjustments and maternal therapeutic drug monitoring are recommended (Arfman 2020, NICE 2022)
Folate and vitamin B: Carbamazepine use has been associated with low serum concentrations of folate, vitamin B2 (riboflavin), B6 (pyridoxine) and B12 (cyanocobalamin), which may contribute to hyperhomocysteinemia. Hyperhomocysteinemia may contribute to cardiovascular disease, venous thromboembolic disease, dementia, neuropsychiatric symptoms, and poor seizure control. Some health care providers recommend administering folic acid, riboflavin, pyridoxine, and cyanocobalamin supplements in patients taking carbamazepine (Apeland 2003; Apeland 2008; Belcastro 2012; Bochyńska 2012).
Baseline and periodic: CBC with platelet count and differential, reticulocytes, serum iron, liver and renal function tests, urinalysis, BUN, serum sodium, ophthalmic exam including intraocular pressure.
As appropriate: Lipid panel, serum carbamazepine levels, carbamazepine-10,11 epoxide levels, thyroid function tests; pregnancy test; observe patient for excessive sedation, especially when instituting or increasing therapy; signs of rash; HLA-B*1502 and HLA-A*3101 genotype screening prior to therapy initiation in patients with ancestry in genetically at-risk populations; suicidality (eg, suicidal thoughts, depression, behavioral changes)
Timing of serum samples: Oral absorption is slow, peak levels occur 8 to 65 hours after ingestion of the first dose; the half-life ranges from 8 to 60 hours, therefore, steady-state is achieved in 2 to 5 days. Serum levels are particularly important during the first few weeks of therapy when autoinduction is occurring (Stoner 2007).
Timing of serum samples: Obtain trough concentration just before next dose. For patients on chronic therapy, after autoinduction has occurred (3 to 5 weeks after initiation of a fixed carbamazepine regimen), steady-state concentrations are achieved in 2 to 4 days (Patsalos 2018, manufacturer’s labeling).
Therapeutic concentration:
Total carbamazepine:
Epilepsy: 4 to 12 mcg/mL (SI: 17 to 51 micromole/L).
Bipolar disorder: 4 to 12 mcg/mL (SI: 17 to 51 micromole/L); the same goal range for epilepsy is applied for bipolar disorder, despite limited data on monitoring serum concentrations in this population (APA [Hirschfeld 2002]).
Free carbamazepine: May consider free (unbound) carbamazepine serum concentrations in patients with renal or hepatic disorders or hypoalbuminemia, because the amount of free carbamazepine may be increased (Dasgupta 1995, Dasgupta 2002).
Epilepsy: 1 to 3 mcg/mL (SI: 4 to 12.5 micromole/L) (Reimers 2018).
Carbamazepine-10,11 epoxide : 0.4 to 4 mcg/mL (SI: 1.6-16 micromole/L); toxicity may occur at serum concentrations ≥9 mg/L (SI: 35.6 micromole/L) (Burianová 2015).
Toxic concentration: Symptoms of toxicity may occur at therapeutic concentrations, toxicity at lower serum concentrations may occur especially in the setting of drug-drug interactions (Besag 1998, Rowan 2005, Weaver 1988).
In addition to antiseizure effects, carbamazepine has anticholinergic, antineuralgic, antidiuretic, muscle relaxant, antimanic, antidepressive, and antiarrhythmic properties; may depress activity in the nucleus ventralis of the thalamus or decrease synaptic transmission or decrease summation of temporal stimulation leading to neural discharge by limiting influx of sodium ions across cell membrane or other unknown mechanisms; stimulates the release of ADH and potentiates its action in promoting reabsorption of water; chemically related to tricyclic antidepressants
Absorption: Slowly from the GI tract
Distribution: Vd: Neonates: 1.52 ± 0.5 L/kg (Rey 1979); Children: 1.94 ± 0.8 L/kg (Rey 1979); Adults: 0.59 to 2 L/kg
Protein binding: Carbamazepine: 75% to 90%, bound to alpha1-acid glycoprotein and nonspecific binding sites on albumin; may be decreased in newborns; Epoxide metabolite: 50%
Metabolism: Induces liver enzymes to increase metabolism and shorten half-life over time; metabolized in the liver by cytochrome P450 3A4 to active epoxide metabolite; epoxide metabolite is metabolized by epoxide hydrolase to the trans-diol metabolite; ratio of serum epoxide to carbamazepine concentrations may be higher in patients receiving polytherapy (vs monotherapy) and in infants (vs older children); boys may have faster carbamazepine clearances and may, therefore, require higher mg/kg/day doses of carbamazepine compared to girls of similar age and weight
Bioavailability: 75% to 85%; relative bioavailability of ER tablet to suspension: 89%
Half-life elimination: Note: Half-life is variable because of autoinduction which is usually complete 3 to 5 weeks after initiation of a fixed carbamazepine regimen.
Carbamazepine: Initial: 25 to 65 hours; Extended release: 35 to 40 hours; Multiple doses: Children and Adolescents: Mean range: 3.1 to 20.8 hours (Battino 1995); Adults: 12 to 17 hours
Epoxide metabolite: Initial: 34 ± 9 hours
Time to peak, serum: Unpredictable:
Immediate release: Multiple doses: Suspension: 1.5 hour; tablet: 4 to 5 hours
Extended release: Carbatrol, Equetro: 12 to 26 hours (single dose), 4 to 8 hours (multiple doses); Tegretol-XR: 3 to 12 hours
Excretion: Urine 72% (1% to 3% as unchanged drug); feces (28%)
