Version November 2024
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.
There are no dosage adjustments provided in the manufacturer's labeling. Use with caution and consider dose reduction; carbamazepine is metabolized primarily in the liver.
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) (Koutsampasopoulos 2014), cardiac arrhythmia, collapse, coronary artery disease (aggravation), edema, heart failure, hypotension, pulmonary embolism, sinus tachycardia (Kasarskis 1992), syncope, thromboembolism, thrombophlebitis
Dermatologic: Acute generalized exanthematous pustulosis (Skalli 2011), alopecia (Ikeda 1997), diaphoresis, dyschromia, erythema multiforme (Upadhyaya 2012), erythema nodosum, erythematous rash, exfoliative dermatitis, maculopapular rash (Hadzić 1990), onychomadesis, pruritic rash, skin photosensitivity, Stevens-Johnson syndrome (Khoo 2016), toxic epidermal necrolysis (Stătescu 2017), urticaria, vitiligo (Assaedi 2022)
Endocrine & metabolic: Acute intermittent porphyria (Yeung Laiwah 1983), albuminuria, decreased serum calcium, decreased thyroid hormones, hirsutism, hyperammonemia (Singh 2015), hyperlipidemia (Mintzer 2020), hyponatremia (Kaeley 2019), porphyria (variegate) (Grieco 2001), porphyria cutanea tarda (Leo 1996), SIADH (Kaeley 2019)
Gastrointestinal: Abdominal pain, anorexia, diarrhea, dysgeusia (Syed 2016), gastric distress, glossitis, glottis edema, pancreatitis (Ali 2021), stomatitis
Genitourinary: Acute urinary retention (Hmouda 2007), azotemia, defective spermatogenesis, glycosuria, impotence, microscopic urine deposits, oliguria, reduced fertility (male), urinary frequency
Hematologic & oncologic: Adenopathy, agranulocytosis (Sobotka 1990), aplastic anemia (Sobotka 1990), bone marrow depression (Sobotka 1990), eosinophilia (Sobotka 1990), hypogammaglobulinemia, leukocytosis (Sobotka 1990), leukopenia (Sobotka 1990), lymphadenopathy (Hadzić 1990), neutropenia (Sobotka 1990), pancytopenia (Sobotka 1990), purpuric disease, thrombocytopenia (Sobotka 1990)
Hepatic: Cholestatic hepatitis (Ganesh 2017), granulomatous hepatitis (Hadzić 1990), hepatic failure (Hadzić 1990), hepatitis (mixed), hepatocellular hepatitis, hepatotoxicity (idiosyncratic) (Chalasani 2021), increased gamma-glutamyl transferase (Hadzagic-Catibusic 2017), increased serum alkaline phosphatase (Hadzagic-Catibusic 2017), increased serum transaminases, intrahepatic cholestasis (vanishing bile duct syndrome), jaundice (Hadzić 1990)
Hypersensitivity: Anaphylaxis, angioedema (Subramanian 2016), drug reaction with eosinophilia and systemic symptoms (Chung 2021), lip edema
Nervous system: Agitation, anxiety (Kennedy 2008), aseptic meningitis (Dang 1996), asterixis (Singh 2015), chills, confusion, depression (Kennedy 2008), fatigue, headache, hyperacusis, involuntary body movements, neuroleptic malignant syndrome (O’Griofa 1991), peripheral neuritis, psychosis (Kennedy 2008), talkativeness, unsteadiness, visual hallucination
Neuromuscular & skeletal: Arthralgia (Hadzić 1990), exacerbation of systemic lupus erythematosus, lower limb cramp, lupus-like syndrome (Kanno 1992, Reiffers-Mettelock 1997), myalgia, osteoporosis
Ophthalmic: Conjunctivitis, diplopia, eye movement disorder, eyelid edema, increased intraocular pressure (Atalay 2014), nystagmus disorder (Fohlen 2022), punctate cataract
Otic: Tinnitus
Renal: Acute kidney injury (Jubert 1994)
Respiratory: Dry throat, laryngeal edema, pulmonary hypersensitivity reaction (Cullinan 1975)
Miscellaneous: Fever (Hadzić 1990)
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 or active liver disease. 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).
• 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.
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, 450 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
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
Suspension (carBAMazepine Oral)
100 mg/5 mL (per mL): $0.17 - $1.33
Suspension (TEGretol Oral)
100 mg/5 mL (per mL): $0.52
Tablet, 12-hour (carBAMazepine ER Oral)
100 mg (per each): $1.10 - $1.14
200 mg (per each): $1.61 - $2.08
400 mg (per each): $3.23 - $4.15
Tablet, 12-hour (TEGretol-XR Oral)
100 mg (per each): $1.93
200 mg (per each): $3.86
400 mg (per each): $7.72
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): $3.61
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.
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: Capsule and tablet, extended release: Some institutions may have specific protocols that conflict with these recommendations; refer to institutional protocols as appropriate. Do not cut, crush, or chew. Switch to IR formulation (tablet, chewable tablet, or oral suspension).
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 CYP2C8 (minor), CYP3A4 (major); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential; Induces BCRP/ABCG2, CYP1A2 (weak), CYP2B6 (moderate), CYP2C9 (weak), CYP3A4 (strong), OATP1B1/1B3 (SLCO1B1/1B3), P-glycoprotein/ABCB1, 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 the serum concentration of Abemaciclib. Risk X: Avoid combination
Abiraterone Acetate: CYP3A4 Inducers (Strong) may decrease the serum concentration of Abiraterone Acetate. Management: Avoid when possible. If the combination cannot be avoided, increase abiraterone acetate dosing frequency from once daily to twice daily during combined use. Reduce abiraterone dose back to the prior dose and frequency once strong inducer is discontinued. Risk D: Consider therapy modification
Acalabrutinib: CYP3A4 Inducers (Strong) may decrease the 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 the metabolism of Acetaminophen. This may 1) diminish the effect of acetaminophen; and 2) increase the risk of liver damage. Risk C: Monitor therapy
Adagrasib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Adagrasib. Risk X: Avoid combination
Adenosine: CarBAMazepine may enhance the adverse/toxic effect 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 therapy
Afatinib: P-glycoprotein/ABCB1 Inducers may decrease the 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 serum concentrations of the active metabolite(s) of Albendazole. Risk C: Monitor therapy
Aldesleukin: May increase the serum concentration of CYP Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors). Risk C: Monitor therapy
Alfacalcidol: CYP3A4 Inducers (Strong) may decrease the serum concentration of Alfacalcidol. Risk C: Monitor therapy
ALfentanil: CYP3A4 Inducers (Strong) may decrease the 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 the serum concentration of Aliskiren. Risk C: Monitor therapy
Alpelisib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Alpelisib. Risk X: Avoid combination
ALPRAZolam: CYP3A4 Inducers (Strong) may decrease the serum concentration of ALPRAZolam. Risk C: Monitor therapy
Amiodarone: CYP3A4 Inducers (Strong) may decrease serum concentrations of the active metabolite(s) of Amiodarone. CYP3A4 Inducers (Strong) may decrease the serum concentration of Amiodarone. Risk C: Monitor therapy
AmLODIPine: CYP3A4 Inducers (Strong) may decrease the serum concentration of AmLODIPine. Risk C: Monitor therapy
Antihepaciviral Combination Products: CYP3A4 Inducers (Strong) may decrease the serum concentration of Antihepaciviral Combination Products. Risk X: Avoid combination
Apixaban: Inducers of CYP3A4 (Strong) and P-glycoprotein may decrease the serum concentration of Apixaban. Risk X: Avoid combination
Apremilast: CYP3A4 Inducers (Strong) may decrease the serum concentration of Apremilast. Risk X: Avoid combination
Aprepitant: CYP3A4 Inducers (Strong) may decrease the serum concentration of Aprepitant. Risk X: Avoid combination
ARIPiprazole: CYP3A4 Inducers (Strong) may decrease the 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
ARIPiprazole Lauroxil: CYP3A4 Inducers (Strong) may decrease serum concentrations of the active metabolite(s) 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
Armodafinil: CarBAMazepine may decrease the serum concentration of Armodafinil. Armodafinil may decrease the serum concentration of CarBAMazepine. Risk C: Monitor therapy
Artemether and Lumefantrine: CYP3A4 Inducers (Strong) may decrease serum concentrations of the active metabolite(s) of Artemether and Lumefantrine. Specifically, concentrations of dihydroartemisinin (DHA), the active metabolite of artemether may be decreased. CYP3A4 Inducers (Strong) may decrease the serum concentration of Artemether and Lumefantrine. Risk X: Avoid combination
Artesunate: CarBAMazepine may decrease serum concentrations of the active metabolite(s) of Artesunate. Risk C: Monitor therapy
Atazanavir: CarBAMazepine may decrease the serum concentration of Atazanavir. Atazanavir may increase the serum concentration of CarBAMazepine. Risk X: Avoid combination
Atogepant: CYP3A4 Inducers (Strong) may decrease the 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 the serum concentration of Atorvastatin. Risk C: Monitor therapy
Avacopan: CarBAMazepine may decrease the serum concentration of Avacopan. Avacopan may increase the serum concentration of CarBAMazepine. Risk X: Avoid combination
Avanafil: CYP3A4 Inducers (Strong) may decrease the serum concentration of Avanafil. Risk X: Avoid combination
Avapritinib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Avapritinib. Risk X: Avoid combination
Axitinib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Axitinib. Risk X: Avoid combination
Barnidipine: CYP3A4 Inducers (Strong) may decrease the serum concentration of Barnidipine. Risk C: Monitor therapy
Bazedoxifene: CarBAMazepine may decrease the 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 therapy
Bedaquiline: CYP3A4 Inducers (Strong) may decrease serum concentrations of the active metabolite(s) of Bedaquiline. CYP3A4 Inducers (Strong) may decrease the serum concentration of Bedaquiline. Risk X: Avoid combination
Belumosudil: CYP3A4 Inducers (Strong) may decrease the 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 the serum concentration of Benidipine. Risk C: Monitor therapy
Benperidol: CYP3A4 Inducers (Strong) may decrease the serum concentration of Benperidol. Risk C: Monitor therapy
Benzhydrocodone: CYP3A4 Inducers (Strong) may decrease the serum concentration of Benzhydrocodone. Specifically, the serum concentrations of hydrocodone may be reduced. Risk C: Monitor therapy
Berotralstat: P-glycoprotein/ABCB1 Inducers may decrease the serum concentration of Berotralstat. Risk X: Avoid combination
Betamethasone (Systemic): CYP3A4 Inducers (Strong) may decrease the serum concentration of Betamethasone (Systemic). Risk C: Monitor therapy
Bictegravir: CarBAMazepine may decrease the 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 the serum concentration of Bisoprolol. Risk C: Monitor therapy
Blonanserin: CYP3A4 Inducers (Strong) may decrease the serum concentration of Blonanserin. Risk C: Monitor therapy
Bortezomib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Bortezomib. Risk X: Avoid combination
Bosutinib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Bosutinib. Risk X: Avoid combination
Brentuximab Vedotin: CYP3A4 Inducers (Strong) may decrease the serum concentration of Brentuximab Vedotin. Specifically, concentrations of the active monomethyl auristatin E (MMAE) component may be decreased. Risk C: Monitor therapy
Brexpiprazole: CYP3A4 Inducers (Strong) may decrease the 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 the serum concentration of Brigatinib. Risk X: Avoid combination
Brivaracetam: May increase serum concentrations of the active metabolite(s) of CarBAMazepine. CarBAMazepine may decrease the serum concentration of Brivaracetam. Risk C: Monitor therapy
Bromocriptine: CYP3A4 Inducers (Strong) may decrease the serum concentration of Bromocriptine. Risk C: Monitor therapy
Bromperidol: CYP3A4 Inducers (Strong) may decrease the serum concentration of Bromperidol. Risk C: Monitor therapy
Brotizolam: CYP3A4 Inducers (Strong) may decrease the serum concentration of Brotizolam. Risk C: Monitor therapy
Bulevirtide: May increase the serum concentration of CYP3A4 Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors). Risk C: Monitor therapy
Buprenorphine: CYP3A4 Inducers (Strong) may decrease the serum concentration of Buprenorphine. Risk C: Monitor therapy
BuPROPion: CYP2B6 Inducers (Moderate) may decrease the serum concentration of BuPROPion. Risk C: Monitor therapy
BusPIRone: CYP3A4 Inducers (Strong) may decrease the 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 the serum concentration of Butorphanol. Risk C: Monitor therapy
Cabazitaxel: CYP3A4 Inducers (Strong) may decrease the serum concentration of Cabazitaxel. Risk C: Monitor therapy
Cabotegravir: UGT1A1 Inducers may decrease the serum concentration of Cabotegravir. Risk X: Avoid combination
Cabozantinib: CYP3A4 Inducers (Strong) may decrease the 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 decrease the serum concentration of Calcifediol. Risk C: Monitor therapy
Calcitriol (Systemic): CYP3A4 Inducers (Strong) may decrease the serum concentration of Calcitriol (Systemic). Risk C: Monitor therapy
Calcium Channel Blockers (Nondihydropyridine): May increase the serum concentration of CarBAMazepine. CarBAMazepine may decrease the 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 concentrations of the active metabolite(s) of Cannabidiol. CYP3A4 Inducers (Strong) may decrease the serum concentration of Cannabidiol. Risk C: Monitor therapy
Cannabis: May increase the serum concentration of CarBAMazepine. CarBAMazepine may decrease the serum concentration of Cannabis. More specifically, tetrahydrocannabinol and cannabidiol serum concentrations may be decreased. Risk C: Monitor therapy
Capivasertib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Capivasertib. Risk X: Avoid combination
Capmatinib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Capmatinib. Risk X: Avoid combination
Cariprazine: CYP3A4 Inducers (Strong) may decrease the serum concentration of Cariprazine. Risk X: Avoid combination
Caspofungin: Inducers of Drug Clearance may decrease the 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 the serum concentration of Celiprolol. Risk C: Monitor therapy
Cenobamate: May decrease the serum concentration of CarBAMazepine. Risk C: Monitor therapy
Ceritinib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Ceritinib. Risk X: Avoid combination
Chlormethiazole: CarBAMazepine may decrease the serum concentration of Chlormethiazole. Risk C: Monitor therapy
ChlorproPAMIDE: CYP3A4 Inducers (Strong) may decrease the serum concentration of ChlorproPAMIDE. Risk C: Monitor therapy
Cilnidipine: CYP3A4 Inducers (Strong) may decrease the serum concentration of Cilnidipine. Risk C: Monitor therapy
Citalopram: CYP3A4 Inducers (Strong) may decrease the serum concentration of Citalopram. Risk C: Monitor therapy
Cladribine: BCRP/ABCG2 Inducers may decrease the serum concentration of Cladribine. Risk C: Monitor therapy
Cladribine: P-glycoprotein/ABCB1 Inducers may decrease the serum concentration of Cladribine. Risk C: Monitor therapy
Clarithromycin: CarBAMazepine may increase serum concentrations of the active metabolite(s) of Clarithromycin. Clarithromycin may increase the serum concentration of CarBAMazepine. CarBAMazepine may decrease the serum concentration 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 the serum concentration of Clindamycin (Systemic). Risk C: Monitor therapy
Clofazimine: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk C: Monitor therapy
ClomiPRAMINE: CarBAMazepine may decrease the serum concentration of ClomiPRAMINE. Risk C: Monitor therapy
ClonazePAM: CYP3A4 Inducers (Strong) may decrease the serum concentration of ClonazePAM. Risk C: Monitor therapy
CloZAPine: CarBAMazepine may enhance the myelosuppressive effect 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 the 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: CarBAMazepine may decrease the serum concentration of Cobicistat. Cobicistat may increase the serum concentration of CarBAMazepine. Risk X: Avoid combination
Cobimetinib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Cobimetinib. Risk X: Avoid combination
Codeine: CYP3A4 Inducers (Strong) may decrease serum concentrations of the active metabolite(s) of Codeine. Risk C: Monitor therapy
Cola-Containing Drinks: May increase the serum concentration of CarBAMazepine. Risk C: Monitor therapy
Colchicine: CYP3A4 Inducers (Strong) may decrease the serum concentration of Colchicine. Risk C: Monitor therapy
Copanlisib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Copanlisib. Risk X: Avoid combination
Crizotinib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Crizotinib. Risk X: Avoid combination
CycloPHOSphamide: CYP2B6 Inducers (Moderate) may increase serum concentrations of the active metabolite(s) of CycloPHOSphamide. Risk C: Monitor therapy
CycloSPORINE (Systemic): CYP3A4 Inducers (Strong) may decrease the 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 the serum concentration of CarBAMazepine. Risk C: Monitor therapy
CYP3A4 Inducers (Strong): May decrease the serum concentration of CarBAMazepine. Risk C: Monitor therapy
CYP3A4 Inducers (Weak): May decrease the serum concentration of CarBAMazepine. Risk C: Monitor therapy
CYP3A4 Inhibitors (Moderate): May increase the serum concentration of CarBAMazepine. Risk C: Monitor therapy
CYP3A4 Inhibitors (Strong): May increase serum concentrations of the active metabolite(s) of CarBAMazepine. CYP3A4 Inhibitors (Strong) may increase the serum concentration of CarBAMazepine. Risk C: Monitor therapy
CYP3A4 Inhibitors (Weak): May increase the serum concentration of CarBAMazepine. Risk C: Monitor therapy
Cyproterone: CYP3A4 Inducers (Strong) may decrease the serum concentration of Cyproterone. Risk C: Monitor therapy
Dabigatran Etexilate: P-glycoprotein/ABCB1 Inducers may decrease the serum concentration of Dabigatran Etexilate. Management: Avoid concurrent use of dabigatran with P-glycoprotein inducers whenever possible. Risk X: Avoid combination
Daclatasvir: CYP3A4 Inducers (Strong) may decrease the serum concentration of Daclatasvir. Risk X: Avoid combination
Dapsone (Systemic): May enhance the adverse/toxic effect of CYP3A4 Inducers (Strong). CYP3A4 Inducers (Strong) may decrease the serum concentration of Dapsone (Systemic). Risk C: Monitor therapy
Daridorexant: CYP3A4 Inducers (Strong) may decrease the serum concentration of Daridorexant. Risk X: Avoid combination
Darolutamide: Inducers of CYP3A4 (Strong) and P-glycoprotein may decrease the serum concentration of Darolutamide. Risk X: Avoid combination
Dasabuvir: CYP3A4 Inducers (Strong) may decrease the serum concentration of Dasabuvir. Risk X: Avoid combination
Dasatinib: CYP3A4 Inducers (Strong) may decrease the 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 the 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 serum concentrations of the active metabolite(s) of Deflazacort. Risk X: Avoid combination
Delamanid: CYP3A4 Inducers (Strong) may decrease the serum concentration of Delamanid. Risk X: Avoid combination
Delavirdine: CarBAMazepine may decrease the serum concentration of Delavirdine. Risk X: Avoid combination
Desmopressin: Hyponatremia-Associated Agents may enhance the hyponatremic effect of Desmopressin. Risk C: Monitor therapy
DexAMETHasone (Systemic): CYP3A4 Inducers (Strong) may decrease the 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 the serum concentration of DiazePAM. Risk C: Monitor therapy
Dienogest: CYP3A4 Inducers (Strong) may decrease the serum concentration of Dienogest. Risk C: Monitor therapy
Digoxin: P-glycoprotein/ABCB1 Inducers may decrease the serum concentration of Digoxin. Risk C: Monitor therapy
Dinutuximab Beta: May increase the serum concentration of CYP Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors). Risk C: Monitor therapy
Disopyramide: CYP3A4 Inducers (Strong) may decrease the serum concentration of Disopyramide. Risk C: Monitor therapy
DOCEtaxel: CYP3A4 Inducers (Strong) may decrease the serum concentration of DOCEtaxel. Risk C: Monitor therapy
Dolutegravir: CarBAMazepine may decrease the 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 the serum concentration of Domperidone. Risk C: Monitor therapy
Doravirine: CYP3A4 Inducers (Strong) may decrease the serum concentration of Doravirine. Risk X: Avoid combination
Doxercalciferol: CYP3A4 Inducers (Strong) may increase serum concentrations of the active metabolite(s) of Doxercalciferol. Risk C: Monitor therapy
DOXOrubicin (Conventional): CYP3A4 Inducers (Strong) may decrease the serum concentration of DOXOrubicin (Conventional). Risk X: Avoid combination
DOXOrubicin (Conventional): P-glycoprotein/ABCB1 Inducers may decrease the serum concentration of DOXOrubicin (Conventional). Risk X: Avoid combination
Doxycycline: CarBAMazepine may decrease the serum concentration of Doxycycline. Risk C: Monitor therapy
DroNABinol: CYP3A4 Inducers (Strong) may decrease the serum concentration of DroNABinol. Risk C: Monitor therapy
Dronedarone: CYP3A4 Inducers (Strong) may decrease the serum concentration of Dronedarone. Risk X: Avoid combination
Duvelisib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Duvelisib. Risk X: Avoid combination
Dydrogesterone: CYP3A4 Inducers (Strong) may decrease the serum concentration of Dydrogesterone. Risk C: Monitor therapy
Ebastine: CYP3A4 Inducers (Strong) may decrease serum concentrations of the active metabolite(s) of Ebastine. CYP3A4 Inducers (Strong) may decrease the serum concentration of Ebastine. Risk C: Monitor therapy
Edoxaban: P-glycoprotein/ABCB1 Inducers may decrease the 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 the serum concentration of Efavirenz. Efavirenz may decrease the serum concentration of CarBAMazepine. Risk X: Avoid combination
Elacestrant: CYP3A4 Inducers (Strong) may decrease the serum concentration of Elacestrant. Risk X: Avoid combination
Elagolix: CYP3A4 Inducers (Strong) may decrease the serum concentration of Elagolix. Risk C: Monitor therapy
Elagolix, Estradiol, and Norethindrone: CYP3A4 Inducers (Strong) may decrease the serum concentration of Elagolix, Estradiol, and Norethindrone. Risk C: Monitor therapy
Elbasvir and Grazoprevir: CYP3A4 Inducers (Strong) may decrease the serum concentration of Elbasvir and Grazoprevir. Risk X: Avoid combination
Elexacaftor, Tezacaftor, and Ivacaftor: CYP3A4 Inducers (Strong) may decrease the serum concentration of Elexacaftor, Tezacaftor, and Ivacaftor. Risk X: Avoid combination
Eliglustat: CYP3A4 Inducers (Strong) may decrease the serum concentration of Eliglustat. Risk X: Avoid combination
Elranatamab: May increase the serum concentration of CYP Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors). Risk C: Monitor therapy
Elvitegravir: CarBAMazepine may decrease the serum concentration of Elvitegravir. Risk X: Avoid combination
Encorafenib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Encorafenib. Risk X: Avoid combination
Enfortumab Vedotin: CYP3A4 Inducers (Strong) may decrease the serum concentration of Enfortumab Vedotin. Specifically, concentrations of the active monomethyl auristatin E (MMAE) component may be decreased. Risk C: Monitor therapy
Entrectinib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Entrectinib. Risk X: Avoid combination
Enzalutamide: CYP3A4 Inducers (Strong) may decrease serum concentrations of the active metabolite(s) of Enzalutamide. CYP3A4 Inducers (Strong) may decrease the serum concentration 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 the serum concentration of CYP Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors). Risk C: Monitor therapy
Eplerenone: CYP3A4 Inducers (Strong) may decrease the serum concentration of Eplerenone. Risk C: Monitor therapy
Eravacycline: CYP3A4 Inducers (Strong) may decrease the 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 the serum concentration of Erdafitinib. Risk X: Avoid combination
Erlotinib: CYP3A4 Inducers (Strong) may decrease the 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 the serum concentration of Escitalopram. Risk C: Monitor therapy
Eslicarbazepine: CarBAMazepine may enhance the adverse/toxic effect of Eslicarbazepine. CarBAMazepine may decrease the serum concentration of Eslicarbazepine. Risk C: Monitor therapy
Estazolam: CYP3A4 Inducers (Strong) may decrease the serum concentration of Estazolam. Risk C: Monitor therapy
Estrogen Derivatives: CYP3A4 Inducers (Strong) may decrease the serum concentration of Estrogen Derivatives. Risk C: Monitor therapy
Eszopiclone: CYP3A4 Inducers (Strong) may decrease the serum concentration of Eszopiclone. Risk C: Monitor therapy
Ethosuximide: CYP3A4 Inducers (Strong) may decrease the serum concentration of Ethosuximide. Risk C: Monitor therapy
Etizolam: CYP3A4 Inducers (Strong) may decrease the serum concentration of Etizolam. Risk C: Monitor therapy
Etoposide: CYP3A4 Inducers (Strong) may decrease the 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
Etoposide Phosphate: CYP3A4 Inducers (Strong) may decrease the 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
Etoricoxib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Etoricoxib. Risk C: Monitor therapy
Etravirine: CYP3A4 Inducers (Strong) may decrease the serum concentration of Etravirine. Risk X: Avoid combination
Everolimus: Inducers of CYP3A4 (Strong) and P-glycoprotein may decrease the 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 the serum concentration of Evogliptin. Risk C: Monitor therapy
Exemestane: CYP3A4 Inducers (Strong) may decrease the 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 the serum concentration of Fedratinib. Risk X: Avoid combination
Felbamate: May increase serum concentrations of the active metabolite(s) of CarBAMazepine. Specifically, concentrations of the carbamazepine epoxide metabolite may be increased. CarBAMazepine may decrease the serum concentration of Felbamate. Felbamate may decrease the serum concentration of CarBAMazepine. 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 the 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 the 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 the serum concentration of FentaNYL. Risk C: Monitor therapy
Fesoterodine: CYP3A4 Inducers (Strong) may decrease serum concentrations of the active metabolite(s) of Fesoterodine. Risk C: Monitor therapy
Fexinidazole: CYP3A4 Inducers (Strong) may increase serum concentrations of the active metabolite(s) of Fexinidazole. Risk X: Avoid combination
Fexofenadine: P-glycoprotein/ABCB1 Inducers may decrease the serum concentration of Fexofenadine. Risk C: Monitor therapy
Finerenone: CYP3A4 Inducers (Strong) may decrease the serum concentration of Finerenone. Risk X: Avoid combination
Fingolimod: CarBAMazepine may decrease the serum concentration of Fingolimod. Risk C: Monitor therapy
Flibanserin: CYP3A4 Inducers (Strong) may decrease the serum concentration of Flibanserin. Risk X: Avoid combination
Fludrocortisone: CYP3A4 Inducers (Strong) may decrease the serum concentration of Fludrocortisone. Risk C: Monitor therapy
Flunarizine: CarBAMazepine may decrease the serum concentration of Flunarizine. Risk C: Monitor therapy
FLUoxetine: May increase the serum concentration of CarBAMazepine. Risk C: Monitor therapy
Fosamprenavir: CYP3A4 Inducers (Strong) may decrease serum concentrations of the active metabolite(s) of Fosamprenavir. Risk C: Monitor therapy
Fosaprepitant: CYP3A4 Inducers (Strong) may decrease the serum concentration of Fosaprepitant. Specifically, CYP3A4 Inducers (Strong) may decrease serum concentrations of the active metabolite aprepitant. Risk X: Avoid combination
Fosnetupitant: CYP3A4 Inducers (Strong) may decrease serum concentrations of the active metabolite(s) of Fosnetupitant. Risk X: Avoid combination
Fosphenytoin-Phenytoin: May decrease the serum concentration of CarBAMazepine. CarBAMazepine may decrease the serum concentration of Fosphenytoin-Phenytoin. CarBAMazepine may increase the serum concentration of Fosphenytoin-Phenytoin. Risk C: Monitor therapy
Fostamatinib: CYP3A4 Inducers (Strong) may decrease serum concentrations of the active metabolite(s) of Fostamatinib. Risk X: Avoid combination
Fostemsavir: CYP3A4 Inducers (Strong) may decrease serum concentrations of the active metabolite(s) of Fostemsavir. Risk X: Avoid combination
Fruquintinib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Fruquintinib. Risk X: Avoid combination
Fusidic Acid (Systemic): May increase the 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 the serum concentration of Futibatinib. Risk X: Avoid combination
Ganaxolone: CYP3A4 Inducers (Strong) may decrease the 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 the 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 concentrations of the active metabolite(s) of Gemigliptin. CYP3A4 Inducers (Strong) may decrease the serum concentration of Gemigliptin. Risk X: Avoid combination
Gepirone: CYP3A4 Inducers (Strong) may decrease the serum concentration of Gepirone. Risk X: Avoid combination
Gestrinone: CarBAMazepine may decrease the serum concentration of Gestrinone. Risk C: Monitor therapy
Gilteritinib: Inducers of CYP3A4 (Strong) and P-glycoprotein may decrease the serum concentration of Gilteritinib. Risk X: Avoid combination
Givinostat: May increase the serum concentration of CYP3A4 Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors). Risk C: Monitor therapy
Glasdegib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Glasdegib. Risk X: Avoid combination
Glecaprevir and Pibrentasvir: CarBAMazepine may decrease the serum concentration of Glecaprevir and Pibrentasvir. Risk X: Avoid combination
Glofitamab: May increase the serum concentration of CYP Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors). Risk C: Monitor therapy
Grapefruit Juice: May increase the serum concentration of CarBAMazepine. Risk C: Monitor therapy
GuanFACINE: CYP3A4 Inducers (Strong) may decrease the 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 the serum concentration of Haloperidol. Risk C: Monitor therapy
Hormonal Contraceptives: CYP3A4 Inducers (Strong) may decrease the 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 the serum concentration of HYDROcodone. Risk C: Monitor therapy
Hydrocortisone (Systemic): CYP3A4 Inducers (Strong) may decrease the serum concentration of Hydrocortisone (Systemic). Risk C: Monitor therapy
Ibrexafungerp: CYP3A4 Inducers (Strong) may decrease the serum concentration of Ibrexafungerp. Risk X: Avoid combination
Ibrutinib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Ibrutinib. Risk X: Avoid combination
Idelalisib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Idelalisib. Risk X: Avoid combination
Ifosfamide: CYP3A4 Inducers (Strong) may increase serum concentrations of the active metabolite(s) of Ifosfamide. CYP3A4 Inducers (Strong) may decrease serum concentrations of the active metabolite(s) of Ifosfamide. Risk C: Monitor therapy
Imatinib: CYP3A4 Inducers (Strong) may decrease the 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 the 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
Infigratinib: CYP3A4 Inducers (Strong) may decrease serum concentrations of the active metabolite(s) of Infigratinib. CYP3A4 Inducers (Strong) may decrease the serum concentration of Infigratinib. Risk X: Avoid combination
Irinotecan Products: CYP3A4 Inducers (Strong) may decrease serum concentrations of the active metabolite(s) of Irinotecan Products. Specifically, serum concentrations of SN-38 may be reduced. CYP3A4 Inducers (Strong) may decrease the serum concentration of Irinotecan Products. 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 serum concentrations of the active metabolite(s) of Isavuconazonium Sulfate. Specifically, CYP3A4 Inducers (Strong) may decrease isavuconazole serum concentrations. Risk X: Avoid combination
Isoniazid: CarBAMazepine may enhance the hepatotoxic effect of Isoniazid. Isoniazid may increase the serum concentration of CarBAMazepine. Risk C: Monitor therapy
Isradipine: CYP3A4 Inducers (Strong) may decrease the serum concentration of Isradipine. Risk C: Monitor therapy
Istradefylline: CYP3A4 Inducers (Strong) may decrease the serum concentration of Istradefylline. Risk X: Avoid combination
Itraconazole: CYP3A4 Inducers (Strong) may decrease serum concentrations of the active metabolite(s) of Itraconazole. CYP3A4 Inducers (Strong) may decrease the serum concentration of Itraconazole. Risk X: Avoid combination
Ivabradine: CYP3A4 Inducers (Strong) may decrease the serum concentration of Ivabradine. Risk X: Avoid combination
Ivacaftor: CYP3A4 Inducers (Strong) may decrease the serum concentration of Ivacaftor. Risk X: Avoid combination
Ivosidenib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Ivosidenib. Risk X: Avoid combination
Ixabepilone: CYP3A4 Inducers (Strong) may decrease the 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 the serum concentration of Ixazomib. Risk X: Avoid combination
Ketamine: CYP3A4 Inducers (Strong) may decrease the serum concentration of Ketamine. Risk C: Monitor therapy
Ketoconazole (Systemic): CYP3A4 Inducers (Strong) may decrease the 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 the serum concentration of Lacidipine. Risk C: Monitor therapy
Lacosamide: Antiseizure Agents (Sodium Channel Blockers) may enhance the adverse/toxic effect of Lacosamide. Specifically the risk for bradycardia, ventricular tachyarrhythmias, or a prolonged PR interval may be increased. Risk C: Monitor therapy
LamoTRIgine: CarBAMazepine may enhance the adverse/toxic effect of LamoTRIgine. Specifically, the risk for hematologic toxicities may be increased. CarBAMazepine may enhance the arrhythmogenic effect of LamoTRIgine. CarBAMazepine may decrease the 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 the 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 the 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
Ledipasvir: P-glycoprotein/ABCB1 Inducers may decrease the serum concentration of Ledipasvir. Risk X: Avoid combination
Lefamulin: CYP3A4 Inducers (Strong) may decrease the 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 the 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
Lefamulin (Intravenous): CYP3A4 Inducers (Strong) may decrease the 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 the 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
Lemborexant: CYP3A4 Inducers (Strong) may decrease the serum concentration of Lemborexant. Risk X: Avoid combination
Lenacapavir: CYP3A4 Inducers (Strong) may decrease the serum concentration of Lenacapavir. Risk X: Avoid combination
Leniolisib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Leniolisib. Risk X: Avoid combination
Lercanidipine: CYP3A4 Inducers (Strong) may decrease the serum concentration of Lercanidipine. Risk C: Monitor therapy
Letermovir: P-glycoprotein/ABCB1 Inducers may decrease the serum concentration of Letermovir. Risk X: Avoid combination
Letermovir: UGT1A1 Inducers may decrease the serum concentration of Letermovir. Risk X: Avoid combination
Leuprolide and Norethindrone: CYP3A4 Inducers (Strong) may decrease the serum concentration of Leuprolide and Norethindrone. Specifically, norethindrone concentrations may be decreased. Risk C: Monitor therapy
Levamlodipine: CYP3A4 Inducers (Strong) may decrease the serum concentration of Levamlodipine. Risk C: Monitor therapy
LevETIRAcetam: May enhance the adverse/toxic effect of CarBAMazepine. CarBAMazepine may decrease the serum concentration of LevETIRAcetam. Risk C: Monitor therapy
Levoketoconazole: CYP3A4 Inducers (Strong) may decrease the serum concentration of Levoketoconazole. Risk X: Avoid combination
Levomethadone: CYP3A4 Inducers (Strong) may decrease the serum concentration of Levomethadone. Risk C: Monitor therapy
Levonorgestrel (IUD): CYP3A4 Inducers (Strong) may diminish the therapeutic effect of Levonorgestrel (IUD). CYP3A4 Inducers (Strong) may decrease the serum concentration of Levonorgestrel (IUD). Risk C: Monitor therapy
Lidocaine (Systemic): CYP3A4 Inducers (Strong) may decrease the serum concentration of Lidocaine (Systemic). Risk C: Monitor therapy
LinaGLIPtin: CYP3A4 Inducers (Strong) may decrease the 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 the 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 enhance the adverse/toxic effect of Lithium. Risk C: Monitor therapy
Lonafarnib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Lonafarnib. Risk X: Avoid combination
Lopinavir: CarBAMazepine may decrease the serum concentration of Lopinavir. Lopinavir may increase the 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 enhance the hepatotoxic effect of Lorlatinib. CYP3A4 Inducers (Strong) may decrease the serum concentration of Lorlatinib. Risk X: Avoid combination
Lovastatin: CYP3A4 Inducers (Strong) may decrease the serum concentration of Lovastatin. Risk C: Monitor therapy
Loxapine: May increase serum concentrations of the active metabolite(s) of CarBAMazepine. Risk C: Monitor therapy
Lumacaftor and Ivacaftor: CYP3A4 Inducers (Strong) may decrease the serum concentration of Lumacaftor and Ivacaftor. Specifically, the serum concentration of ivacaftor may be decreased. Risk X: Avoid combination
Lumateperone: CYP3A4 Inducers (Strong) may decrease the serum concentration of Lumateperone. Risk X: Avoid combination
Lurasidone: CYP3A4 Inducers (Strong) may decrease the serum concentration of Lurasidone. Risk X: Avoid combination
Lurbinectedin: CYP3A4 Inducers (Strong) may decrease the serum concentration of Lurbinectedin. Risk X: Avoid combination
Macimorelin: CYP3A4 Inducers (Strong) may decrease the serum concentration of Macimorelin. Risk X: Avoid combination
Macitentan: CYP3A4 Inducers (Strong) may decrease the serum concentration of Macitentan. Risk X: Avoid combination
Manidipine: CYP3A4 Inducers (Strong) may decrease the 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 the 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 the 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 the serum concentration of Mavacamten. Risk X: Avoid combination
Mavorixafor: CYP3A4 Inducers (Strong) may decrease the serum concentration of Mavorixafor. Risk X: Avoid combination
Mebendazole: CarBAMazepine may decrease the serum concentration of Mebendazole. Risk C: Monitor therapy
Mefloquine: May diminish the therapeutic effect of CarBAMazepine. CarBAMazepine may decrease the serum concentration of Mefloquine. Mefloquine may decrease the 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 increase serum concentrations of the active metabolite(s) of Meperidine. Specifically, concentrations of normeperidine, the CNS stimulating metabolite, may be increased. CYP3A4 Inducers (Strong) may decrease the serum concentration of Meperidine. Risk C: Monitor therapy
Methadone: CYP3A4 Inducers (Strong) may decrease the serum concentration of Methadone. Risk C: Monitor therapy
Methylergonovine: CYP3A4 Inducers (Strong) may decrease the serum concentration of Methylergonovine. Risk C: Monitor therapy
MethylPREDNISolone: CYP3A4 Inducers (Strong) may decrease the 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: Antiseizure Agents may diminish the diagnostic effect of MetyraPONE. Management: Consider alternatives to the use of the metyrapone test in patients taking antiseizure agents. Risk D: Consider therapy modification
Mianserin: May diminish the therapeutic effect of CarBAMazepine. CarBAMazepine may decrease the serum concentration of Mianserin. Risk C: Monitor therapy
Midazolam: CYP3A4 Inducers (Strong) may decrease the serum concentration of Midazolam. Risk C: Monitor therapy
Midostaurin: CYP3A4 Inducers (Strong) may decrease the serum concentration of Midostaurin. Risk X: Avoid combination
MiFEPRIStone: CYP3A4 Inducers (Strong) may decrease the 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 the serum concentration of Mirabegron. Risk C: Monitor therapy
Mirodenafil: CYP3A4 Inducers (Strong) may decrease the 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 the serum concentration of Mirtazapine. Risk C: Monitor therapy
Mitapivat: CYP3A4 Inducers (Strong) may decrease the serum concentration of Mitapivat. Risk X: Avoid combination
Mobocertinib: CYP3A4 Inducers (Strong) may decrease serum concentrations of the active metabolite(s) of Mobocertinib. CYP3A4 Inducers (Strong) may decrease the serum concentration of Mobocertinib. Risk X: Avoid combination
Monoamine Oxidase Inhibitors: CarBAMazepine may enhance the adverse/toxic effect 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 combination
Mosunetuzumab: May increase the serum concentration of CYP Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors). Risk C: Monitor therapy
Naldemedine: CYP3A4 Inducers (Strong) may decrease the serum concentration of Naldemedine. Risk X: Avoid combination
Naloxegol: CYP3A4 Inducers (Strong) may decrease the serum concentration of Naloxegol. Risk X: Avoid combination
Nateglinide: CYP3A4 Inducers (Strong) may decrease the serum concentration of Nateglinide. Risk C: Monitor therapy
Nefazodone: May increase the serum concentration of CarBAMazepine. Also, concentrations of the active CarBAMazepine epoxide metabolite may be reduced. CarBAMazepine may decrease the serum concentration of Nefazodone. Concentrations of active Nefazodone metabolites may also be reduced. Risk X: Avoid combination
Nelfinavir: CYP3A4 Inducers (Strong) may decrease the serum concentration of Nelfinavir. Risk C: Monitor therapy
Neratinib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Neratinib. Risk X: Avoid combination
Netupitant: CYP3A4 Inducers (Strong) may decrease the serum concentration of Netupitant. Risk X: Avoid combination
Neuromuscular-Blocking Agents (Nondepolarizing): CarBAMazepine may decrease the serum concentration of Neuromuscular-Blocking Agents (Nondepolarizing). Risk C: Monitor therapy
Nevirapine: CarBAMazepine may decrease the serum concentration of Nevirapine. Risk X: Avoid combination
NiCARdipine: CYP3A4 Inducers (Strong) may decrease the serum concentration of NiCARdipine. Risk C: Monitor therapy
NIFEdipine: CYP3A4 Inducers (Strong) may decrease the 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 the serum concentration of Nilotinib. Risk X: Avoid combination
Nilvadipine: CYP3A4 Inducers (Strong) may decrease the serum concentration of Nilvadipine. Risk C: Monitor therapy
NiMODipine: CYP3A4 Inducers (Strong) may decrease the serum concentration of NiMODipine. Risk X: Avoid combination
Nintedanib: Inducers of CYP3A4 (Strong) and P-glycoprotein may decrease the serum concentration of Nintedanib. Risk X: Avoid combination
Nirmatrelvir and Ritonavir: May increase the serum concentration of CarBAMazepine. CarBAMazepine may decrease the serum concentration of Nirmatrelvir and Ritonavir. Risk X: Avoid combination
Nirogacestat: CYP3A4 Inducers (Strong) may decrease the serum concentration of Nirogacestat. Risk X: Avoid combination
Nisoldipine: CYP3A4 Inducers (Strong) may decrease the serum concentration of Nisoldipine. Risk X: Avoid combination
Nitrazepam: CYP3A4 Inducers (Strong) may decrease the serum concentration of Nitrazepam. Risk C: Monitor therapy
Nitrendipine: CYP3A4 Inducers (Strong) may decrease the serum concentration of Nitrendipine. Risk C: Monitor therapy
OLANZapine: CarBAMazepine may decrease the serum concentration of OLANZapine. Risk C: Monitor therapy
Olaparib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Olaparib. Risk X: Avoid combination
Oliceridine: CYP3A4 Inducers (Strong) may decrease the serum concentration of Oliceridine. Risk C: Monitor therapy
Olmutinib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Olmutinib. Risk C: Monitor therapy
Olutasidenib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Olutasidenib. Risk X: Avoid combination
Omaveloxolone: CYP3A4 Inducers (Strong) may decrease the serum concentration of Omaveloxolone. Risk X: Avoid combination
Omeprazole: CarBAMazepine may decrease the serum concentration of Omeprazole. Omeprazole may increase the serum concentration of CarBAMazepine. Risk C: Monitor therapy
Ondansetron: CYP3A4 Inducers (Strong) may decrease the serum concentration of Ondansetron. Risk C: Monitor therapy
Orelabrutinib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Orelabrutinib. Risk X: Avoid combination
Orlistat: May decrease the serum concentration of Antiseizure Agents. Risk C: Monitor therapy
Osilodrostat: CYP3A4 Inducers (Strong) may decrease the serum concentration of Osilodrostat. Risk C: Monitor therapy
Osimertinib: CYP3A4 Inducers (Strong) may decrease the 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 the serum concentration of OXcarbazepine. Specifically, the concentrations of the 10-monohydroxy active metabolite of oxcarbazepine may be decreased. Risk C: Monitor therapy
OxyCODONE: CYP3A4 Inducers (Strong) may decrease the serum concentration of OxyCODONE. Risk C: Monitor therapy
PACLitaxel (Conventional): CYP3A4 Inducers (Strong) may decrease the serum concentration of PACLitaxel (Conventional). Risk C: Monitor therapy
PACLitaxel (Protein Bound): CYP3A4 Inducers (Strong) may decrease the serum concentration of PACLitaxel (Protein Bound). Risk C: Monitor therapy
Pacritinib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Pacritinib. Risk X: Avoid combination
Pacritinib: May increase the serum concentration of CYP3A4 Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors). Risk X: Avoid combination
Palbociclib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Palbociclib. Risk X: Avoid combination
Paliperidone: Inducers of CYP3A4 (Strong) and P-glycoprotein may decrease the serum concentration of Paliperidone. Management: Monitor for reduced paliperidone effects when combined with strong inducers of both CYP3A4 and P-gp. Avoid use of these inducers with extended-release injectable paliperidone and instead manage patients with paliperidone extended-release tablets. Risk C: Monitor therapy
Palovarotene: CYP3A4 Inducers (Strong) may decrease the serum concentration of Palovarotene. Risk X: Avoid combination
Panobinostat: CYP3A4 Inducers (Strong) may decrease the serum concentration of Panobinostat. Risk X: Avoid combination
PAZOPanib: CYP3A4 Inducers (Strong) may decrease the serum concentration of PAZOPanib. Risk X: Avoid combination
Pemigatinib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Pemigatinib. Risk X: Avoid combination
Perampanel: CYP3A4 Inducers (Strong) may decrease the 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
Pexidartinib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Pexidartinib. Risk X: Avoid combination
Pimavanserin: CYP3A4 Inducers (Strong) may decrease the serum concentration of Pimavanserin. Risk X: Avoid combination
Piperaquine: CYP3A4 Inducers (Strong) may decrease the serum concentration of Piperaquine. Risk X: Avoid combination
Pirtobrutinib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Pirtobrutinib. Risk X: Avoid combination
Pitolisant: CYP3A4 Inducers (Strong) may decrease the 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 the serum concentration of Polatuzumab Vedotin. Exposure to unconjugated MMAE, the cytotoxic small molecule component of polatuzumab vedotin, may be decreased. Risk C: Monitor therapy
PONATinib: CYP3A4 Inducers (Strong) may decrease the 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
Ponesimod: UGT1A1 Inducers may decrease the serum concentration of Ponesimod. Risk X: Avoid combination
Pralsetinib: CYP3A4 Inducers (Strong) may decrease the 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 the serum concentration of Pravastatin. Risk C: Monitor therapy
Praziquantel: CYP3A4 Inducers (Strong) may decrease the serum concentration of Praziquantel. Risk X: Avoid combination
PrednisoLONE (Systemic): CYP3A4 Inducers (Strong) may decrease the serum concentration of PrednisoLONE (Systemic). Risk C: Monitor therapy
PredniSONE: CYP3A4 Inducers (Strong) may decrease the serum concentration of PredniSONE. Risk C: Monitor therapy
Pretomanid: CYP3A4 Inducers (Strong) may decrease the serum concentration of Pretomanid. Risk X: Avoid combination
Propacetamol: CarBAMazepine may increase the metabolism of Propacetamol. This may 1) diminish the desired effects of propacetamol; and 2) increase the risk of liver damage. Risk C: Monitor therapy
Propafenone: CYP3A4 Inducers (Strong) may decrease the serum concentration of Propafenone. Risk C: Monitor therapy
QUEtiapine: May increase serum concentrations of the active metabolite(s) of CarBAMazepine. CarBAMazepine may decrease the serum concentration of QUEtiapine. 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 the serum concentration of QuiNIDine. Risk C: Monitor therapy
QuiNINE: CarBAMazepine may decrease the serum concentration of QuiNINE. QuiNINE may increase the 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 the serum concentration of Quizartinib. Risk X: Avoid combination
Radotinib: CYP3A4 Inducers (Strong) may decrease the 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 the serum concentration of Ramelteon. Risk C: Monitor therapy
Ranolazine: CYP3A4 Inducers (Strong) may decrease the serum concentration of Ranolazine. Risk X: Avoid combination
Reboxetine: CYP3A4 Inducers (Strong) may decrease the serum concentration of Reboxetine. Risk C: Monitor therapy
Regorafenib: CYP3A4 Inducers (Strong) may increase serum concentrations of the active metabolite(s) of Regorafenib. CYP3A4 Inducers (Strong) may decrease the serum concentration of Regorafenib. Risk X: Avoid combination
Relugolix: Inducers of CYP3A4 (Strong) and P-glycoprotein may decrease the 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
Relugolix, Estradiol, and Norethindrone: Inducers of CYP3A4 (Strong) and P-glycoprotein may decrease the serum concentration of Relugolix, Estradiol, and Norethindrone. Risk X: Avoid combination
Repaglinide: CYP3A4 Inducers (Strong) may decrease the serum concentration of Repaglinide. Risk C: Monitor therapy
Repotrectinib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Repotrectinib. Risk X: Avoid combination
Ribociclib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Ribociclib. Risk X: Avoid combination
Rifabutin: CYP3A4 Inducers (Strong) may decrease the serum concentration of Rifabutin. Risk C: Monitor therapy
Rilpivirine: CarBAMazepine may decrease the serum concentration of Rilpivirine. Risk X: Avoid combination
Rimegepant: CYP3A4 Inducers (Strong) may decrease the serum concentration of Rimegepant. Risk X: Avoid combination
Riociguat: CYP3A4 Inducers (Strong) may decrease the serum concentration of Riociguat. Risk C: Monitor therapy
Ripretinib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Ripretinib. Risk X: Avoid combination
RisperiDONE: CYP3A4 Inducers (Strong) may decrease serum concentrations of the active metabolite(s) of RisperiDONE. CYP3A4 Inducers (Strong) may decrease the serum concentration 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 the serum concentration of Ritlecitinib. Risk X: Avoid combination
Ritonavir: CarBAMazepine may decrease the serum concentration of Ritonavir. Ritonavir may increase the 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 the serum concentration of Rivaroxaban. Risk X: Avoid combination
Roflumilast (Systemic): CYP3A4 Inducers (Strong) may decrease serum concentrations of the active metabolite(s) of Roflumilast (Systemic). CYP3A4 Inducers (Strong) may decrease the serum concentration of Roflumilast (Systemic). Risk X: Avoid combination
Rolapitant: CYP3A4 Inducers (Strong) may decrease the serum concentration of Rolapitant. Risk X: Avoid combination
RomiDEPsin: CYP3A4 Inducers (Strong) may decrease the serum concentration of RomiDEPsin. Risk X: Avoid combination
Rosuvastatin: CarBAMazepine may decrease the serum concentration of Rosuvastatin. Risk C: Monitor therapy
Rufinamide: May decrease the serum concentration of CarBAMazepine. CarBAMazepine may decrease the serum concentration of Rufinamide. Risk C: Monitor therapy
Ruxolitinib (Systemic): CYP3A4 Inducers (Strong) may increase serum concentrations of the active metabolite(s) of Ruxolitinib (Systemic). CYP3A4 Inducers (Strong) may decrease the serum concentration of Ruxolitinib (Systemic). Risk C: Monitor therapy
Sacituzumab Govitecan: UGT1A1 Inducers may decrease serum concentrations of the active metabolite(s) of Sacituzumab Govitecan. Specifically, concentrations of SN-38 may be decreased. Risk X: Avoid combination
Samidorphan: CYP3A4 Inducers (Strong) may decrease the serum concentration of Samidorphan. Risk X: Avoid combination
Saquinavir: CarBAMazepine may decrease the serum concentration of Saquinavir. Risk X: Avoid combination
SAXagliptin: CYP3A4 Inducers (Strong) may decrease the serum concentration of SAXagliptin. Risk C: Monitor therapy
Selpercatinib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Selpercatinib. Risk X: Avoid combination
Selumetinib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Selumetinib. Risk X: Avoid combination
Sertindole: CYP3A4 Inducers (Strong) may decrease the serum concentration of Sertindole. Risk C: Monitor therapy
Sertraline: CarBAMazepine may decrease the serum concentration of Sertraline. Risk C: Monitor therapy
Sildenafil: CYP3A4 Inducers (Strong) may decrease the serum concentration of Sildenafil. Risk C: Monitor therapy
Simeprevir: CYP3A4 Inducers (Strong) may decrease the serum concentration of Simeprevir. Risk X: Avoid combination
Simvastatin: CYP3A4 Inducers (Strong) may decrease the serum concentration of Simvastatin. Risk C: Monitor therapy
Siponimod: CarBAMazepine may decrease the serum concentration of Siponimod. Risk X: Avoid combination
Sirolimus (Conventional): CYP3A4 Inducers (Strong) may decrease the 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 the serum concentration of Sirolimus (Protein Bound). Risk X: Avoid combination
Sofosbuvir: P-glycoprotein/ABCB1 Inducers may decrease the serum concentration of Sofosbuvir. Risk X: Avoid combination
Solifenacin: CYP3A4 Inducers (Strong) may decrease the serum concentration of Solifenacin. Risk C: Monitor therapy
Sonidegib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Sonidegib. Risk X: Avoid combination
SORAfenib: CYP3A4 Inducers (Strong) may decrease the serum concentration of SORAfenib. Risk X: Avoid combination
Sotorasib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Sotorasib. Risk X: Avoid combination
Sparsentan: CYP3A4 Inducers (Strong) may decrease the serum concentration of Sparsentan. Risk X: Avoid combination
Spironolactone: May increase the serum concentration of CYP3A4 Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors). Risk C: Monitor therapy
Stiripentol: CarBAMazepine may decrease the serum concentration of Stiripentol. Stiripentol may increase the 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 the 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 the serum concentration of Sulthiame. Risk C: Monitor therapy
SUNItinib: CYP3A4 Inducers (Strong) may decrease the 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 the serum concentration of Suvorexant. Risk C: Monitor therapy
Tacrolimus (Systemic): CYP3A4 Inducers (Strong) may decrease the serum concentration of Tacrolimus (Systemic). Management: Monitor for decreased tacrolimus concentrations and effects when combined with strong CYP3A4 inducers. Tacrolimus dose increases will likely be needed during concomitant use. Risk D: Consider therapy modification
Tadalafil: CYP3A4 Inducers (Strong) may decrease the 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 the serum concentration of CYP Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors). Risk C: Monitor therapy
Tamoxifen: CYP3A4 Inducers (Strong) may decrease serum concentrations of the active metabolite(s) of Tamoxifen. CYP3A4 Inducers (Strong) may decrease the serum concentration of Tamoxifen. Risk X: Avoid combination
Tasimelteon: CYP3A4 Inducers (Strong) may decrease the serum concentration of Tasimelteon. Risk X: Avoid combination
Taurursodiol: CYP3A4 Inducers (Strong) may decrease the serum concentration of Taurursodiol. Specifically, the concentrations of phenylbutyrate may be decreased. Risk C: Monitor therapy
Tazemetostat: CYP3A4 Inducers (Strong) may decrease the serum concentration of Tazemetostat. Risk X: Avoid combination
Teclistamab: May increase the serum concentration of CYP Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors). Risk C: Monitor therapy
Temsirolimus: CYP3A4 Inducers (Strong) may decrease serum concentrations of the active metabolite(s) of Temsirolimus. Specifically, concentrations of sirolimus may be decreased. CYP3A4 Inducers (Strong) may decrease the serum concentration of Temsirolimus. 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 the serum concentration of Teniposide. Risk C: Monitor therapy
Tenofovir Alafenamide: CarBAMazepine may decrease the serum concentration of Tenofovir Alafenamide. Risk X: Avoid combination
Tetrahydrocannabinol: CYP3A4 Inducers (Strong) may decrease the serum concentration of Tetrahydrocannabinol. Risk C: Monitor therapy
Tetrahydrocannabinol and Cannabidiol: CYP3A4 Inducers (Strong) may decrease the 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
Tezacaftor and Ivacaftor: CYP3A4 Inducers (Strong) may decrease the serum concentration of Tezacaftor and Ivacaftor. Risk X: Avoid combination
Theophylline Derivatives: CarBAMazepine may decrease the serum concentration of Theophylline Derivatives. Theophylline Derivatives may decrease the 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 serum concentrations of the active metabolite(s) of Thiotepa. CYP3A4 Inducers (Strong) may decrease the 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 the serum concentration of Thiothixene. Risk C: Monitor therapy
Thyroid Products: CarBAMazepine may decrease the serum concentration of Thyroid Products. Risk C: Monitor therapy
TiaGABine: CYP3A4 Inducers (Strong) may decrease the serum concentration of TiaGABine. Risk C: Monitor therapy
Ticagrelor: CYP3A4 Inducers (Strong) may decrease serum concentrations of the active metabolite(s) of Ticagrelor. CYP3A4 Inducers (Strong) may decrease the serum concentration of Ticagrelor. Risk X: Avoid combination
Tipranavir: CYP3A4 Inducers (Strong) may decrease the serum concentration of Tipranavir. Risk C: Monitor therapy
Tivozanib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Tivozanib. Risk X: Avoid combination
Tofacitinib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Tofacitinib. Risk X: Avoid combination
Tolvaptan: CYP3A4 Inducers (Strong) may decrease the serum concentration of Tolvaptan. Risk X: Avoid combination
Topiramate: May enhance the CNS depressant effect of CarBAMazepine. CarBAMazepine may decrease the serum concentration of Topiramate. Risk C: Monitor therapy
Toremifene: CYP3A4 Inducers (Strong) may decrease serum concentrations of the active metabolite(s) of Toremifene. CYP3A4 Inducers (Strong) may decrease the serum concentration of Toremifene. Risk X: Avoid combination
Trabectedin: CYP3A4 Inducers (Strong) may decrease the serum concentration of Trabectedin. Risk X: Avoid combination
TraMADol: May enhance the CNS depressant effect of CarBAMazepine. TraMADol may diminish the therapeutic effect of CarBAMazepine. CarBAMazepine may decrease the serum concentration of TraMADol. Risk X: Avoid combination
TraZODone: CarBAMazepine may decrease the serum concentration of TraZODone. TraZODone may increase the 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 the serum concentration of CYP3A4 Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors). Risk X: Avoid combination
Triamcinolone (Systemic): CYP3A4 Inducers (Strong) may decrease the serum concentration of Triamcinolone (Systemic). Risk C: Monitor therapy
Triazolam: CYP3A4 Inducers (Strong) may decrease the 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 the serum concentration of Tricyclic Antidepressants. Risk C: Monitor therapy
Trofinetide: May increase the serum concentration of CYP3A4 Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors). Risk C: Monitor therapy
Tropisetron: CYP3A4 Inducers (Strong) may decrease the serum concentration of Tropisetron. Risk C: Monitor therapy
Tucatinib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Tucatinib. Risk X: Avoid combination
Ubrogepant: CYP3A4 Inducers (Strong) may decrease the serum concentration of Ubrogepant. Risk X: Avoid combination
Udenafil: CYP3A4 Inducers (Strong) may decrease the serum concentration of Udenafil. Risk C: Monitor therapy
Ulipristal: CYP3A4 Inducers (Strong) may decrease the serum concentration of Ulipristal. Risk X: Avoid combination
Upadacitinib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Upadacitinib. Risk X: Avoid combination
Valbenazine: CYP3A4 Inducers (Strong) may decrease serum concentrations of the active metabolite(s) of Valbenazine. CYP3A4 Inducers (Strong) may decrease the serum concentration of Valbenazine. Risk X: Avoid combination
Valproate Products: May increase serum concentrations of the active metabolite(s) of CarBAMazepine. Parent carbamazepine concentrations may be increased, decreased, or unchanged. CarBAMazepine may decrease the serum concentration of Valproate Products. Risk C: Monitor therapy
Vandetanib: CYP3A4 Inducers (Strong) may increase serum concentrations of the active metabolite(s) of Vandetanib. CYP3A4 Inducers (Strong) may decrease the serum concentration of Vandetanib. Risk X: Avoid combination
Vecuronium: CarBAMazepine may decrease the serum concentration of Vecuronium. Risk C: Monitor therapy
Velpatasvir: CYP2B6 Inducers (Moderate) may decrease the serum concentration of Velpatasvir. Risk X: Avoid combination
Velpatasvir: CYP3A4 Inducers (Strong) may decrease the serum concentration of Velpatasvir. Risk X: Avoid combination
Vemurafenib: CYP3A4 Inducers (Strong) may decrease the 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 the serum concentration of Venetoclax. Risk X: Avoid combination
Vilazodone: CYP3A4 Inducers (Strong) may decrease the 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 the serum concentration of VinCRIStine. Risk C: Monitor therapy
VinCRIStine (Liposomal): CYP3A4 Inducers (Strong) may decrease the serum concentration of VinCRIStine (Liposomal). Risk X: Avoid combination
VinCRIStine (Liposomal): P-glycoprotein/ABCB1 Inducers may decrease the serum concentration of VinCRIStine (Liposomal). Risk X: Avoid combination
Vinflunine: CYP3A4 Inducers (Strong) may decrease the serum concentration of Vinflunine. Risk X: Avoid combination
Vinorelbine: CYP3A4 Inducers (Strong) may decrease the serum concentration of Vinorelbine. Risk C: Monitor therapy
Vitamin K Antagonists (eg, warfarin): CarBAMazepine may decrease the 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 the serum concentration of Voclosporin. Risk X: Avoid combination
Vonoprazan: CYP3A4 Inducers (Strong) may decrease the serum concentration of Vonoprazan. Risk X: Avoid combination
Vorapaxar: CYP3A4 Inducers (Strong) may decrease the serum concentration of Vorapaxar. Risk X: Avoid combination
Voriconazole: CarBAMazepine may decrease the serum concentration of Voriconazole. Risk X: Avoid combination
Vortioxetine: CYP3A4 Inducers (Strong) may decrease the 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 the 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 the serum concentration of Voxilaprevir. Risk X: Avoid combination
Zaleplon: CYP3A4 Inducers (Strong) may decrease the 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 the serum concentration of Zanubrutinib. Risk X: Avoid combination
Zavegepant: OATP1B1/1B3 (SLCO1B1/1B3) Inducers may decrease the serum concentration of Zavegepant. Risk X: Avoid combination
Ziprasidone: CYP3A4 Inducers (Strong) may decrease the serum concentration of Ziprasidone. Risk C: Monitor therapy
Zolpidem: CYP3A4 Inducers (Strong) may decrease the serum concentration of Zolpidem. Risk C: Monitor therapy
Zonisamide: CYP3A4 Inducers (Strong) may decrease the serum concentration of Zonisamide. Risk C: Monitor therapy
Zopiclone: CarBAMazepine may enhance the CNS depressant effect of Zopiclone. CarBAMazepine may decrease the serum concentration of Zopiclone. Risk C: Monitor therapy
Zuclopenthixol: CYP3A4 Inducers (Strong) may decrease the serum concentration of Zuclopenthixol. Risk C: Monitor therapy
Zuranolone: CYP3A4 Inducers (Strong) may decrease the serum concentration of Zuranolone. Risk X: Avoid combination
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 may decrease plasma concentrations of hormonal contraceptives (consult drug interactions database); alternate or back-up methods of contraception should be considered.
Carbamazepine is associated with adverse pregnancy outcomes; when alternative therapies are not appropriate, folic acid supplementation is recommended for patients who could become pregnant.
Carbamazepine and its active metabolite cross the placenta; concentrations are variable but correlate with maternal serum concentrations (Kacirova 2016).
Carbamazepine may be associated with teratogenic effects, including spina bifida, craniofacial defects, and cardiovascular malformations. Data from the International Registry of Antiepileptic Drugs and Pregnancy (EURAP) and the UK and Ireland Epilepsy Pregnancy Registers (UKEPR) note the risk of congenital malformations increases with higher doses (Campbell 2014; Tomson 2011). The risk of teratogenic effects is higher with antiseizure polytherapy than monotherapy. Developmental delays have also been observed following in utero exposure to carbamazepine (per manufacturer). Folic acid supplementation is recommended if treatment is required during pregnancy.
Due to pregnancy-induced physiologic changes, some pharmacokinetic properties of carbamazepine may be altered; however, available studies have slightly conflicting results (Deligiannidis 2014; Tomson 2013). Therapeutic drug monitoring of carbamazepine is recommended in pregnant patients (Harden 2009; Hiemke 2018).
Carbamazepine is not recommended for the treatment of bipolar disorder in pregnancy (Larsen 2015).
Data collection to monitor pregnancy and infant outcomes following exposure to carbamazepine is ongoing. Patients exposed to carbamazepine during pregnancy are encouraged to enroll themselves into the North American Antiepileptic Drug (NAAED) Pregnancy Registry by calling 1-888-233-2334. Additional information is available at www.aedpregnancyregistry.org.
Carbamazepine and its active epoxide metabolite are present in breast milk.
Carbamazepine can also be detected in the serum of breastfed infants (Wisner 1998). Respiratory depression, seizures, nausea, vomiting, diarrhea, and/or decreased feeding have been observed in some neonates exposed to carbamazepine and may represent a neonatal withdrawal syndrome
According to the manufacturer, the estimated dose of carbamazepine to a breastfeeding infant is ~2 to 5 mg/day (~1 to 2 mg/day for the metabolite). Milk concentrations have been reported to be 39.4% ± 19.3% of the maternal serum (Kaneko 1979) and have no correlation with maternal carbamazepine dose (Froescher 1984). Concentrations of carbamazepine and the metabolite in breast milk are influenced by maternal use of other medications which influence its metabolism (Kacirova 2011).
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. The WHO considers carbamazepine to be compatible with breastfeeding; infants should be monitored for adverse events (WHO 2002). When used for the treatment of bipolar disorder, carbamazepine is considered acceptable for use in breastfeeding patients (Larsen 2015).
Measuring carbamazepine concentrations in the serum of breastfeeding infants is not recommended; however, breastfeeding should be discontinued if adverse events are observed (ACOG 2008).
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, 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).
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%)
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