Your activity: 75 p.v.
your limit has been reached. plz Donate us to allow your ip full access, Email: sshnevis@outlook.com

Carbamazepine: Drug information

Carbamazepine: Drug information
(For additional information see "Carbamazepine: Patient drug information" and see "Carbamazepine: Pediatric drug information")

For abbreviations, symbols, and age group definitions used in Lexicomp (show table)
ALERT: US Boxed Warning
Serious dermatologic reactions and HLA-B*1502 allele:

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:

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.

Brand Names: US
  • Carbatrol;
  • Epitol;
  • Equetro;
  • TEGretol;
  • TEGretol-XR
Brand Names: Canada
  • APO-CarBAMazepine;
  • DOM-CarBAMazepine;
  • DOM-CarBAMazepine CR;
  • Mazepine;
  • PMS-CarBAMazepine;
  • PMS-CarBAMazepine CR;
  • PMS-CarBAMazepine-CR;
  • SANDOZ CarBAMazepine CR;
  • SANDOZ CarBAMazepine [DSC];
  • TARO-CarBAMazepine;
  • TEGretol;
  • TEGretol CR;
  • TEVA-Carbamazepine
Pharmacologic Category
  • Anticonvulsant, Miscellaneous;
  • Antimanic Agent
Dosing: Adult

Note:

Safety: Before prescribing, test for the HLA-B*1502 allele in patients at increased genetic risk (eg, those of Asian ancestry, including South Asian Indian patients) for carbamazepine-associated serious cutaneous adverse reactions (SCAR). For patients who test positive for HLA-B*1502, reevaluate need for therapy and do not use carbamazepine if other medications are available. SCAR may still occur in patients without HLA-B*1502. Testing for other alleles associated with hypersensitivity (eg, HLA-A*3101, HLA-A*24:02) is not well established (Amstutz 2014; Leckband 2013; Schachter 2020a; Shi 2017).

Therapeutic drug monitoring: May be useful, particularly in patients with seizure disorder; monitor more closely during the first few weeks of therapy because carbamazepine induces its own metabolism, which may lead to a decrease in serum levels in the first 3 to 5 weeks of therapy and require subsequent dosage adjustment(s).

Dosage forms: 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. Available oral preparations include: Immediate release (suspension, tablet, chewable tablet) (usually dosed 2 to 4 times daily) and 12-hour extended release (dosed twice daily).

Bipolar disorder, hypomania and mild to moderate mania or episodes with mixed features and bipolar major depression

Bipolar disorder, hypomania and mild to moderate mania or episodes with mixed features (alternative agent) and bipolar major depression (alternative agent) (BAP [Goodwin 2016]; Bobo 2022):

Acute treatment (monotherapy): Oral: Initial: 100 to 400 mg/day; 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; maximum dose: 1.6 g/day (Stovall 2019; WFSBP [Grunze 2009]; manufacturer's labeling). Doses up to 1.8 g/day may be necessary in some patients for optimal response (Stoval 2019).

Maintenance (monotherapy) (off-label use): Oral: Continue dose that was used to achieve control of the acute episode (Peselow 2016).

Focal onset seizures and generalized onset seizures

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) or up to 400 mg/day (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). After 2 to 3 months of treatment, serum concentrations may decrease due to hepatic enzyme autoinduction and dose may need to be further increased to 15 to 20 mg/kg/day; doses up to ~2 g/day may be needed in some patients for optimal effect (Schachter 2020a).

Neuropathic pain

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) (Pandey 2005; SCCM [Devlin 2018]).

Oral: Initial: 200 to 400 mg/day, gradually increasing (eg, over several weeks) in increments of 200 mg/day as needed. Usual maintenance dose: 600 to 800 mg/day; maximum dose: 1.2 g/day (Ho 2021; manufacturer's labeling).

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 (Chen 2014; Medical Research Council Antiepileptic Drug Withdrawal Study Group 1991; Schachter 2020b). In patients discontinuing therapy for treatment of bipolar disorder, close monitoring for several weeks to months for reemergence of mania/hypomania is recommended (Post 2021).

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing: Kidney Impairment: Adult

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 (Tutor-Crespo 2008).

Mild to severe impairment: Initial: No dosage adjustment necessary (Anderson 2014). 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 (Lee 1980; expert opinion). Subsequent dose adjustments should be based on patient response, tolerability, and serum concentrations.

Peritoneal dialysis: Initial: No dosage adjustment necessary (Mora Rodríguez 2018). Subsequent dose adjustments should be based on patient response, tolerability, and serum concentrations.

CRRT: Initial: No dosage adjustment necessary (Mahmoud 2017). Subsequent dose adjustments should be based on patient response, tolerability, and serum concentrations.

Dosing: Hepatic Impairment: Adult

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.

Dosing: Pediatric

(For additional information see "Carbamazepine: Pediatric drug information")

Note: 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 (Amstutz 2014; Leckband 2013). 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 (Leckband 2013; Shi 2017). A negative genetic test does not entirely rule out the possibility of a hypersensitivity or cutaneous reaction, and patients should be monitored throughout therapy.

Seizure disorder: Dosage must be adjusted according to patient's response and serum concentrations.

Oral:

Infants and Children <6 years:

Immediate-release formulations:

Tablets: 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: 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: 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: 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: 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: 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: 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: 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: 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 (Graves 1987).

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 (Beghi 2013; Specchio 2004; Strozzi 2015).

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing: Kidney Impairment: Pediatric

Altered kidney function: Infants, Children, and Adolescents:

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 (Tutor-Crespo 2008).

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 (Anderson 2014).

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 (Mora Rodríguez 2018).

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 (Mora Rodríguez 2018).

Continuous renal replacement therapy (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 (Mahmoud 2017).

Dosing: Hepatic Impairment: Pediatric

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.

Dosing: Older Adult

Refer to adult dosing.

Dosage Forms: US

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)]

Carbatrol: 200 mg, 300 mg

Equetro: 100 mg, 200 mg, 300 mg [contains fd&c blue #2 (indigotine)]

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]

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

Generic Equivalent Available: US

Yes

Dosage Forms: Canada

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

Medication Guide and/or Vaccine Information Statement (VIS)

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/2013/020712s032s035mg.pdf

Equetro: https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/021710s11s012lbl.pdf#page=22

TEGretol, TEGretol-XR: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/016608s115_018281_s058_018927s055_020234_s047.pdf#page=19

Administration: Adult

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).

Administration: Pediatric

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 administer; if defecation occurs within the first 2 hours, repeat the dose (Graves 1987).

Hazardous Drugs Handling Considerations

Hazardous agent (NIOSH 2016 [group 2]).

Use appropriate precautions for receiving, handling, administration, and disposal. Gloves (single) should be worn during receiving, unpacking, and placing in storage.

NIOSH recommends single gloving for administration of intact tablets or capsules. If manipulating tablets/capsules (eg, to prepare an oral suspension), NIOSH recommends double gloving, a protective gown, and preparation in a controlled device; if not prepared in a controlled device, respiratory and eye/face protection as well as ventilated engineering controls are recommended. NIOSH recommends double gloving, a protective gown, and (if there is a potential for vomit or spit up) eye/face protection for administration of an oral liquid/feeding tube administration (NIOSH 2016). Assess risk to determine appropriate containment strategy (USP-NF 2017).

Use: Labeled Indications

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.

Use: Off-Label: Adult

Bipolar major depression; Maintenance treatment for bipolar disorder

Medication Safety Issues
Sound-alike/look-alike issues:

CarBAMazepine may be confused with OXcarbazepine

Epitol may be confused with Epinal

TEGretol, TEGretol-XR may be confused with Mebaral, Toprol-XL, Toradol, TRENtal

High alert medication:

The Institute for Safe Medication Practices (ISMP) includes this medication among its list of drugs that have a heightened risk of causing significant patient harm when used in error.

Geriatric Patients: High-Risk Medication:

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 2019]).

Adverse Reactions (Significant): Considerations
Blood dyscrasias

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)

Cardiac effects

Carbamazepine has been reported to increase the risk of cardiac 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)

Hepatotoxicity

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 within 5 to 7 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 up to 6 to 12 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)

Hypersensitivity reactions (delayed)

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)

Hyponatremia

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)

Neuropsychiatric effects

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

Suicidal ideation/tendencies

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)

Adverse Reactions

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)

Carbamazepine: Adverse Reaction: Ataxia

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

Carbamazepine: Adverse Reaction: Dizziness

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

Carbamazepine: Adverse Reaction: Drowsiness

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%)

Dermatologic: Pruritus (8%), skin rash (7%)

Gastrointestinal: Constipation (10%), xerostomia (8%)

Nervous system: Abnormality in thinking (2%), paresthesia (2%), speech disturbance (6%), twitching (2%), vertigo (2%)

Neuromuscular & skeletal: Asthenia (8%), tremor (3%)

Ophthalmic: Blurred vision (6%)

Frequency not defined: Nervous system: Suicidal tendencies

Postmarketing:

Cardiovascular: Arterial insufficiency (cerebral artery), atrioventricular block (Koutsampasopoulos 2014), cardiac arrhythmia, cardiac failure, collapse, coronary artery disease (aggravation), edema, exacerbation of hypertension, hypotension, lip edema, pulmonary embolism, sinus tachycardia (Kasarskis 1992), syncope, thromboembolism, thrombophlebitis

Dermatologic: Acute generalized exanthematous pustulosis (Skalli 2011), alopecia, diaphoresis, dyschromia, erythema multiforme, erythema nodosum, erythematous rash, exfoliative dermatitis, maculopapular rash, onychomadesis, pruritic rash, skin photosensitivity, Stevens-Johnson syndrome (Khoo 2016), toxic epidermal necrolysis (Stătescu 2017), urticaria

Endocrine & metabolic: Acute intermittent porphyria (Yeung Laiwah 1983), albuminuria, decreased serum calcium, decreased thyroid hormones, glycosuria, hirsutism, hyponatremia (Kaeley 2019), increased gamma-glutamyl transferase (Hadzagic-Catibusic 2017), porphyria cutanea tarda (Leo 1996), porphyria (variegate) (Grieco 2001), SIADH (Kaeley 2019)

Gastrointestinal: Abdominal pain, anorexia, diarrhea, dysgeusia (Syed 2016), gastric distress, glossitis, glottis edema, pancreatitis (Ali 2021), stomatitis

Genitourinary: Acute urinary retention, azotemia, defective spermatogenesis, 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, neutropenia (Sobotka 1990), pancytopenia (Sobotka 1990), purpuric disease, thrombocytopenia (Sobotka 1990)

Hepatic: Cholestatic hepatitis, hepatic failure, hepatitis (mixed), hepatocellular hepatitis, hepatotoxicity (idiosyncratic) (Chalasani 2021), increased serum alkaline phosphatase (Hadzagic-Catibusic 2017), increased serum transaminases, intrahepatic cholestasis (vanishing bile duct syndrome)

Hypersensitivity: Anaphylaxis, angioedema (Subramanian 2016)

Immunologic: Drug reaction with eosinophilia and systemic symptoms (Chung 2021)

Nervous system: Agitation, anxiety (Kennedy 2008), aseptic meningitis (Dang 1996), 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, 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, punctate cataract

Otic: Tinnitus

Renal: Acute kidney injury (Jubert 1994)

Respiratory: Dry throat, laryngeal edema, pulmonary hypersensitivity reaction (Cullinan 1975)

Miscellaneous: Fever

Contraindications

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.

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.

Warnings/Precautions

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.

• Elderly: May activate latent psychosis, confusion, or agitation.

• Pediatric: Exacerbation of certain seizure types have been seen after initiation of therapy in children with mixed seizure disorders.

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.

Warnings: Additional Pediatric Considerations

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).

Metabolism/Transport Effects

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

Drug Interactions

5-Aminosalicylic Acid Derivatives: May enhance the myelosuppressive effect of Myelosuppressive Agents. Risk C: Monitor therapy

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 whenever possible. If such a combination cannot be avoided, increase abiraterone acetate dosing frequency from once daily to twice daily during concomitant use. 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

Adenosine: CarBAMazepine may enhance the adverse/toxic effect of Adenosine. Specifically, the risk of higher degree heart block may be increased. Management: Consider using a lower initial dose of adenosine in patients who are receiving carbamazepine. Risk D: Consider therapy modification

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

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

Allopurinol: May increase the serum concentration of CarBAMazepine. 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

Asunaprevir: CYP3A4 Inducers (Strong) may decrease the serum concentration of Asunaprevir. Risk X: Avoid combination

Atazanavir: CarBAMazepine may decrease the serum concentration of Atazanavir. Atazanavir may increase the serum concentration of CarBAMazepine. Management: Coadministration of carbamazepine and atazanavir without ritonavir is not recommended. Carbamazepine dose reductions may be necessary for patients taking carbamazepine who initiate atazanavir/ritonavir. Risk D: Consider therapy modification

Atogepant: CYP3A4 Inducers (Strong) may decrease the serum concentration of Atogepant. Management: The recommended dose of atogepant is 30 mg once daily or 60 mg once daily when combined with strong or moderate CYP3A4 inducers. 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

BCG (Intravesical): Myelosuppressive Agents may diminish the therapeutic effect of BCG (Intravesical). Risk X: Avoid combination

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

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

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

Capmatinib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Capmatinib. Risk X: Avoid combination

Carbonic Anhydrase Inhibitors: May increase the serum concentration of CarBAMazepine. Risk C: Monitor therapy

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

Chloramphenicol (Ophthalmic): May enhance the adverse/toxic effect of Myelosuppressive Agents. Risk C: Monitor therapy

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: May enhance the myelosuppressive effect of Myelosuppressive Agents. Risk X: Avoid combination

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

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

Deferiprone: Myelosuppressive Agents may enhance the neutropenic effect of Deferiprone. Management: Avoid the concomitant use of deferiprone and myelosuppressive agents whenever possible. If this combination cannot be avoided, monitor the absolute neutrophil count more closely. 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: Consider dexamethasone dose increases in patients receiving strong CYP3A4 inducers and monitor closely for reduced dexamethasone efficacy. Consider avoiding this combination when treating life threatening conditions (ie, multiple myeloma). Risk D: Consider therapy modification

DiazePAM: CYP3A4 Inducers (Strong) may decrease the serum concentration of DiazePAM. Risk C: Monitor therapy

Digoxin: P-glycoprotein/ABCB1 Inducers may decrease the serum concentration of Digoxin. Risk C: Monitor therapy

Dipyrone: May enhance the adverse/toxic effect of Myelosuppressive Agents. Specifically, the risk for agranulocytosis and pancytopenia may be increased Risk X: Avoid combination

Disopyramide: CYP3A4 Inducers (Strong) may decrease the serum concentration of Disopyramide. 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. See interaction monograph for details. Seek alternative to carbamazepine if suspected INSTI resistance. 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. Management: Consider increasing the doxycycline dose, or using another tetracycline derivative due to the potential for reduced doxycycline therapeutic effects when coadministered wth carbamazepine. If combined, monitor for reduced doxycyline efficacy. Risk D: Consider therapy modification

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

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

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

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

Ezogabine: CarBAMazepine may decrease the serum concentration of Ezogabine. Management: Consider increasing the ezogabine dose when adding carbamazepine. Monitor patients using the combination closely for evidence of adequate ezogabine therapy. 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

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

Fexinidazole: Myelosuppressive Agents may enhance the myelosuppressive effect 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

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

Fusidic Acid (Systemic): May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk X: Avoid combination

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

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

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

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

Lercanidipine: CYP3A4 Inducers (Strong) may decrease the serum concentration of Lercanidipine. Risk C: Monitor therapy

Lesinurad: CarBAMazepine may decrease the serum concentration of Lesinurad. Lesinurad may decrease the serum concentration of CarBAMazepine. Risk C: Monitor therapy

Letermovir: P-glycoprotein/ABCB1 Inducers may decrease the serum concentration of Letermovir. Risk X: Avoid combination

Letermovir: May increase the serum concentration of UGT1A1 Inducers. 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

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

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 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

Methylfolate: May decrease the serum concentration of CarBAMazepine. 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

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. Risk X: Avoid combination

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

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

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: CYP3A4 Inducers (Strong) may decrease the serum concentration of Nirmatrelvir. Risk X: Avoid combination

Nisoldipine: CYP3A4 Inducers (Strong) may decrease the serum concentration of Nisoldipine. Risk X: Avoid combination

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

Ondansetron: CYP3A4 Inducers (Strong) may decrease the serum concentration of Ondansetron. Risk C: Monitor therapy

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

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

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

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

Promazine: May enhance the myelosuppressive effect of Myelosuppressive Agents. Risk C: Monitor therapy

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

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

Remdesivir: CYP3A4 Inducers (Strong) may decrease the serum concentration of Remdesivir. Risk C: Monitor therapy

Repaglinide: CYP3A4 Inducers (Strong) may decrease the serum concentration of Repaglinide. Risk C: Monitor therapy

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

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: CYP3A4 Inducers (Strong) may decrease serum concentrations of the active metabolite(s) of Roflumilast. CYP3A4 Inducers (Strong) may decrease the serum concentration of Roflumilast. 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

Ropeginterferon Alfa-2b: Myelosuppressive Agents may enhance the myelosuppressive effect of Ropeginterferon Alfa-2b. Management: Avoid coadministration of ropeginterferon alfa-2b and other myelosuppressive agents. If this combination cannot be avoided, monitor patients for excessive myelosuppressive effects. Risk D: Consider therapy modification

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

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

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

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

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

Tazemetostat: CYP3A4 Inducers (Strong) may decrease the serum concentration of Tazemetostat. Risk X: Avoid combination

Telithromycin: CYP3A4 Inducers (Strong) may decrease the serum concentration of Telithromycin. Risk X: Avoid combination

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

Tepotinib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Tepotinib. 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

Thiazide and Thiazide-Like Diuretics: May enhance the adverse/toxic effect of CarBAMazepine. Specifically, there may be an increased risk for hyponatremia. Risk C: Monitor therapy

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: 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

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

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

Ziprasidone: CarBAMazepine 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

Food Interactions

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.

Reproductive Considerations

Carbamazepine may decrease plasma concentrations of hormonal contraceptives; alternate or back-up methods of contraception should be considered. Carbamazepine may interfere with some pregnancy tests.

Pregnancy Considerations

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).

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 women (Harden 2009; Hiemke 2018).

Carbamazepine is not recommended for the treatment of bipolar disorder in pregnancy (Larsen 2015).

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.

Breastfeeding Considerations

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 continue or discontinue breastfeeding during therapy should take into account the risk of exposure 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 women (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).

Dietary Considerations

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).

Monitoring Parameters

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)

Reference Range

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: Draw trough just before next dose (APA [Hirschfeld 2002])

Epilepsy: Therapeutic levels: 4 to 12 mcg/mL (SI: 17 to 51 micromole/L). The same goal range is applied for bipolar disorder, despite limited data on monitoring serum concentrations in this population (APA [Hirschfeld 2002]).

Toxic concentration: >15 mcg/mL; patients who require higher levels of 8 to 12 mcg/mL (SI: 34 to 51 micromole/L) should be watched closely. Side effects including CNS effects occur commonly at higher dosage levels. If other antiseizure medications are given therapeutic range is 4 to 8 mcg/mL.

Mechanism of Action

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

Pharmacokinetics

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%)

Pricing: US

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): $0.45

Suspension (TEGretol Oral)

100 mg/5 mL (per mL): $0.44

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): $1.63

200 mg (per each): $3.25

400 mg (per each): $6.49

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): $3.04

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.

Brand Names: International
  • Actinerval (AR, PY);
  • Anleptic 200 CR (LK);
  • Apo-Carbamazepine (MY);
  • Arbateg (EG);
  • Arbil (GB);
  • Azepal (HU);
  • Bamgetol (ID);
  • Brucarcer (MX);
  • Calzepin (VN);
  • Camapine (TW);
  • Carazepin (AE, CY, IQ, IR, JO, KW, LY, OM, SA, SY, YE);
  • Carbadac (BF, BJ, CI, ET, GH, GM, GN, KE, LR, MA, ML, MR, MU, MW, NE, NG, SC, SD, SL, SN, TN, TZ, UG, ZM, ZW);
  • Carbagen (GB);
  • Carbalex (EE, LV, UA);
  • Carbam (EC);
  • Carbamazepin-B (HU);
  • Carbapex (EG);
  • Carbapin (PE, UA);
  • Carbatec (SY);
  • Carbatol (BH, ET, IN, JO, TW);
  • Carbatol CR (LK, SG);
  • Carbazedin (PH);
  • Carbazene (TH);
  • Carbazina (MX);
  • Carbilepp (PH);
  • Carmapine (TH);
  • Carmaz (BD, IN);
  • Carmine (KR);
  • Carpin (MX);
  • Carzepin (HK, MY);
  • Ceplep (BD);
  • Convulax (KW);
  • Convulex (VE);
  • Degranol (ZA);
  • Elebe (AR);
  • Elpenor (DE);
  • Epazin (PH);
  • Epicarb (ZW);
  • Epilep (BD);
  • Epilep CR (BD);
  • Epileptol (KR);
  • Epileptol CR (KR);
  • Eposal Retard (CO);
  • Finlepsin (BG, HU, LV, PL, RO, UA);
  • Fitzecalm (AE, BH, QA);
  • Hermolepsin (SE);
  • Karbamazepin (DK);
  • Lepsitol (ID);
  • Li Zhen (CN);
  • Mezacar SR (PH);
  • Neugeron (MX);
  • Neurolep (MX);
  • Neurotol (FI);
  • Neurotop (AT, BG, HU, LB);
  • Sepibest (MX);
  • Sirtal (DE);
  • Stazepine (HU);
  • Storilat (MT);
  • Tanfedin (VE);
  • Taver (MY, VN);
  • Tegol (TW);
  • Tegral (PK);
  • Tegrepin (PH);
  • Tegretal (CL, DE);
  • Tegretard (BR);
  • Tegretol (AR, AU, BB, BD, BE, BF, BH, BJ, BM, BR, BS, BZ, CH, CI, CN, CO, CR, CY, CZ, DK, DO, EC, EE, EG, ES, ET, FI, FR, GB, GH, GM, GN, GR, GT, GY, HK, HN, HR, HU, ID, IE, IL, IQ, IR, IS, IT, JM, JO, JP, KE, KR, KW, LB, LK, LR, LT, LU, LY, MA, ML, MR, MT, MU, MW, MX, MY, NE, NG, NI, NL, NO, NZ, OM, PA, PE, PH, PK, PL, PT, PY, QA, RO, RU, SA, SC, SD, SE, SG, SI, SL, SN, SR, SV, SY, TH, TN, TR, TT, TW, TZ, UA, UG, UY, VE, YE, ZA, ZM, ZW);
  • Tegretol CR (BE, CZ, EE, EG, HR, IL, KR, LB, LU, LV, MT, NL, NZ, PE, QA, RO, SA, SG, SI, SK, TR, ZW);
  • Tegretol-XR (BB);
  • TegretolCR (BD);
  • Tegrex (BR);
  • Temporol (HU);
  • Teril (AU, IL, NZ, TR);
  • Timonil (DE, HU);
  • Timonil Retard (CH, DE, IL);
  • Timonol SR (KR);
  • Torbarec (ZW);
  • Trepina (MX);
  • Trimonil (SE);
  • Trimonil Retard (NO);
  • Vulsivan (CO);
  • Zeptol CR (LK);
  • Zigma CR (LK)


For country abbreviations used in Lexicomp (show table)

REFERENCES

  1. <800> Hazardous Drugs—Handling in Healthcare Settings. United States Pharmacopeia and National Formulary (USP 40-NF 35). Rockville, MD: United States Pharmacopeia Convention; 2017:83-102.
  2. 2019 American Geriatrics Society Beers Criteria Update Expert Panel. American Geriatrics Society 2019 updated AGS Beers Criteria for Potentially Inappropriate Medication Use in Older Adults. J Am Geriatr Soc. 2019;67(4):674-694. doi: 10.1111/jgs.15767. [PubMed 30693946]
  3. ACOG Committee on Practice Bulletins-Obstetrics, "ACOG Practice Bulletin: Clinical Management Guidelines for Obstetrician-Gynecologists Number 92, April 2008 (Replaces Practice Bulletin Number 87, November 2007). Use of Psychiatric Medications During Pregnancy and Lactation," Obstet Gynecol, 2008, 111(4):1001-20. [PubMed 18378767]
  4. Adler NR, Aung AK, Ergen EN, Trubiano J, Goh MSY, Phillips EJ. Recent advances in the understanding of severe cutaneous adverse reactions. Br J Dermatol. 2017;177(5):1234-1247. doi:10.1111/bjd.15423 [PubMed 28256714]
  5. Ahluwalia J, Abuabara K, Perman MJ, Yan AC. Human herpesvirus 6 involvement in paediatric drug hypersensitivity syndrome. Br J Dermatol. 2015;172(4):1090-1095. doi:10.1111/bjd.13512 [PubMed 25369238]
  6. Ali A, Anugwom GO, Naqvi W, Saeeduddin MO, Singh R. A case of carbamazepine-induced acute pancreatitis: a rare etiology. Cureus. 2021;13(5):e15199. doi:10.7759/cureus.15199 [PubMed 34178519]
  7. American Academy of Pediatrics Committee on Drugs. "Inactive" ingredients in pharmaceutical products: update (subject review). Pediatrics. 1997;99(2):268-278. [PubMed 9024461]
  8. Amstutz U, Shear NH, Rieder MJ, et al; CPNDS Clinical Recommendation Group. Recommendations for HLA-B*15:02 and HLA-A*31:01 genetic testing to reduce the risk of carbamazepine-induced hypersensitivity reactions. Epilepsia. 2014;55(4):496-506. doi:10.1111/epi.12564 [PubMed 24597466]
  9. Anderson GD, Hakimian S. Pharmacokinetic of antiepileptic drugs in patients with hepatic or renal impairment. Clin Pharmacokinet. 2014;53(1):29-49. doi: 10.1007/s40262-013-0107-0. [PubMed 24122696]
  10. Andrade RJ; European Association for the Study of the Liver panel members. EASL clinical practice guidelines: drug-induced liver injury. J Hepatol. 2019;70(6):1222-1261. doi:10.1016/j.jhep.2019.02.014 [PubMed 30926241]
  11. Apeland T, Frøyland ES, Kristensen O, Strandjord RE, Mansoor MA. Drug-induced pertubation of the aminothiol redox-status in patients with epilepsy: improvement by B-vitamins. Epilepsy Res. 2008;82(1):1-6. [PubMed 18644700]
  12. Apeland T, Mansoor MA, Pentieva K, McNulty H, Strandjord RE. Fasting and post-methionine loading concentrations of homocysteine, vitamin B2, and vitamin B6 in patients on antiepileptic drugs. Clin Chem. 2003;49(6 Pt 1):1005-1008. [PubMed 12766014]
  13. Arana A, Wentworth CE, Ayuso-Mateos JL, Arellano FM. Suicide-related events in patients treated with antiepileptic drugs. N Engl J Med. 2010;363(6):542-551. doi:10.1056/NEJMoa0909801 [PubMed 20818889]
  14. Atalay E, Tamçelik N, Capar O. High intraocular pressure after carbamazepine and gabapentin intake in a pseudoexfoliative patient. J Glaucoma. 2014;23(8):574-576. doi:10.1097/IJG.0b013e318287aca7 [PubMed 23429633]
  15. Atanasković-Marković M, Janković J, Tmušić V, et al. Hypersensitivity reactions to antiepileptic drugs in children. Pediatr Allergy Immunol. 2019;30(5):547-552. doi:10.1111/pai.13055 [PubMed 30951222]
  16. Barr J, Fraser G, Puntillo K, et al; American College of Critical Care Medicine. Clinical practice guidelines for the management of pain, agitation, and delirium in adult patients in the intensive care unit. Crit Care Med. 2013;41(1):263-306. doi: 10.1097/CCM.0b013e3182783b72. [PubMed 23269131]
  17. Battino D, Estienne M, Avanzini G. Clinical pharmacokinetics of antiepileptic drugs in paediatric patients. Part II. Phenytoin, carbamazepine, sulthiame, lamotrigine, vigabatrin, oxcarbazepine and felbamate. Clin Pharmacokinet. 1995;29(5):341-369. [PubMed 8582119]
  18. Beghi E, Giussani G, Grosso S, et al. Withdrawal of antiepileptic drugs: guidelines of the Italian League Against Epilepsy. Epilepsia. 2013;54(suppl 7):S2-S12. [PubMed 24099051]
  19. Belcastro V, Striano P. Antiepileptic drugs, hyperhomocysteinemia and B-vitamins supplementation in patients with epilepsy. Epilepsy Res. 2012;102(1-2):1-7. [PubMed 22824326]
  20. Bell GS, Gaitatzis A, Bell CL, Johnson AL, Sander JW. Suicide in people with epilepsy: how great is the risk? Epilepsia. 2009;50(8):1933-1942. doi:10.1111/j.1528-1167.2009.02106.x [PubMed 19453718]
  21. Bellivier F, Belzeaux R, Scott J, Courtet P, Golmard JL, Azorin JM. Anticonvulsants and suicide attempts in bipolar I disorders. Acta Psychiatr Scand. 2017;135(5):470-478. doi:10.1111/acps.12709 [PubMed 28190254]
  22. Bellón T. Mechanisms of severe cutaneous adverse reactions: recent advances. Drug Saf. 2019;42(8):973-992. doi:10.1007/s40264-019-00825-2 [PubMed 31020549]
  23. Berg I, Butler A, Ellis M, Foster J. Psychiatric aspects of epilepsy in childhood treated with carbamazepine, phenytoin or sodium valproate: a random trial. Dev Med Child Neurol. 1993;35(2):149-157. doi:10.1111/j.1469-8749.1993.tb11616.x [PubMed 8444328]
  24. Bermeo-Ovalle A. Making rash decisions in epilepsy: evaluating hypersensitivity reactions to anti-seizure medications. Epilepsy Curr. 2019;19(2):96-98. doi:10.1177/1535759719835672 [PubMed 30955419]
  25. Björnsson E. Hepatotoxicity associated with antiepileptic drugs. Acta Neurol Scand. 2008;118(5):281-290. doi:10.1111/j.1600-0404.2008.01009.x [PubMed 18341684]
  26. Błaszczyk B, Lasoń W, Czuczwar SJ. Antiepileptic drugs and adverse skin reactions: An update. Pharmacol Rep. 2015;67(3):426-434. doi:10.1016/j.pharep.2014.11.009 [PubMed 25933949]
  27. Błaszczyk B, Szpringer M, Czuczwar SJ, Lasoń W. Single centre 20 year survey of antiepileptic drug-induced hypersensitivity reactions. Pharmacol Rep. 2013;65(2):399-409. doi:10.1016/s1734-1140(13)71015-6 [PubMed 23744424]
  28. Bobo WV, Shelton RC. Bipolar major depression in adults: Efficacy and adverse effects of antidepressants. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed January 13, 2022.
  29. Bochyńska A, Lipczyńska-Łojkowska W, Gugała-Iwaniuk M, et al. The effect of vitamin B supplementation on homocysteine metabolism and clinical state of patients with chronic epilepsy treated with carbamazepine and valproic acid. Seizure. 2012;21(4):276-281. [PubMed 22360846]
  30. Brockow K, Przybilla B, Aberer W, et al. Guideline for the diagnosis of drug hypersensitivity reactions: S2K-Guideline of the German Society for Allergology and Clinical Immunology (DGAKI) and the German Dermatological Society (DDG) in collaboration with the Association of German Allergologists (AeDA), the German Society for Pediatric Allergology and Environmental Medicine (GPA), the German Contact Dermatitis Research Group (DKG), the Swiss Society for Allergy and Immunology (SGAI), the Austrian Society for Allergology and Immunology (ÖGAI), the German Academy of Allergology and Environmental Medicine (DAAU), the German Center for Documentation of Severe Skin Reactions and the German Federal Institute for Drugs and Medical Products (BfArM). Allergo J Int. 2015;24(3):94-105. doi:10.1007/s40629-015-0052-6 [PubMed 26120552]
  31. Campbell E, Kennedy F, Russell A, et al. Malformation risks of antiepileptic drug monotherapies in pregnancy: updated results from the UK and Ireland Epilepsy and Pregnancy Registers. J Neurol Neurosurg Psychiatry. 2014;85(9):1029-1034. [PubMed 24444855]
  32. Carbatrol (carbamazepine) [prescribing information]. Lexington, MA: Shire US; February 2018.
  33. Carbatrol (carbamazepine) [prescribing information]. Lexington, MA: Takeda Pharmaceuticals America, Inc; December 2021.
  34. Carbamazepine. In: LiverTox: Clinical and Research Information on Drug-Induced Liver Injury. National Institute of Diabetes and Digestive and Kidney Diseases; 2017. https://www.ncbi.nlm.nih.gov/books/NBK548097/
  35. Carbamazepine [prescribing information]. North Wales, PA: Teva; December 2018.
  36. Carbamazepine [prescribing information] tablets and chewable tablets. Parsippany, NJ: Teva Pharmaceuticals USA Inc; April 2020.
  37. Chalasani NP, Maddur H, Russo MW, Wong RJ, Reddy KR; Practice Parameters Committee of the American College of Gastroenterology. ACG clinical guideline: diagnosis and management of idiosyncratic drug-induced liver injury. Am J Gastroenterol. 2021;116(5):878-898. doi:10.14309/ajg.0000000000001259 [PubMed 33929376]
  38. Chen MJ, Zhang WJ, Guo ZL, Zhang WH, Chai Y, Li YW. Withdrawal reaction of carbamazepine after neurovascular decompression for trigeminal neuralgia: a preliminary study. J Neurol Sci. 2014;338(1-2):43-45. doi: 10.1016/j.jns.2013.12.013. [PubMed 24387898]
  39. Chung SJ, Ahn KM, Oh JH, Shim JS, Park HW. Incidence rates of severe cutaneous adverse reactions due to antiseizure medication: a nationwide study using health claims data in Korea. Epilepsia. 2021;62(1):250-257. doi:10.1111/epi.16751 [PubMed 33188522]
  40. Cooney GF, Mochon M, Kaiser B, et al, “Effects of Carbamazepine on Cyclosporine Metabolism in Pediatric Renal Transplant Recipients,” Pharmacotherapy, 1995, 15(3):353-6. [PubMed 7667170]
  41. Cullinan SA, Bower GC. Acute pulmonary hypersensitivity to carbamazepine. Chest. 1975;68(4):580-581. doi:10.1378/chest.68.4.580 [PubMed 1175419]
  42. Dang CT, Riley DK. Aseptic meningitis secondary to carbamazepine therapy. Clin Infect Dis. 1996;22(4):729-730. doi:10.1093/clinids/22.4.729 [PubMed 8729227]
  43. Deligiannidis KM, Byatt N, Freeman MP. Pharmacotherapy for mood disorders in pregnancy: a review of pharmacokinetic changes and clinical recommendations for therapeutic drug monitoring. J Clin Psychopharmacol. 2014;34(2):244-255. [PubMed 24525634]
  44. Devarbhavi H, Andrade RJ. Drug-induced liver injury due to antimicrobials, central nervous system agents, and nonsteroidal anti-inflammatory drugs. Semin Liver Dis. 2014;34(2):145-161. doi:10.1055/s-0034-1375956 [PubMed 24879980]
  45. Devlin JW, Skrobik Y, Gélinas C, et al. Clinical practice guidelines for the prevention and management of pain, agitation/sedation, delirium, immobility, and sleep disruption in adult patients in the ICU. Crit Care Med. 2018;46(9):e825-e873. doi: 10.1097/CCM.0000000000003299. [PubMed 30113379]
  46. Epitol (carbamazepine) [prescribing information]. Parsippany, NJ: Teva Pharmaceuticals USA, Inc; April 2020.
  47. Equetro (carbamazepine) [prescribing information]. Parsippany, NJ: Validus Pharmaceuticals LLC; June 2021.
  48. Frey N, Bodmer M, Bircher A, et al. The risk of Stevens-Johnson syndrome and toxic epidermal necrolysis in new users of antiepileptic drugs. Epilepsia. 2017;58(12):2178-2185. doi:10.1111/epi.13925 [PubMed 29027197]
  49. Fricke-Galindo I, LLerena A, Jung-Cook H, López-López M. Carbamazepine adverse drug reactions. Expert Rev Clin Pharmacol. 2018;11(7):705-718. doi:10.1080/17512433.2018.1486707 [PubMed 29898616]
  50. Froescher W, Eichelbaum M, Niesen M, et al, "Carbamazepine Levels in Breast Milk," Ther Drug Monit, 1984, 6(3):266-71. [PubMed 6390794]
  51. Furst SM and Uetrecht JP, “The Effect of Carbamazepine and Its Reactive Metabolite 9-Acridine Carboxaldehyde, on Immune Cell Function in vitro,” Int J Immunopharmacol, 1995, 17(5):445-52. [PubMed 7591369]
  52. Gilman JT, “Carbamazepine Dosing for Pediatric Seizure Disorders: The Highs and Lows,” DICP, 1991, 25(10):1109-12. [PubMed 1803802]
  53. Goodwin GM, Haddad PM, Ferrier IN, et al. Evidence-based guidelines for treating bipolar disorder: revised third edition recommendations from the British Association for Psychopharmacology. J Psychopharmacol. 2016;30(6):495-553. doi: 10.1177/0269881116636545. [PubMed 26979387]
  54. Graves NM, Kriel RL. Rectal administration of antiepileptic drugs in children. Pediatr Neurol. 1987;3(6):321-326. [PubMed 3334021]
  55. Grieco A, Alfei B, Di Rocco P, et al. Non-alcoholic steatohepatitis induced by carbamazepine and variegate porphyria. Eur J Gastroenterol Hepatol. 2001;13(8):973-975. doi:10.1097/00042737-200108000-00018 [PubMed 11507366]
  56. Grunze H, Vieta E, Goodwin GM, et al. The World Federation of Societies of Biological Psychiatry (WFSBP) guidelines for the biological treatment of bipolar disorders: update 2009 on the treatment of acute mania [published correction appears in World J Biol Psychiatry. 2009;10(3):255]. World J Biol Psychiatry. 2009;10(2):85-116. doi: 10.1080/15622970902823202. [PubMed 19347775]
  57. Guvenir H, Dibek Misirlioglu E, Civelek E, et al. The frequency and clinical features of hypersensitivity reactions to antiepileptic drugs in children: a prospective study. J Allergy Clin Immunol Pract. 2018;6(6):2043-2050. doi:10.1016/j.jaip.2018.02.018 [PubMed 29501520]
  58. Hadzagic-Catibusic F, Hasanbegovic E, Melunovic M, Zubcevic S, Uzicanin S. Effects of carbamazepine and valproate on serum aspartate aminotransferase, alanine aminotransferase and gamma - glutamyltransferase in children. Med Arch. 2017;71(4):239-242. doi:10.5455/medarh.2017.71.239-242 [PubMed 28974841]
  59. Hans P, Brichant JF, Pieron F, et al, “Elevated Plasma Alpha 1-Acid Glycoprotein Levels: Lack of Connection to Resistance to Vecuronium Blockade Induced by Anticonvulsant Therapy,” J Neurosurg Anesthesiol, 1997, 9(1):3-7. [PubMed 9016432]
  60. Harden CL, Hopp J, Ting TY, et al; American Academy of Neurology; American Epilepsy Society. Practice parameter update: management issues for women with epilepsy--focus on pregnancy (an evidence-based review): obstetrical complications and change in seizure frequency: report of the Quality Standards Subcommittee and Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology and American Epilepsy Society. Neurology. 2009;73(2):126-132. [PubMed 19398682]
  61. Hesdorffer DC, Kanner AM. The FDA alert on suicidality and antiepileptic drugs: Fire or false alarm? Epilepsia. 2009;50(5):978-986. doi:10.1111/j.1528-1167.2009.02012.x [PubMed 19496806]
  62. Hiemke C, Bergemann N, Clement HW, et al. Consensus guidelines for therapeutic drug monitoring in neuropsychopharmacology: update 2017. Pharmacopsychiatry. 2018;51(1-02):9-62. [PubMed 28910830]
  63. Hirschfeld RMA, Bowden CL, Gitlin MJ, et al. Practice guideline for the treatment of patients with bipolar disorder, 2nd ed. Washington, DC: American Psychiatric Association; April 2002.
  64. Ho CC, Khan SA, Whealy MA. Trigeminal neuralgia. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed March 29, 2021.
  65. Iwahashi IS, Miyatake R, Suwaki H, et al, “The Drug-Drug Interaction Effects of Haloperidol on Plasma Carbamazepine Levels,” Clin Neuropharmacol, 1995, 18:233-6. [PubMed 8635181]
  66. Jubert P, Almirall J, Casanovas A, Garcia M. Carbamazepine-induced acute renal failure. Nephron. 1994;66(1):121. doi:10.1159/000187784 [PubMed 8107947]
  67. Kacirova I, Grundmann M, Brozmanova H. Therapeutic monitoring of carbamazepine concentrations in breastfeeding mothers, maternal milk and nursed infants. Ther Drug Monit. 2011;33:503.
  68. Kacirova I, Grundmann M, Brozmanova H. Concentrations of carbamazepine and carbamazepine-10,11-epoxide in maternal and umbilical cord blood at birth: Influence of co-administration of valproic acid or enzyme-inducing antiepileptic drugs. Epilepsy Res. 2016;122:84-90. [PubMed 26991491]
  69. Kaeley N, Kabi A, Bhatia R, Mohanty A. Carbamazepine-induced hyponatremia - a wakeup call. J Family Med Prim Care. 2019;8(5):1786-1788. doi:10.4103/jfmpc.jfmpc_185_19 [PubMed 31198759]
  70. Kaneko S, Sato T, Suzuki K. The levels of anticonvulsants in breast milk. Br J Clin Pharmacol. 1979;7(6):624-627. [PubMed 465285]
  71. Kanno T, Miyata M, Kazuta Y, Sato Y, Nishimaki T, Kasukawa R. Carbamazepine-induced systemic lupus erythematosus-like disease. Intern Med. 1992;31(11):1303-1305. doi:10.2169/internalmedicine.31.1303 [PubMed 1295628]
  72. Kasarskis EJ, Kuo CS, Berger R, Nelson KR. Carbamazepine-induced cardiac dysfunction. Characterization of two distinct clinical syndromes. Arch Intern Med. 1992;152(1):186-191. doi:10.1001/archinte.152.1.186 [PubMed 1728915]
  73. Keating A and Blahunka P, “Carbamazepine-Induced Stevens-Johnson Syndrome in a Child,” Ann Pharmacother, 1995, 29(5):538-9. [PubMed 7655141]
  74. Kennebäck G, Bergfeldt L, Vallin H, Tomson T, Edhag O. Electrophysiologic effects and clinical hazards of carbamazepine treatment for neurologic disorders in patients with abnormalities of the cardiac conduction system. Am Heart J. 1991;121(5):1421-1429. doi:10.1016/0002-8703(91)90148-b [PubMed 2017974]
  75. Kennedy GM, Lhatoo SD. CNS adverse events associated with antiepileptic drugs. CNS Drugs. 2008;22(9):739-760. doi:10.2165/00023210-200822090-00003 [PubMed 18698874]
  76. Ketter TA, Kalali AH, and Weisler RH, “A 6-Month, Multicenter, Open-Label Evaluation of Beaded, Extended-Release Carbamazepine Capsule Monotherapy in Bipolar Disorder Patients With Manic or Mixed Episodes: SPD417 Study Group,” J Clin Psychiatry, 2004, 65(5):668-73. [PubMed 15163253]
  77. Khoo AB, Ali FR, Yiu ZZ, Ferguson JE. Carbamazepine induced Stevens-Johnson syndrome. BMJ Case Rep. 2016;2016:bcr2016214926. doi:10.1136/bcr-2016-214926 [PubMed 26969368]
  78. Kleindienst N, Greil W. Differential efficacy of lithium and carbamazepine in the prophylaxis of bipolar disorder: results of the MAP study. Neuropsychobiology. 2000;42(suppl 1):2-10. doi: 10.1159/000054844. [PubMed 11093063]
  79. Knowles SR, Dewhurst N, Shear NH. Anticonvulsant hypersensitivity syndrome: an update. Expert Opin Drug Saf. 2012;11(5):767-778. doi:10.1517/14740338.2012.705828 [PubMed 22794330]
  80. Korinthenberg R, Haug C, and Hannak D, “The Metabolization of Carbamazepine to CBZ-10,11 Epoxide in Children From the Newborn Age to Adolescence,” Neuropediatrics, 1994, 25(4):214-6. [PubMed 7824094]
  81. Koutsampasopoulos K, Zotos A, Papamichalis M, Papaioannou K. Carbamazepine induced atrial tachycardia with complete AV block. Hippokratia. 2014;18(2):185-186. [PubMed 25336888]
  82. Kuz GM, Manssourian A. Carbamazepine-induced hyponatremia: assessment of risk factors. Ann Pharmacother. 2005;39(11):1943-1946. doi:10.1345/aph.1G209 [PubMed 16189283]
  83. Larsen ER, Damkier P, Pedersen LH, et al. Use of psychotropic drugs during pregnancy and breast-feeding. Acta Psychiatr Scand Suppl. 2015;(445):1-28. [PubMed 26344706]
  84. Leach JP. Antiepileptic drug therapy. In: Encyclopedia of the Neurological Sciences. Vol 1. Elsevier; 2014:224-232.
  85. Leckband SG, Kelsoe JR, Dunnenberger HM, et al; Clinical Pharmacogenetics Implementation Consortium. Clinical Pharmacogenetics Implementation Consortium guidelines for HLA-B genotype and carbamazepine dosing. Clin Pharmacol Ther. 2013;94(3):324-328. doi:10.1038/clpt.2013.103 [PubMed 23695185]
  86. Lee CS, Wang LH, Marbury TC, Bruni J, Perchalski RJ. Hemodialysis clearance and total body elimination of carbamazepine during chronic hemodialysis. Clin Toxicol. 1980;17(3):429-438. doi: 10.3109/15563658008989993. [PubMed 7449356]
  87. Leo RJ, Cannuli AR. Porphyria cutanea tarda associated with carbamazepine treatment. Am J Psychiatry. 1996;153(3):443-444. doi:10.1176/ajp.153.3.443b [PubMed 8610843]
  88. Lerer B, Moore N, Meyendorff E, et al, “Carbamazepine Versus Lithium in Mania: A Double-Blind Study,” J Clin Psychiatry, 1987, 48(3):89-93. [PubMed 3546274]
  89. Levy M, Goodman MW, Van Dyne BJ, Sumner HW. Granulomatous hepatitis secondary to carbamazepine. Ann Intern Med. 1981;95(1):64-65. doi:10.7326/0003-4819-95-1-64 [PubMed 7247130]
  90. Lin YT, Chang YC, Hui RC, et al. A patch testing and cross-sensitivity study of carbamazepine-induced severe cutaneous adverse drug reactions. J Eur Acad Dermatol Venereol. 2013;27(3):356-364. doi:10.1111/j.1468-3083.2011.04418.x [PubMed 22211830]
  91. Liu H and Delgado MR, “Influence of Sex, Age, Weight, and Carbamazepine Dose on Serum Concentrations, Concentration Ratios, and Level/Dose Ratios of Carbamazepine and Its Metabolites,” Ther Drug Monit, 1994, 16(5):469-76. [PubMed 7846744]
  92. Luke DR, Tomaszewski K, Damle B, Schlamm HT. Review of the basic and clinical pharmacology of sulfobutylether-beta-cyclodextrin (SBECD). J Pharm Sci. 2010;99(8):3291-3301. [PubMed 20213839]
  93. Mahmoud SH. Antiepileptic drug removal by continuous renal replacement therapy: a review of the literature. Clin Drug Investig. 2017;37(1):7-23. doi: 10.1007/s40261-016-0457-0. [PubMed 27587068]
  94. Matos ME, Burns MM, and Shannon MW, “False-Positive Tricyclic Antidepressant Drug Screen Results Leading to the Diagnosis of Carbamazepine Intoxication,” Pediatrics, 2000, 105(5):e66 [PubMed 10799630]
  95. McCormack M, Alfirevic A, Bourgeois S, et al, "HLA-A*3101 and Carbamazepine-Induced Hypersensitivity Reactions in Europeans," N Engl J Med, 2011, 364(12):1134-43. [PubMed 21428769]
  96. Medical Research Council Antiepileptic Drug Withdrawal Study Group. Randomised study of antiepileptic drug withdrawal in patients in remission. Lancet. 1991;337(8751):1175-1180. [PubMed 1673736]
  97. Mehrizi M, Fontem RF, Gearhart TR, Pascuzzi RM. Medications and Myasthenia Gravis (a Reference for Health Care Professionals). Indiana University School of Medicine's Department of Neurology; 2012.
  98. Mehta M, Shah J, Khakhkhar T, Shah R, Hemavathi KG. Anticonvulsant hypersensitivity syndrome associated with carbamazepine administration: case series. J Pharmacol Pharmacother. 2014;5(1):59-62. doi:10.4103/0976-500X.124428 [PubMed 24554914]
  99. Miles MV, Lawless ST, Tennison MB, et al, “Rapid Loading of Critically Ill Patients With Carbamazepine Suspension,” Pediatrics, 1990, 86(2):263-6. [PubMed 2371100]
  100. Miliszewski MA, Kirchhof MG, Sikora S, Papp A, Dutz JP. Stevens-Johnson syndrome and toxic epidermal necrolysis: an analysis of triggers and implications for improving prevention. Am J Med. 2016;129(11):1221-1225. doi:10.1016/j.amjmed.2016.03.022 [PubMed 27086495]
  101. Mizukami K, Naito Y, Yoshida M, Nakanishi T, Koizumi J. Mental disorders induced by carbamazepine. Jpn J Psychiatry Neurol. 1990;44(1):59-63. doi:10.1111/j.1440-1819.1990.tb00441.x [PubMed 2362393]
  102. Mora Rodríguez KA, Benbadis SR. Managing antiepileptic medication in dialysis patients. Curr Treat Options Neurol. 2018;20(11):45. doi: 10.1007/s11940-018-0530-5. [PubMed 30259204]
  103. Mula M, Kanner AM, Schmitz B, Schachter S. Antiepileptic drugs and suicidality: an expert consensus statement from the Task Force on Therapeutic Strategies of the ILAE Commission on Neuropsychobiology. Epilepsia. 2013;54(1):199-203. doi:10.1111/j.1528-1167.2012.03688.x [PubMed 22994856]
  104. National Institute for Health and Care Excellence. Drug allergy: diagnosis and management. Published September 3, 2014. Accessed October 15, 2021. https://www.nice.org.uk/guidance/cg183
  105. O'Griofa FM, Voris JC. Neuroleptic malignant syndrome associated with carbamazepine. South Med J. 1991;84(11):1378-1380. doi:10.1097/00007611-199111000-00023 [PubMed 1948228]
  106. Okuma T, Inanaga K, Otsuki S, et al, “Comparison of the Antimanic Efficacy of Carbamazepine and Chlorpromazine: A Double-Blind Controlled Study,” Psychopharmacology, 1979, 66(3):211-7. [PubMed 119267]
  107. Ory JP, Bourscheld D, Lebrun C, et al, “Drug-Induced Pseudolymphoma in a Lupus Patient: One Case Due to Carbamazepine,” Clin Exp Rheumatol, 1995, 12(Suppl 11):93. [PubMed 8162652]
  108. Oussalah A, Yip V, Mayorga C, et al. Genetic variants associated with T cell-mediated cutaneous adverse drug reactions: a PRISMA-compliant systematic review-An EAACI position paper. Allergy. 2020;75(5):1069-1098. doi:10.1111/all.14174 [PubMed 31899808]
  109. Page RL 2nd, O'Bryant CL, Cheng D, et al; American Heart Association Clinical Pharmacology and Heart Failure and Transplantation Committees of the Council on Clinical Cardiology; Council on Cardiovascular Surgery and Anesthesia; Council on Cardiovascular and Stroke Nursing; and Council on Quality of Care and Outcomes Research. Drugs That May Cause or Exacerbate Heart Failure: A Scientific Statement From the American Heart Association [published correction appears in Circulation. 2016;134(12):e261]. Circulation. 2016;134(6):e32-e69. doi: 10.1161/CIR.0000000000000426. [PubMed 27400984]
  110. Pandey CK, Raza M, Tripathi M, Navkar DV, Kumar A, Singh UK. The comparative evaluation of gabapentin and carbamazepine for pain management in Guillain-Barré syndrome patients in the intensive care unit. Anesth Analg. 2005;101(1):220-225. doi: 10.1213/01.ANE.0000152186.89020.36. [PubMed 15976235]
  111. Park CS, Kang DY, Kang MG, et al. Severe cutaneous adverse reactions to antiepileptic drugs: a nationwide registry-based study in Korea. Allergy Asthma Immunol Res. 2019;11(5):709-722. doi:10.4168/aair.2019.11.5.709 [PubMed 31332981]
  112. Patterson BD, “Possible Interaction Between Metronidazole and Carbamazepine,” Ann Pharmacother, 1994, 28(11):1303-1304. [PubMed 7849350]
  113. Patorno E, Bohn RL, Wahl PM, et al. Anticonvulsant medications and the risk of suicide, attempted suicide, or violent death [published correction appears in JAMA. 2010;303(22):2252]. JAMA. 2010;303(14):1401-1409. doi:10.1001/jama.2010.410 [PubMed 20388896]
  114. Pedley TA, Hauser WA. Sudden death in epilepsy: a wake-up call for management. Lancet. 2002;359(9320):1790-1791. doi:10.1016/S0140-6736(02)08726-3 [PubMed 12044369]
  115. Peselow ED, Clevenger S, IsHak WW. Prophylactic efficacy of lithium, valproic acid, and carbamazepine in the maintenance phase of bipolar disorder: a naturalistic study. Int Clin Psychopharmacol. 2016;31(4):218-223. doi: 10.1097/YIC.0000000000000097. [PubMed 26523730]
  116. Phillips EJ, Sukasem C, Whirl-Carrillo M, et al. Clinical pharmacogenetics implementation consortium guideline for HLA genotype and use of carbamazepine and oxcarbazepine: 2017 update. Clin Pharmacol Ther. 2018;103(4):574-581. doi:10.1002/cpt.1004 [PubMed 29392710]
  117. Placidi GF, Lenzi A, Lazzerini F, et al, “The Comparative Efficacy and Safety of Carbamazepine Versus Lithium: A Randomized, Double-blind 3-year Trial in 83 Patients,” J Clin Psychiatry, 1986, 47(10):490-4. [PubMed 3093468]
  118. Post RM. Bipolar disorder in adults: choosing maintenance treatment. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed September 30, 2021.
  119. Rabins PV, Blacker D, Rovner BW, et al, “American Psychiatric Association Practice Guideline for the Treatment of Patients With Alzheimer's Disease and Other Dementias. Second Edition,” Am J Psychiatry, 2007, 164(12 Suppl):5-56. [PubMed 18340692]
  120. Ramos AM, Gayotto LC, Clemente CM, Mello ES, Luz KG, Freitas ML. Reversible vanishing bile duct syndrome induced by carbamazepine. Eur J Gastroenterol Hepatol. 2002;14(9):1019-1022. doi:10.1097/00042737-200209000-00014 [PubMed 12352223]
  121. Reiffers-Mettelock J, Hentges F, Humbel RL. Syndrome resembling systemic lupus erythematosus induced by carbamazepine. Dermatology. 1997;195(3):306. doi:10.1159/000245973 [PubMed 9407192]
  122. Rey E, d'Athis P, de Lauture D, Dulac O, Aicardi J, Olive G. Pharmacokinetics of carbamazepine in the neonate and in the child. Int J Clin Pharmacol Biopharm. 1979;Feb;17(2):90-96. [PubMed 422308]
  123. Richard A, Girard F, Girard DC, et al, “Cisatracurium-Induced Neuromuscular Blockade is Affected by Chronic Phenytoin or Carbamazepine Treatment in Neurosurgical Patients,” Anesth Analg, 2005, 100(2):538-44. [PubMed 15673889]
  124. Rispal P, Lasseur C, Labouyrie E, et al. Pseudolymphoma-Induced by Carbamazepine. Report of Two Cases. Rev Med Interne. 1995;16(3):214-218. [PubMed 7740234]
  125. Schachter SC. Antiseizure drugs: Mechanism of action, pharmacology, and adverse effects. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed December 8, 2020a.
  126. Schachter SC. Overview of the management of epilepsy in adults. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed December 9, 2020b.
  127. Schmitz B, Trimble MR. Carbamazepine and PIP-syndrome in temporal lobe epilepsy. Epilepsy Res. 1995;22(3):215-220. doi:10.1016/0920-1211(95)00038-0 [PubMed 8991788]
  128. Schrijvers R, Gilissen L, Chiriac AM, Demoly P. Pathogenesis and diagnosis of delayed-type drug hypersensitivity reactions, from bedside to bench and back. Clin Transl Allergy. 2015;5:31. doi:10.1186/s13601-015-0073-8 [PubMed 26339470]
  129. Shehab N, Lewis CL, Streetman DD, Donn SM. Exposure to the pharmaceutical excipients benzyl alcohol and propylene glycol among critically ill neonates. Pediatr Crit Care Med. 2009;10(2):256-259. [PubMed 19188870]
  130. Shi YW, Min FL, Zhou D, et al. HLA-A*24:02 as a common risk factor for antiepileptic drug-induced cutaneous adverse reactions. Neurology. 2017;88(23):2183-2191. doi:10.1212/WNL.0000000000004008 [PubMed 28476759]
  131. Sierra NM, García B, Marco J, Plaza S, Hidalgo F, Bermejo T. Cross hypersensitivity syndrome between phenytoin and carbamazepine. Pharm World Sci. 2005;27(3):170-174. doi:10.1007/s11096-004-1736-z [PubMed 16096883]
  132. Skalli S, Barret P, Villier C, Bussières JF. Carbamazepine-induced acute generalized exanthematous pustulosis: a case report. J Pediatr Pharmacol Ther. 2011;16(1):61-65. [PubMed 22477826]
  133. Sobotka JL, Alexander B, Cook BL. A review of carbamazepine's hematologic reactions and monitoring recommendations. DICP. 1990;24(12):1214-1219. doi:10.1177/106002809002401214 [PubMed 2089834]
  134. Soria A, Bernier C, Veyrac G, Barbaud A, Puymirat E, Milpied B. Drug reaction with eosinophilia and systemic symptoms may occur within 2 weeks of drug exposure: a retrospective study. J Am Acad Dermatol. 2020;82(3):606-611. doi:10.1016/j.jaad.2019.09.036 [PubMed 31562941]
  135. Soriano SG, Sullivan LJ, Venkatakrishnan K, et al, “Pharmacokinetics and Pharmacodynamics of Vecuronium in Children Receiving Phenytoin or Carbamazepine for Chronic Anticonvulsant Therapy,” Br J Anaesth, 2001, 86(2):223-9. [PubMed 11573664]
  136. Specchio LM, Beghi E. Should antiepileptic drugs be withdrawn in seizure-free patients? CNS Drugs. 2004;18(4):201-212. [PubMed 15015901]
  137. Stafstrom CE, Nohria V, Loganbill H, et al, “Erythromycin-Induced Carbamazepine Toxicity: A Continuing Problem,” Arch Pediatr Adolesc Med, 1995, 149(1):99-101. [PubMed 7827672]
  138. Stătescu L, Constantin M, Morariu HS, Solovăstru LG. Toxic epidermal necrolysis - a case report. J Crit Care Med (Targu Mures). 2017;3(1):29-33. doi:10.1515/jccm-2017-0002 [PubMed 29967868]
  139. Stephens C, Lucena MI, Andrade RJ. Genetic risk factors in the development of idiosyncratic drug-induced liver injury. Expert Opin Drug Metab Toxicol. 2021;17(2):153-169. doi:10.1080/17425255.2021.1854726 [PubMed 33222552]
  140. Stephens C, Robles-Diaz M, Medina-Caliz I, et al. Comprehensive analysis and insights gained from long-term experience of the Spanish DILI Registry. J Hepatol. 2021;75(1):86-97. doi:10.1016/j.jhep.2021.01.029 [PubMed 33539847]
  141. Stoner SC, Nelson LA, Lea JW, et al. Historical review of carbamazepine for the treatment of bipolar disorder. Pharmacotherapy. 2007;27(1):68-88. [PubMed 17192163]
  142. Stovall J. Acute bipolar mania and hypomania in adults: General principles of pharmacotherapy. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed March 1, 2019.
  143. Strozzi I, Nolan SJ, Sperling MR, Wingerchuk DM, Sirven J. Early versus late antiepileptic drug withdrawal for people with epilepsy in remission. Cochrane Database Syst Rev. 2015;(2):CD001902. [PubMed 25922863]
  144. Stübner S, Grohmann R, Engel R, et al. Blood dyscrasias induced by psychotropic drugs. Pharmacopsychiatry. 2004;37 Suppl 1:S70-S78. doi:10.1055/s-2004-815513 [PubMed 15052517]
  145. Subramanian A, Adhimoolam M, Gopalakrishnan S, Rajamohammed MA. Carbamazepine-induced angioedema. J Basic Clin Pharm. 2016;7(4):120-122. doi:10.4103/0976-0105.189436 [PubMed 27999472]
  146. Suppes T, Dennehy EB, Hirschfeld RMA, et al, “The Texas Implementation of Medication Algorithms: Update to the Algorithms for the Treatment of Bipolar I Disorder,” J Clin Psychiatry, 2005, 66(7):870-86. [PubMed 16013903]
  147. Syed Q, Hendler KT, Koncilja K. The impact of aging and medical status on dysgeusia. Am J Med. 2016;129(7):753.e1-6. [PubMed 26899755]
  148. Tegretol and Tegretol-XR (carbamazepine) [prescribing information]. East Hanover, NJ: Pharmaceuticals Co.; March 2020.
  149. Tegretol (carbamazepine) [product monograph]. Dorval, Quebec, Canada: Novartis Pharmaceuticals Canada Inc; May 2021.
  150. Timmings PL. Sudden unexpected death in epilepsy: is carbamazepine implicated? Seizure. 1998;7(4):289-291. doi:10.1016/s1059-1311(98)80020-4 [PubMed 9733403]
  151. Tohen M, Castillo J, Baldessarini RJ, et al. Blood Dyscrasias With Carbamazepine and Valproate: A Pharmacoepidemiological Study of 2,228 Patients at Risk. Am J Psychiatry. 1995;152(3):413-418. [PubMed 7864268]
  152. Tomson T, Battino D, Bonizzoni E, et al. Dose-dependent risk of malformations with antiepileptic drugs: an analysis of data from the EURAP epilepsy and pregnancy registry. Lancet Neurol. 2011;10(7):609-617. [PubMed 21652013]
  153. Tomson T, Landmark CJ, Battino D. Antiepileptic drug treatment in pregnancy: changes in drug disposition and their clinical implications. Epilepsia. 2013;54(3):405-414. [PubMed 23360413]
  154. Trent JT, Bowes LE, Romanelli P, Kerdel FA. Toxic epidermal necrolysis of the scalp following anticonvulsant use and cranial irradiation. J Cutan Med Surg. 2001;5(6):475-478. doi:10.1007/s10227-001-0012-2 [PubMed 11907855]
  155. Tripathi M, Kaushik S. Carbamazepine for pain management in Guillain-Barré syndrome patients in the intensive care unit. Crit Care Med. 2000;28(3):655-658. [PubMed 10752810]
  156. Tutor-Crespo MJ, Hermida J, Tutor JC. Relative proportions of serum carbamazepine and its pharmacologically active 10,11-epoxy derivative: effect of polytherapy and renal insufficiency. Ups J Med Sci. 2008;113(2):171-180. doi: 10.3109/2000-1967-225. [PubMed 18509811]
  157. US Department of Health and Human Services; Centers for Disease Control and Prevention; National Institute for Occupational Safety and Health. NIOSH list of antineoplastic and other hazardous drugs in healthcare settings 2016. http://www.cdc.gov/niosh/topics/antineoplastic/pdf/hazardous-drugs-list_2016-161.pdf. Updated September 2016. Accessed October 5, 2016.
  158. Wang XQ, Lang SY, Shi XB, Tian HJ, Wang RF, Yang F. Cross-reactivity of skin rashes with current antiepileptic drugs in Chinese population. Seizure. 2010;19(9):562-566. doi:10.1016/j.seizure.2010.09.003 [PubMed 20888266]
  159. Weisler RH, Kalali AH, and Ketter TA, “A Multicenter, Randomized, Double-Blind, Placebo-Controlled Trial of Extended-Release Carbamazepine Capsules as Monotherapy for Bipolar Disorder Patients With Manic or Mixed Episodes: SPD417 Study Group,” J Clin Psychiatry, 2004, 65(4):478-84. [PubMed 15119909]
  160. Wisner KL, Perel JM. Serum levels of valproate and carbamazepine in breastfeeding mother-infant pairs. J Clin Psychopharmacol. 1998;18(2):167-169. [PubMed 9555601]
  161. Woolston JL, “Case Study: Carbamazepine Treatment of Juvenile-Onset Bipolar Disorder,” J Am Acad Child Adolesc Psychiatry, 1999, 38(3):335-8. [PubMed 10087696]
  162. World Health Organization (WHO). Breastfeeding and maternal medication, recommendations for drugs in the eleventh WHO model list of essential drugs. 2002. http://www.who.int/maternal_child_adolescent/documents/55732/en/
  163. Yatham LN, Kennedy SH, Parikh SV, et al. Canadian Network for Mood and Anxiety Treatments (CANMAT) and International Society for Bipolar Disorders (ISBD) 2018 guidelines for the management of patients with bipolar disorder. Bipolar Disord. 2018;20(2):97-170. doi: 10.1111/bdi.12609. [PubMed 29536616]
  164. Yeung Laiwah AA, Rapeport WG, Thompson GG, et al. Carbamazepine-induced non-hereditary acute porphyria. Lancet. 1983;1(8328):790-792. doi:10.1016/s0140-6736(83)91850-0 [PubMed 6132132]
  165. Zhang ZJ, Kang WH, Tan QR, et al. Adjunctive herbal medicine with carbamazepine for bipolar disorders: a double-blind, randomized, placebo-controlled study. J Psychiatr Res. 2007;41(3-4):360-369. doi: 10.1016/j.jpsychires.2005.06.002. [PubMed 16081106]
Topic 9198 Version 538.0