Carbamazepine (Tegretol)
Anticonvulsant • Last reviewed 2025-09-24
General information
Carbamazepine is an anticonvulsant with mood-stabilizing properties approved for epilepsy, trigeminal neuralgia, and bipolar I disorder (acute manic and mixed episodes). It is commonly used off-label for bipolar maintenance when lithium is not tolerated. First approved in 1968 (Tegretol), carbamazepine is a prototypical voltage-gated sodium channel blocker and potent enzyme inducer.
Formulations include immediate-release tablets (100, 200 mg), chewable tablets (100 mg), suspension (100 mg/5 mL), and extended-release capsules/tablets (100, 200, 300, 400 mg). Bipolar mania treatment typically starts at 200 mg twice daily, increasing by 200 mg every few days to a target of 800-1,000 mg/day; some patients require up to 1,200 mg/day. Therapeutic serum levels of 4-12 mcg/mL correlate with response.
Mechanistically, carbamazepine stabilizes hyperexcited nerve membranes by inhibiting voltage-gated sodium channels and attenuating glutamate release. It also modulates adenosine and GABAergic systems, contributing to antimanic effects. Autoinduction of CYP3A4 leads to declining plasma levels over the first 3-5 weeks unless doses are adjusted.
The drug is metabolized hepatically via CYP3A4 and epoxide hydrolase to active carbamazepine-10,11-epoxide. The parent half-life is 25-65 hours initially, shortening to 12-17 hours with chronic dosing due to autoinduction. Metabolites and enzyme induction lead to numerous drug interactions.
Dosing & administration
Bipolar I mania/maintenance: start 200 mg twice daily; increase by 200 mg/day every 4-7 days to 800-1,000 mg/day; maximum 1,200-1,600 mg/day.
Epilepsy: adults start 200 mg twice daily; titrate weekly to 800-1,200 mg/day divided 2-3 times.
Therapeutic drug monitoring: aim for 4-12 mcg/mL measured at trough after 3-5 days at stable dose.
Switching formulations: extended-release products are not bioequivalent; consult conversion guidance.
Dose adjustments and monitoring
- Hepatic impairment
- Use cautiously; monitor LFTs regularly; dose reductions may be required.
- Renal impairment
- Limited data; monitor for accumulation of metabolites.
- Autoinduction
- Expect clearance to increase after 2-3 weeks; may need dose increase of 30-50%.
- HLA-B*1502 positive
- Avoid use due to risk of Stevens-Johnson syndrome/TEN in patients of Asian ancestry.
Mechanism of action
Carbamazepine blocks voltage-gated sodium channels (state-dependent), stabilizing neuronal membranes and reducing repetitive firing. This underlies anticonvulsant and antimanic effects.
It enhances adenosine-mediated inhibition and modulates NMDA receptors, reducing excitatory neurotransmission; metabolites may also contribute to mood stabilization.
- Sodium channel blockade reduces excitatory neurotransmitter release.
- Induces CYP3A4, CYP1A2, CYP2C9, and P-gp, leading to autoinduction and many drug interactions.
- Weak antidiuretic hormone activity may cause SIADH and hyponatremia.
Metabolism & pharmacokinetics
Carbamazepine is slowly absorbed with peak concentrations in 4-8 hours (IR) or 12-24 hours (ER). Food does not significantly alter bioavailability.
Autoinduction results in a declining half-life over the first month; the active epoxide metabolite reaches steady state parallel to parent drug and contributes to efficacy and toxicity.
- Bioavailability
- ~70%
- Initial half-life
- 25-65 h (reduces to 12-17 h with autoinduction)
- Therapeutic serum range
- 4-12 mcg/mL
Drug interactions
Potent inducer of CYP3A4 and other enzymes; reduces levels of oral contraceptives, antipsychotics, anticonvulsants, and many other drugs.
Strong inhibitors (erythromycin, ketoconazole) raise carbamazepine levels, risking toxicity.
Combination with clozapine increases risk of agranulocytosis; avoid when possible.
| Mechanism | Agents / factors | Management |
|---|---|---|
| Enzyme induction | Oral contraceptives, antipsychotics (quetiapine), DOACs | Use alternative contraception; monitor efficacy of co-medications. |
| Enzyme inhibition | Erythromycin, azole antifungals | Reduce carbamazepine dose; monitor serum levels. |
| Bone marrow suppression | Clozapine | Avoid combination or monitor counts closely. |
Monitoring & safety checks
CBC with differential
Baseline, monthly for first 2 months, then periodically • Detect aplastic anemia or agranulocytosis.
Liver function tests
Baseline and periodically • Hepatotoxicity risk due to hepatic metabolism.
Serum sodium
Baseline and during titration • Hyponatremia/SIADH possible.
Serum levels
After dose changes and if toxicity suspected • Ensure therapeutic range and detect autoinduction.
Screen patients of Asian ancestry for HLA-B*1502; consider HLA-A*3101 testing in European descent.
Educate about signs of serious rash and hepatic dysfunction; discontinue at first sign.
Discontinuation guidance
Taper gradually over at least 2 weeks to avoid seizure precipitation and mood destabilization.
Monitor serum levels during taper to correlate with symptom changes, especially if transitioning to another mood stabilizer.
Special populations
Pregnancy: associated with neural tube defects; recommend high-dose folic acid preconception and vitamin K near delivery.
Older adults: start at lower doses (100 mg twice daily) due to higher susceptibility to hyponatremia and ataxia.
Renal impairment: limited data; consider dose reduction and monitor metabolites.
Adverse effects
Common: dizziness, diplopia, ataxia, nausea, sedation.
Serious: Stevens-Johnson syndrome/TEN, aplastic anemia, agranulocytosis, hepatic failure.
Hyponatremia and SIADH can lead to confusion and seizures.
References
- TEGRETOL (carbamazepine) prescribing information — DailyMed (2024)
- CANMAT/ISBD 2021 guidelines for the management of bipolar disorder — Bipolar Disorders (2021) DOI: 10.1111/bdi.13135
- Clinical pharmacokinetics of carbamazepine — Clinical Pharmacokinetics (2016) DOI: 10.1007/s40262-016-0442-1
Educational use only — verify details in current prescribing information and authoritative clinical guidelines before making prescribing decisions.