Carbamazepine
Tegretol · Epitol
Mechanism of Action Carbamazepine has demonstrated anticonvulsant properties in rats and mice with electrically and chemically induced seizures. It appears to act by reducing polysynaptic responses and blocking the post-tetanic potentiation. Carbamazepine greatly reduces or abolishes pain induced by stimulation of the infraorbital nerve in cats and rats. It depresses thalamic potential and bulbar and polysynaptic reflexes, including the linguomandibular reflex in cats. Carbamazepine is chemically unrelated to other anticonvulsants or other drugs used to control the pain of trigeminal neuralgia. The mechanism of action remains unknown. The principal metabolite of carbamazepine, carbamazepine-10,11-epoxide, has anticonvulsant activity as demonstrated in several in vivo animal models of seizures. Though clinical activity for the epoxide has been postulated, the significance of its activity with respect to the safety and efficacy of carbamazepine has not been established.
Compare Carbamazepine →FDA-Approved Indications
- Partial seizures with complex symptomatology (adults; pediatric)
- Generalized tonic-clonic seizures (adults; pediatric)
- Mixed seizure patterns (adults; pediatric)
- Trigeminal neuralgia (adults)
- Acute mania/mixed episodes in Bipolar I (adults; Equetro brand)
Common Off-Label Uses
- Neuropathic pain
- Alcohol withdrawal
- Impulse control/aggression
- Restless legs syndrome
What Sets This Drug Apart
- Potent CYP3A4 autoinducer (half-life drops from 25-65h to 12-17h over 3-5 weeks) — induces its own metabolism and dramatically reduces levels of CYP3A4 substrates including oral contraceptiv…
- Mandatory HLA-B*1502 screening before initiation in patients of Asian descent (SJS/TEN risk 1-6 per 10,000, ~10x higher with this allele); HLA-A*3101 screening recommended for European descent
- FDA-approved for acute bipolar mania/mixed episodes and epilepsy; sometimes preferred for mania with irritable/dysphoric features
- Teratogenicity 5.5% (Tomson EURAP) — lower than valproate but substantially higher than lamotrigine
- Aplastic anemia and agranulocytosis are rare but labeled risks; baseline and periodic CBC mandatory
- Hyponatremia (SIADH) occurs in 5-40% of patients, more common in elderly; monitor sodium especially when combining with other hyponatremic drugs