Drug Breakdown: carbamazepine

Day 1: #carbamazepine was discovered mid 1950s as a tricyclic compound related to imipramine and was found to be effective for trigeminal neuralgia. Animal studies showed an anti-epileptic effect, which led to licensing in the 1960s as an anti-convulsant. Enteral formulations only.

Day 2: #carbamazepine adult indications include trigeminal neuralgia, focal primary and secondary tonic/clonic seizures (children too) and bipolar prophylaxis. Many off-label uses including acute alcohol withdrawal, diabetic neuropathy, restless legs.

Day 2 (cont): Elements of a narrow therapeutic index drug, requiring early plasma concentration testing and individualised response. Dose range depends on condition, eg trigeminal neuralgia 200-400 mg 3-4 times daily, but anticonvulsant dose can be higher. Gradual titration important up and down.

Day 3: Kinetics. #carbamazepine has high oral bioavailability, with moderate protein binding. It crosses the placenta, warranting pregnancy test before initiation. Liver metabolism by CYP3A4 yields an active metabolite. Mean t½ 35 hrs, but this reduces over time because of auto-induction of liver enzymes, increasing rate of breakdown. Renal excretion of inactivated drug.