Drug Comparison
Phenytoin
- Zero-order kinetics — narrow therapeutic window
- Gingival hyperplasia, hirsutism, coarse features
- Fetal hydantoin syndrome
- Cytochrome P450 inducer
- Intravenous: cardiac risk → use fosphenytoin
Carbamazepine
- Autoinduction — levels fall in first month
- First-line for trigeminal neuralgia
- Hyponatremia (syndrome of inappropriate antidiuretic hormone secretion-like)
- Aplastic anemia / agranulocytosis
- Stevens-Johnson syndrome — HLA-B*1502
- Neural tube defect teratogenicity
Lamotrigine
- Broad spectrum — includes absence
- Glucuronidation — fewer cytochrome P450 interactions
- Stevens-Johnson syndrome — slow titration mandatory
- Valproate doubles Stevens-Johnson syndrome risk
- Preferred in pregnancy over older agents
Figure 1 — Phenytoin Adverse Effects (Gemini)
Critical Drug Interactions
Enzyme Inducers
Phenytoin & Carbamazepine
- Induce cytochrome P450 3A4 and cytochrome P450 2C9
- Reduce warfarin effect → clotting risk
- Reduce oral contraceptive efficacy
- Accelerate lamotrigine metabolism → higher lamotrigine doses needed
Valproate + Lamotrigine
The Dangerous Combination
- Valproate inhibits lamotrigine glucuronidation
- Lamotrigine levels double
- Stevens-Johnson syndrome risk doubles
- Start lamotrigine at half dose when adding to valproate
Figure 2 — Drug Comparison Table (Gemini)
Class Rule — All Sodium Channel Blockers
None are effective for absence seizures. Giving phenytoin, carbamazepine, or gabapentin to a patient with absence epilepsy can worsen seizure frequency. Seizure type must be confirmed before prescribing.