epilepsy
13 interactions related to epilepsy
carbamazepine + biotin
Carbamazepine gradually lowers biotin (vitamin B7) status by reducing intestinal absorption, increasing urinary loss, and accelerating breakdown of the vitamin. The effect is biomarker-level and well documented over decades; frank deficiency and serious adult harm are uncommon.
valproate + carnitine
Valproate (valproic acid) depletes carnitine by sequestering it as valproyl-carnitine for mitochondrial transport and by reducing renal reabsorption of free carnitine. Carnitine depletion can impair fatty-acid oxidation and the urea cycle, contributing to raised blood ammonia (hyperammonemia), liver stress, and in some cases encephalopathy.
lamotrigine + folate
In a randomized controlled trial of bipolar depression (CEQUEL), adding folic acid to lamotrigine appeared to blunt lamotrigine's antidepressant benefit, an effect seen mainly in people carrying the COMT Met allele. The interaction is pharmacodynamic, not pharmacokinetic, so lamotrigine blood levels stay unchanged. The exact mechanism is not established, and the signal is limited to bipolar depression rather than epilepsy.
phenytoin + st. john's wort
St. John's Wort activates the pregnane X receptor and induces drug-metabolizing enzymes (CYP3A4, CYP2C9, CYP2C19) and P-glycoprotein. Because phenytoin is cleared mainly by CYP2C9 and CYP2C19, taking St. John's Wort alongside it could speed phenytoin's breakdown and lower its blood levels, raising the theoretical risk of breakthrough seizures. Direct human data for phenytoin specifically are limited, so regulators treat this as a mechanism-based precaution rather than a documented loss of control.
phenytoin + ginkgo
Ginkgo biloba can induce CYP2C19, an enzyme involved in clearing phenytoin, which may lower phenytoin blood levels and raise the risk of breakthrough seizures. A published fatal case report described subtherapeutic phenytoin and valproate levels in a patient who had been self-administering ginkgo. Ginkgo also carries its own seizure-related signal. If you take phenytoin, avoid ginkgo and review any supplement changes with your doctor or pharmacist.
grapefruit + carbamazepine
Grapefruit juice inhibits the intestinal CYP3A4 enzyme that performs first-pass metabolism of carbamazepine, allowing more of each oral dose to reach the bloodstream. A human study in epilepsy patients found grapefruit juice raised carbamazepine blood levels, which matters because carbamazepine has a narrow safety margin.
star fruit + phenytoin
Star fruit (Averrhoa carambola) contains caramboxin, a neurotoxin that excites neurons, plus soluble oxalates that can injure the kidneys. In people with reduced kidney function, who cannot clear caramboxin, eating star fruit has triggered intractable seizures and status epilepticus. This is the fruit's own toxicity rather than a chemical reaction with phenytoin, but for someone taking phenytoin to prevent seizures it adds a serious, avoidable risk.
phenytoin + folate
Phenytoin and folate interact in both directions: long-term phenytoin lowers folate through enzyme induction and reduced absorption, while supplemental folate can speed phenytoin clearance and lower its blood level enough to allow seizures to return in some people. The interaction is real but monitorable, so changes should be coordinated with your neurologist rather than avoided.
valproate + aspirin
Aspirin and other salicylates push valproate off its plasma-protein binding sites and slow one of its breakdown pathways, so the active, unbound portion of valproate can rise even when the standard total valproate blood level looks unchanged. This can mask a clinically meaningful increase in active drug and raise the risk of valproate toxicity such as sedation, tremor, confusion, raised ammonia, and liver strain, while aspirin's own anti-clotting effect adds to valproate's tendency to lower platelets.
levetiracetam + vitamin b6
Levetiracetam (Keppra) commonly causes behavioral side effects including irritability, agitation, anxiety, and mood changes (sometimes called 'Keppra rage'). Randomized trials and case series in children and adults suggest that adding pyridoxine (vitamin B6) eases these behavioral symptoms in a meaningful subset of patients, though the evidence is mixed: two pediatric trials were positive while one adult trial was null. This is a potential benefit, not a harmful interaction.
carbamazepine + st. john's wort
Both carbamazepine and St. John's Wort induce CYP3A4, the liver enzyme that primarily breaks carbamazepine down. The combined effect is hard to predict: carbamazepine already induces its own metabolism, so adding the herb may lower exposure most before that self-induction is fully established. The bigger danger comes at transitions — especially stopping St. John's Wort while still on carbamazepine, when the loss of enzyme induction can let carbamazepine levels climb toward toxicity.
cbd + clobazam
CBD inhibits CYP2C19, the enzyme that clears N-desmethylclobazam, the active metabolite of clobazam. Taking the two together raises N-desmethylclobazam levels substantially, increasing sedation, drowsiness, drooling, and unsteadiness. This interaction is documented in the FDA-approved Epidiolex prescribing information and in clinical studies in children with epilepsy.
cbd + valproate
Taking CBD (including prescription Epidiolex and over-the-counter products) together with valproate raises the chance of liver enzyme elevations well above either drug alone, and the combination has been linked to high blood ammonia that can cause confusion or worsening seizures even when liver tests look only mildly abnormal. This pairing should be managed by the prescribing neurologist with baseline and follow-up liver testing.