epilepsy
13 interactions related to epilepsy
carbamazepine + biotin
Carbamazepine reduces biotin status by inhibiting sodium-dependent biotin uptake in the intestine, decreasing renal reabsorption, and accelerating biotin catabolism through enzyme induction; long-term users often have measurably lower plasma biotin and elevated organic-acid markers of biotin insufficiency.
valproate + carnitine
Valproate (valproic acid) depletes carnitine by sequestering it as valproyl-carnitine for mitochondrial transport and by inhibiting renal tubular reabsorption, which can impair the urea cycle and contribute to hyperammonemia, hepatotoxicity, and encephalopathy.
lamotrigine + folate
Lamotrigine inhibits dihydrofolate reductase, the enzyme that converts dihydrofolate to active tetrahydrofolate, and high-dose folic acid supplementation has been shown to blunt lamotrigine's antidepressant effect in bipolar depression (CEQUEL trial), particularly in COMT Met allele carriers. The interaction is pharmacodynamic rather than pharmacokinetic, so lamotrigine blood levels remain unchanged.
phenytoin + st. john's wort
St. John's Wort is a potent inducer of CYP3A4, CYP2C9, CYP2C19, and P-glycoprotein via activation of the pregnane X receptor. Because phenytoin is heavily metabolized by CYP2C9 and CYP2C19, concurrent St. John's Wort can lower phenytoin plasma concentrations into the subtherapeutic range, increasing the risk of breakthrough seizures.
phenytoin + ginkgo
Ginkgo biloba induces CYP2C19, the primary enzyme responsible for phenytoin metabolism. A published case report described a fatal breakthrough seizure in a patient on phenytoin and valproate whose autopsy revealed subtherapeutic anticonvulsant levels and self-administration of ginkgo biloba. Ginkgo also has independent pro-convulsant potential at high doses and through ginkgotoxin contamination.
grapefruit + carbamazepine
Grapefruit juice irreversibly inhibits intestinal CYP3A4, reducing first-pass metabolism of carbamazepine and increasing its bioavailability. Clinical study in epilepsy patients showed AUC rose by roughly 40 percent with concomitant grapefruit juice, pushing plasma levels toward the toxic range.
star fruit + phenytoin
Star fruit (Averrhoa carambola) contains caramboxin, a neurotoxin that activates excitatory neuroreceptors and inhibits GABA, and high oxalate content that causes acute kidney injury. In patients with renal impairment, star fruit ingestion has triggered refractory status epilepticus, directly antagonizing phenytoin's seizure-prevention purpose.
phenytoin + folate
Phenytoin lowers serum and red-cell folate through enzyme induction and impaired absorption of polyglutamate folates, but high-dose folate supplementation in turn accelerates phenytoin metabolism and can drop drug levels enough to cause seizure breakthrough.
valproate + aspirin
Aspirin (and other salicylates) displace valproate from plasma albumin binding sites and also inhibit valproate's beta-oxidation, leading to increases in the free (active) valproate fraction by up to fourfold. Even total valproate levels may not rise dramatically, masking the increase in pharmacologically active free drug and raising the risk of valproate toxicity (sedation, tremor, hyperammonemia, hepatotoxicity).
levetiracetam + vitamin b6
Levetiracetam (Keppra) commonly causes behavioral side effects including irritability, agitation, anxiety, and mood changes (sometimes called 'Keppra rage'). Several observational studies and case series in both pediatric and veteran populations suggest that adjunctive pyridoxine (vitamin B6) supplementation reduces these behavioral symptoms in roughly 40-50% of patients, though randomized controlled trial data are mixed.
carbamazepine + st. john's wort
Both carbamazepine and St. John's Wort are strong inducers of CYP3A4, the enzyme that primarily metabolizes carbamazepine. Although healthy-volunteer studies have shown limited additional effect on chronic carbamazepine kinetics (because carbamazepine already maximally autoinduces its own metabolism), starting or stopping St. John's Wort can destabilize carbamazepine levels, and the herb can lower exposure to single carbamazepine doses by up to 21% before autoinduction is established.
cbd + clobazam
CBD strongly inhibits CYP2C19, the enzyme that clears N-desmethylclobazam (the active metabolite of clobazam). Co-administration triples plasma N-desmethylclobazam levels, causing excess sedation, ataxia, and somnolence; this is documented in the FDA-approved Epidiolex prescribing information.
cbd + valproate
Concomitant CBD (Epidiolex) and valproate use produces a significantly higher rate of ALT/AST elevations than either drug alone - up to ~17% of patients in the combination group versus ~1-2% on valproate alone in pooled Epidiolex trial data. Postmarketing reports also describe hyperammonemia in patients on the combination.