Carbamazepine Interactions

Carbamazepine activates the pregnane X receptor and strongly induces hepatic CYP3A4 and CYP24A1, accelerating catabolism of 25-hydroxyvitamin D into inactive metabolites; meta-analyses confirm consistently lower 25(OH)D in long-term users along with secondary hyperparathyroidism and reduced bone mineral density.

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.

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.

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.