Drug Interactions between albendazole and fosphenytoin

MONITOR: Coadministration with anticonvulsant drugs such as carbamazepine, phenytoin, phenobarbital, and primidone may decrease the plasma concentrations and half-life of the active metabolite of albendazole, albendazole sulfoxide. The mechanism is unknown, but induction of hepatic metabolism by these anticonvulsant drugs has been proposed. In a study of 32 adult patients with neurocysticercosis receiving albendazole 7.5 mg/kg every 12 hours for 8 days, mean systemic exposure (AUC) on day 8 for the (+) enantiomer of albendazole sulfoxide in patients on concomitant anticonvulsant therapy with carbamazepine (n=9), phenytoin (n=9) or phenobarbital (n=5) was 49%, 66% and 61% lower, respectively, than in control patients who were not on anticonvulsants (n=9), while mean peak plasma concentration (Cmax) was 50%, 63% and 63% lower, respectively. For the (-) enantiomer of albendazole sulfoxide, mean AUC on day 8 was 67% 78% and 72% lower, and mean Cmax was 50%, 70% and 50% lower in the carbamazepine, phenytoin and phenobarbital groups, respectively, compared to the control group. Mean half-life was 3.1 to 4.2 hours shorter for (+) albendazole sulfoxide and 2.2 to 2.4 hours shorter for (-) albendazole sulfoxide in patients receiving anticonvulsants than in controls. The clinical impact of this interaction is expected to be minimal in the treatment of intestinal infections but may be increased when albendazole is used for systemic helminthic diseases such as neurocysticercosis. However, the clinical relevance of plasma concentrations of albendazole and albendazole sulfoxide during treatment of neurocysticercosis has not been established. In case reports and studies in the medical literature of patients with neurocysticercosis, albendazole was generally given without dosage adjustment in the presence of anticonvulsants such as carbamazepine, phenytoin and phenobarbital, and there have been no specific reports of therapeutic failure of albendazole attributed to suspected interaction with these anticonvulsants.

MANAGEMENT: Caution and monitoring for altered clinical efficacy are recommended if albendazole is used concomitantly with anticonvulsant drugs such as carbamazepine, phenytoin, phenobarbital, or primidone in patients treated for systemic helminthic infections. Dose adjustments or alternative treatments may be required if an interaction is suspected.