Phenobarbital Albendazole

The pharmacological interactions of the antiepileptic drugs phenjdoin, carbamazepine, and phenobarbital with albendazole have been studied in 32 adults with active intraparenchjmatous neurocysticercosis (41) ... 

All were treated with albendazole 7.5 mg/kg every 12 hours on 8 consecutive days. Phenytoin, carbamaze-pine, and phenobarbital all induced the oxidative metabolism of albendazole to a similar extent in a non-enantioselective manner. In consequence, there was a significant reduction in the plasma concentration of the active metabolite of albendazole, albendazole sulfoxide. 

Clinically important, potentially hazardous interactions with albendazole, aminoglutethimide, aspirin, bexarotene, carbamazepine, cyclophosphamide, dasatinib, diuretics, ephedrine, imatinib, itraconazole, lapatinib, live vaccines, lopinavir, methotrexate, phenobarbital, phenytoin, praziquantel, primidone, rifampicin, rifampin, temsirolimus, warfarin... 

Inducers of hepatic CYPs such as carbamazepine and phenobarbital reduce the bioavaUabihty of praziquantel. Dexamethasone reduces the bioavailability of praziquantel, but the mechanism is not understood. Under certain conditions, praziquantel may increase the bioavailability of albendazole. 

Phenytoin, carbamazepine and phenobarbital lower the plasma levels of albendazole and mebendazole, and they therefore might reduce their efficacy for systemic infections. Valproate does not lower plasma mebendazole levels. 

In one study, 32 patients with intraparenehymatous neurocysticercosis were given albendazole 7.5 mg/kg every 12 hours for 8 days. These patients were also taking either phenytoin 200 to 300 mg daily (9 patients), carbamazepine 600 to 1200 mg daily (9 patients), or phenobarbital 100 to 300 mg daily (5 patients) all for at least 3 months, and a eontrol group consisting of 9 patients who did not receive any antiepilepties. The AUCs for (+)-albendazole sulfoxide were 66%, 49%, and 61% lower than the control group for the phenytoin, carbamazepine, and phenobarbital groups respectively. The maximum plasma levels of (+)-albendazole sulfoxide were 50 to 63% lower and the half lives about 3 to 4 hours shorter. The AUCs, peak plasma levels and half-life of (-)-albendazole sulfoxide (present in much lower levels than the (+)-isomer) were similarly reduced by the antiepileptics. ... 

Phenytoin, carbamazepine and phenobarbital appear to induce the oxidative metabolism of albendazole by the cytochrome P450 isoenzyme CYP3A to roughly the same extent, resulting in significantly reduced levels of albendazole sulfoxide. Phenytoin, and to a lesser extent carbamazepine, may also induce the metabolism of albendazole sulfone by CYP2C. Mebendazole is similarly affected. 

These pharmacokinetic interactions are established, and are likely to be clinically important when these anthelmintics are used to treat systemic worm infections. For these infections it may be necessary to increase the albendazole or mebendazole dosage in patients taking phenytoin, carbamazepine or phenobarbital. Monitor the outcome of concurrent use. The interactions are of no importance when these anthelmintics are used for intestinal worm infections (where their action is a local effect on the worms in the gut), which is the most common use of mebendazole in particular. 

---