The co-administration of ivermectin and albendazole - safety, pharmacokinetics and efficacy againstOnchocerca volvulus

Abstract

A randomized, double-blind, placebo-controlled trial was conducted, to determine whether the co-administration of ivermectin with albendazole is safe and more effective against Onchocerca volvulus than ivermectin alone, and whether a significant pharmacokinetic interaction occurs. Forty-two male onchocerciasis patients received ivermectin (200 mug/kg) alone, albendazole (400 mg) alone or the combination. Safety was determined from the results of detailed clinical and laboratory examinations before treatment, during hospitalization and on day 30. Microfilaricidal efficacy was estimated from the reductions in skin counts between day 0 (pretreatment) and day 30. To determine efficacy against the adult worms, two independent observers examined histology slides prepared from nodules excised on day 180; changes in the skin counts of skin microfilariae between days 30 and 365 provided additional indicators of the level of adulticidal activity. Pharmacokinetic parameters for ivermectin and albendazole sulphoxide were defined over 72 h post-treatment. The co-administration of ivermectin with albendazole did not produce more severe adverse effects than ivermectin alone. Both nodule examiners found that the combination was not macrofilaricidal and that it was not clearly superior to ivermectin alone in the effects on reproductive activity; this was supported by the similar efficacy of the two regimens in the suppression of skin microfilariae. There was no significant pharmacokinetic interaction. Although the co-administration of ivermectin with albendazole appears safe, it offers no advantage over ivermectin alone in the control of onchocerciasis. The combination does not require an alteration in the dosage of either component.

In Vitro and In Vivo Drug Interaction Study of Two Lead Combinations, Oxantel Pamoate plus Albendazole and Albendazole plus Mebendazole, for the Treatment of Soil-Transmitted Helminthiasis

“…However, before two drugs can be recommended for simultaneous treatment, in vitro and in vivo studies are necessary to rule out potential drug interactions. To our knowledge, to date only the coadministration of albendazole plus ivermectin has been thoroughly studied (8,9). The aim of the present work was therefore to assess the combined therapies of albendazole plus oxantel pamoate and albendazole plus mebendazole for potential drug-drug interactions.…”

“…When coadministering multiple drugs, drug-drug interactions should be ruled out. While the combination of albendazole plus ivermectin has been carefully evaluated in preclinical and clinical studies (8,9) albendazole combined with mebendazole or oxantel pamoate…”

The Pharmacokinetics and Interactions of Ivermectin in Humans—A Mini-review

“…Other studies showed that, to control onchocerciasis, the combination of ivermectin with other drugs offers no advantage over ivermectin alone. Thus, in infected patients, the ingestion of ivermectin had no effect on the kinetics of an oral dose of albendazole and there was no additive effect of both drugs against the parasite compared to ivermectin given alone (25,26,27). Albendazole (400 mg) did not modify the kinetic behavior of a single oral ivermectin dose (12 mg) (27).…”

“…Thus, in infected patients, the ingestion of ivermectin had no effect on the kinetics of an oral dose of albendazole and there was no additive effect of both drugs against the parasite compared to ivermectin given alone (25,26,27). Albendazole (400 mg) did not modify the kinetic behavior of a single oral ivermectin dose (12 mg) (27). Also in onchocerciasis patients, the antiparasitary efficacy was similar when administering a single ivermectin dose (150 μg/kg, on day 1) followed by amorcazine (3 mg/kg twice daily, on days 8, 9 and 10) than when administering ivermectin alone (28).…”

Rationale for the Coadministration of Albendazole and Ivermectin to Humans for Malaria Parasite Transmission Control

“…91 Although coadministration of albendazole and ivermectin did not seem to enhance the mosquitolethal, sublethal, or sporontocidal effects of ivermectin, it is important to note that it does not inhibit these phenomena. Because albendazole does not alter the systemic exposure of ivermectin, [92][93][94] it is likely that coadministration of these drugs by MDA would produce the same impact on Plasmodium transmission as ivermectin alone but would maximize impact against STHs. To assess whether albendazole coadministered with ivermectin during MDA alters the mosquito-lethal effect of ivermectin MDA, An.…”