Pharmacology Update

Albendazole: A Major New Antiparasitic Agent

By David O. Freedman, MD

Albendazole, a synthetic nitroimidazole with a broad spectrum of antinematodal activity similar to mebendazole, but also with anticestodal and some anti-protozoal action, is now commercially available in the United States. Available under the trade name Albenza in this country, it has been sold under the names Zentel and Eskazole for many years in most other countries. Albendazole represents a major advance in our anthelminthic armamentarium. It should now probably be considered the drug of choice for neurocysticercosis, echinococcal disease, intestinal helminthiasis, and cutaneous larva migrans, though the manufacturer has only had it officially licensed in the United States for the first two indications listed.

Pharmacology

Albendazole binds irreversibly to colchicine-sensitive sites on tubulin, blocking microtubule assembly. Glucose uptake by the organism is thus inhibited without affecting serum glucose levels in humans. Though bioavailability is still poor, albendazole’s better absorption from the gastrointestinal tract than mebendazole accounts for its systemic efficacy against cysticercosis and hydatid disease. Rapid hepatic biotransformation occurs and systemic activity is attributable to the primary metabolite, albendazole sulfoxide. The drug is highly plasma bound but is distributed into bile, CSF, and cyst fluid. Serum levels are increased five-fold if taken with a fatty meal. Time to peak serum level is 2-3 hours, and elimination half-life is 8-15 hours. Renal excretion is minimal, so dosage adjustment for renal function is unnecessary. The major route of excretion from the body is not clear.

Clinical Usage

Intestinal helminthiasis. Albendazole’s advantage over mebendazole is its high activity in a single oral dose of 400 mg (200 mg for children under 2 years of age) against ascariasis, hookworm infection, enterobiasis, trichostrongyliasis, and, to a slightly lesser extent, trichuriasis. Since intestinal helminthiasis is typically multifactorial, albendazole is an almost ideal agent. Albendazole at 400 mg/d for three days is much better tolerated and at least as effective as thiabendazole for intestinal strongyloidiasis. Ivermectin, however, will likely soon be available in the United States and will probably become the treatment of choice for strongyloides infection.

Cutaneous Larva Migrans. Therapy of cutaneous larva migrans with either topical or oral thiabendazole has always been difficult. Albendazole 200 mg po bid for three days is unequivocally the treatment of choice now for this relatively common affliction.

Neurocysticercosis. The necessity for anticestodal chemotherapy in cases of neurocysticercosis with viable cysts is somewhat controversial. Those with only calcified lesions or with lesions with surrounding edema suggesting the death of the cyst definitely need not be treated. In comparative non-blinded trials, albendazole appears to have slightly higher activity than praziquantel. Anywhere from eight to 30 days of therapy with 15 mg/kg/d, up to 800 mg in two divided doses, have been used and cycles repeated based on clinical judgment.

Corticosteroids, which may increase plasma levels of albendazole, are usually administered concomitantly. Those with previous seizures need prolonged anti-epileptic medication even after albendazole is completed and lesions are resolved. All patients should be observed for a day or two in hospital when therapy is commenced. Albendazole has activity in multiple doses against adult Taenia sp., but its use is discouraged for this indication.

Hydatid Disease. Prolonged high-dose regimens of albendazole constitute by far the most effective medical treatment of larval cestode disease caused by Echinococcus granulosus, E. multilocularis, and E. vogeli. Some studies suggest that an initial trial of medical therapy may obviate the need for any surgical intervention in relatively uncomplicated disease. Treatment needs to be individualized to response and normally consists of 15 mg/kg/d (max, 800 mg/d) for cycles of 28 days, with 14 days rest prior to the next cycle. Initially, a minimum of three cycles is recommended and should be started prior to any surgical intervention to minimize the effect of intraoperative spillage of cyst contents. Recent data suggest that, if well tolerated, the 12 weeks of initial therapy may be given without any intermittent two-week rest periods.

Other Parasites. Successful treatment of visceral larva migrans with 400 mg po bid for 3-5 days has been reported. Good microfilaricidal activity against loiasis is reported, and ongoing studies in lymphatic filariasis suggest good efficacy. Reports with limited numbers of patients have documented the activity of albendazole in giardiasis, microsporidiosis, clonorchiasis, trichinosis, and capillariasis, but its role in the treatment of these infections has yet to be defined. The benefit of any existing chemotherapy at all for gnathostomiasis or angiostrongyliasis is doubtful, but albendazole is thought to be the most active benzimidazole.

Adverse Effects

Side effects of low-dose therapy are minimal and consist of diarrhea, abdominal pain, migration of ascaris through the mouth or nose, and, rarely, hypersensitivity. With high-dose therapy, increased hepatic transaminases, dizziness, neutropenia, and alopecia are most common. Liver function tests and blood counts should be monitored every two weeks in high-dose daily therapy and drug stopped until abnormalities return to normal. A very rare irreversible neutropenia has been reported. No pediatric- or geriatric-specific problems have been documented for high-dose therapy, but experience is limited. Significant embryotoxic potential precludes the use of albendazole in pregnancy, and it may be excreted in breast milk. No pediatric suspension is presently available in the United States. (Dr. Freedman is Director, UAB Travelers Health Clinic, University of Alabama at Birmingham.)