Albendazole

ALBENDAZOLE

Albendazole, a broad-spectrum oral antihelminthic, is the drug of choice and is approved in the USA for treatment of hydatid disease and cysticercosis. It is also used in the treatment of pinworm and hookworm infections, ascariasis, trichuriasis, and strongyloidiasis.

Basic Pharmacology

Albendazole is a benzimidazole carbamate. After oral administra-tion, it is erratically absorbed (increased with a fatty meal) and then rapidly undergoes first-pass metabolism in the liver to the active metabolite albendazole sulfoxide. It reaches variable maxi-mum plasma concentrations about 3 hours after a 400-mg oral dose, and its plasma half-life is 8–12 hours. The sulfoxide is mostly protein-bound, distributes well to tissues, and enters bile, cerebrospinal fluid, and hydatid cysts. Albendazole metabolites are excreted in the urine.

Benzimidazoles are thought to act against nematodes by inhibiting microtubule synthesis. Albendazole also has larvicidal effects in hydatid disease, cysticercosis, ascariasis, and hookworm infection and ovicidal effects in ascariasis, ancylostomiasis, and trichuriasis.

Clinical Uses

Albendazole is administered on an empty stomach when used against intraluminal parasites but with a fatty meal when used against tissue parasites.

A. Ascariasis, Trichuriasis, and Hookworm and Pinworm Infections

For adults and children older than 2 years of age with ascariasis and hookworm infections, the treatment is a single dose of 400 mgorally (repeated for 2–3 days for heavy ascaris infections and in 2 weeks for pinworm infections). These treatments typically achieve good cure rates and marked reduction in egg counts in those not cured. For trichuriasis, three daily 400-mg oral doses of albendazole are now recommended. A recent meta-analysis showed albendazole to be superior to mebendazole or pyrantel pamoate for treatment of hookworm infection; other studies showed that three doses of mebendazole and albendazole increased stool clearance of eggs compared with single treatments, with albendazole superior to mebendazole. Cure rates for trichuriasis with single-dose albenda-zole or mebendazole were less than 30%, which suggests that the three-dose regimen just noted, or other drugs (eg, ivermectin), might be superior.

B. Hydatid Disease

Albendazole is the treatment of choice for medical therapy and is a useful adjunct to surgical removal or aspiration of cysts. It is more active against Echinococcus granulosus than against E mul-tilocularis. Dosing is 400 mg twice daily with meals for 1 monthor longer. Daily therapy for up to 6 months has been well toler-ated. One reported therapeutic strategy is to treat with albenda-zole and praziquantel, to assess response after 1 month or more, and, depending on the response, to then manage the patient with continued chemotherapy or combined surgical and drug therapy.

C. Neurocysticercosis

Indications for medical therapy for neurocysticercosis are contro-versial, since antihelminthic therapy is not clearly superior to therapy with corticosteroids alone and may exacerbate neurologic disease. Therapy is probably most appropriate for symptomatic parenchymal or intraventricular cysts. Corticosteroids are usually given with the antihelminthic drug to decrease inflammation caused by dying organisms. Albendazole is now generally consid-ered the drug of choice over praziquantel because of its shorter course, lower cost, improved penetration into the subarachnoid space, and increased drug levels (as opposed to decreased levels of praziquantel) when administered with corticosteroids. Albendazole is given in a dosage of 400 mg twice daily for up to 21 days.

D. Other Infections

Albendazole is the drug of choice in the treatment of cutaneous larva migrans (400 mg daily for 3 days), visceral larva migrans (400 mg twice daily for 5 days), intestinal capillariasis (400 mg daily for 10 days), microsporidial infections (400 mg twice daily for 2 weeks or longer), and gnathostomiasis (400 mg twice daily for 3 weeks). It also has activity against trichinosis (400 mg twice daily for 1–2 weeks) and clonorchiasis (400 mg twice daily for 1 week). There have been reports of some effectiveness in treat-ment of opisthorchiasis, toxocariasis, and loiasis, and conflicting reports of effectiveness in giardiasis and taeniasis. Albendazole is included in programs to control lymphatic filariasis, but it appears to be less active than diethylcarbamazine or ivermectin for this purpose. Albendazole has been recommended as empiric therapy to treat those who return from the tropics with persistent unex-plained eosinophilia.

Adverse Reactions, Contraindications, & Cautions

When used for 1–3 days, albendazole is nearly free of significant adverse effects. Mild and transient epigastric distress, diarrhea, headache, nausea, dizziness, lassitude, and insomnia can occur. In long-term use for hydatid disease, albendazole is well tolerated, but it can cause abdominal distress, headaches, fever, fatigue, alo-pecia, increases in liver enzymes, and pancytopenia.

Blood counts and liver function studies should be monitored during long-term therapy. The drug should not be given to patients with known hypersensitivity to other benzimidazole drugs or to those with cirrhosis. The safety of albendazole in pregnancy and in children younger than 2 years of age has not been established.