Ivermectin

IVERMECTIN

Ivermectin is the drug of choice in strongyloidiasis and onchocer-ciasis. It is also an alternative drug for a number of other helmin-thic infections.

Basic Pharmacology

Ivermectin, a semisynthetic macrocyclic lactone, is a mixture of avermectin B_1a and B_1b. It is derived from the soil actinomycete Streptomyces avermitilis.Ivermectin is used only orally in humans. The drug is rapidly absorbed, reaching maximum plasma concentrations 4 hours after a 12 mg dose. The drug has a wide tissue distribution and a volume of distribution of about 50 L. Its half-life is about 16 hours. Excretion of the drug and its metabolites is almost exclusively in the feces.

Ivermectin appears to paralyze nematodes and arthropods by intensifying γ-aminobutyric acid (GABA)–mediated transmission of signals in peripheral nerves. In onchocerciasis, ivermectin is microfilaricidal. It does not effectively kill adult worms but blocks the release of microfilariae for some months after therapy. After a single standard dose, microfilariae in the skin diminish rapidly within 2–3 days, remain low for months, and then gradually increase; microfilariae in the anterior chamber of the eye decrease slowly over months, eventually clear, and then gradually return. With repeated doses of ivermectin, the drug appears to have a low-level macrofilaricidal action and to permanently reduce microfi-larial production.

Clinical Uses

A. Onchocerciasis

Treatment is with a single oral dose of ivermectin, 150 mcg/kg, with water on an empty stomach. Doses are repeated; regimens vary from monthly to less frequent (every 6–12 months) dosing schedules. After acute therapy, treatment is repeated at 12-month intervals until the adult worms die, which may take 10 years or longer. With the first treatment only, patients with microfilariae in the cornea or anterior chamber may be treated with corticoster-oids to avoid inflammatory eye reactions.

Ivermectin also now plays a key role in onchocerciasis control. Annual mass treatments have led to major reductions in disease transmission. However, evidence of diminished responsiveness after mass administration of ivermectin has raised concern regard-ing selection of drug-resistant parasites.

B. Strongyloidiasis

Treatment consists of two daily doses of 200 mcg/kg. In immuno-suppressed patients with disseminated infection, repeated treat-ment is often needed, and cure may not be possible. In this case, suppressive therapy—ie, once monthly—may be helpful.

C. Other Parasites

Ivermectin reduces microfilariae in B malayi and M ozzardi infec-tions but not in M perstans infections. It has been used with dieth-ylcarbamazine and albendazole for the control of W bancrofti, but it does not kill adult worms. In loiasis, although the drug reduces microfilaria concentrations, it can occasionally induce severe reac-tions and appears to be more dangerous in this regard than dieth-ylcarbamazine. Ivermectin is also effective in controlling scabies, lice, and cutaneous larva migrans and in eliminating a large pro-portion of ascarid worms.

Adverse Reactions, Contraindications, & Cautions

In strongyloidiasis treatment, infrequent adverse effects include fatigue, dizziness, nausea, vomiting, abdominal pain, and rashes. In onchocerciasis treatment, adverse effects are principally from the killing of microfilariae and can include fever, headache, dizzi-ness, somnolence, weakness, rash, increased pruritus, diarrhea, joint and muscle pains, hypotension, tachycardia, lymphadenitis, lymphangitis, and peripheral edema. This reaction starts on the first day and peaks on the second day after treatment. This reac-tion occurs in 5–30% of persons and is generally mild, but it may be more frequent and more severe in individuals who are not long-term residents of onchocerciasis-endemic areas. A more intense reaction occurs in 1–3% of persons and a severe reaction in 0.1%, including high fever, hypotension, and bronchospasm. Corticosteroids are indicated in these cases, at times for several days. Toxicity diminishes with repeated dosing. Swellings and abscesses occasionally occur at 1–3 weeks, presumably at sites of adult worms.

Some patients develop corneal opacities and other eye lesions several days after treatment. These are rarely severe and generally resolve without corticosteroid treatment.

It is best to avoid concomitant use of ivermectin with other drugs that enhance GABA activity, eg, barbiturates, benzodiaz-epines, and valproic acid. Ivermectin should not be used during pregnancy. Safety in children younger than 5 years has not been established.