Page 956 - Basic _ Clinical Pharmacology ( PDFDrive )

942 SECTION VIII Chemotherapeutic Drugs

Doses are repeated; regimens vary from monthly to less frequent MEBENDAZOLE
(every 6–12 months) dosing schedules. After acute therapy,
treatment is repeated at 12-month intervals until the adult Mebendazole is a synthetic benzimidazole that has a wide spec-
worms die, which may take 10 years or longer. With the first trum of antihelminthic activity and a low incidence of adverse
treatment only, patients with microfilariae in the cornea or effects.
anterior chamber may be treated with corticosteroids to avoid
inflammatory eye reactions. Basic Pharmacology
Ivermectin also now plays a key role in onchocerciasis control.
Annual mass treatments have led to major reductions in disease Less than 10% of orally administered mebendazole is absorbed.
transmission. However, evidence of diminished responsiveness The absorbed drug is protein-bound (>90%), is rapidly converted
after mass administration of ivermectin has raised concern regard- to inactive metabolites (primarily during its first pass in the liver),
ing selection of drug-resistant parasites. and has a half-life of 2–6 hours. It is excreted mostly in the urine,
principally as decarboxylated derivatives, as well as in the bile.
2. Strongyloidiasis—Treatment consists of 200 mcg/kg once Absorption is increased if the drug is ingested with a fatty meal.
daily for 2 days. In immunosuppressed patients with dissemi- Mebendazole probably acts by inhibiting microtubule synthe-
nated infection, repeated treatment is often needed, and cure sis; the parent drug appears to be the active form. Efficacy of the
may not be possible. In this case, suppressive therapy—ie, once drug varies with gastrointestinal transit time, with intensity of
monthly—may be helpful. infection, and perhaps with the strain of parasite. The drug kills
hookworm, Ascaris, and Trichuris eggs.
3. Other parasites—Ivermectin reduces microfilariae in
B malayi and M ozzardi infections but not in M perstans infec- Clinical Uses
tions. It has been used with diethylcarbamazine and albendazole Mebendazole is indicated for use in ascariasis, trichuriasis, hook-
for the control of W bancrofti, but it does not kill adult worms. worm and pinworm infections, and certain other helminthic
In loiasis, although the drug reduces microfilaria concentrations, infections. It can be taken before or after meals; the tablets should
it can occasionally induce severe reactions and appears to be more be chewed before swallowing. For pinworm infection, the dose
dangerous in this regard than diethylcarbamazine. Ivermectin is 100 mg once, repeated at 2 weeks. For ascariasis, trichuriasis,
is also effective in controlling scabies, lice, and cutaneous larva hookworm, and Trichostrongylus infections, a dosage of 100 mg
migrans and in eliminating a large proportion of ascarid worms.
twice daily for 3 days is used for adults and for children older than
2 years. Cure rates are good for pinworm infections and ascaria-
Adverse Reactions, Contraindications, & sis but have been disappointing in recent studies of trichuriasis,
Cautions although efficacy for trichuriasis is better than that of albendazole.
Cure rates are also low for hookworm infections, but a marked
In strongyloidiasis treatment, infrequent adverse effects of iver- reduction in the worm burden occurs in those not cured. For
mectin include fatigue, dizziness, nausea, vomiting, abdominal intestinal capillariasis, mebendazole is used at a dosage of 200 mg
pain, and rashes. In onchocerciasis treatment, adverse effects twice daily for 21 or more days. In trichinosis, limited reports
are principally from the killing of microfilariae and can suggest efficacy against adult worms in the intestinal tract and
include fever, headache, dizziness, somnolence, weakness, rash, tissue larvae. Treatment is three times daily, with fatty foods, at
increased pruritus, diarrhea, joint and muscle pains, hypoten- 200–400 mg per dose for 3 days and then 400–500 mg per dose
sion, tachycardia, lymphadenitis, lymphangitis, and peripheral for 10 days; corticosteroids should be co-administered for severe
edema. This reaction starts on the first day and peaks on the infections.
second day after treatment. It occurs in 5–30% of persons and
is generally mild, but it may be more frequent and more severe Adverse Reactions, Contraindications,
in individuals who are not long-term residents of onchocercia-
sis-endemic areas. A more intense reaction occurs in 1–3% of & Cautions
persons and a severe reaction in 0.1%, including high fever, Short-term mebendazole therapy for intestinal nematodes is nearly
hypotension, and bronchospasm. Corticosteroids are indicated free of adverse effects. Mild nausea, vomiting, diarrhea, and
in these cases, at times for several days. Toxicity diminishes abdominal pain have been reported infrequently. Rare side effects,
with repeated dosing. Swellings and abscesses occasionally usually with high-dose therapy, are hypersensitivity reactions (rash,
occur at 1–3 weeks, presumably at sites of adult worms. Some urticaria), agranulocytosis, alopecia, and elevation of liver enzymes.
patients develop corneal opacities and other eye lesions several Mebendazole is teratogenic in animals and therefore contrain-
days after treatment. These are rarely severe and generally dicated in pregnancy. It should be used with caution in children
resolve without corticosteroid treatment. It is best to avoid younger than 2 years because of limited experience and rare
concomitant use of ivermectin with other drugs that enhance reports of convulsions in this age group. Plasma levels may be
GABA activity, eg, barbiturates, benzodiazepines, and valproic decreased by concomitant use of carbamazepine, phenytoin, or
acid. Ivermectin should not be used during pregnancy. Safety ritonavir, and increased by cimetidine. Mebendazole should be
in children younger than 5 years has not been established. used with caution in patients with cirrhosis.