Antihelminthic Drugs

Antihelminthic drugs kill or expel parasitic worms (nematodes, trematodes and cestodes). Most work by paralysing worms or disrupting their energy metabolism or cytoskeleton, and many are given as a single dose. They underpin mass drug administration programmes for soil-transmitted helminths, schistosomiasis, filariasis and onchocerciasis.

Mechanisms.

• Benzimidazoles (albendazole, mebendazole, triclabendazole): bind beta-tubulin and impair glucose uptake.
• Macrocyclic lactones (ivermectin, moxidectin): open glutamate-gated chloride channels, causing paralysis.
• Praziquantel: increases calcium permeability, causing tetanic contraction.
• Pyrantel pamoate: depolarising neuromuscular blocker in worms.
• Diethylcarbamazine: alters microfilarial surface and host immune clearance.
• Niclosamide: uncouples oxidative phosphorylation in tapeworms.

• Soil-transmitted helminths: albendazole 400 mg single dose (200 mg for ages 12 to 23 months), or mebendazole 500 mg single dose.
• Strongyloides: ivermectin; albendazole is less effective.
• Schistosomes and tapeworms: praziquantel.
• Filariae: diethylcarbamazine, ivermectin, albendazole.
• Fasciola: triclabendazole.

Representative regimens (adult).

• Ascaris, hookworm: albendazole 400 mg single dose. Trichuris: albendazole 400 mg daily for 3 days.
• Strongyloidiasis: ivermectin 200 micrograms/kg daily for 2 days; hyperinfection: daily until stool and sputum are negative for 2 weeks.
• Schistosomiasis: praziquantel 40 mg/kg single dose.
• Neurocysticercosis: albendazole 15 mg/kg daily in two doses for 10 to 14 days with corticosteroids and antiseizure drugs.
• Onchocerciasis: ivermectin 150 micrograms/kg single dose every 6 to 12 months.
• Lymphatic filariasis: ivermectin 200 micrograms/kg, diethylcarbamazine 6 mg/kg and albendazole 400 mg single dose, where Loa loa and onchocerciasis are absent.

Strongyloides screening. Treat empirically before corticosteroids or other immunosuppression in people from endemic areas.

Region. In East Africa, mass treatment with albendazole and praziquantel in school-age children is common. Neurocysticercosis is a frequent cause of adult-onset epilepsy where pigs are kept. Ivermectin and diethylcarbamazine are given only where Loa loa is excluded.

Contraindications. Albendazole in first trimester; ocular cysticercosis (treatment can damage the eye); diethylcarbamazine with onchocerciasis or heavy Loa loa infection; ivermectin in heavy Loa loa infection.

Serious adverse effects. Albendazole: hepatotoxicity, leukopenia, alopecia with prolonged courses. Ivermectin and diethylcarbamazine: Mazzotti reaction (fever, itch, hypotension), and encephalopathy in loiasis. Praziquantel: dizziness, abdominal pain; worsening neurological signs if neurocysticercosis is unrecognised.

Monitoring. Liver enzymes and full blood count every 2 weeks for courses over 14 days. Stool counts for efficacy 2 to 4 weeks after treatment.

Interactions. Phenytoin, carbamazepine, phenobarbital and rifampicin lower albendazole and praziquantel levels. Dexamethasone and cimetidine raise albendazole levels. Ivermectin may raise warfarin INR.

Special groups.

• Pregnancy: albendazole and mebendazole after the first trimester; praziquantel is used where benefit is clear; avoid ivermectin unless necessary.
• Breastfeeding: compatible.
• Children: albendazole from 12 months; ivermectin generally from 15 kg.
• Liver impairment: avoid prolonged albendazole.

Referral and escalation. Refer neurocysticercosis, hydatid disease, hyperinfection syndrome, and suspected loiasis before ivermectin.