Macrocyclic Lactone Antiparasitic Drugs

Macrocyclic lactones (ivermectin and moxidectin) bind glutamate-gated chloride channels in invertebrate nerve and muscle cells, causing paralysis and death of the parasite. Ivermectin is the main drug for strongyloidiasis, onchocerciasis, scabies and lymphatic filariasis. Moxidectin is a longer-acting alternative for onchocerciasis.

Pharmacokinetics. Ivermectin is lipophilic, absorption is increased by fatty food, and it is metabolised by CYP3A4 with a half-life of about 18 hours. Moxidectin has a half-life of about 20 days. Neither crosses the human blood-brain barrier well because of P-glycoprotein.

• Ivermectin: adults and children over about 15 kg; tablets of 3 mg or 6 mg.
• Moxidectin: 8 mg single dose for onchocerciasis in patients aged 12 years and over.

Ivermectin doses.

• Strongyloidiasis: 200 micrograms/kg daily for 2 days; hyperinfection or disseminated disease: daily until stool and sputum are negative for 2 weeks, with antibiotic cover for enteric bacteria.
• Onchocerciasis: 150 micrograms/kg single dose every 6 to 12 months for the life of the adult worm (about 10 to 15 years).
• Scabies: 200 micrograms/kg, repeat after 7 to 14 days. Crusted scabies: repeat doses on days 1, 2, 8, 9 and 15 with topical treatment, adding days 22 and 29 in severe cases.
• Lymphatic filariasis: 200 micrograms/kg in combination with diethylcarbamazine and albendazole.
• Cutaneous larva migrans: 200 micrograms/kg for 1 to 2 days.

Loiasis. Before mass or individual treatment in areas where Loa loa occurs, assess microfilarial load. Counts over about 20,000 microfilariae/mL risk severe encephalopathy after ivermectin.

Screening before steroids. Treat suspected strongyloidiasis before corticosteroids or other immunosuppression. HTLV-1 infection raises hyperinfection risk.

Dose adjustment.

• Kidney and liver: no routine adjustment.
• Children: used from about 15 kg; scabies treatment in lighter children needs specialist judgement.

Contraindications. Hypersensitivity; heavy Loa loa infection; meningitis or conditions that may increase blood-brain barrier permeability.

Serious adverse effects. Mazzotti reaction in onchocerciasis (fever, pruritus, rash, tender lymph nodes, hypotension) within 48 hours, treated with antihistamines, paracetamol and rarely corticosteroids. Neurotoxicity in loiasis (confusion, coma, retinal haemorrhage). Pruritus and increased scabies itching early in treatment.

Monitoring. Clinical review for reaction after first treatment; stool or sputum clearance in strongyloidiasis; INR if on warfarin.

Interactions. Warfarin (may raise INR); P-glycoprotein inhibitors and CYP3A4 inhibitors raise levels.

Special groups.

• Pregnancy: avoid unless the benefit is clear, such as hyperinfection.
• Breastfeeding: acceptable after the first week of the infant's life.
• Older adults: no dose change.

Referral and escalation. Refer hyperinfection, suspected loiasis, neurological symptoms after treatment, and persistent scabies after two courses.