Ivermectin

Ivermectin is a macrocyclic lactone (avermectin) antiparasitic. FDA-approved US products are Stromectol oral tablets, Soolantra cream 1% and Sklice lotion 0.5%. Lake Hills Pharmacy compounds oral and topical ivermectin preparations as a 503A pharmacy on patient-specific prescriptions.

• Oral (Stromectol): strongyloidiasis of the intestinal tract due to Strongyloides stercoralis, and onchocerciasis due to Onchocerca volvulus.
• Topical cream (Soolantra): inflammatory lesions of rosacea in adults.
• Topical lotion (Sklice): head lice infestation in patients 6 months and older.
• FDA has not approved ivermectin for the prevention or treatment of COVID-19.

Ivermectin binds glutamate-gated chloride channels in invertebrate nerve and muscle cells, increasing chloride permeability, causing hyperpolarization, paralysis and death of the parasite. Mammals lack glutamate-gated chloride channels, and the blood-brain barrier, supported by P-glycoprotein efflux, limits ivermectin access to mammalian GABA-gated channels in the CNS. In rosacea, anti-inflammatory effects and activity against Demodex mites are proposed.

Oral: peak plasma levels occur in about 4 hours; a high-fat meal raises bioavailability about 2.5-fold. Ivermectin is highly protein bound and lipophilic, is metabolized mainly by CYP3A4, is a P-glycoprotein substrate, and is excreted almost entirely in feces; half-life is about 18 hours. Topical cream produces low systemic exposure.

• Hypersensitivity to ivermectin or any component of the product.

• Loa loa encephalopathy: patients with heavy Loa loa microfilaremia can develop serious or fatal encephalopathy after oral ivermectin. Assess exposure in West or Central Africa and screen before treatment.
• Mazzotti reaction: in onchocerciasis, death of microfilariae can cause fever, pruritus, rash, lymphadenopathy, arthralgia, edema, tachycardia and orthostatic hypotension.
• Immunocompromised patients, including those with HIV, may need repeated courses for strongyloidiasis and follow-up stool examinations; hyperinfection can occur.
• Safety in children weighing under 15 kg has not been established for oral use.
• Topical: avoid the eyes, lips and mucous membranes.

• Warfarin: increased INR has been reported with concomitant oral ivermectin; monitor INR.
• Strong CYP3A4 or P-glycoprotein inhibitors may raise ivermectin exposure, including CNS exposure.
• CNS depressants: possible additive effects.

Oral: dizziness, pruritus, nausea, diarrhea, headache, rash, and transient liver enzyme elevation; rare serious reactions include encephalopathy, confusion, ataxia, seizures, and severe skin reactions. Topical: burning, irritation, pruritus and dry skin; eye irritation with lotion.

Animal studies showed teratogenicity at maternotoxic doses, and human data are limited. Ivermectin passes into breast milk in low concentrations. Use in pregnancy or breastfeeding is a prescriber decision, considering systemic versus topical exposure.

Oral: response by follow-up stool examination or skin snip as appropriate, neurologic status in patients at risk of Loa loa, and INR with warfarin. Topical: skin tolerability.

• Stromectol (ivermectin) Tablets Prescribing Information, Merck Sharp & Dohme.
• Soolantra (ivermectin) Cream 1% Prescribing Information, Galderma Laboratories.
• Sklice (ivermectin) Lotion 0.5% Prescribing Information.
• Lexicomp Drug Information, Wolters Kluwer.