Ivermectin
Ivermectin
Generic Name
Ivermectin
Mechanism
Ivermectin selectively binds with high affinity to invertebrate GABA‑ and glutamate‑gated chloride channels, enhancing chloride influx and hyperpolarizing neuronal membranes. This leads to:
• Paralysis and death of parasites by blocking neurotransmission
• Inhibition of parasite feeding and reproduction
Because mammalian chloride channels are not sensitive to ivermectin, the drug exhibits a wide therapeutic index in humans.
Pharmacokinetics
| Parameter | Typical Value |
| Absorption | Rapid; ~99 % oral bioavailability (oral solution) Peak plasma conc. 1–2 h post‑dose |
| Distribution | Extensive tissue penetration; highly lipophilic, ~93 % protein‑bound (serum albumin & α‑1‑acid glycoprotein) |
| Metabolism | Hepatic oxidation via CYP3A4/CYP3A5 → 3‑hydroxy‑IVM (inactive) |
| Elimination | Biliary excretion of metabolites; urinary excretion < 1 % Half‑life: 12–36 h (dependent on dose) |
| Special Populations | Safe in pregnancy (Category B) but avoid late gestation; minimal trans‑placental transfer |
Indications
- Strongyloides stercoralis (hyperinfection prophylaxis and treatment)
- Onchocerca volvulus (African river blindness) – 12 mg every 6–12 weeks
- Scabies (uncomplicated & crusted) – single 12 mg dose; repeat in 1–2 weeks if needed
- Chytridiomycosis (veterinary)
- Dermatophytosis (tinea corporis, corporis? – limited evidence, adjunctive)
Contraindications
- Hypersensitivity to ivermectin or any excipients
- Neuro‑muscular disorders: Guillain‑Barré, myasthenia gravis, severe hepatic impairment
- Pregnancy: Use only if potential benefit outweighs risk (late pregnancy caution)
- Use with drugs that prolong QT: minimal, but avoid concurrent quinine or chlorpromazine
- CYP3A4 inhibitors (e.g., ketoconazole, ritonavir) → ↑ ivermectin levels
Warning: Neurologic toxicity (ataxia, visual disturbances) can occur in patients with congenital GABA‑transporter gene mutations (e.g., L1CAM). Monitor neuro‑function in high‑dose or repeat‑dose settings.
Dosing
| Indication | Dose | Administration |
| Strongyloides | 200 µg/kg PO once | 12 mg for 70 kg adult |
| Scabies (uncomplicated) | 200 µg/kg PO once | 12 mg single dose |
| Scabies (crusted) | 200 µg/kg PO once daily for 2 days | 24 mg/day |
| Onchocerciasis | 200 µg/kg PO once every 6–12 weeks | 12 mg for 70 kg adult |
| Veterinary | 0.015–0.02 mg/kg PO | Per species guidelines |
| Topical use | 0.5 % cream (rare) | Apply to affected skin |
Note: Oral solution (10 mg/mL) contains 10% propylene glycol; weigh doses carefully for infants < 10 kg.
Monitoring
- Liver Function Tests (baseline, then per protocol)
- Neuro‑clinical exam pre‑ and post‑dose (especially in high doses)
- Platelet count – in strongyloides (possible thrombo‑cytopenia)
- QT interval – if combined with QT‑prolonging drugs
- Pregnancy test for females of childbearing potential
- Drug–drug interaction checklist (CYP3A4 inhibitors/inducers)
Clinical Pearls
- Single‑dose safety: The standard 200 µg/kg has an exceptionally low neuro‑toxicity risk; higher doses (> 400 µg/kg) should be reserved for refractory cases and monitored closely.
- Avoid first‑pass hepatic overload: Administer with a light meal to reduce GI upset while not affecting absorption.
- Crusted scabies: Twice‑daily dosing is superior to single‑dose; adjunctive permethrin can accelerate clearance.
- Pregnancy & lactation: Category B; minimal evidence of teratogenicity, but discontinue drug if a fetus is confirmed during the third trimester.
- Drug interactions: Ritonavir, cobicistat, ketoconazole increase ivermectin exposure by > 50%; consider dose reduction when co‑administered.
- Veterinary cross‑reference: While dosing regimens differ, the human dose (200 µg/kg) is often used as a benchmark for translating veterinary protocols.
- COVID‑19 caution: Current randomized data shows no mortality benefit; use ivermectin solely within well‑controlled clinical trials.
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• References
• World Health Organization. Ivermectin: Pharmacology and use. 2023.
• FDA Drug Approvals: Ivermectin for scabies, onchocerciasis. 2022.
• Goodman & Gilman's: The Pharmacological Basis of Therapeutics, 14th ed. 2021.