What is ivermectin?

What is Ivermectin

Ivermectin is a semisynthetic, broad-spectrum antiparasitic medication derived from avermectins (fermentation products of Streptomyces avermitilis) that is FDA-approved for treating specific parasitic infections, particularly onchocerciasis (river blindness) and strongyloidiasis. 1

Mechanism of Action

Ivermectin works by binding selectively to glutamate-gated chloride ion channels in invertebrate nerve and muscle cells, causing hyperpolarization that results in paralysis and death of the parasite 1. Key pharmacologic features include:

• Selective toxicity: The drug has low affinity for mammalian ligand-gated chloride channels and does not readily cross the blood-brain barrier in humans, which accounts for its safety profile 1
• Metabolism: Primarily metabolized by CYP3A4 in the liver, with a plasma half-life of approximately 18 hours 1
• Excretion: Almost exclusively eliminated in feces over 12 days, with less than 1% excreted in urine 1
• Food effect: High-fat meals increase bioavailability approximately 2.5-fold 1

FDA-Approved Indications

Strongyloidiasis

• Dosing: Single oral dose of 200 mcg/kg 2
• Efficacy: Cure rates of 83-100% in clinical trials, superior to albendazole (45-55% cure rate) 1
• Important caveat: Recrudescence can occur up to 106 days post-treatment, requiring at least three stool examinations over three months using concentration techniques (Baermann apparatus) to confirm eradication 1

Onchocerciasis (River Blindness)

• Dosing: Single dose of 150 mcg/kg annually 2, 3
• Efficacy: Produces 83.2% reduction in skin microfilariae at 3 days and 99.5% reduction at 3 months, with >90% reduction maintained for 12 months 1
• Mechanism: Active against tissue microfilariae but not adult worms; temporarily interrupts microfilariae production 4
• Critical safety warning: Must exclude loiasis infection before treatment to prevent fatal encephalopathy 2

Off-Label Uses (Evidence-Based)

The following uses are supported by clinical guidelines but require specialist consultation 2, 5:

• Cutaneous larva migrans: 200 mcg/kg single dose 2
• Lymphatic filariasis: Used in mass treatment programs 5
• Scabies and crusted scabies: Considered better therapeutic option for severe cases 5
• Pediculosis, gnathostomiasis: Alternative treatment options 2, 5

What Ivermectin Should NOT Be Used For

COVID-19 (Strong Evidence Against Use)

The Infectious Diseases Society of America and World Health Organization explicitly recommend against ivermectin for COVID-19 treatment. 6, 2, 7

• Ambulatory patients: Strong recommendation against use with moderate certainty of evidence—no benefit for mortality, mechanical ventilation need, symptom resolution, or viral clearance 2, 7
• Hospitalized patients: Conditional recommendation against use with very low certainty of evidence 6, 2
• Pharmacologic rationale: In vitro antiviral activity requires concentrations considerably higher than achievable in human plasma and lung tissue, making therapeutic effects implausible 6, 7
• Resource diversion concern: Using ivermectin diverts attention from evidence-based treatments like nirmatrelvir/ritonavir, remdesivir, and molnupiravir 6

Safety Profile

Common Adverse Effects

Higher doses (beyond approved indications) may cause dizziness, nausea, fever, headache, muscle/joint pain, and skin reactions 6

Serious Risks

• Loiasis co-infection: Fatal encephalopathy can occur when treating onchocerciasis in patients with concurrent loiasis due to massive microfilarial die-off 2, 5
• Severe liver disease: Higher toxicity risk requiring close monitoring 6
• Emerging resistance: First documented cases of resistance in scabies treatment have been reported 5

Drug Interactions

Ivermectin does not significantly inhibit CYP3A4, CYP2D6, CYP2C9, CYP1A2, or CYP2E1 at clinically relevant concentrations 1

Clinical Pearls

• Always exclude loiasis before treating onchocerciasis—this is an absolute requirement to prevent fatal complications 2
• Use concentration techniques for stool examinations in strongyloidiasis, as larval counts may be very low 1
• Administer with food to enhance absorption if higher bioavailability is desired 1
• Patients with severe liver disease require dose adjustment and monitoring 6