Introduction
Ivermectin is a broad-spectrum antiparasitic agent belonging to the avermectin class. First discovered in the 1970s, it has become an essential medication in global public health, particularly for neglected tropical diseases. The drug's developers were awarded the 2015 Nobel Prize in Physiology or Medicine for its impact on parasitic disease treatment.
Mechanism of Action
Ivermectin exerts its antiparasitic effects through selective binding to glutamate-gated chloride ion channels in invertebrate nerve and muscle cells. This binding increases cell membrane permeability to chloride ions, resulting in hyperpolarization of the cells, paralysis, and death of the parasites. The drug has minimal effect on mammalian chloride channels due to their different structure and distribution, contributing to its selective toxicity against parasites.
Indications
FDA-Approved Indications:- Strongyloidiasis caused by Strongyloides stercoralis
- Onchocerciasis caused by Onchocerca volvulus
- Lymphatic filariasis caused by Wuchereria bancrofti (in combination with albendazole)
- Scabies (in mass drug administration programs)
- Other intestinal helminth infections
Dosage and Administration
Standard Dosing:- Strongyloidiasis: 200 mcg/kg orally as a single dose
- Onchocerciasis: 150 mcg/kg orally as a single dose, repeated every 6-12 months
- Lymphatic filariasis: 200 mcg/kg orally combined with albendazole 400 mg
- Taken orally on an empty stomach with water
- Tablets should be swallowed whole
- Dosing based on actual body weight
- Renal impairment: No dosage adjustment required
- Hepatic impairment: Use with caution
- Pediatric patients: Safety established for children ≥15 kg
- Geriatric patients: No specific dosage adjustment needed
Pharmacokinetics
Absorption: Well absorbed orally with high fat meals increasing bioavailability Distribution: Widely distributed with high volume of distribution; crosses blood-brain barrier poorly Metabolism: Primarily hepatic via CYP3A4 Elimination: Half-life approximately 18 hours; primarily excreted in feces (>90%) with minimal renal excretion Protein Binding: Approximately 93%Contraindications
- Hypersensitivity to ivermectin or any component of the formulation
- Meningococcal infection or suspected meningitis (due to potential for Mazzotti reaction in onchocerciasis treatment)
- Concomitant use with other drugs that increase blood-brain barrier permeability
Warnings and Precautions
Black Box Warning: None Important Precautions:- Mazzotti reaction: Inflammatory response occurring in onchocerciasis treatment characterized by fever, pruritus, lymphadenopathy
- CNS toxicity possible with high doses or in patients with disrupted blood-brain barrier
- Use caution in patients with asthma or severe hepatic impairment
- Not recommended during pregnancy (Category C) unless potential benefit justifies risk
- Breastfeeding: Excreted in human milk; use with caution
Drug Interactions
Significant Interactions:- CYP3A4 inhibitors (ketoconazole, ritonavir): May increase ivermectin concentrations
- CYP3A4 inducers (rifampin, carbamazepine): May decrease ivermectin concentrations
- Warfarin: Potential for increased anticoagulant effect
- CNS depressants: Additive effects possible with high doses
- P-glycoprotein substrates/inhibitors: Potential for altered distribution
Adverse Effects
Common (≥1%):- Pruritus
- Rash
- Fever
- Headache
- Dizziness
- Diarrhea
- Nausea
- Myalgia
- Hypotension
- Severe skin reactions
- Hepatitis
- Neutropenia
- Mazzotti reaction (in onchocerciasis treatment)
- Encephalopathy (with high doses or in susceptible populations)
Monitoring Parameters
- Clinical response to therapy
- Signs of parasitic infection clearance
- Symptoms of Mazzotti reaction in onchocerciasis treatment
- Liver function tests in patients with hepatic impairment
- Complete blood count with prolonged use
- Neurological status in patients at risk for CNS toxicity
Patient Education
- Take on empty stomach with water
- Report any signs of allergic reaction (rash, itching, swelling)
- Be aware of potential Mazzotti reaction symptoms if treating onchocerciasis
- Do not use for unapproved indications without medical supervision
- Inform healthcare providers of all medications being taken
- Avoid high-fat meals around time of administration
- Understand that repeat dosing may be necessary for certain conditions
References
1. FDA Prescribing Information for Stromectol (ivermectin). 2022 2. WHO Model Formulary. World Health Organization. 2021 3. Ottesen EA, et al. Clinical Pharmacology of Ivermectin. Bull World Health Organ. 1995 4. González Canga A, et al. Ivermectin: Pharmacology and Applications. Clin Pharmacokinet. 2008 5. Temple ME, et al. Ivermectin: A Review of Clinical Applications. Am J Health Syst Pharm. 2003 6. Centers for Disease Control and Prevention. Parasitic Disease Information: Ivermectin. 2023 7. Clinical Pharmacology [Internet]. Tampa (FL): Elsevier. Ivermectin monograph. 2023
This monograph is intended for educational purposes only and should not replace professional medical advice. Always consult with a qualified healthcare provider for medical guidance.