IVERMECTIN
Clinical safety rating: safe
Animal studies have demonstrated safety
Ivermectin is a macrocyclic lactone that binds selectively and with high affinity to glutamate-gated chloride ion channels in invertebrate nerve and muscle cells, leading to increased chloride ion influx, hyperpolarization, and paralysis of the parasite. It also interacts with other ligand-gated chloride channels, such as those gated by gamma-aminobutyric acid (GABA). In mammals, these channels are largely confined to the central nervous system, but ivermectin does not readily cross the blood-brain barrier, providing a safety margin.
| Metabolism | Ivermectin is primarily metabolized in the liver by the cytochrome P450 enzyme CYP3A4. It is also a substrate of P-glycoprotein (P-gp). |
| Excretion | Primarily fecal (≥90% as unchanged drug and metabolites); renal excretion is minimal (<1% of dose). Biliary excretion contributes to fecal elimination. |
| Half-life | Terminal elimination half-life is approximately 18 hours (range 12-24 hours) in healthy adults; prolonged in hepatic impairment. |
| Protein binding | Approximately 93% bound to plasma proteins, primarily albumin and possibly alpha-1-acid glycoprotein. |
| Volume of Distribution | Apparent volume of distribution is 3.1-3.5 L/kg (large, indicating extensive tissue distribution including fat and skin). |
| Bioavailability | Oral bioavailability is approximately 60-80% (due to extensive first-pass metabolism). Topical bioavailability is negligible (<1% systemic absorption). |
| Onset of Action | Oral: Onset of clinical effect against parasitic infections occurs within 2-4 hours (e.g., microfilarial reduction). Topical: Onset for scabies is variable, with symptom improvement typically within 24-48 hours. |
| Duration of Action | Oral: Single dose provides therapeutic effect for 8-14 days for most parasites (e.g., Strongyloides, onchocerciasis). Topical: For scabies, residual activity lasts up to 7 days. |
| Molecular Weight | 875.1 |
150–200 mcg/kg orally once, with repeat dose in 2 weeks for strongyloidiasis; for scabies, 200 mcg/kg orally once, repeat in 2 weeks if needed.
| Dosage form | TABLET |
| Renal impairment | No dose adjustment required for any degree of renal impairment. |
| Liver impairment | Use with caution in severe hepatic impairment; specific Child-Pugh-based dosing not established. |
| Pediatric use | Weight-based: 150–200 mcg/kg orally once, same as adult; safety for children weighing less than 15 kg not established. |
| Geriatric use | No specific dose adjustment; monitor for adverse effects due to potential age-related organ dysfunction. |
| 1st trimester | Ivermectin is contraindicated in the first trimester due to embryotoxicity and teratogenicity observed in animal studies. Use only if benefit outweighs risk and no alternative exists, with careful monitoring. |
| 2nd trimester | Limited human data; animal studies show fetal harm. Use only if clearly needed and no safer alternatives are available. Assess risk-benefit carefully. |
| 3rd trimester | Use with caution; no specific safety data in third trimester. Potential for neurotoxicity in neonates. Avoid near term unless necessary for life-threatening conditions. |
Clinical note
No significant drug interactions Can cause Mazzotti reaction (inflammatory response) in patients with high parasitic load.
| Placental transfer | Ivermectin crosses the placenta in animal studies, with fetal concentrations reaching up to 10% of maternal plasma levels. Human data are limited but suggest placental transfer occurs. |
| Breastfeeding |
■ FDA Black Box Warning
No FDA black box warnings.
| Common Effects | Dizziness Itching Peripheral edema Fever Joint pain Swelling of lymph nodes Synovitis Nausea Diarrhea Orthostatic hypotension sudden lowering of blood pressure on standing Facial swelling Fast heart rate Increased white blood cell count eosinophils Increased hemoglobin Increased alanine aminotransferase Increased aspartate aminotransferase Decreased white blood cell count |
| Serious Effects |
Hypersensitivity to ivermectin or any componentConcurrent use of drugs known to inhibit P-glycoprotein (e.g., ketoconazole, itraconazole) in patients with certain infections (e.g., strongyloides) unless benefit outweighs riskSevere hepatic impairment (Child-Pugh C) due to altered metabolism
| Precautions | Severe skin reactions (Mazzotti reaction) when treating onchocerciasis, including pruritus, urticaria, fever, arthralgias, syncope, and lymphadenitis., Neurological toxicity in high doses or with compromised blood-brain barrier (e.g., due to meningitis, African trypanosomiasis, or Loa loa infection with high microfilarial loads)., Ocular reactions in onchocerciasis: exacerbation of eye lesions, including optic neuritis and chorioretinitis., Potential for drug interactions with CYP3A4 inhibitors (e.g., ketoconazole, erythromycin) or P-gp inhibitors (e.g., verapamil, cyclosporine), leading to increased ivermectin exposure., Hypersensitivity reactions., Use in pregnancy only if clearly needed (data limited)., Not recommended in children under 5 years of age or weighing less than 15 kg. |
Loading safety data…
| Ivermectin is excreted into breast milk in low concentrations (estimated relative infant dose <1% of maternal weight-adjusted dose). No adverse effects reported in breastfed infants. However, due to potential neurotoxicity in immature nervous system, caution is advised, especially in preterm infants. Use only when clearly indicated. |
| Lactation Rating | L2 (Probably Compatible) |
| Teratogenic Risk | FDA Category C. Animal studies show teratogenicity at high doses. Human data limited; avoid in first trimester unless benefit outweighs risk. No increased malformation risk in second/third trimester from observational studies. |
| Fetal Monitoring | Monitor maternal hepatic function due to potential toxicity. Fetal ultrasound growth scans recommended if used in second/third trimester. Observe newborn for signs of CNS depression or hypotonia if used near term. |
| Fertility Effects | No adverse effects on fertility reported in animal studies. Human data insufficient. May impair sperm motility at high doses (reversible). |
| Food/Dietary | Ivermectin should be taken on an empty stomach with water. Administration with food, particularly high-fat meals, can significantly increase absorption (up to 2.5-fold), potentially increasing the risk of adverse effects. Therefore, avoid food for at least 2 hours before and 1 hour after dosing. Grapefruit juice may inhibit CYP3A4 and could theoretically increase ivermectin levels; caution is advised. |
| Clinical Pearls | Ivermectin is a broad-spectrum antiparasitic agent that causes parasite death by increasing chloride ion conductance in invertebrate nerve and muscle cells. It is the drug of choice for onchocerciasis and strongyloidiasis, and is also used for scabies and head lice. For onchocerciasis, it is given as a single dose of 150 mcg/kg, repeated every 6-12 months. For strongyloidiasis, the recommended dose is 200 mcg/kg daily for 2 days. For crusted scabies, multiple doses (e.g., on days 1, 2, 8, 9) may be required. Note: Ivermectin does not kill adult Onchocerca worms but reduces microfilarial load. Severe adverse effects (Mazzotti reaction) can occur in onchocerciasis due to rapid microfilarial killing. Avoid in patients with Loa loa co-infection due to risk of encephalopathy. Ivermectin is not recommended for children under 15 kg or pregnant women unless benefits outweigh risks. Drug interactions: caution with CYP3A4 inhibitors or inducers; consider dose adjustment with strong inhibitors like ketoconazole. |
| Patient Advice | Take ivermectin exactly as prescribed, usually on an empty stomach with water. · For strongyloidiasis or scabies, you may need a second dose; complete the full course. · Do not take with food, especially high-fat meals, as they may increase absorption and risk of side effects. · Common side effects include dizziness, pruritus, and gastrointestinal upset. · Report any severe skin rash, swelling, or difficulty breathing immediately. · If being treated for onchocerciasis, you may experience a reaction (fever, itching, joint pain) due to dying parasites; this is usually mild and treatable. · Avoid driving or operating machinery if you experience dizziness or drowsiness. · Inform your doctor if you are pregnant, breastfeeding, or taking other medications. · Do not use ivermectin for COVID-19; it is not approved for viral infections. |