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. |
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 | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
No significant drug interactions Can cause Mazzotti reaction (inflammatory response) in patients with high parasitic load.
| Breastfeeding | Ivermectin is excreted into breast milk; M/P ratio unknown. Limited human data suggests low levels. Caution in infants weighing <15 kg due to potential CNS effects. Consider temporary cessation of breastfeeding during therapy. |
| 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. |
■ 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 component of the formulation.","Concurrent use with drugs that inhibit CYP3A4 or P-gp may require caution, but absolute contraindication is rare.","Loa loa infection with high microfilarial loads (risk of severe encephalopathy)."]
| 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."] |
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| 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). |