How does ivermectin interact with other medications and substances to increase risk of adverse effects?
Executive summary
Ivermectin can interact with many prescription drugs and with alcohol, raising risks such as increased central nervous system (CNS) depression, altered blood levels of co‑administered drugs, and bleeding with blood‑thinners; drug databases list about 100+ potential interacting medicines including warfarin, ketoconazole and erythromycin, and alcohol can worsen dizziness and sleepiness [1] [2] [3]. Clinical reviews and regulators warn that interactions occur via P‑glycoprotein (P‑gp) transport and hepatic metabolism and that co‑administration with CNS depressants or P‑gp inhibitors can increase ivermectin exposure and toxicity [4] [5] [6].
1. How clinicians and databases catalog ivermectin interactions — breadth, not just a few drugs
Professional checkers and reviews show ivermectin has a long list of possible interactions — Drugs.com reports 106 interacting medicines and notes alcohol as an interaction, WebMD and Optum list specific concerns such as warfarin and anticonvulsants, and MedicalNewsToday/Optum caution that some interactions are clinically important even though a single approved dose often has lower risk [1] [3] [7] [8]. These resources emphasize that even if many interactions are “moderate” rather than “major,” the cumulative risk rises when people take multiple medications or use non‑prescription products concurrently [1] [9].
2. Two main pharmacologic mechanisms that raise interaction risk — P‑glycoprotein and liver enzymes
Reviews and drug references highlight P‑glycoprotein (MDR1/ABCB1) transport and hepatic metabolism as key mechanisms. Drugs that inhibit P‑gp (e.g., certain antivirals or protease inhibitors, quinidine is cited) can raise ivermectin blood and CNS levels, increasing neurotoxicity risk; conversely, P‑gp inducers can lower ivermectin efficacy [4] [5]. The pharmacokinetics mini‑review states ivermectin’s interactions with enzyme‑modifying drugs and food/alcohol should be considered because they alter exposure [5].
3. CNS depressants and neurological risk — why combining matters
Public‑health advisories and case reports warn that ivermectin may potentiate other CNS depressant drugs (benzodiazepines, barbiturates) and that overdoses produce neurologic effects including confusion, seizures, stupor and coma; the CDC and regional boards have explicitly said ivermectin can make other CNS depressants more potent [6] [10]. Medscape and pharmacology sources recommend avoiding coadministration or using careful spacing when interacting P‑gp substrates or drugs with narrow therapeutic windows are involved [4] [10].
4. Blood‑thinners, antibiotics and antifungals — bleeding and level changes
Regulatory warnings mention blood‑thinners: the FDA notes that even approved ivermectin doses can interact with anticoagulants like warfarin, and interaction checkers list warfarin among flagged drugs [11] [1]. Macrolide antibiotics (erythromycin) and azole antifungals (ketoconazole) appear on interaction lists — these agents can inhibit metabolic pathways or transporters and thereby alter ivermectin levels or the levels of the co‑drug [1].
5. Alcohol and common OTC substances — additive side effects
Multiple consumer resources state that alcohol can increase sedative effects (dizziness, sleepiness) and may increase ivermectin blood levels or side effects; Drugs.com and WebMD specifically caution against alcohol use with ivermectin because it can add to adverse events such as dizziness, nausea and even seizures in severe cases [2] [3]. Consumer sites and drug checkers also stress disclosing herbal supplements and vitamins to clinicians because interactions with less‑studied products are possible though not always documented [3] [2].
6. Context and limitations in current reporting — single‑dose therapy vs off‑label higher or repeated dosing
Several sources note that the usual approved human regimen is a single weight‑based dose for many parasitic infections, which reduces interaction likelihood, but off‑label or repeated dosing (as promoted by some groups) raises interaction and toxicity risk; Optum and review articles make this distinction [7] [5]. Available sources do not mention specific interaction rates in large prospective trials comparing co‑medication scenarios; much of the interaction guidance is mechanistic, pharmacokinetic modeling, case reports and database flags [5] [10].
7. Practical advice and competing viewpoints
Drug references and regulators uniformly advise telling your clinician and pharmacist about all prescription drugs, OTCs, alcohol and supplements before taking ivermectin, and to avoid veterinary formulations (FDA and Pharmacy Times warn of safety concerns with veterinary products and expanded OTC access raising interaction risk) [11] [12]. Some advocacy and anecdotal sites argue ivermectin is broadly safe even at higher or chronic doses, but these claims conflict with pharmacologic reviews, CDC and FDA cautions about overdose and drug‑drug potentiation and are not supported by authoritative safety data cited here [13] [6].
Bottom line: authoritative sources and interaction checkers document many potential interactions (≈100+) and highlight P‑gp and metabolic pathway interactions, additive CNS depression with sedatives/alcohol, and possible effects on anticoagulants; disclose all substances to a clinician and avoid untested veterinary products or unsupervised high‑dose regimens [1] [4] [2] [11].