What are documented drug interactions between ivermectin and other hepatically metabolized drugs (e.g., warfarin, statins)?
Executive summary
The literature documents a small but consistent signal that ivermectin can interact with hepatically metabolized drugs—most notably case reports and drug-interaction databases that link ivermectin with increased warfarin effect and rare rises in INR, and reviews that flag potential interactions with statins and other CYP-processed medicines that can increase risk of myopathy or alter drug levels [1] [2] [3] [4]. Overall, the evidence is sparse, largely based on post‑marketing reports, single case reports, and pharmacokinetic inferences rather than large controlled trials, so clinicians are advised to monitor clinically relevant labs (e.g., INR) and adverse effects when co‑prescribing [1] [5] [6].
1. Warfarin: rare but documented bleeding risk and INR changes
Multiple clinical sources and a peer‑reviewed case report describe warfarin–ivermectin interaction manifesting as increased anticoagulant effect with bleeding and elevated INR, and drug interaction compendia label the interaction as “moderate,” recommending caution and monitoring [1] [2] [7] [8]. The first published human case report described a large sublingual hematoma temporally associated with starting ivermectin while on warfarin and referenced ivermectin’s capacity—shown in some in vivo studies—to disrupt vitamin K–dependent clotting factors, which plausibly explains prolonged prothrombin time [1] [9]. Post‑marketing summaries from the manufacturer and prescribing information likewise note rare increased INR reports when ivermectin was coadministered with warfarin [10] [8]. Drug information sites therefore advise informing prescribers about warfarin use and increasing INR monitoring if both drugs are used concurrently [2] [11].
2. Statins and myopathy risk: mechanistic concerns and literature flags
A pharmacology review that cataloged ivermectin interactions specifically warned that commonly used statins and fibrates are among drugs that may interact with ivermectin to increase the risk and severity of myopathy, rhabdomyolysis, and myoglobinuria—indicating a clinically important potential interaction between ivermectin and hepatically metabolized lipid‑lowering agents [4]. That review lists statins among several drug classes where co‑use with ivermectin has been associated with increased muscle toxicity risk or altered elimination, implying either pharmacokinetic competition or additive myotoxic mechanisms [4]. However, primary evidence in humans appears to be sparse and inferential—based on pharmacology and case or pharmacokinetic reports rather than controlled trials—so the review’s warnings should be treated as precautionary signals rather than definitive incidence rates [4].
3. Broader pattern: CYP, transporters, and mixed pharmacokinetic signals
Comprehensive interaction lists from clinical databases identify over 100 potential ivermectin interactions, including antifungals and macrolides that are known CYP inhibitors or P‑glycoprotein substrates, suggesting ivermectin can be involved in complex pharmacokinetic interactions that alter the metabolism or transport of co‑medications [3]. The Muller review and drug compendia report heterogeneous findings: ivermectin has been reported to increase the metabolism of some drugs and to increase serum concentrations of others (for example, reported increased serum haloperidol), indicating the net effect depends on the specific pathways and concomitant drugs [4]. These mixed signals reflect the limited human pharmacokinetic dataset and reliance on in vivo animal studies or isolated reports, making mechanistic generalizations risky without drug‑specific evaluation [4] [6].
4. Clinical takeaways and limits of evidence
Authoritative prescribing information and major drug databases advise caution: tell clinicians about warfarin use, monitor INR more frequently if coadministered, and watch for signs of bleeding or muscle toxicity when ivermectin is combined with anticoagulants, statins, or other hepatically metabolized drugs [2] [5] [6]. At the same time, the body of human evidence is limited to rare post‑marketing reports and case studies plus pharmacology reviews extrapolating from in vivo findings, so definitive incidence estimates and clear mechanistic pathways for many hepatically metabolized drugs remain poorly characterized in humans [1] [4]. Clinical judgment requires individualized risk assessment, lab monitoring, and consideration of alternative agents when high‑risk combinations are contemplated [2] [6].