Are there clinically significant drug interactions that affect ivermectin elimination?
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Executive summary
Available sources report multiple potential drug interactions with ivermectin, most commonly via P‑glycoprotein (P‑gp/MDR1) transport or additive CNS effects and rare reports of warfarin INR increases; clinical significance varies by interaction and is often described as “monitor closely” or “rare” (examples: fostamatinib raising P‑gp–mediated ivermectin levels; post‑marketing INR increases with warfarin) [1] [2]. Comprehensive interaction lists (Drugs.com, Drugs.com Food interactions) enumerate over 100 possible interacting drugs but do not distinguish how many produce clinically meaningful changes in ivermectin elimination [3] [4].
1. P‑glycoprotein: the transport gate that matters
Pharmacologic literature and clinical references point to P‑glycoprotein (MDR1/P‑gp) as a central determinant of ivermectin disposition: drugs that inhibit P‑gp can increase ivermectin concentrations by reducing efflux, while P‑gp inducers could theoretically lower exposure. Medscape flags fostamatinib and eliglustat as agents that can increase ivermectin levels via P‑gp interactions and recommends monitoring or dose modification [1]. DrugBank highlights ivermectin’s interactions with drug‑transport proteins, including multidrug resistance proteins and ABC transporters, indicating a mechanistic basis for altered elimination [5].
2. Many listed interactions; few clearly proven to change elimination clinically
Commercial interaction checkers list large numbers — Drugs.com reports 106 drugs that “interact” with ivermectin — but these databases mix pharmacodynamic interactions, theoretical CYP/transport concerns, and rare post‑marketing reports without separating mechanistic probability from proven clinical impact [3] [6]. The primary sources in the record do not systematically quantify how many of those interactions produce clinically significant changes in ivermectin elimination or require dose changes [3] [4].
3. Warfarin and clotting tests: rare signals, post‑marketing reports
Regulatory and clinical summaries note post‑marketing reports of increased INR when ivermectin was co‑administered with warfarin, described as rare; those reports warrant INR monitoring but are not presented as conclusive evidence that ivermectin reliably alters warfarin metabolism [2]. WebMD and RxList both advise clinicians to be alert to warfarin interactions and to monitor coagulation parameters [7] [2].
4. Central nervous system (CNS) additive effects and safety, not elimination
CDC and other public health notices emphasize that ivermectin can potentiate CNS‑depressant drugs — benzodiazepines and barbiturates — increasing risk of sedation and toxicity; these are pharmacodynamic interactions (additive CNS depression), not described in the sources as affecting ivermectin elimination [8]. Clinical guidance therefore focuses on toxicity risk rather than altered clearance [8].
5. Antimalarials and CYP‑mediated concerns remain under active study
Emerging research in malaria settings raises the possibility that co‑administered antimalarials could change ivermectin exposure through effects on metabolism or absorption; an in vitro study and a 2025 Malaria Journal report recommend evaluating CYP‑mediated interactions where ivermectin is given with antimalarials in mass drug administration programs [9]. That research suggests potential for altered elimination but does not establish widespread clinically significant changes in standard therapeutic use [9].
6. Older pharmacokinetic reviews call for caution but note limited human data
A mini‑review of ivermectin pharmacokinetics notes that clinical pharmacokinetic data in humans are fewer than in animals and that drug–drug interactions are possible, recommending attention when co‑prescribing but acknowledging limitations in the evidence base [10]. This gap explains why interaction checkers err on the side of inclusive lists while definitive clinical trials are sparse [10].
7. Practical takeaway for clinicians and patients
Available sources advise clinicians to review concomitant medications, monitor relevant labs (e.g., INR with warfarin), and be cautious with known P‑gp inhibitors (fostamatinib, eliglustat identified in Medscape) or CNS depressants [1] [2] [8]. Broad interaction lists (Drugs.com, Drugs.com food interactions) are useful screening tools but do not substitute for clinical judgment or targeted monitoring [3] [4].
Limitations and open questions: the sources do not quantify how many listed interactions change ivermectin elimination in a clinically meaningful way, nor do they provide large randomized trials demonstrating routine dose adjustments for most interacting drugs [3] [10]. Future controlled DDI studies — particularly for P‑gp modulators and common antimalarials — would resolve which interactions require systematic management [9] [1].