Are there clinical studies on ivermectin and anticoagulant interactions?
Executive summary
Clinical evidence specifically testing interactions between ivermectin and anticoagulants is extremely limited: the literature includes at least one published human case report of presumed ivermectin–warfarin interaction with supratherapeutic INR and hematoma (a single-patient report) [1]. Several clinical studies and trials of ivermectin in COVID-19 have used anticoagulants as part of care bundles (for example enoxaparin in combination regimens) but they do not test drug–drug interactions with anticoagulants as primary endpoints [2] [3].
1. A single case report stands at the center
The clearest clinical signal of an ivermectin–anticoagulant interaction in humans comes from a case report describing a patient on chronic warfarin who developed a large sublingual hematoma and a supratherapeutic INR after two doses of ivermectin; the authors conclude ivermectin may have contributed to warfarin toxicity and advise heightened INR monitoring or empirical dose adjustments when co-administering the drugs [1]. That case report explicitly notes a paucity of human data and frames the finding as the first published clinical signal linking ivermectin to elevated prothrombin time [1].
2. Controlled trials and larger studies do not test interactions
Randomized controlled trials and meta-analyses of ivermectin for COVID-19 focus on efficacy and broad safety outcomes; they generally do not include planned pharmacodynamic or pharmacokinetic interaction studies with anticoagulants [4] [5]. Some clinical trials and observational treatment protocols included anticoagulant drugs (for example enoxaparin or aspirin used in regimens combining ivermectin, dexamethasone and anticoagulants), but those protocols used anticoagulants to treat COVID-associated coagulopathy rather than to study ivermectin’s interaction with them [2] [3]. These studies therefore cannot be interpreted as evidence for or against specific drug–drug interactions [2] [3].
3. Pharmacology suggests plausible mechanisms worth studying
Ivermectin is highly protein bound and is metabolized by hepatic CYP3A4; therefore its serum levels can be affected by drug–drug interactions [6]. Warfarin’s activity is sensitive to changes in vitamin K–dependent clotting factors and to inhibitors or inducers of CYP enzymes; the case report cites preclinical evidence that ivermectin can affect vitamin K–dependent clotting factors in vivo, which offers a plausible biological route for interaction [1]. DrugBank and pharmacokinetic work note variability in plasma ivermectin levels and potential interactions via transporters such as P‑glycoprotein [7] [8].
4. Conflicting or absent data in vitro and observational sources
In vitro coagulation tests reported no change in prothrombin time or activated clotting times after adding therapeutic concentrations of ivermectin to human plasma in one laboratory report, a finding cited by reviewers and secondary sources that complicates the clinical picture [9]. Conversely, the single clinical case and some animal/in vivo data suggest an anticoagulant effect, so available sources present contradictory signals rather than a settled conclusion [1] [9].
5. Guidelines and practice: cautious approaches, not definitive rules
WHO and systematic reviewers evaluated ivermectin mainly on efficacy and overall safety in COVID-19 and advised restricting use to clinical trials; WHO guidance on anticoagulation in COVID-19 recommends low‑dose anticoagulants for hospitalized patients but does not address ivermectin interactions specifically [10]. Some practical pharmacy advisories warn patients that combining ivermectin with blood thinners may increase bleeding risk and call for closer monitoring, but these are guidance statements rather than results of formal interaction trials [11].
6. What the literature does not show
Available sources do not report randomized or prospective pharmacokinetic/pharmacodynamic clinical trials designed to quantify interactions between ivermectin and specific anticoagulants (for example warfarin, direct oral anticoagulants, or low‑molecular‑weight heparins) as primary outcomes; clinical trials that include anticoagulants did not test interaction mechanisms [2] [3]. Large meta-analyses of ivermectin in COVID-19 assess clinical endpoints like mortality and ventilation but do not supply focused interaction data [4] [5].
7. Practical takeaways for clinicians and patients
Given one documented human case of possible warfarin toxicity temporally linked to ivermectin [1], ivermectin’s hepatic metabolism and protein binding [6], and the absence of dedicated interaction trials [2] [3], clinicians should be alert: obtain medication histories, consider increased INR monitoring if ivermectin must be given to a patient on warfarin, and treat single‑case reports as signals requiring formal study rather than proof of causation [1] [6]. Clinical trial data including anticoagulants exist but do not answer whether ivermectin alters anticoagulant pharmacology [2] [3].
Limitations: This analysis is limited to the provided sources; other unpublished or later studies not in the supplied set may exist.