Are there drug–drug interactions or P-glycoprotein effects that altered ivermectin dosing in cancer patients?
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Executive summary
Drug–drug interactions and P‑glycoprotein (P‑gp) considerations have been raised in reviews of ivermectin’s repositioning for cancer, but available clinical evidence in cancer patients is sparse and mainly preclinical; most reporting notes potential interactions (including with blood thinners) and toxicity risk at high doses rather than documented trial‑proven dose changes in oncology practice [1] [2]. Preclinical work and early trials exploring ivermectin with immunotherapy or other agents exist, but none establish routine dose modifications driven by P‑gp or drug–drug interaction data in cancer patients [3] [4].
1. The evidence base: mostly preclinical, limited human data
Systematic reviews and literature searches show a surge of preclinical studies (cell lines and animal models) but virtually no robust randomized clinical evidence supporting ivermectin as an anticancer therapy; one review found numerous in vitro reports and only limited human use reports, and the 2025 Annals of Oncology review identified 269 PubMed items but no completed clinical trials demonstrating anticancer efficacy in people [3] [1]. Early-phase clinical activity has been reported as abstracts (for example, an ASCO phase I/II combining ivermectin with the PD‑1 agent balstilimab in metastatic TNBC), but those abstracts do not supply full human pharmacokinetic, interaction, or dosing‑adjustment data that would demonstrate regimen changes based on P‑gp effects [4].
2. What reviewers and public health monitors say about interactions and toxicity
Multiple reviews and health‑information outlets caution that ivermectin can cause serious adverse effects at high or unsupervised doses and can interact with other drugs, notably anticoagulants, and perhaps immunosuppressants or CNS‑active agents; watchdog reporting cites FDA warnings about interactions and overdose risks including seizures or coma [2] [5]. Patient‑facing summaries likewise emphasize that safety at antiparasitic dosing does not directly translate to oncology dosing needs and note possible drug–drug interactions as an important clinical concern [6] [7].
3. Mechanistic rationale linking ivermectin, P‑gp and interactions — seen mostly in bench work
Mechanistic reviews describe ivermectin’s multiple cellular effects (PAK1 kinase modulation, autophagy, induction of immunogenic cell death) that underpin interest in combining it with other therapies, including checkpoint inhibitors [8] [9] [10]. Those molecular and immunologic mechanisms do not, in the cited sources, provide clinical PK/PD data showing P‑gp‑mediated interactions in human cancer patients or clear dosing algorithms; the literature primarily reports laboratory mechanisms and proposes combinations without documented clinical dose alterations for P‑gp considerations [8] [9].
4. Pharmacology questions left unanswered by current reporting
Reviews explicitly flag divergence in doses used in preclinical experiments and question whether antitumor effects occur at clinically achievable plasma concentrations — a key pharmacologic gap that affects how one would manage interactions or adjust dosing [1]. The sources do not report standardized dose‑adjustment rules for cancer patients based on P‑gp modulation or co‑medication profiles; available reporting focuses on theoretical risks and the need for formal pharmacokinetic studies [1].
5. Early clinical trials and abstracts show safety/efficacy but not interaction‑driven dosing changes
Trials and meeting abstracts (for example, the ASCO phase I/II combining ivermectin with balstilimab) indicate that investigators are testing combinations in patients, but abstracts cited do not report that investigators adjusted ivermectin doses because of documented P‑gp interactions or identified specific drug–drug interaction management strategies in cancer cohorts [4]. Media and patient advocacy coverage of those trials emphasize that trials so far have shown no clear benefit and raise concerns about adverse events and interactions [7].
6. Two practical takeaways for clinicians and patients
First, clinicians should treat ivermectin as an experimental agent in oncology: the preclinical promise does not equal proven clinical safety or efficacy, and the literature repeatedly warns against unsupervised use and notes interaction risks [3] [2]. Second, because the reviewed sources do not provide concrete P‑gp interaction data or dosing algorithms in cancer patients, any use in trials should include formal pharmacokinetic and drug‑interaction assessments rather than extrapolation from antiparasitic regimens [1] [4].
Limitations of this report: the sources used here are primarily reviews, preclinical reports, meeting abstracts and public‑facing summaries; they do not include full pharmacokinetic trial reports documenting P‑gp mediated dose changes in cancer patients [3] [1] [4]. Available sources do not mention specific, validated ivermectin dose adjustments driven by documented P‑gp interactions in cancer cohorts.