Are there known drug interactions or patient factors (age, liver disease) that increase risk of ivermectin overdose?
Executive summary
Known patient factors that raise concern for higher ivermectin exposure or adverse effects include very low body weight (children <15 kg), advanced age with comorbid organ disease, and impaired liver or kidney function; product warnings and reviews note hepatic metabolism and reports of liver injury and neurologic toxicity in overdoses [1] [2] [3]. Drug–drug interactions reported or flagged in the literature center on agents that alter ivermectin clearance (CYP3A4 inhibitors, some immunosuppressants and antiparasitic/antimalarial combinations), which could increase ivermectin exposure and theoretical overdose risk [4] [5] [6].
1. Age and body‑size: children and elderly as special groups
Packaging and clinical guidance emphasize weight-based dosing: most oral ivermectin regimens use mcg/kg and many authorities restrict or caution use in children under weight cutoffs (commonly <15 kg) because safety data are limited; some observational studies report use in lighter children without neurologic events, but the lack of randomized evidence is explicit [1] [7] [8]. For older adults, formal trials did not enroll large numbers ≥65 to detect age‑specific effects, and geriatrics guidance warns that age‑related liver, kidney, or heart disease can require dose caution because organ impairment affects drug handling [9] [1].
2. Liver and kidney disease: pharmacology and clinical caveats
Ivermectin is metabolized and transported by hepatic systems; multiple reviews and manufacturer notes caution that liver impairment can alter metabolism and increase side‑effect risk, and animal or cellular studies have shown hepatic effects after ivermectin exposure — though human datasets are limited and sources diverge about whether routine dose adjustment is established [2] [5] [10]. Some clinical summaries and drug resources advise caution and monitoring in liver disease while others (including advocacy groups citing reference texts) assert no standard dose change is required; this disagreement reflects limited human pharmacokinetic and outcome data [11] [6] [12].
3. Medicines that can raise ivermectin levels or interact clinically
In vitro and pharmacokinetic work shows ivermectin interacts with CYP3A4 and hepatic transporters; co‑administering strong CYP3A4 inhibitors or drugs that affect transporter function (for example some antimalarials like piperaquine, or potent protease/antiretroviral regimens) can raise ivermectin exposure in laboratory models or animal studies — the papers recommend studying these combinations because higher exposure could increase toxicity [4] [5]. Clinical resources and interaction databases list notable interactions with immunosuppressants (cyclosporine, tacrolimus), certain antifungals and antiretrovirals where monitoring is advised, and warn of many possible interacting drugs even if clinical outcome data are sparse [6] [13].
4. Overdose presentations and consequences documented by regulators and poison centers
Regulatory agencies and poison center reports document that ivermectin overdose can produce gastrointestinal, cardiovascular and serious neurologic effects (dizziness, ataxia, seizures, coma) and even death in extreme cases; the FDA consumer update and poison‑center case series cite nausea, hypotension, neurologic toxicity and fatal outcomes as recognized consequences of overdose or misuse, underscoring real clinical risk when unapproved doses or veterinary products are taken [3] [14] [15].
5. Conflicting guidance and gaps in evidence — what reporting does and does not say
Some clinical summaries and advocacy pages state “no dose adjustments required in liver disease” or that ivermectin is broadly safe, while manufacturers’ labels, pharmacology reviews, and poison‑center data urge caution — this split arises because randomized dose‑adjustment trials and large pharmacokinetic outcome studies in hepatic/renal impairment are limited or absent in the provided sources [6] [12] [10]. Available reporting does not provide a definitive, universally accepted list of interacting drugs that reliably cause clinically meaningful ivermectin overdosing in humans; instead, it identifies plausible mechanisms and several specific drug classes warranting monitoring [5] [4].
6. Practical takeaways for clinicians and patients
Follow weight‑based dosing, avoid off‑label high‑dose use (including veterinary formulations), and treat liver or renal impairment as a flag for extra caution and monitoring; review concomitant medications for CYP3A4 inhibitors, immunosuppressants, antimalarials and other agents that alter hepatic transporters and consider therapeutic‑drug monitoring or alternative therapies when data are lacking [1] [4] [3]. If overdose or unexpected neurologic/GI symptoms occur, consult poison‑control resources and emergency care—regulatory alerts document real harms tied to misuse and overdoses [3] [14].
Limitations: the sources include regulatory advisories, in vitro and animal studies, observational reports and some meta‑analyses; randomized clinical pharmacokinetic trials specifically quantifying dose adjustments for liver/kidney disease or enumerating clinically confirmed drug interactions in large human cohorts are not fully represented in the provided materials — available sources do not mention comprehensive human dose‑adjustment guidelines for all comorbid conditions.