What are safe therapeutic dosing ranges of ivermectin and how is overdose defined?
Executive summary
Ivermectin’s standard, evidence-backed human dosing for parasitic infections is generally in the 150–200 micrograms per kilogram (mcg/kg) single-dose range, with some indications and expert guides extending that to about 250 mcg/kg or repeating the dose for specific infections; mass‑treatment and specialty regimens sometimes use higher single doses (up to 400 mcg/kg) or annual 0.15–0.4 mg/kg schedules for filarial diseases (150–400 mcg/kg) [1] [2] [3] [4]. Clinical and pharmacology literature also documents that much higher doses have been studied and often tolerated — single doses up to 800 mcg/kg in onchocerciasis and escalation trials testing doses up to 2,000 mcg/kg without consistent CNS toxicity — but these are experimental or programmatic regimens, not routine practice [5] [6] [7].
1. What clinicians mean by “therapeutic range” for ivermectin
The commonly used therapeutic range for routine human parasitic indications is roughly 150–200 mcg/kg taken as a single oral dose, with dermatology and tropical-medicine sources recommending 150–250 mcg/kg and repeat dosing for scabies or strongyloidiasis on day 7–14 when indicated [1] [3]. For mass‑drug‑administration programs or filarial control, regimens cited in the literature include annual or periodic doses of 0.15–0.4 mg/kg (150–400 mcg/kg) depending on local protocols and co-administered drugs [4] [2].
2. Higher and experimental dosing — what the evidence shows
Randomized and dose‑finding trials have deliberately tested substantially higher doses to explore new indications (malaria transmission, antiviral hypotheses), and PK/safety reports show single doses up to 800 mcg/kg have been used for onchocerciasis and that dose‑escalation studies have tested regimens up to about 2,000 mcg/kg with generally acceptable tolerability in small cohorts, supporting the drug’s relatively wide therapeutic index compared with many repurposed agents [5] [6] [8].
3. Pharmacology and factors that change safety margins
Ivermectin is metabolized in the liver and eliminated mainly in feces; food (high‑fat meals) increases bioavailability substantially, and coadministration with P‑glycoprotein inhibitors or certain drugs (eg, erdafitinib, ivacaftor) can raise systemic exposure, potentially narrowing the safety margin in specific patients [7] [9]. The label and clinical references caution special consideration for patients with hepatic impairment, the elderly, and drug interactions that alter P‑gp function [7] [9].
4. How “overdose” is defined clinically (no single universal number)
There is no universally adopted single plasma concentration or absolute mg/kg threshold that clinicians use to define “overdose” for ivermectin; instead, overdose is identified by clinical toxicity — central nervous system depression, ataxia, tremors, mydriasis, bradypnea, seizures, coma — and by history of ingestion of excessive doses or use of highly concentrated veterinary formulations [10] [11] [6]. Regulatory and public‑health warnings emphasize that human toxicity has been driven by misuse (veterinary products) or very large ingestions rather than routine therapeutic dosing [4] [11].
5. Reported toxic presentations and outcomes
Preclinical lethal overdoses in rodents occurred at many‑fold higher doses with progressive CNS signs; human reports and pharmacovigilance describe neurotoxicity (drowsiness, ataxia, coma), gastrointestinal symptoms, and, in settings of heavy Loa loa microfilaremia, severe inflammatory reactions after treatment [10] [11]. Case series and label data underscore that serious adverse events are uncommon at standard doses but increase with very high exposures or coexisting high parasitic burdens [7] [10].
6. Practical safety takeaways and caveats
The practical safety boundary is: use only prescriptions intended for humans at recommended weight‑based doses (typically 150–200 mcg/kg), avoid veterinary products, account for drug interactions and fed vs fasted administration which affect blood levels, and treat suspected overdoses based on clinical status and exposure history because there is no single numeric “overdose cutoff” used in routine care; published dose‑escalation trials and mass‑treatment programs provide context that higher doses have been studied but are not equivalent to standard, approved regimens [1] [4] [6] [7]. Limitations of this report: specifics about numeric plasma concentration thresholds for toxicity in humans are not established in the provided sources, and clinicians rely on symptoms, dose history, and supportive care guidelines in managing suspected overdose [10] [7].