What clinical trial evidence exists for repeated ivermectin dosing schedules (weekly or monthly) in humans?
Executive summary
Clinical-trial evidence for repeated ivermectin dosing in humans exists primarily in parasitic-disease programs and a few focused trials that used serial dosing over weeks to months, not routine weekly or monthly prophylaxis for other diseases; mass-drug-administration studies have tested multi-dose schedules spaced by weeks and some clinicians recommend periodic retreatment for onchocerciasis or immunocompromised patients with strongyloidiasis [1] [2] [3]. Trials that explored repeated dosing for viral illnesses used short intensive courses (daily for several days) rather than true weekly or monthly maintenance, and regulators caution against broad off‑label use without randomized evidence and safety data [4] [5] [6].
1. What randomized trials have actually used repeat doses on a weekly-to-monthly cadence?
The clearest randomized, cluster‑level human evidence of repeated dosing at roughly monthly cadence comes from RIMDAMAL, a cluster‑randomized trial in Burkina Faso that administered an initial single ivermectin dose (150–200 μg/kg) then five additional ivermectin doses at 3‑week intervals over an 18‑week period to village residents, and evaluated effects on malaria incidence in children [1]. That study tested frequent repeat mass drug administrations (every three weeks, not weekly or monthly exactly) and reported outcomes and tolerability in a mass‑administration context [1]. Beyond RIMDAMAL, most clinical trials of ivermectin for non‑parasitic targets have used short repeated daily courses (e.g., 5–6 days) rather than weekly or monthly maintenance schedules [5] [4].
2. Where clinical practice or guidance supports periodic retreatment (months rather than weeks)?
Authoritative clinical references and prescribing guides note that ivermectin is commonly given as single doses for onchocerciasis and other helminth infections but that repeat treatments are routine on a months‑to‑year cadence for control programs—treatment may be repeated every 3 to 12 months for onchocerciasis in practice guidance (Mayo Clinic) and annual or biannual dosing is used in endemic community programs [2] [7]. Drug monographs and prescribing information similarly emphasize that adult worms are not killed by a single dose and that repeat follow‑up and retreatment are usually necessary, particularly in endemic control settings [8].
3. Special populations where repeated short or suppressive dosing has been trialed or recommended
Immunocompromised patients with strongyloidiasis (e.g., HIV, HTLV‑1) are discussed repeatedly in the clinical literature as sometimes requiring repeated courses or ongoing suppressive therapy—guidance and reviews note that repeated doses (for example every 2 weeks or monthly suppressive regimens) may be used to prevent hyperinfection, but they also emphasize that robust randomized‑trial evidence to define optimal regimens in these groups is sparse [3] [9] [8]. Available sources describe clinical experience and programmatic practice more than definitive randomized comparisons of weekly vs monthly schedules for such patients [3] [8].
4. What about repeated dosing for COVID‑19, malaria vector control, or other off‑label indications?
Trials for COVID‑19 mostly evaluated higher daily doses for several days (for example 200 μg/kg daily for 5 days or 600 μg/kg daily for 6 days) and larger outpatient platform trials found no clear clinical benefit—these are short intensive repeat dosing regimens, not weekly/monthly maintenance [5] [4]. The RIMDAMAL malaria study used repeated 3‑week interval dosing as a vector‑control strategy in a community setting and is an example of exploiting repeated human dosing to affect mosquito survival rather than treating humans for disease directly [1]. Regulators such as the EMA reviewed the evidence and advised against use for COVID‑19 outside trials, noting safety concerns if much higher or more frequent dosing were attempted [6].
5. Safety and evidence gaps for true weekly or monthly prophylactic regimens
Safety data for repeated long‑term weekly or monthly human dosing beyond programmatic parasitic control are limited: most safety and pharmacology work supports standard weight‑based single doses or short courses and animal or small higher‑dose human studies have been used to probe tolerability, but comprehensive randomized trials comparing weekly versus monthly maintenance schedules in humans are lacking in the available literature [10] [11]. Critics and clinicians warn that enthusiasm for off‑label repetitive use has returned in popular discourse despite absence of robust evidence for many claimed benefits and potential for harm, a dynamic flagged by mainstream reporting [12] [6].
6. Bottom line for policymakers and clinicians
Randomized clinical evidence supports repeat ivermectin dosing chiefly in the context of parasitic‑disease control programs (e.g., repeat doses every 3–12 months or multi‑dose campaigns spaced weeks apart) and for certain immunocompromised patients clinical practice supports repeat or suppressive dosing, but definitive randomized comparisons of weekly versus monthly regimens for broad prophylaxis or non‑parasitic indications are not present in the cited literature and regulators advise limiting use to clinical trials when the indication is outside established parasitic therapy [1] [2] [3] [6].