What potential drug interactions occur between ivermectin and common antibiotics?
Executive summary
Ivermectin has documented interactions with many drugs — online checkers list "106 medications" known to interact, and specific antibiotics such as macrolides (clarithromycin, erythromycin) are flagged for raising ivermectin levels or effects [1] [2]. Laboratory and clinical reports show mixed findings: biophysical studies report direct binding between ivermectin and antibiotics like ampicillin and chloramphenicol (about 3:1 ampicillin:ivermectin binding; 1:1 chloramphenicol:ivermectin) while clinical trials combining ivermectin with doxycycline reported no observed drug–drug interactions [3] [4].
1. Broad landscape: many potential interactions, but details matter
Public drug-interaction tools and reviews emphasize that ivermectin can interact with dozens of other medicines — one interaction database enumerates 106 interacting drugs and lists examples including erythromycin and ketoconazole [1]. Clinical reference sites and prescribing information repeatedly advise checking concomitant drugs [5] [6]. These lists are comprehensive but heterogeneous: they mix pharmacokinetic alerts, theoretical mechanisms, and clinically significant interactions [1] [7].
2. Macrolide antibiotics (clarithromycin, erythromycin): a flag for increased ivermectin exposure
Drug-checker summaries specifically warn that clarithromycin may increase blood levels and effects of ivermectin, and erythromycin appears among flagged antibiotics [1] [2]. This signal aligns with the general pharmacology principle that macrolides can inhibit metabolic pathways or transporters that affect co‑administered drugs, raising the potential for enhanced ivermectin exposure and side effects [1] [2]. Sources recommend dose review and closer monitoring when both are used [2].
3. Laboratory evidence: direct binding between ivermectin and some antibiotics
Biophysical research using isothermal titration calorimetry found that ivermectin binds directly to certain antibiotics in vitro — roughly three ampicillin molecules per ivermectin and roughly one chloramphenicol per ivermectin — suggesting chemical interaction potential outside human pharmacokinetics [3]. These experiments demonstrate molecular affinity in controlled conditions but do not by themselves prove clinically meaningful interactions in patients [3].
4. Doxycycline/tetracyclines: clinical co‑use with little evidence of interaction
Clinical trials that paired ivermectin with doxycycline (tetracycline family) for COVID‑19 treatment reported no observed drug–drug interactions and required no dose adjustments in the trial context [4]. Reviews also discuss ivermectin’s proposed antiviral mechanisms alongside doxycycline’s anti‑inflammatory properties, which explains why the combination was trialed, but the available trial data cited report no pharmacologic interaction detected [8] [4].
5. Mechanisms to watch: transporters, metabolism, and off‑target binding
Sources note ivermectin interacts with cellular transporters such as P‑glycoprotein (MDR1) in the context of drug interactions — for example, some drugs can decrease ivermectin levels via P‑gp or conversely increase its effects by inhibiting efflux [7]. Reviews also emphasize ivermectin’s multiple biochemical activities (binding to host proteins such as importins in antiviral studies) and the potential for off‑target interactions flagged in databases [8] [9]. The laboratory binding data (ivermectin + antibiotics) indicate another possible non‑metabolic mechanism of interaction [3].
6. Clinical significance: a spectrum from theoretical to observed
The sources show three tiers: (a) theoretical or database‑flagged interactions (many antibiotics listed; general advisories to check interactions) [1] [5]; (b) in vitro molecular binding suggesting possible interaction chemistry (ampicillin, chloramphenicol) [3]; and (c) clinical trial evidence of safe co‑administration (ivermectin + doxycycline) with no reported drug‑drug interaction in that study [4]. Which tier applies depends on the specific antibiotic, dose, patient factors, and monitoring.
7. Practical guidance and reporting gaps
Clinicians and patients should treat macrolides (clarithromycin, erythromycin) as higher‑priority alerts and review therapy with a pharmacist because databases explicitly flag increased ivermectin levels with clarithromycin [2]. For doxycycline and related tetracyclines, current trial data report no interactions, but broader pharmacovigilance and context (other co‑medications, liver function, transporter inhibitors) matter [4] [8]. Available sources do not mention routine clinical guidance for ampicillin or chloramphenicol co‑use beyond the in vitro binding data — clinical outcome data for those combinations are not found in current reporting [3].
8. Takeaway: check specifics, monitor when combining
The reliable pattern in the sources is clear: check interaction databases for the specific antibiotic, pay special attention to macrolides (clarithromycin/erythromycin) for potential increased ivermectin exposure [1] [2], note that in vitro binding has been observed with some antibiotics [3], and recognize that doxycycline has been co‑administered in trials without observed pharmacologic interaction [4]. For any real‑world combination, clinicians should consult prescribing information and interaction checkers and monitor patients closely; generalized statements about "no interactions" or "safe together" are not supported across all antibiotics by the available sources [1] [4].