Drug-Drug Interactions With Over-The-Counter Medicines: Mind the Unprescribed

This review provides a summary of the currently available clinical data on drug-drug interactions (DDIs) involving over-the-counter (OTC) medicines. It aims to educate and increase awareness among health care providers and to support decisions in daily practice.

An extensive literature search was performed using bibliographic databases available through PubMed.gov. An initial structured search was performed using the keywords "drug-drug-interaction AND (over-the-counter OR OTC)," without further restrictions except for the language. The initial results were screened for all described DDIs involving OTC drugs, and further information was gathered specifically on these drugs using dedicated database searches and references found in the bibliography from the initial hits.

From more than 1200 initial hits (1972-June 2021), 408 relevant publications were screened for DDIs involving OTC drugs, leading to 2 major findings: first, certain types of drug regimens are more prone to DDIs or have more serious DDI-related consequences, such as antiretroviral, anti-infective, and oral anticancer therapies. Second, although most DDIs involve OTC drugs as the perpetrators, some prescription drugs (statins or phosphodiesterase-5 inhibitors) that currently have OTC status can be identified as the victims in DDIs. The following groups were identified to be frequently involved in DDIs: nonsteroidal anti-inflammatory drugs, food supplements, antacids, proton-pump inhibitors, H2 antihistamines, laxatives, antidiarrheal drugs, and herbal drugs.

The most significant finding was the lack of high-quality evidence for commonly acknowledged interactions. High-quality interaction studies involving different phenotypes in drug metabolism (cytochrome P450) and distribution (transporters) are urgently needed. This should include modern and critical drugs, such as oral anticancer medications and direct oral anticoagulants.