BackgroundPost-COVID syndrome (PCS) causes lasting symptoms like fatigue and cognitive issues. PCS treatment is non-specific, focusing on symptom management, potentially increasing the risk of polypharmacy. ObjectivesTo describe medication use patterns among patients with Post-COVID Syndrome (PCS) and estimate the prevalence of polypharmacy, potential drug-drug interactions, and anticholinergic/sedative burden. MethodsA cross-sectional analysis of baseline data from the Quebec Action for Post-COVID cohort, consisting of individuals self-identifying with persistent COVID-19 symptoms beyond 12 weeks. Medications were categorized using Anatomical Therapeutic Classification (ATC) codes. Polypharmacy was defined as using five or more concurrent medications. The Anticholinergic and Sedative Burden Catalog assessed anticholinergic and sedative loads. The Lexi-Interact checker identified potential drug-drug interactions, which were categorized into three severity tiers. ResultsOut of 414 respondents, 154 (average age 47.7 years) were prescribed medications related to persistent COVID-19 symptoms. Drugs targeting the nervous system were predominant at 54.5%. The median number of medications was 2, while 11.7% reported polypharmacy. Over half of the participants prescribed medications used at least one anticholinergic or sedative medication, and 25% had the potential risk for clinically significant drug-drug interactions, primarily needing therapy monitoring. ConclusionsOur study reveals prescription patterns for PCS, underscoring the targeted management of nervous system symptoms. The risks associated with polypharmacy, potential drug-drug interactions, and anticholinergic/sedative burden stress the importance of judicious prescribing. While limitations like recall bias and a regional cohort are present, the findings underscore the imperative need for vigilant PCS symptom management.