Potential drug–drug interactions among U.S. adults treated with nirmatrelvir/ritonavir: A cross‐sectional study of the National Covid Cohort Collaborative (N3C)

Abstract

ImportanceNirmatrelvir/ritonavir has potential to interact with many drugs.ObjectiveTo estimate the prevalence of potential moderate to severe drug‐drug interactions (DDIs) involving nirmatrelvir/ritonavir, identify interacting medications, and evaluate risk factors associated with potential DDIs.Design, Setting, and ParticipantsCross‐sectional study using electronic health records from the National COVID Cohort Collaborative Enclave, one of the largest COVID‐19 data resources in the United States. Study participants were outpatients aged ≥18 years and started nirmatrelvir/ritonavir between December 23, 2021 and March 31, 2022.Main Outcome and MeasuresPotential moderate to severe DDIs, defined as starting interacting medications reported by National Institutes of Health 30 days before or 10 days after starting nirmatrelvir/ritonavir.ResultsOf 3214 outpatients who started nirmatrelvir/ritonavir, the mean age was 56.8±17.1 years, 39.5% were male, and 65.8% were non‐Hispanic white. Overall, 521 (16.2%) were potentially exposed to at least one moderate to severe DDI, most commonly to atorvastatin (19.2% of all DDIs), hydrocodone (14.0%), or oxycodone (14.0%). After adjustment for covariates, potential DDIs were more likely among individuals who were older (odds ratio [OR] 1.16 per 10‐year increase, 95% confidence interval [CI] 1.08‐1.25), male (OR 1.36, CI 1.09‐1.71), smokers (OR 1.38, CI 1.10‐1.73), on more co‐medications (OR 1.35, CI 1.31‐1.39), and with a history of solid organ transplant (OR 3.63, CI 2.05‐6.45).Conclusions and RelevanceOne in six of individuals receiving nirmatrelvir/ritonavir were at risk of a potential moderate or severe DDI, underscoring the importance of clinical and pharmacy systems to mitigate such risks.

Question

“…In summary, nirmatrelvir may not be relevant for clozapine metabolism. I completed a PubMed search "nirmatrelvir [Title] and drug interactions," which produced a study 16 in Pharmacotherapy, a pharmacy journal that I trust. This article confirmed that DDIs due to nirmatrelvir/ritonavir as the perpetrator drug are really explained by ritonavir's effects; several times, I have been consulted on the risk-benefits of the combination of ritonavir with antipsychotics.…”

Influence of a Short Course of Ritonavir Used as Booster in Antiviral Therapies Against SARS-CoV-2 on the Exposure of Atorvastatin and Rosuvastatin

“…Its component ritonavir is used as a boosting agent to reach and maintain therapeutic drug concentrations of nirmatrelvir throughout the dosing interval by inhibiting a variety of cytochrome P450 (CYP) isozymes including CYP3A4, which is the main CYP involved in nirmatrelvir metabolism. Older patients or patients with chronic conditions such as cardiovascular disease or diabetes have a higher risk of suffering a severe course of SARS-CoV-2 and often concurrently take additional medications [1]. Intake of nirmatrelvir/ritonavir within 3 days after being positive for SARS-CoV-2 significantly reduces the risk in this population [2].…”