Real-World Analysis of Potential Drug-Drug Interactions with Nirmatrelvir/Ritonavir Based on the Hospital Prescription Analysis (HPA) Database in 9 Cities of China

To determine the real-world patterns and extent of potential drug-drug interactions (DDIs) related to nirmatrelvir/ritonavir (NMVr) in China. Data on NMVr-treated patients from over 160 hospitals across 9 Chinese cities from January 2022 to December 2023 were extracted from the Hospital Prescription Analysis (HPA) database, which was established in Beijing in 1997 to promote rational medication use in China. Grade C, D and X DDIs from the Lexicomp database were defined as clinically significant and analyzed in this study. Statistical analyses included descriptive statistics (continuous variables as mean ± SD; categorical variables as counts and percentages) and multivariate binary logistic regression, which was used to identify factors associated with potential DDIs, with adjustment for confounding variables (sex, age, cities, number of co-administered drugs, comorbidities). Analyses were performed using R software (v4.2.2) with P < 0.05 as statistically significant, and figures were generated via GraphPad Prism (v10.3.1). Of 15,567 patients receiving NMVr, the mean age was 62.4 ±18.2 years, and 53.1% were male. 8542 patients received at least one co-administration, and 5391 patients exhibited at least one potential DDI. A total of 10,694 potential DDIs were identified, with a breakdown of 8310 grade C, 2093 grade D and 291 grade X. Systemic corticosteroids (n=3608) and drugs for obstructive airway diseases (n=2220) had the highest frequencies in grade C DDIs, and the lipid modifying agents (n=601) in grade D DDIs, and cardiac therapy drugs (n=130) in grade X DDIs. Co-administration of drugs significantly increased odds of potential DDIs with the risk escalating markedly as the number of drugs increased, and the comorbidities of hypertension (odds ratio [OR]=1.50), asthma (OR=4.28) and mental disorders (OR=7.02) significantly increased it as well. In this large-scale cross-sectional study in China, approximately one-third of the patients treated with NMVr were at risk of clinically significant potential DDIs, highlighting the importance of making efforts to diminish these risks, such as close monitoring and dose adjustment.