In response to the COVID-19 pandemic, nirmatrelvir/ritonavir was approved as the first per os treatment to prevent severe disease progression. This study explores patients’ self-management of nirmatrelvir/r and its impact on their long-term medications, and their experience of the information provided by pharmacists and physicians. Adults receiving nirmatrelvir/r from September 2022 to March 2023 were interviewed via a semistructured telephone survey. Sociodemographic, clinical data, and experience with nirmatrelvir/r and cotreatments were collected and analyzed descriptively. Of the 281 patients receiving nirmatrelvir/r, 100 (36%) participated in this study. Ninety (90%) adhered to nirmatrelvir/r, while 5 (5%) reported early discontinuation and 5 (5%) increased time between dosages. Information gaps regarding side effects, risks, benefits, and mechanisms of action were identified. Due to interactions with nirmatrelvir/r, 43% (n = 43/85) of cotreatments were temporarily interrupted, and 13% (n = 11/85) of doses were adjusted. Patient management of nirmatrelvir/r and cotreatments was successful, but satisfaction toward nirmatrelvir/r information could be improved. This study highlights the importance of ongoing efforts to ensure communication strategies, patient education, and interprofessional collaboration in providing treatments with drug–drug interactions.