Aims. Nirmatrelvir/ritonavir is the preferred treatment of vulnerable COVID-19 patients. Current manufacturer’s recommendations are inadequate in addressing diverse medication errors due to full or partially missed nirmatrelvir/ritonavir doses. We aimed to develop a decision tree to mitigate these medication errors using a published physiologically-based pharmacokinetic (PBPK) model. Methods. Medication errors of missed nirmatrelvir/ritonavir doses were documented from 1st January 2023 to 31st March 2024 in a local hospital. We performed PBPK simulations in adults, including those with moderate renal impairment and Chinese elderly under different scenarios of missed doses and mitigation measures. The decision tree was verified in clinically reported medication error scenarios. Results. Ten errors were reported. In adults and Chinese elderly who missed the full standard nirmatrelvir/ritonavir (300 mg/100 mg) dose or full nirmatrelvir component (300 mg), administering the missed dose after 8 hours simulated sub-therapeutic nirmatrelvir troughs for at least one dosing interval. This problem was circumvented by skipping and administering the missed nirmatrelvir/ritonavir dose 12 hours after completing the last scheduled dose in line with manufacturer’s recommendation. When a tablet of nirmatrelvir (150 mg) was missed in a standard or renal dose, no therapeutic consequence was found. No sub-therapeutic nirmatrelvir trough was simulated with a missed ritonavir dose. For the clinically reported medication error scenarios, our decision tree ensured minimally 120 hours of therapeutic nirmatrelvir troughs during the treatment duration. Conclusion. PBPK model-informed mitigation measures to address missed nirmatrelvir/ritonavir doses were successfully verified. Further studies should investigate the implementation and efficacy of these mitigation measures.