Assessing the proportion of the Danish population at risk of clinically significant drug-drug interactions with new oral antivirals for early treatment of COVID-19

OBJECTIVES: The oral antiviral drugs nirmatrelvir/ritonavir (NMV/r) and molnupiravir have been approved for early outpatient treatment of COVID-19 to prevent severe disease. Ritonavir, contained in NMV/r, is known to have significant drug-drug interactions (DDI) with several drugs frequently used by the elderly. This communication puts the problem with DDI with oral antiviral COVID-19 treatment into perspective by assessing the percentage of the elderly population at risk of severe COVID-19, using drugs with significant DDI with oral antivirals. METHODS: We estimated the size of the Danish population at risk of significant DDI with antiviral COVID-19 treatment using the number of claimed prescriptions for drugs predicted to interact with NMV/r in Denmark in 2020. RESULTS: Danish prescription data demonstrate the extensive use of drugs likely to interact with NMV/r. Anticoagulants contraindicated during NMV/r treatment were used by 20% of people ≥65 years and 30% of people ≥80 years. Statins that must be paused during NMV/r treatment were used by 15-18%. More than one in five used either analgesics, calcium channel blockers, or digoxin. CONCLUSION: There is major potential for significant DDI with NMV/r in the elderly population at risk of severe COVID-19 disease. This calls for clear guidance for prescribers to ensure patient safety and treatment success.