Potential clinically significant life-threatening drug–drug interactions (DDIs) of lopinavir (LPV) and ritonavir (RTV) used in the treatment of COVID-19 is not systematically reviewed. It was aimed to identify severe DDI pairs of LPV/RTV from international resources predicted to cause life-threatening adverse drug reactions (ADRs). Severe DDI pairs predicted to cause life-threatening ADRs were identified from the FDA and Liverpool COVID-19 prescribing information of LPV/RTV. In total, 62 severe DDI pairs were identified from the FDA and Liverpool COVID-19 resources predicted to cause life-threatening ADRs in patients with COVID-19. Of these, seven unique DDI pairs (11.3%; 95% CI 3%–19%) were identified from the FDA only whereas 45 unique DDI pairs (72.6%; 95% CI 61%–84%) were identified from the Liverpool COVID-19 drug interactions resource. Of interest, only 10 DDI pairs (16.1%; 95% CI 7%–25%) were recognized by both of these drug interaction resources. Clinicians should not entirely rely on any individual DDI resource for checking life threatening ADRs of LPV/RTV in patients with COVID-19.
