Potential clinically significant life-threatening drug–drug interactions of lopinavir and ritonavir used in the treatment of COVID-19

Mohitosh Biswas,Martin Michaelis

doi:10.1017/exp.2020.53

Abstract

AbstractPotential 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.

Highlights

It is identified in the literature that considerable proportion of patients infected with severe acute respiratory syndrome corona virus-2 (SARS-CoV-2) are using combination of lopinavir (LPV) and ritonavir (RTV) as first line antiviral therapy for the treatment of this pandemic virus (Yousefifard et al, 2020)
Seven unique DDI pairs (11.3%; 95% CI 3%–19%) were identified from the Food and Drug Administration (FDA) only whereas 45 unique DDI pairs (72.6%; 95% CI 61%–84%) were identified from the Liverpool COVID-19 drug interactions resource
Systematic cross-comparison between these two well-recognized evidenced-based DDI resources indicated that discrepancies were existed in between these two resources for enlisting contraindicated drugs potentially causing life-threatening adverse drug reactions (ADRs) of LPV/RTV

Summary

Introduction

It is identified in the literature that considerable proportion of patients infected with severe acute respiratory syndrome corona virus-2 (SARS-CoV-2) are using combination of lopinavir (LPV) and ritonavir (RTV) as first line antiviral therapy for the treatment of this pandemic virus (Yousefifard et al, 2020). CYP3A4 inducer drugs may expedite the hepatic clearance of LPV/RTV and may cause therapeutic failure leading to reduced virologic control (Hughes et al, 2015). Being acting as the FDA prescribing information of LPV/RTV indicated that this combination therapy is ‘contraindicated with drugs that are highly dependent on CYP3A4 for clearance and for which elevated plasma concentrations are associated with serious and/or life-threatening reactions’. It is ‘contraindicated with drugs that are potent CYP3A4 inducers where significantly reduced lopinavir plasma concentrations may be associated with the potential for loss of virologic response and possible resistance and cross-resistance’ (FDA, 2020)

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