Safety and effectiveness concerns of lopinavir/ritonavir in COVID-19 affected patients: a retrospective series. (3rd July 2021)

• Record Type: Journal Article
• Authors: Lepage, Marc-Antoine; Rozza, Nicholas; Kremer, Richard; Grunbaum, Ami
• Is Part Of: Clinical toxicology. Volume 59:Number 7(2021)
• Page Start: 644
• Page End: 647
• Publication Date: 2021-07-03
• Subjects: Lopinavir/ritonavir -- COVID-19 -- SARS-CoV-2 -- safety profile -- case series; Toxicology -- Periodicals; Toxicological emergencies -- Periodicals; 615.9
• DOI: 10.1080/15563650.2020.1842882
• Languages: English
• ISSNs: 1556-3650

Abstract

Abstract: Context: Originally developed for treatment of human immunodeficiency virus (HIV), the antiviral combination lopinavir/ritonavir (LPV/r) is being repurposed for treating the novel coronavirus disease (COVID-19) despite minimal experience in this markedly different population and an in-vitro derived EC50 against SARS-CoV-2 several hundred-fold greater than for HIV. We present a case series including a case of severe hyponatremia and a 32-fold overdose raising safety and effectiveness concerns in COVID-19 patients. Methods: We measured LPV trough concentrations in 12 patients and reviewed their clinical charts for side effects known to occur in HIV patients. Findings: Compared to established LPV trough concentrations in HIV patients, concentrations in COVID-19 patients were 3-fold greater (19.37 ± 10.12 mcg/mL versus 6.25 mcg/mL). In addition, cholestasis and dyslipidemia toxicity thresholds were exceeded in 12/12 and 11/12 patients respectively. No patients achieved the presumed therapeutic concentration. Side effects included gastrointestinal symptoms (5/12), electrolyte imbalances (4/12), liver enzyme disturbances (5/12) and triglyceride elevations (2/12). Conclusion: No patients reached presumed therapeutic LPV concentrations despite experiencing side effects and exceeding cholestasis and dyslipidemia toxicity thresholds. This raises concerns for the safety and effectiveness of LPV/r. Clinicians should consider closely monitoring for side effects and not necessarily attribute them to COVID-19.