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.
Keywords: COVID-19; Lopinavir/ritonavir; SARS-CoV-2; case series; safety profile.
【저자키워드】 COVID-19, SARS-CoV-2, Lopinavir/ritonavir, Case series, safety profile, 【초록키워드】 Treatment, coronavirus disease, HIV, Lopinavir/ritonavir, Antiviral, hyponatremia, Lopinavir, Ritonavir, Toxicity, novel coronavirus disease, Novel coronavirus, overdose, Case series, therapeutic, Patient, Effectiveness, Triglyceride, Side effects, Human immunodeficiency virus, threshold, dyslipidemia, safety profile, COVID-19 patients, cholestasis, Combination, gastrointestinal symptoms, Concentration, COVID-19 patient, In-vitro, liver enzyme, Side effect, immunodeficiency virus, Elevation, side, thresholds, HIV patients, EC50, Gastrointestinal symptom, Effect, electrolyte imbalance, raise, greater, addition, case sery, occur, reached, exceeded, LPV, raising, 【제목키워드】 Lopinavir/ritonavir, Safety, Effectiveness, retrospective, affected,