Safety and effectiveness concerns of lopinavir/ritonavir in COVID-19 affected patients: a retrospective series.

Autor: Lepage MA; McGill University Health Centre, Montreal, Canada.; McGill Faculty of Medecine and Health Sciences, Montreal, Canada., Rozza N; McGill Faculty of Medecine and Health Sciences, Montreal, Canada., Kremer R; McGill University Health Centre, Montreal, Canada.; McGill Faculty of Medecine and Health Sciences, Montreal, Canada., Grunbaum A; McGill University Health Centre, Montreal, Canada.; McGill Faculty of Medecine and Health Sciences, Montreal, Canada.
Jazyk: angličtina
Zdroj: Clinical toxicology (Philadelphia, Pa.) [Clin Toxicol (Phila)] 2021 Jul; Vol. 59 (7), pp. 644-647. Date of Electronic Publication: 2021 Mar 01.
DOI: 10.1080/15563650.2020.1842882
Abstrakt: 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.
Databáze: MEDLINE
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