ritonavir and Drug-Overdose

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.. We measured LPV trough concentrations in 12 patients and reviewed their clinical charts for side effects known to occur in HIV patients.. 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).. 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.

Topics: Adult; Aged; Aged, 80 and over; Antiviral Agents; COVID-19; COVID-19 Drug Treatment; Drug Combinations; Drug Monitoring; Drug Overdose; Female; Host-Pathogen Interactions; Humans; Hyponatremia; Lopinavir; Male; Middle Aged; Patient Safety; Retrospective Studies; Risk Assessment; Risk Factors; Ritonavir; SARS-CoV-2; Time Factors; Treatment Outcome

Topics: Acquired Immunodeficiency Syndrome; Anticoagulants; Drug Overdose; HIV Protease Inhibitors; Humans; Lopinavir; Male; Middle Aged; Pyrimidinones; Ritonavir; Warfarin

Topics: Adult; Drug Overdose; Drug Therapy, Combination; HIV Infections; HIV Protease Inhibitors; Humans; Male; Recurrence; Renin; Renin-Angiotensin System; Ritonavir; Saquinavir; Syncope