Plasma Concentrations and Safety of Lopinavir/Ritonavir in COVID-19 Patients

Ther Drug Monit. 2021 Feb 1;43(1):131-135. doi: 10.1097/FTD.0000000000000838.

Abstract

Background: Although the efficacy of lopinavir/ritonavir has not been proven, it has been proposed as an off-label treatment for COVID-19. Previously, it has been reported that the plasma concentrations of lopinavir significantly increase in inflammatory settings. As COVID-19 may be associated with major inflammation, assessing the plasma concentrations and safety of lopinavir in COVID-19 patients is essential.

Methods: Real-world COVID-19 data based on a retrospective study.

Results: Among the 31 COVID-19 patients treated with lopinavir/ritonavir between March 18, 2020 and April 1, 2020, higher lopinavir plasma concentrations were observed, which increased by 4.6-fold (interquartile range: 3.6-6.2), compared with the average plasma concentrations in HIV. Lopinavir concentrations in all except one patient were above the upper limit of the concentration range of HIV treatment. Approximately one to 5 patients prematurely stopped treatment mainly because of an ADR related to hepatic or gastrointestinal disorders.

Conclusions: Lopinavir plasma concentrations in patients with moderate-to-severe COVID-19 were higher than expected, and they were associated with the occurrence of hepatic or gastrointestinal adverse drug reactions. However, a high plasma concentration may be required for in vivo antiviral activity against SARS-CoV-2, as suggested by previous studies. Therefore, in the absence of adverse drug reaction, lopinavir dosage should not be reduced. Caution is essential because off-label use can be associated with a new drug safety profile.

MeSH terms

  • Aged
  • Antiviral Agents / administration & dosage
  • Antiviral Agents / adverse effects
  • Antiviral Agents / blood*
  • Antiviral Agents / therapeutic use*
  • COVID-19 Drug Treatment*
  • Comorbidity
  • Drug Combinations
  • Female
  • Humans
  • Lopinavir / administration & dosage
  • Lopinavir / adverse effects
  • Lopinavir / blood*
  • Lopinavir / therapeutic use*
  • Male
  • Middle Aged
  • Retrospective Studies
  • Ritonavir / administration & dosage
  • Ritonavir / adverse effects
  • Ritonavir / blood*
  • Ritonavir / therapeutic use*
  • SARS-CoV-2
  • Severity of Illness Index

Substances

  • Antiviral Agents
  • Drug Combinations
  • lopinavir-ritonavir drug combination
  • Lopinavir
  • Ritonavir