Pharmacokinetics and Safety of Remdesivir in Pregnant and Nonpregnant Women With COVID-19: Results From IMPAACT 2032

Overview

Journal J Infect Dis

Publisher Oxford University Press

Specialty Infectious Diseases

Date 2024 Jun 5

PMID 38839047

Authors

Kristina M Brooks

Kristin Baltrusaitis

Diana F Clarke

Sharon Nachman

Jennifer Jao

Murli U Purswani

Allison Agwu

Christy Beneri

Jaime G Deville

Kathleen M Powis

Alice M Stek

Ahizechukwu C Eke

David E Shapiro

Edmund Capparelli

Elizabeth Greene

Kathleen George

Dwight E Yin

Patrick Jean-Philippe

Nahida Chakhtoura

Frederic Bone

Kira Bacon

Benjamin Johnston

Christina Reding

Kathryn Kersey

Rita Humeniuk

Brookie M Best

Mark Mirochnick

Jeremiah D Momper

Affiliations

Soon will be listed here.

Abstract

Background: Pregnant people with coronavirus disease 2019 (COVID-19) experience higher risk for severe disease and adverse pregnancy outcomes, but no pharmacokinetic (PK) data exist to support dosing of COVID-19 therapeutics during pregnancy. We report PK and safety data for intravenous remdesivir in pregnancy.

Methods: IMPAACT 2032 was a phase 4 prospective, open-label, nonrandomized opportunistic study of hospitalized pregnant and nonpregnant women receiving intravenous remdesivir as part of clinical care. Intensive PK sampling was performed on infusion days 3, 4, or 5 with collection of plasma and peripheral blood mononuclear cells (PBMCs). Safety data were recorded from first infusion through 4 weeks after last infusion and at delivery. Geometric mean ratios (GMR) (90% confidence intervals [CI]) of PK parameters between pregnant and nonpregnant women were calculated.

Results: Fifty-three participants initiated remdesivir (25 pregnant; median gestational age, 27.6 weeks; interquartile range, 24.9-31.0 weeks). Plasma exposures of remdesivir, its 2 major metabolites (GS-704277 and GS-441524), and the free remdesivir fraction were similar between pregnant and nonpregnant participants. Concentrations of the active triphosphate (GS-443902) in PBMCs increased 2.04-fold (90% CI, 1.35-3.03) with each additional infusion in nonpregnant versus pregnant participants. Three adverse events in nonpregnant participants were related to treatment (1 grade 3; 2 grade 2 resulting in treatment discontinuation). There were no treatment-related adverse pregnancy outcomes or congenital anomalies detected.

Conclusions: Plasma remdesivir PK parameters were comparable between pregnant and nonpregnant women, and no safety concerns were identified based on our limited data. These findings suggest no dose adjustments are indicated for intravenous remdesivir during pregnancy.

Clinical Trials Registration: NCT04582266.

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