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

IMPAACT 2032 Study Team

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Pages (from-to)878-888
Number of pages11
JournalJournal of Infectious Diseases
Volume230
Issue number4
DOIs
StatePublished - Oct 15 2024

Funding

Financial support. This work was supported by the National Institute of Allergy and Infectious Diseases, the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), and the National Institute of Mental Health, all components of the NIH (grant numbers UM1AI068632 to International Maternal Pediatric Adolescent AIDS Clinical Trials Network (IMPAACT) Leadership and Operations Center (LOC), UM1AI068616 to IMPAACT Statistical and Data Management Center (SDMC), and UM1AI106716 to IMPAACT Laboratory Center (LC); and NICHD contract number HHSN275201800001I). Additional support was provided by Gilead Sciences, Inc. We thank the study participants and families, clinical providers, the IMPAACT 2032 Protocol Team, and the following study sites and personnel: Lurie Children's Hospital of Chicago (Emanuela Lartey, RN; Rohit Kalra, MS, CCRP; Lynn Yee, MD, MPH; James Etta Stewart); Bronx-Lebanon Hospital Center (Martha Cavallo, PNP; Mirza Baig, MD); Johns Hopkins University Baltimore (Aleisha Collinson-Streng, BSN, RN; Thuy Anderson, BSN, RN; Bonnie Addison, BA); SUNY Stony Brook (Barsha Chakraborty, MPH; Cecilia Avila, MD, MPH; Giuseppe Caso, MD, PhD); David Geffen School of Medicine at UCLA (Carla Janzen, MD, PhD; Michele F. Carter, BS, RN); Baylor College of Medicine/Texas Children's Hospital (Mary Paul, MD; Ruth Eser-Jose, MSN, RN, CPN; Mariam Pontifes, CCRP; Chivon McMullen Jackson, RN); Pediatric Perinatal HIV Clinical Trials Unit, Miami Fl (Nicolette Gomez, CCRP; Grace Alvarez FMD, CCRP; Charles Mitchell, MD; JoNell Potter, PhD); Emory University School of Medicine (Martina L. Badell, MD; Sierra Jordan-Thompson, MPH; Riaun Floyd, BA; LaTeshia Thomas-Seaton, MS, APRN, CCRC); University of Colorado Denver (Adriana Weinberg, MD; Shane Curran-Hays, MS; Christine Kwon, BS; Carrie Glenny, RN, BSN; ); Rush University Cook County Hospital Chicago (Mariam Aziz, MD; Maureen McNichols, RN CCRC). We also thank Gilead Sciences, Inc and the following representatives: Rich Clark, Heather Maxwell, Gina Brown, Chris Blair, and James Rooney. The University of Colorado is a Certara Center of Excellence. The Center of Excellence program supports leading institutions with Certara's state-of-the-art model-informed drug development software. This work was supported by the National Institute of Allergy and Infectious Diseases, the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), and the National Institute of Mental Health, all components of the NIH (grant numbers UM1AI068632 to International Maternal Pediatric Adolescent AIDS Clinical Trials Network (IMPAACT) Leadership and Operations Center (LOC), UM1AI068616 to IMPAACT Statistical and Data Management Center (SDMC), and UM1AI106716 to IMPAACT Laboratory Center (LC); and NICHD contract number HHSN275201800001I). Additional support was provided by Gilead Sciences, Inc.

Keywords

  • SARS-CoV-2
  • antiviral
  • pharmacology
  • pregnancy
  • remdesivir

ASJC Scopus subject areas

  • General Medicine

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