Pfizer PAXLOVID™ – Safety in pregnancy

Background: Paxlovid is an oral combination of protease inhibitors nirmatrelvir and ritonavir licensed in January 2022 in Europe to treat COVID 19 in patients who do not require supplemental oxygen and are at increased risk for progression to severe COVID 19. Here, we describe preliminary results from a post-authorization safety study to assess the safety of Paxlovid in pregnancy because clinical trials excluded such patients, and EU and UK summary of product characteristics (SmPCs) do not recommend its use in pregnancy.

Objectives: To assess the risk of adverse pregnancy, offspring, and maternal outcomes in women exposed to Paxlovid or to other COVID-19 treatments during pregnancy.

Methods: This ongoing cohort study used data from SIDIAP (Spain), CPRD Aurum (UK), and SNDS (France) from January 2022 until December 2023/January 2024.The ConcePTION common data model and common analytics were used in SIDIAP and CPRD. Aggregated user counts from the general population were obtained via Open Medic in France.

The study included pregnant patients who had been enrolled in the data source for ≥12 months, had COVID-19, and started treatment up to 6 days after COVID-19 diagnosis, and their offspring. Follow-up started at the first treatment during pregnancy and ended at the earliest of the following: 6 months after the end of pregnancy (age 1 year for offspring), outcome, death, disenrollment, or end of study period.

Primary outcomes were spontaneous abortion, elective termination, stillbirth, preterm delivery, major congenital malformations, intrauterine growth retardation/small for gestational age, gestational diabetes, gestational hypertension, postpartum hemorrhage, and maternal death. Exploratory outcomes were empirically assessed from diagnoses in eligible Paxlovid-exposed individuals in the 30 days after exposure.

Results: In SIDIAP and in CPRD, no eligible pregnancy was exposed to Paxlovid; 1≤n≤4 were exposed to molnupiravir in CPRD; they had unknown outcomes. No other primary or exploratory study outcomes were observed. In France, 206,069 patients had ≥1 Paxlovid dispensing (≈70% aged ≥60 years; >55% female); fewer patients used anakinra (5,895; ≈40% aged ≥60 years, ≈50% female) or tocilizumab (22,306; ≈60% aged ≥60 years, ≈70% female); use in pregnancy will be assessed in future analyses.

Conclusions: Although the study period was relatively short, the lack of Paxlovid-exposed pregnancies is consistent with the literature and in alignment with recommendations in the EU and UK SmPCs. Future reports will include a longer study period and individual-level data from SNDS in France.