Safety of Paxlovid During Pregnancy

Study type

• Study topic:
  Human medicinal product
• Study type:
  Non-interventional study
• Scope of the study:
  Safety study (incl. comparative)
• Data collection methods:
  Secondary use of data

Non-interventional study

• Non-interventional study design:
  Cohort

Study drug and medical condition

• Medicinal product name:
  PAXLOVID
• Study drug International non-proprietary name (INN) or common name:
  NIRMATRELVIR

  RITONAVIR
• Anatomical Therapeutic Chemical (ATC) code:
  (J05AE) Protease inhibitors

  Protease inhibitors

  (J05AE30) nirmatrelvir and ritonavir

  nirmatrelvir and ritonavir
• Medical condition to be studied:
  Abortion spontaneous

  Abortion induced

  Stillbirth

  Congenital anomaly

  Foetal growth restriction

  Small for dates baby

  Gestational diabetes

  Postpartum haemorrhage

  Maternal death
• Additional medical condition(s):
  Elective termination of pregnancy, congenital malformations

Population studied

• Short description of the study population:
  Pregnant women with documented COVID-19 who had at least 12 months of inclusion in the data source population before time zero (which is defined below) and were users of Paxlovid, or comparator medication molnupiravir or other comparable medications, or were unexposed to study medications, and their offspring.
• Age groups:
  • Preterm newborn infants (0 – 27 days)
  • Term newborn infants (0 – 27 days)
  • Infants and toddlers (28 days – 23 months)
  • Children (2 to < 12 years)
  • Adolescents (12 to < 18 years)
  • Adults (18 to < 46 years)
  • Adults (46 to < 65 years)
• Special population of interest:
  Pregnant women

Study design details

• Study design:
  This non-interventional study had a cohort design.
• Main study objective:
  Estimate birth prevalence, prevalence ratio, and prevalence difference of adverse pregnancy, maternal and birth outcomes in pregnant women with COVID-19 exposed to Paxlovid compared with pregnant women with COVID-19 exposed to molnupiravir, other COVID-19 treatments or unexposed to any treatment.
• Setting:
  The study included populations from 3 data sources in France, Spain, and the UK making use of secondary data collected primarily for healthcare purposes
• Comparators:
  Comparator medication molnupiravir or other comparable medications
• Outcomes:
  Birth prevalence, prevalence ratio, and prevalence difference of spontaneous abortion, elective termination, stillbirth, preterm delivery (pregnancy outcomes), major congenital malformations, intrauterine growth retardation/small for gestational age (offspring outcomes), gestational diabetes, postpartum haemorrhage, maternal death (maternal outcomes).
• Data analysis plan:
  The study will have a cohort design. Focusing on the target populations, the descriptive component will include tabulations of age, sex, comorbidities, selected concurrent medications, COVID-19 vaccination status, history of COVID-19, current COVID-19 status and setting of Paxlovid use (among Paxlovid users). Comparative analyses will be based on the estimation of risk/prevalence, risk/prevalence ratios, and risk/prevalence differences. Comparative analyses will control for measured confounding within each data source. Aggregated results from each data source will be combined using meta-analytic techniques as numbers allow. If a study population is too small, analyses will be only descriptive, pooling of results from various data sources will be undertaken only if at least 3 independent data points are available.
• Summary results:
  In conclusion, a limited number of Paxlovid-exposed pregnancies was identified in the French SNDS database and no Paxlovid-exposed pregnancies were identified in the Spanish SIDIAP and UK CPRD databases in this study. This finding is consistent with the EU and UK SmPCs, which do not recommend using Paxlovid in pregnancy and recommend preventing pregnancy during treatment. Due to the limited number of Paxlovid-exposed pregnancies identified in the SNDS database, the resulting risk estimates in the comparative analyses lacked precision and did not provide evidence of increased or decreased risk for pregnancy, infant or maternal outcomes compared with unexposed pregnancies.