Safety of Paxlovid (Nirmatrelvir/Ritonavir) During Pregnancy
Paxlovid is contraindicated in pregnancy due to embryo-fetal toxicity observed in animal studies, and pregnancy testing should be performed before starting treatment. 1
Evidence on Paxlovid in Pregnancy
FDA Label Information
The FDA label for nirmatrelvir (Paxlovid) clearly states that available data on its use during pregnancy are insufficient to evaluate drug-associated risks of major birth defects, miscarriage, or adverse maternal/fetal outcomes 2. Animal studies showed:
- Reduced fetal body weights in rabbits at exposures approximately 11 times higher than clinical exposure
- No other adverse developmental outcomes at exposures ≥3 times higher than clinical exposure
The FDA label notes that all pregnancies carry background risks, with the U.S. general population having a 2-4% risk of major birth defects and 15-20% risk of miscarriage 2.
Ritonavir Component
While ritonavir (one component of Paxlovid) has more extensive pregnancy data from HIV treatment:
- Prospective registry data on over 7,000 live births exposed to ritonavir showed no difference in birth defect rates compared to the general population (2.4% in first-trimester exposure) 2
- Placental transfer of ritonavir is generally low, though detectable levels have been observed in cord blood and neonate hair 2
Recent Research Findings
Despite the contraindication, some recent studies have examined Paxlovid use in pregnant women:
A 2023 study of 30 pregnant women treated with Paxlovid found shorter COVID-19 symptom duration compared to untreated women (10.10 vs. 15.59 days), but noted higher cesarean delivery rates (76.92% vs. 42.86%) and a trend toward more small-for-gestational-age newborns (23.08% vs. 3.57%) 3
A 2023 survey of pregnant/lactating individuals found that among those who took nirmatrelvir-ritonavir, 91.7% experienced dysgeusia and 50.0% had COVID rebound symptoms or positive test results 4
A 2025 meta-analysis of 427 pregnant patients treated with nirmatrelvir-ritonavir found low hospitalization rates (2%), but noted new-onset gestational diabetes in 4.0% and gestational hypertension in 4% of patients 5
Clinical Decision-Making
Contraindications
- Pregnancy is listed as a contraindication for Paxlovid 1
- Reliable contraception should be used during treatment and for at least 4 days after the last dose for women of childbearing potential 1
Alternative Approaches
For pregnant women with COVID-19:
- Vaccination remains the primary preventive measure 1
- Remdesivir may be considered as an alternative when Paxlovid is contraindicated, requiring intravenous administration over 3 days 1
Key Considerations and Pitfalls
Pregnancy testing: Always perform pregnancy testing before prescribing Paxlovid to women of childbearing potential 1
Risk-benefit assessment: While Paxlovid is contraindicated in pregnancy, untreated COVID-19 in pregnancy carries significant risks including preeclampsia, eclampsia, preterm birth, and venous thromboembolic disease 2
Timing considerations: If treatment is deemed necessary despite contraindications, Paxlovid must be initiated within 5 days of symptom onset to be effective 1
Drug interactions: Ritonavir is a strong CYP3A inhibitor that can significantly increase serum levels of many medications, requiring careful medication review 1
In conclusion, while some emerging research suggests potential benefits of Paxlovid in pregnant women with COVID-19, the current FDA labeling and treatment guidelines contraindicate its use during pregnancy due to insufficient safety data and potential embryo-fetal toxicity observed in animal studies.