Paxlovid Use in Pregnancy
Primary Recommendation
Paxlovid (nirmatrelvir/ritonavir) may be considered for use in pregnant women with non-severe COVID-19 who are at high risk of hospitalization, after discussing potential risks and benefits. 1, 2
Evidence-Based Rationale
Guideline Support for Use
The WHO Living Guideline explicitly states that pregnant people with non-severe COVID-19 may consider use of nirmatrelvir/ritonavir, based on data available through WHO Vigibase showing no reports of serious adverse reactions in parent or child to date. 1
The recommendation for pregnant women mirrors the strong recommendation for high-risk non-pregnant patients, where nirmatrelvir/ritonavir demonstrates high certainty evidence for reducing hospitalization risk and moderate certainty for survival benefit. 1
FDA Drug Label Safety Data
Available data on nirmatrelvir use during pregnancy are insufficient to evaluate for drug-associated risk of major birth defects, miscarriage, or adverse maternal/fetal outcomes. 3
Published observational studies on ritonavir use in pregnant women (over 3,500 live births exposed in first trimester and over 3,500 in second/third trimesters) have not identified an increase in major birth defects compared to the 2.7% background rate in the U.S. general population. 3
Animal studies with nirmatrelvir showed reduced fetal body weights in rabbits only at exposures 11 times higher than clinical doses, with no other adverse developmental outcomes at exposures ≥3 times clinical exposure. 3
Clinical Context: Disease Risk vs. Treatment Risk
COVID-19 in pregnancy carries significant maternal and fetal risks including preeclampsia, eclampsia, preterm birth, premature rupture of membranes, venous thromboembolic disease, and fetal death. 3 This disease burden must be weighed against the limited but reassuring pregnancy data for Paxlovid.
Clinical Implementation
Patient Selection Criteria
Pregnant women with non-severe COVID-19 at high risk of hospitalization (e.g., those with comorbidities such as diabetes, hypertension, obesity, or immunosuppression). 1
Treatment must be initiated within 5 days of symptom onset for optimal effectiveness. 4
Dosing in Pregnancy
Standard dosing: 300 mg nirmatrelvir with 100 mg ritonavir, taken twice daily for 5 days. 4
For moderate renal impairment (eGFR 30-60 mL/min): reduce to 150 mg nirmatrelvir with 100 mg ritonavir twice daily for all 5 days. 4
Critical Safety Checks Before Prescribing
Drug-drug interactions are the primary safety concern with Paxlovid. 4 Ritonavir is a strong CYP3A inhibitor that causes interactions during active treatment and possibly for several days after completion. 4
Use the Liverpool COVID-19 Drug Interaction Tool to systematically check for contraindicated medications or those requiring dose adjustment. 4
Common problematic medications include certain statins, antiarrhythmics, immunosuppressants, and anticoagulants. 4
Expected Adverse Effects
Dysgeusia (altered taste) occurs in approximately 92% of pregnant patients taking Paxlovid. 5
Diarrhea is common but does not typically lead to drug discontinuation. 4
Rebound symptoms or positive test results occur in approximately 50% of pregnant patients, though this does not indicate treatment failure or require retreatment. 5
Monitoring During and After Treatment
Monitor for common adverse effects (dysgeusia, diarrhea) which are generally mild and self-limited. 4
If clinical deterioration occurs during treatment, reassess renal function as COVID-19 itself can cause acute kidney injury. 4
After discontinuation, monitor for ALT flares every 3 months for 6 months (extrapolated from hepatitis B treatment guidance in pregnancy). 1
Breastfeeding Considerations
Breastfeeding is not contraindicated in women taking Paxlovid. 1 The ritonavir component is minimally excreted in breast milk based on extensive HIV treatment experience. 1
Real-World Pregnancy Outcomes
A Taiwanese cohort study of 30 pregnant women treated with Paxlovid showed:
- Shorter duration of COVID-19 symptoms (10.1 days vs. 15.6 days) compared to untreated controls. 6
- No severe adverse events attributed to Paxlovid use. 6
- Higher cesarean delivery rate in the Paxlovid group (76.9% vs. 42.9%), though this may reflect underlying disease severity rather than drug effect. 6
Key Clinical Pitfalls to Avoid
Do not delay treatment while awaiting "more data" – the known risks of severe COVID-19 in pregnancy outweigh the theoretical risks of Paxlovid based on current evidence. 3
Do not prescribe without checking drug interactions – this is the most common preventable adverse event. 4
Do not use in severe hepatic impairment – trials excluded these patients and safety is unknown. 4
Do not counsel patients that rebound symptoms indicate treatment failure – this is a common phenomenon that does not require retreatment. 5