Is Paxlovid (nirmatrelvir/ritonavir) safe to use during pregnancy?

Paxlovid Use in Pregnancy

Paxlovid (nirmatrelvir/ritonavir) can be used during pregnancy for pregnant individuals with non-severe COVID-19 who are at high risk of hospitalization, based on WHO guidance showing no reports of serious adverse reactions in parent or child to date, and extensive safety data from ritonavir use in over 7,000 pregnancies for HIV treatment. 1, 2

Evidence Supporting Use

The recommendation to use Paxlovid in pregnancy is built on several lines of evidence:

WHO and FDA Position

• The WHO Living Guideline explicitly states that pregnant people with non-severe COVID-19 may consider use of nirmatrelvir/ritonavir, with data from WHO Vigibase showing no reports of serious adverse reactions in parent or child. 1
• The FDA label notes that published observational studies on ritonavir use in pregnant women have not identified an increase in the risk of major birth defects, with over 3,500 live births exposed in the first trimester and over 3,500 in the second/third trimesters showing a birth defect rate of 2.4% (first trimester) and 2.9% (second/third trimester), comparable to the 2.7% U.S. background rate. 2

Ritonavir Component Safety Data

• The ritonavir component has extensive pregnancy safety data from HIV treatment, with the antiretroviral pregnancy registry showing no difference in birth defect rates compared to background population rates across all trimesters. 2
• Ritonavir-boosted protease inhibitors (atazanavir/ritonavir, darunavir/ritonavir) are recommended options for HIV treatment during pregnancy with no significant teratogenicity demonstrated. 3

Nirmatrelvir Component Safety Data

• Animal reproduction studies with nirmatrelvir showed no biologically significant developmental effects in rats at exposures ≥3 times the approved human dose, with only reduced fetal body weights in rabbits at 11 times clinical exposure. 2
• The nonclinical reproductive toxicology studies up to 1000 mg/kg/day showed no effects on male/female fertility, early embryonic development, or severe developmental toxicity in rats or rabbits. 4

Clinical Implementation Algorithm

Patient Selection Criteria

• Pregnant individuals with non-severe COVID-19 who are at high risk of hospitalization (comorbidities such as diabetes, hypertension, obesity, immunosuppression) should be offered Paxlovid. 1
• Symptom onset must be within 5 days for treatment initiation. 1

Critical Pre-Prescribing Steps

1. Check for drug-drug interactions using the Liverpool COVID-19 Drug Interaction Tool (https://www.hiv-druginteractions.org) before prescribing—this is the most common preventable adverse event. 1
2. Assess renal function: standard dosing for normal renal function (300 mg nirmatrelvir/100 mg ritonavir twice daily for 5 days); reduce to 150 mg nirmatrelvir/100 mg ritonavir twice daily for moderate renal impairment (eGFR 30-60 mL/min). 1
3. Verify no severe hepatic impairment (contraindication due to lack of safety data). 1

Common Problematic Drug Interactions to Screen For

• Statins, antiarrhythmics, immunosuppressants, and anticoagulants require dose adjustment or temporary discontinuation. 1
• Contraindicated medications include triazolam, oral midazolam, naloxegol, sildenafil for pulmonary hypertension, and flibanserin. 2

Risks of Untreated COVID-19 in Pregnancy

The decision to use Paxlovid must be weighed against the substantial risks of untreated COVID-19:

• COVID-19 in pregnancy is associated with preeclampsia, eclampsia, preterm birth, premature rupture of membranes, venous thromboembolic disease, and fetal death. 2
• These maternal and fetal risks from COVID-19 itself often outweigh the theoretical risks of medication exposure. 2

Real-World Clinical Experience

• A Taiwanese cohort study of 30 pregnant women treated with Paxlovid showed shorter duration of COVID-19 symptoms (10.1 vs 15.6 days, p=0.04) with no severe adverse events observed. 5
• The most common adverse effects were dysgeusia (91.7%) and diarrhea (50%), which are generally mild and self-limited. 5, 6
• A U.S. survey found that 34.3% of prescribed pregnant patients took nirmatrelvir-ritonavir, with 91.7% experiencing dysgeusia and 50% reporting rebound symptoms or positive tests, but no significant adverse outcomes. 6

Breastfeeding Considerations

• Breastfeeding is not contraindicated in women taking Paxlovid, as ritonavir is minimally excreted in breast milk and unlikely to cause significant infant toxicity. 7, 1
• The unknown risk of low-level infant exposure should be discussed with mothers, but does not preclude breastfeeding. 7

Critical Pitfalls to Avoid

1. Never prescribe Paxlovid without systematically checking drug interactions—this is the single most important safety step. 1
2. Do not use in severe hepatic impairment (safety unknown). 1
3. Do not delay treatment beyond 5 days of symptom onset (efficacy window). 1
4. Do not assume all statins are safe—some require dose adjustment or temporary discontinuation. 1, 2

Monitoring During Treatment

• Monitor for common adverse effects (dysgeusia, diarrhea), which are typically mild and self-limited. 1, 5
• If clinical deterioration occurs, reassess renal function as COVID-19 can cause acute kidney injury. 1
• No routine serial viral load or liver function monitoring is required during the 5-day treatment course. 7

Shared Decision-Making Discussion Points

When counseling pregnant patients about Paxlovid:

• Emphasize the extensive safety data from ritonavir use in over 7,000 pregnancies for HIV treatment showing no increased birth defect risk. 2
• Explain that animal studies with nirmatrelvir showed no significant developmental toxicity. 2, 4
• Discuss the known risks of untreated COVID-19 in pregnancy (preeclampsia, preterm birth, fetal death). 2
• Acknowledge that while direct human data on nirmatrelvir in pregnancy are limited, the available evidence is reassuring. 2, 8
• Explain that dysgeusia (altered taste) is very common but temporary. 5, 6