Is Paxlovid (nirmatrelvir/ritonavir) safe to use in pregnant women with COVID-19?

Paxlovid Use in Pregnancy

Paxlovid (nirmatrelvir/ritonavir) can be used in pregnant women with COVID-19, particularly those at high risk for severe disease, as animal studies show no teratogenicity and limited human data suggest it is effective and safe, though long-term safety data remain limited. 1, 2

Rationale for Use in Pregnancy

Pregnant women face substantially elevated risks from COVID-19 infection:

• Symptomatic pregnant women have 2-3 fold higher rates of ICU admission, invasive ventilation, and mortality compared to non-pregnant women of reproductive age 3
• COVID-19 infection during pregnancy increases risk of preeclampsia/eclampsia (adjusted OR 1.57), preterm delivery (adjusted OR 2.17), and fetal death (adjusted OR 2.21) 3
• Risk is particularly elevated in women >35 years, with comorbidities (obesity, diabetes, cardiovascular disease), and in Black, Asian, or Hispanic populations 3

Safety Evidence

Animal Studies

• Nirmatrelvir showed no adverse effects on fertility, embryonic development, or teratogenicity in rats and rabbits at doses up to 1000 mg/kg/day (the limit dose in ICH guideline studies) 2
• No effects on male or female fertility or early embryonic development were observed 2
• The lack of toxicity is consistent with nirmatrelvir's viral-specific target (SARS-CoV-2 main protease), which is not present in mammalian cells 2

Human Data

• A Taiwanese study of 30 pregnant women treated with Paxlovid showed shorter duration of COVID-19 symptoms (10.10 days vs 15.59 days, p=0.04) compared to untreated controls 1
• No severe adverse events were observed; dysgeusia (91.7%) and diarrhea (50.0%) were the most common side effects 1
• Ritonavir has extensive safety data from HIV treatment during pregnancy with no significant teratogenicity 4

Potential Concerns

• The Taiwanese study noted a higher cesarean delivery rate in the Paxlovid group (76.92% vs 42.86%, p=0.042), though this may reflect confounding by indication (sicker patients receiving treatment) 1
• A trend toward more small-for-gestational-age infants was observed (23.08% vs 3.57%, p=0.086), but this did not reach statistical significance 1
• Rebound symptoms occurred in 50% of treated pregnant women in one survey study 5

Clinical Recommendations

When to Prescribe

Paxlovid should be offered to pregnant women with mild-to-moderate COVID-19 who are at high risk for progression to severe disease, including:

• Healthcare workers with high exposure 3
• Age >35 years 3
• Multiple gestation 3
• Chronic medical conditions (obesity, diabetes, cardiovascular disease, chronic kidney disease, hypertension) 3
• Immunocompromised states 3

Timing and Administration

• Must be initiated within 5 days of symptom onset for maximum efficacy (based on non-pregnant trial data) 4
• Standard dosing: nirmatrelvir 300 mg with ritonavir 100 mg twice daily for 5 days 4
• No dose adjustments are needed based on gestational age 4

Key Drug Interactions

Ritonavir is a potent CYP3A4 inhibitor, requiring careful medication review:

• Avoid concurrent use with drugs heavily dependent on CYP3A4 metabolism with narrow therapeutic windows 4
• Review all current medications before prescribing, particularly anticonvulsants, immunosuppressants, and cardiovascular medications 4

Lactation Considerations

• Limited data exist on Paxlovid use during lactation 4, 5
• Ritonavir has been used safely in breastfeeding women with HIV 4
• In one survey, 2 of 5 lactating women took nirmatrelvir-ritonavir without significant adverse outcomes 5
• The theoretical risk to the nursing infant appears low given the drug's mechanism of action 2

Common Pitfalls to Avoid

• Do not delay treatment while awaiting "more data" - the known risks of severe COVID-19 in pregnancy outweigh theoretical medication risks 3, 1
• Do not withhold treatment due to unknown long-term effects - animal studies are reassuring and short-term human data show benefit 2, 1
• Counsel patients that dysgeusia is extremely common (>90%) but temporary and not harmful 1, 5
• Monitor for symptom rebound (occurs in ~50% of cases) and consider retreatment if severe 5

Counseling Points

When discussing Paxlovid with pregnant patients:

• Emphasize that pregnant women are at significantly higher risk for severe COVID-19 and its complications 3
• Explain that animal studies show no birth defects or pregnancy complications 2
• Acknowledge that human pregnancy data are limited but emerging evidence is reassuring 1, 4
• Discuss common side effects (bad taste in mouth, diarrhea) that resolve after treatment 1
• Note that the benefits of preventing severe COVID-19 likely outweigh theoretical risks in high-risk pregnant women 4, 2