Nirmatrelvir / ritonavir Pregnancy and Breastfeeding Warnings

Brand names: Paxlovid

Medically reviewed by Drugs.com. Last updated on Apr 9, 2025.

Nirmatrelvir / ritonavir Pregnancy Warnings

According to some authorities: This product should not be used during pregnancy or in patients of childbearing potential not using contraception.

AU TGA pregnancy category: B3
US FDA pregnancy category: Not assigned

Risk summary: Insufficient data are available on the use of nirmatrelvir in pregnant women to inform a drug-related risk; published observational studies on ritonavir use in pregnant women have not identified an increase in the risk of major birth defects.

Comments:
-Patients of childbearing potential should use effective contraception during therapy.
-Ritonavir may reduce the efficacy of combined hormonal contraceptives; patients of childbearing potential using these products should be advised to use an effective alternative contraceptive method or an additional barrier method of contraception during therapy.

Animal studies with nirmatrelvir have failed to reveal evidence of adverse developmental outcomes at systemic exposures (AUC) 3 to 10 times higher than clinical exposure at the approved human dose of this product; in rabbits, reduced fetal body weights were observed at systemic exposures (AUC) about 11 times higher than clinical exposure at the approved human dose of this product. Animal studies with ritonavir have failed to reveal evidence of adverse developmental outcomes at systemic exposures (AUC) 5 (rat) or 8 (rabbit) times higher than clinical exposure at the approved human dose of this product. There are no controlled data in human pregnancy.

Placental transfer of ritonavir to the fetus has been reported as low (cord blood/maternal delivery plasma drug ratio less than 0.3). While placental transfer and fetal drug levels are generally low, detectable levels of ritonavir have been found in cord blood samples and neonate hair.

The Antiretroviral Pregnancy Registry has received prospective reports of over 7000 exposures to ritonavir-containing regimens (over 3500 exposed in the first trimester; over 3500 exposed in the second/third trimester) resulting in live births; there was no difference in the rate of overall birth defects for ritonavir compared with the background birth defect rate of 2.7% in the US reference population. For ritonavir, enough first trimester exposures have been monitored to detect at least a 1.5-fold increase in risk of overall birth defects and a 2-fold increase in risk of cardiovascular and genitourinary defects (the more common classes); no such increases detected. The prevalence of birth defects/live births with first trimester and second/third trimester exposures to ritonavir was 2.5% and 3%, respectively.

COVID-19 is associated with adverse maternal and fetal outcomes, including preeclampsia, eclampsia, preterm birth, premature rupture of membranes, venous thromboembolic disease, and fetal death.

AU TGA pregnancy category B3: Drugs which have been taken by only a limited number of pregnant women and women of childbearing age, without an increase in the frequency of malformation or other direct or indirect harmful effects on the human fetus having been observed. Studies in animals have shown evidence of an increased occurrence of fetal damage, the significance of which is considered uncertain in humans.

US FDA pregnancy category Not Assigned: The US FDA has amended the pregnancy labeling rule for prescription drug products to require labeling that includes a summary of risk, a discussion of the data supporting that summary, and relevant information to help health care providers make prescribing decisions and counsel women about the use of drugs during pregnancy. Pregnancy categories A, B, C, D, and X are being phased out.

See references

Nirmatrelvir / ritonavir Breastfeeding Warnings

According to some authorities: Breastfeeding is not recommended during use of this product and for 48 hours after the last dose.

Excreted into human milk: Yes (nirmatrelvir, ritonavir)

Comments:
-Developmental and health benefits of breastfeeding should be considered as well as the mother's clinical need for this product.
-The effects in the nursing infant are unknown; potential adverse effects in the breastfed child due to this product or the mother's underlying condition should be considered.
---According to some authorities: A risk to the neonate/infant cannot be excluded.
-Breastfeeding patients with COVID-19 should follow practices according to clinical guidelines to avoid exposing the infant to COVID-19.

Nirmatrelvir is administered in combination with ritonavir, which enhances its bioavailability; nirmatrelvir level in breast milk is low. Measurable levels of ritonavir are excreted in milk and low levels can be found in the blood of some breastfed infants; no adverse effects have been reported in breastfed infants. Due to the poor oral bioavailability of nirmatrelvir and small amounts of both components in milk, this combination is unlikely to adversely affect nursing infants. In a cross-sectional study of women who had COVID-19 and received this product, 2 women breastfed their infants; no adverse effects were reported in the infants.

Both components are present in human breast milk in small amounts (less than 2%). In a lactation study in 8 healthy women, the mean daily amount of nirmatrelvir and ritonavir in breast milk was 0.752 and 0.027 mg, respectively, representing 0.13% and 0.014% of the corresponding maternal daily doses (unadjusted for weight); the milk to plasma AUC ratios for nirmatrelvir and ritonavir were 0.26 and 0.07, respectively. The estimated infant dose for nirmatrelvir and ritonavir (assuming average milk consumption of 150 mL/kg/day) was 0.16 and 0.006 mg/kg/day (1.8% and 0.2% of the maternal weight-adjusted daily dose), respectively.

In another study, breast milk from 8 women taking nirmatrelvir-ritonavir was collected and analyzed. The peak nirmatrelvir and ritonavir levels in milk occurred at 4 hours after dosing and were 1107 and 55.6 mcg/L, respectively; the average nirmatrelvir and ritonavir levels in milk were 729 and 33.5 mcg/L, respectively. This data suggested an infant nirmatrelvir dose of 0.108 mg/kg/day (or relative infant dose of 1.4%) and an infant ritonavir dose of 0.005 mg/kg (or relative infant dose of 0.19%).

See references

Further information

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