Nirmatrelvir use while Breastfeeding

Summary of Use during Lactation

Nirmatrelvir is given in combination with ritonavir, which enhances its bioavailability. The concentration of nirmatrelvir in breastmilk is low. Ritonavir is excreted into milk in measurable concentrations and low levels can be found in the blood of some breastfed infants. No adverse reactions in breastfed infants have been reported. For more information, refer to the LactMed record on ritonavir. Because of the poor oral bioavailability of nirmatrelvir and small amounts of both drugs in milk, this combination is unlikely to adversely affect the nursing infant.[1,2]

Drug Levels

Maternal Levels. Eight women who were taking nirmatrelvir-ritonavir and had donated milk samples to a breastmilk repository had their milk analyzed for nirmatrelvir. All were taking a nirmatrelvir dose of 300 mg twice daily and reported taking milk samples at 0, 1, 2, 4, 6, 8, 10, and 12 hours after a dose. The peak nirmatrelvir concentration in milk occurred at 4 hours after the dose was 1107 mcg/L and the average concentration was 729 mcg/L. This translated into a daily infant dose of 0.108 mg/kg or a relative infant dose of 1.4%.[3]

The manufacturer reported a clinical pharmacokinetic study of 8 healthy lactating women who were at least 12 weeks postpartum. They were administered 3 oral doses every 12 hours of 300 mg of nirmatrelvir and 100 mg of ritonavir. The mean daily amount of nirmatrelvir and ritonavir recovered in breast milk was 0.752 mg and 0.027 mg, respectively, representing 0.13% and 0.014% of the corresponding administered daily maternal doses (unadjusted for weight). The estimated daily infant dosages (assuming average milk consumption of 150 mL/kg/day), were 0.16 mg/kg and 0.006 mg/kg or 1.8% and 0.2% of the maternal dose, respectively, for nirmatrelvir and ritonavir.[4]

Infant Levels. Relevant published information was not found as of the revision date.

Effects in Breastfed Infants

In a cross-sectional study of women who had COVID-19 and received nirmatrelvir in combination ritonavir, two women breastfed their infants. No adverse effects were reported in the infants.[5]

Effects on Lactation and Breastmilk

Relevant published information was not found as of the revision date.

Alternate Drugs to Consider

Remdesevir

References

1.

Chourasia P, Maringanti BS, Edwards-Fligner M, et al. Paxlovid (nirmatrelvir and ritonavir) use in pregnant and lactating woman: Current evidence and practice guidelines-a scoping review. Vaccines (Basel) 2023;11:107. [PMC free article: PMC9866309] [PubMed: 36679952]

2.

Anderson PO. COVID-19 drugs and breastfeeding update. Breastfeed Med 2022;17:377-9. [PubMed: 35384717]

3.

Dai J, Fuquay T, Huseman S, et al. Low nirmatrelvir and ritonavir exposure through breastmilk: Analyzing milk concentrations and infant risk. Clin Pharmacol Ther 2024;116:1217-21. [PubMed: 38923506]

4.

Pfizer. A study to learn about the medicine (PF-07321332 or nirmatrelvir/ritonavir) in healthy lactating women (NCT05441215). 2024. https://clinicaltrials.gov/study/NCT05441215?term=NCT05441215&rank=1#study-overview

5.

Lin CY, Cassidy AG, Li L, et al. Nirmatrelvir-ritonavir (Paxlovid) for mild coronavirus disease 2019 (COVID-19) in pregnancy and lactation. Obstet Gynecol 2023;141:957-60. [PMC free article: PMC10147578] [PubMed: 36928334]

Substance Name

Nirmatrelvir

CAS Registry Number

2628280-40-8

Drug Class

Breast Feeding

Lactation

Milk, Human

Antiviral Agents

Protease Inhibitors