Low Nirmatrelvir and Ritonavir Exposure through Breastmilk: Analyzing Milk Concentrations and Infant Risk

Area of Science:

• Pharmacology
• Maternal-Child Health
• Infectious Diseases

Background:

• Nirmatrelvir with ritonavir is recommended for high-risk COVID-19 patients.
• Its use in lactating women is advised, but data on milk transfer is lacking.
• Understanding drug transfer is crucial for managing COVID-19 in breastfeeding individuals.

Purpose of the Study:

• To quantify nirmatrelvir and ritonavir transfer into human milk.
• To assess infant exposure and tolerance to these drugs via breastfeeding.
• To inform clinical decisions regarding COVID-19 treatment for lactating women.

Main Methods:

• Analysis of human milk samples from eight mother-infant dyads using liquid chromatography-mass spectrometry.
• Measurement of nirmatrelvir and ritonavir concentrations in milk.
• Calculation of estimated infant dose and relative infant dose (RID).

Main Results:

• Nirmatrelvir and ritonavir were measurable in all milk samples.
• Mean concentrations: 729 ng/mL (nirmatrelvir) and 33.48 ng/mL (ritonavir).
• Estimated RIDs were 1.43% (nirmatrelvir) and 0.19% (ritonavir), below the 10% safety threshold. No adverse events were reported in infants.

Conclusions:

• Nirmatrelvir with ritonavir transfers into human milk at low, likely safe levels.
• The findings support the current recommendation for using nirmatrelvir/ritonavir in lactating women.
• Healthcare providers can confidently prescribe this treatment when indicated, regardless of lactation status.