Summary of Use during Lactation

Limited information indicates that maternal doses of darunavir up to 800 mg daily with ritonavir produce low to unmeasurable levels in milk and would not be expected to cause any adverse effects in breastfed infants. The combination of darunavir and cobicistat is expected to produce similar results. In the US and other countries where access to clean water and affordable replacement feeding are available, it is recommended that mothers living with HIV not breastfeed their infants to avoid postnatal transmission of HIV-1 infection. Achieving and maintaining viral suppression with antiretroviral therapy decreases breastfeeding transmission risk to less than 1%, but not zero. Individuals with HIV who are on antiretroviral therapy with a sustained undetectable viral load and who choose to breastfeed should be supported in this decision.[1]

Drug Levels

Maternal Levels. Four mothers taking darunavir 800 mg plus ritonavir 100 mg once daily provided milk samples at a median of 15.4 hours after a dose. The median drug concentration in milk was 316 mcg/L, which resulted in an estimated infant dosage of 50 mcg/kg daily and a relative infant dose of 0.12% of the maternal weight-adjusted dosage.[2]

Infant Levels. An infant was breastfed by a mother taking darunavir 800 mg plus ritonavir 100 mg once daily, although the extent of breastfeeding was not sated. The infant’s serum concentrations taken 16 hours after maternal drug intake at 1 month of age was undetectable.[2]

Effects in Breastfed Infants

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

Effects on Lactation and Breastmilk

Gynecomastia has been reported among men receiving highly active antiretroviral therapy. Gynecomastia is unilateral initially, but progresses to bilateral in about half of cases. No alterations in serum prolactin were noted and spontaneous resolution usually occurred within one year, even with continuation of the regimen.[3-5] Some case reports and in vitro studies have suggested that protease inhibitors might cause hyperprolactinemia and galactorrhea in some male patients,[6,7] although this has been disputed.[8] The relevance of these findings to nursing mothers is not known. The prolactin level in a mother with established lactation may not affect her ability to breastfeed.

References

1.

Department of Health and Human Services. Recommendations for the use of antiretroviral drugs during pregnancy and interventions to reduce perinatal HIV transmission in the United States. Infant feeding for individuals with HIV in the United States. 2023 https:​//clinicalinfohivgov​/en/guidelines​/perinatal/infant-feeding-individuals-hiv-united-states?view=full.

2.

Aebi-Popp K, Kahlert CR, Crisinel PA, et al. Transfer of antiretroviral drugs into breastmilk: A prospective study from the Swiss Mother and Child HIV Cohort Study. J Antimicrob Chemother. 2022;77:3436–42. [PMC free article: PMC9704434] [PubMed: 36177836]

3.

García-Benayas T, Blanco F, Martin-Carbonero L, et al. Gynecomastia in HIV-infected patients receiving antiretroviral therapy. AIDS Res Hum Retroviruses. 2003;19:739–41. [PubMed: 14585204]

4.

Pantanowitz L, Evans D, Gross PD, et al. HIV-related gynecomastia. Breast J. 2003;9:131–2. [PubMed: 12603389]

5.

Evans DL, Pantanowitz L, Dezube BJ, et al. Breast enlargement in 13 men who were seropositive for human immunodeficiency virus. Clin Infect Dis. 2002;35:1113–9. [PubMed: 12384846]

6.

Hutchinson J, Murphy M, Harries R, et al. Galactorrhoea and hyperprolactinaemia associated with protease-inhibitors. Lancet. 2000;356:1003–4. [PubMed: 11041407]

7.

Orlando G, Brunetti L, Vacca M. Ritonavir and saquinavir directly stimulate anterior pituitary prolactin secretion, in vitro. Int J Immunopathol Pharmacol. 2002;15:65–8. [PubMed: 12593790]

8.

Montero A, Bottasso OA, Luraghi MR, et al. Galactorrhoea, hyperprolactinaemia, and protease inhibitors. Lancet. 2001;357:473–4. [PubMed: 11273087]

Substance Name

Darunavir

CAS Registry Number

618109-00-5

Drug Class

Breast Feeding

Lactation

Milk, Human

Anti-Infective Agents

Anti-HIV Agents

Antiviral Agents

Anti-Retroviral Agents

HIV Protease Inhibitors