Doravirine and Breastfeeding

Summary of use during lactation

No information is available on the clinical use of doravirine during breastfeeding. However, amounts in breastmilk appear to be low and would not be expected to cause any adverse effects in breastfed infants. 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. If a viral load is not suppressed, banked pasteurized donor milk or formula is recommended.[1,2]

Drug levels in milk and infant serum

Maternal Levels. In a study of a new analytic technique, one healthy lactating volunteer took a single 100 mg dose of doravirine. A peak milk concentration of about 0.42 mg/L occurred at about 2 hours after the dose. By 24 hours after the dose, the milk concentration was about 0.05 mg/L.[3] Eight lactating women were given a single oral dose of 100 mg of doravirine was administered, with plasma samples collected at 0, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24 hours after the dose. Breastmilk samples were collected with an electric breast pump, emptying both breasts, at 0, 2, 4, 6, 12, 24 hours after the dose. A median peak milk concentration of 0.31 mg/L occurred at a mean of 11.56 hours after the dose. The authors reported an RID of 0.86%, based on the actual milk volumes reported by the study participants. Based on the reported AUC value and standard daily milk volume of 150 mL/kg , the median milk concentrations was 0.22 mg/L resulting in a median daily dosage of 0.033 mg/kg. This dose resulted in a relative infant dose of 2.7%. The authors went on to create a PBPK model that predicted these values relatively well, with an RID of 1.9%.[4] Infant Levels. Relevant published information was not found as of the revision date.

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.[5-7] Some case reports and in vitro studies have suggested that protease inhibitors might cause hyperprolactinemia and galactorrhea in some male patients,[8,9] although this has been disputed.[10] 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. World Health Organization. Consolidated guidelines on HIV prevention, testing, treatment, service delivery and monitoring: Recommendations for a public health approach. 2021 https://www.who.int/publications/i/item/9789240031593 PubMed
2. 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. 2024 https://clinicalinfo.hiv.gov/sites/default/files/guidelines/documents/perinatal-hiv/guidelines-perinatal.pdf
3. van der Wekken-Pas LC, van Ewijk Beneken Kolmer EWJ, te Brake LHM, et al. Quantification of dolutegravir, bictegravir, raltegravir and doravirine in human breastmilk with UPLC-MS/MS. J Chromatogr B Analyt Technol Biomed Life Sci 2025;1264:124739.40712298 PubMed
4. van der Wekken-Pas L, Burger D, Greupink R, et al. Physiologically based pharmacokinetic model combined with a clinical lactation study to determine doravirine concentrations in human breastmilk. Br J Clin Pharmacol 202541199575 PubMed
5. García-Benayas T, Blanco F, Martin-Carbonero L, et al. Gynecomastia in HIV-infected patients receiving antiretroviral therapy. AIDS Res Hum Retroviruses 2003;19:739–41.14585204 PubMed
6. Pantanowitz L, Evans D, Gross PD, et al. HIV-related gynecomastia. Breast J 2003;9:131–2.12603389 PubMed
7. Evans DL, Pantanowitz L, Dezube BJ, et al. Breast enlargement in 13 men who were seropositive for human immunodeficiency virus. Clin Infect Dis 2002;35:1113–9.12384846 PubMed
8. Hutchinson J, Murphy M, Harries R, et al. Galactorrhoea and hyperprolactinaemia associated with protease-inhibitors. Lancet 2000;356:1003–4.11041407 PubMed
9. Orlando G, Brunetti L, Vacca M. Ritonavir and saquinavir directly stimulate anterior pituitary prolactin secretion, in vitro. Int J Immunopathol Pharmacol 2002;15:65–8.12593790 PubMed
10. Montero A, Bottasso OA, Luraghi MR, et al. Galactorrhoea, hyperprolactinaemia, and protease inhibitors. Lancet 2001;357:473–5.11273087 PubMed
11. Substance Identification