Is Dolutegravir safe while breastfeeding?

Effects on the breastfed infant

An HIV-positive mother took a combination tablet containing dolutegravir 50 mg, abacavir sulfate 600 mg and lamivudine 300 mg (Triumeq) once daily. Her infant was exclusively breastfed for about 30 weeks and partially breastfed for about 20 weeks more. No obvious side effects were noted.[ 3 ] In a study of African women with HIV infection received a dolutegravir-based regimen of 50 mg dolutegravir, 300 mg tenofovir disoproxil fumarate, and either 200 mg emtricitabine in South Africa or 300 mg lamivudine in Uganda during pregnancy and breastfeeding. This regimen was as safe for breastfed as an efavirenz-based regimen with the same other drugs.[ 13 ] An open-label, controlled, multicenter phase 3 trial women who were confirmed HIV-positive were randomized to receive one of 3 regimens: dolutegravir, emtricitabine, and tenofovir alafenamide (n = 208); dolutegravir, emtricitabine, and tenofovir disoproxil fumarate (n = 202); or efavirenz, emtricitabine, and tenofovir disoproxil fumarate (n = 207). The regimens were started at 14 to 28 weeks of pregnancy and continued postpartum. Of the 617 liveborn infants, 99% were breastfeeding at time of last infant HIV test, which was as late as 50 weeks of age. The mean infant duration on the study was 47.6 weeks of age. Infants who had any clinical or laboratory adverse event of grade 3 or higher ranged from 25 to 31%, but was not statistically significant between groups. Dolutegravir-containing regimens resulted in lower rates of virological failure, HIV drug resistance, and infant mortality up to 50 weeks postpartum compared with efavirenz, emtricitabine, and tenofovir disoproxil fumarate.[ 14 ] A woman with newly diagnosed HIV infection began dolutegravir 50 mg and lamivudine 300 mg daily at week 23 of pregnancy. She breastfed (extent not stated) her infant who remained HIV-negative after 10 month of breastfeeding and had normal growth- and neurological development.[ 15 ]

Effects on milk supply

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

Levels in milk

Maternal Levels. An HIV-positive mother took a combination tablet containing dolutegravir 50 mg, abacavir sulfate 600 mg and lamivudine 300 mg (Triumeq) once daily. Her breastmilk dolutegravir concentrations were measured periodically over a 10-month period and averaged about 100 mcg/L at 11 hours after the dose. The authors estimated a daily infant dosage of 15 mcg/kg of dolutegravir.[ 3 ] Two HIV-positive women taking dolutegravir (dose not stated, but presumably 50 mg daily) plus 2 unspecified nonnucleoside reverse transcriptase inhibitors donated two milk samples each. At 2 weeks postpartum, steady-state breastmilk dolutegravir levels in one woman were 154.2 mcg/L at 4 hours after the dose and 40.9 mcg/L at 24 hours after a dose. In the other woman, steady-state breastmilk dolutegravir levels were 116.3 mcg/L at 3 hours after the dose and 17.7 mcg/L at 24 hours after a dose. At 2 and 9 days, respectively, after discontinuing the drug, breastmilk levels were undetectable ( 10 mcg/L).[ 4 ] Twenty-eight pregnant HIV-positive women were randomized to receive an antiretroviral regimen containing oral dolutegravir 50 mg once daily. Of these, 17 women underwent extensive postpartum sampling of breastmilk and maternal serum at a median of 10 days postpartum. Median dolutegravir peak concentration in milk was 84.6 mcg/L and minimum of 22.3 mcg/L. Only one woman had 14 mcg/L of dolutegravir in milk at 48 hours; all other milk samples at 48, 72 and 96 hours after drug discontinuation were negative for dolutegravir.[ 5 ] Data from this study were used to create a pharmacokinetic model of dolutegravir into milk. Using the model, the average concentration of dolutegravir in breastmilk over 24 hours was 0.05 mg/L (range 0.029-0.10 mg/L), corresponding to an absolute infant dose of 2.2 mcg/kg daily. This corresponds to a weight-adjusted infant dosage of 0.27% of the maternal dose.[ 6 ] Three mothers taking dolutegravir 50 mg once daily provided 6 milk samples at a median of 15

Alternatives LactMed lists

• Raltegravir