Can you take dolutegravir while breastfeeding?

What LactMed would consider instead

LactMed ends this record by naming the drugs it would consider in place of dolutegravir. Whether any of them fits depends on what you are treating — this is the database’s list, not a recommendation from us.

• Raltegravir

How much dolutegravir gets into breastmilk

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.

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).

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. 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.

Three mothers taking dolutegravir 50 mg once daily provided 6 milk samples at a median of 15 hours after a dose. The median drug concentration in milk was 107 mcg/L, which resulted in an estimated infant dosage of 20 mcg/kg daily and a relative infant dose of 1% of the maternal weight-adjusted dosage.

A physiologically based pharmacokinetic model was constructed for dolutegravir and compared to data from a study conducted in Uganda in nursing mothers. The model reasonably predicted maternal levels and the predicted exposure in breastfed neonates and infants was 1.28-and 2-fold higher in UGT1A1 poor metabolizers(PMs) with PM mothers compared to extensive metabolizers (EMs) with EM mothers, but remained 51-and108-fold lower than that observed in the lactating mothers, respectively.

A new method of determination of dolutegravir in milk was used to detect the drug in milk samples from 10 individuals prescribed dolutegravir collected at various times. Dolutegravir was quantifiable in 9 of the samples, with concentrations ranging from 466 mcg/L to 2013 mcg/L. One sample collected 24 days after discontinuation of dolutegravir was unquantifiable.

In a retrospective study in a German hospital of mothers who were receiving antiretroviral prophylaxis, one mother was receiving dolutegravir 50 mg once daily. Breastmilk levels obtained at unspecified times with respect to the dose at 1, 4, and 6 months postpartum were <50 mcg/L, 648 mcg/L and 680 mcg/L, respectively.

Women in a 9-country clinical trial were randomly assigned to receive either dolutegravir 50 mg once daily with a fixed-dose combination of emtricitabine 200 mcg plus tenofovir alafenamide 25 mg once daily, or dolutegravir 50 mg once daily with a fixed-dose combination of emtricitabine 200 mg plus tenofovir disoproxil fumarate 300 mg once daily. One milk sample was obtained at 6 weeks postpartum (n = 180). The median concentrations in breastmilk was 91 mcg/L (IQR 67 to 123 mcg/L). The median RID of dolutegravir was estimated to be 1.92% (range 0.00 to 4.89%).

Infant 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 infant had a plasma dolutegravir concentration of 100 mcg/L during the period of exclusive breastfeeding up to about 30 weeks postpartum. As supplemental feeding was introduced, the plasma concentrations dropped to about 30 mcg/L at 35 weeks, and to 0 with no breastfeeding after about 50 weeks postpartum.

Two HIV-positive women taking dolutegravir (dose not stated, but presumably 50 mg daily) plus 2 unspecified nonnucleoside reverse transcriptase inhibitors breastfed their infants (extent not stated, but presumably exclusively). At 2 weeks postpartum, the plasma levels in one infant were 67.8 mcg/L and 75.5 mcg/L at 4 and 24 hours after the maternal dose, respectively. Two days after drug discontinuation, the infant had a plasma level of 58.6 mcg/L at a time when the maternal plasma level was 103.8 mcg/L. In the other infant, the plasma level was 16.3 mcg/L at 24 hours after the maternal dose.

Seventeen women were receiving oral dolutegravir 50 mg daily as part of a study. Their breastfed infants had serum levels obtained at a median of 10 days postpartum. Their median dolutegravir peak serum concentration was 66.7 mcg/L and minimum was 60.9 mcg/L. After discontinuation of maternal dolutegravir, detectable concentrations were noted in 100%, 80% and 80% of breastfed infants at 48, 72 and 96 hours following final maternal dose, respectively. The ratio of paired maternal and infant serum concentrations was 0.03 at the peak and 0.08 at the trough.

Twenty-one breastfed infants whose mothers were receiving dolutegravir postpartum had a total of 65 serum concentration measured postpartum. Infant serum concentrations were 4.9% of maternal plasma concentration in the first 24 hours after the final maternal dose, increasing to 11% of maternal plasma concentration when measured over the 96 hours after the final maternal dose. The increase indicates a slower drug elimination in infants compared to their mothers.

Two infants were breastfed by mothers taking dolutegravir 50 mg once daily, although the extent of breastfeeding was not sated. Infant serum concentrations taken at 1 month of age were 279 mcg/L at 15 hours after the dose in one infant and 100 mcg/L at 13 hours after the dose in the other.

A physiologically based pharmacokinetic computer model was developed to simulate infant exposure to dolutegravir from the milk of Black African mothers. The model predicted that with a maternal dosage of 50 mg daily, the infant dose would be 0.008 mg/kg daily with a maximum relative infant dosage of less than 2%, including infants who were uridine diphosphate-glucuronosyltransferase 1A1 (UGT1A) poor metabolizers. This dosage was predicted to result in a peak serum level in breastfed neonatal plasma of 55.1 mcg/L (range 21 to 125 mcg/L).

In a retrospective study in a German hospital, two mothers who were receiving dolutegravir 50 mg once daily breastfed their infants. Infant serum concentrations obtained at unspecified times in one of the infants was 5780 mcg/L at 4 months of age with exclusive breastfeeding and 4040 mcg/L at 6 months of age with partial breastfeeding. The second infant who was partially breastfed had serum levels of <50 mcg/L at 1 and 4 months of age.

Women in a 9-country clinical trial were randomly assigned to receive either dolutegravir 50 mg once daily with a fixed-dose combination of emtricitabine 200 mcg plus tenofovir alafenamide 25 mg once daily, or dolutegravir 50 mg once daily with a fixed-dose combination of emtricitabine 200 mg plus tenofovir disoproxil fumarate 300 mg once daily. One infant blood sample was obtained at 6 weeks postpartum (n = 180). The median concentration in infant plasma was 69 mcg/L (IQR 41 to 9569 mcg/L).

What has been seen in breastfed infants

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.

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.

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.

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.

A study in rural Tanzania compared HIV-uninfected children born to women living with HIV on dolutegravir- and efavirenz-based antiretroviral regimens. Exclusive breastfeeding was reported in 945 of 1002 (94%) infants shortly after birth, and 340 of 579 (59%) at 6 months. At 12 months, 436 of 488 (89%) infants had complementary feeding. The study found no evidence of a difference in length-for-age or weight-for-length z-scores through 18 months of follow-up between the groups. HIV-exposed, but uninfected, infants have poorer growth outcomes compared to children not exposed to HIV. Although dolutegravir causes weight gain in adults it appears to have limited impact on birthweight and growth in infants from mothers on dolutegravir-based regimens during pregnancy and breastfeeding compared to regimens not containing dolutegravir.

Effects on milk supply

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