(Last updated: August 6, 2015; last reviewed: August 6, 2015)
Dolutegravir was not genotoxic or mutagenic in vitro. No carcinogenicity was detected in 2-year long-term studies in mice at exposures up to 14-fold higher than that achieved with human systemic exposure at the recommended dose, or in rats at exposures up to 10-fold higher in males and 15-fold higher in females than human exposure at the recommended dose.
Dolutegravir did not affect fertility in male and female rats and rabbits at exposures approximately 27-fold higher than human clinical exposure, based on area under the curve, at the recommended dose.
Animal Teratogenicity/Developmental Toxicity
Studies in rats and rabbits have shown no evidence of developmental toxicity, teratogenicity or effect on reproductive function with dolutegravir.
Placental and Breast Milk Passage
Studies in rats have demonstrated that dolutegravir crosses the placenta in animal studies and is excreted into breast milk in rats.
Human Studies in Pregnancy
No studies of dolutegravir use in human pregnancy have been reported. No human data on placental passage or breast milk excretion are available.
|Formulation||Dosing Recommendations||Use in Pregnancy|
|Standard Adult Dose
ARV-Naive or ARV-Experienced but Integrase Inhibitor-Naive Patients
|Unknown placental transfer to fetus.
Insufficient data to assess for teratogenicity in humans. No evidence of teratogenicity in mice, rats, or rabbits.
a Individual antiretroviral drug dosages may need to be adjusted in renal or hepatic insufficiency (for details, see Adult Guidelines, Appendix B, Table 7).
Key to Abbreviations: 3TC = lamivudine; ABC = abacavir; ARV = antiretroviral; DTG = dolutegravir EFV = efavirenz; FPV/r = fosamprenavir/ritonavir; PK = pharmacokinetic; TPV/r = tipranavir/ritonavir