Acriptega Use In Pregnancy & Lactation

Pregnancy: Lamivudine/Tenofovir Disoproxil Fumarate: Animal studies do not indicate direct or indirect harmful effects of tenofovir disoproxil fumarate with respect to pregnancy, foetal development, parturition or postnatal development (see Pharmacology: Toxicology under Actions). In humans, the safety of tenofovir in pregnancy has not been fully established. Sufficient numbers of first trimester exposures have been monitored, however, to detect at least a twofold increase in the risk of overall birth defects. No increase in birth defects was seen (www.apregistry.com).
No increased risk of birth defects has been reported for lamivudine (www.apregistry.com). However, risks to the fetus cannot be ruled out.
Dolutegravir: Risk Summary: Preliminary data from an observational study has identified a possible increased risk of neural tube defects when Dolutegravir is administered at the time of conception compared with non-dolutegravir-containing antiretroviral regimens. As defects related to closure of the neural tube occur from conception through the first 6 weeks of gestation, embryos exposed to dolutegravir from the time of conception through the first 6 weeks of gestation are at potential risk. In addition, 2 of the 4 birth defects (encephalocele and iniencephaly), which have been observed with dolutegravir use, although often termed neural tube defects, may occur post-neural tube closure, the time period of which may be later than 6 weeks of gestation, but within the first trimester. Due to the limited understanding of the types of reported neural tube defects associated with dolutegravir use and because the date of conception may not be determined with precision, avoid use of Dolutegravir at the time of conception through the first trimester of pregnancy. No neural tube defects have been reported in infants born to mothers who have started Dolutegravir after the first trimester of pregnancy (see Data).
If there are plans to become pregnant or if pregnancy is confirmed while on Dolutegravir during the first trimester, if possible, switch to an alternative regimen. Advise pregnant adolescents and adults of the potential risk to the embryo exposed to Dolutegravir from the time of conception through the first trimester of pregnancy.
There are insufficient human data on the use of Dolutegravir during pregnancy to definitively assess a drug-associated risk for birth defects and miscarriage. The background risk for major birth defects for the indicated population is unknown.
In animal reproduction studies, no evidence of adverse developmental outcomes was observed with dolutegravir at systemic exposures (AUC) less than (rabbits) and approximately 27 times (rats) the exposure in humans at the maximum recommended human dose (MRHD) of Dolutegravir (see Data).
Human Data: As of May 2018, in an ongoing birth outcome surveillance study in Botswana, there have been 4 cases of neural tube defects reported out of 426 births (0.94%) to mothers who were exposed to dolutegravir-containing regimens at the time of conception. In comparison, the neural tube defect prevalence rates were 0.12% (14/11,300) in the non-dolutegravir arm and 0.09% (61/66,057) in the HIV-uninfected arm. Four cases reported with dolutegravir included one case each of encephalocele, anencephaly, myelomeningocele, and iniencephaly. No infant born to a woman who started dolutegravir during pregnancy had a neural tube defect (n = 2,812).
Data analyzed to date from other sources including the APR, clinical trials, and post marketing data are insufficient to address the risk of neural tube defects with dolutegravir.
Animal Data: Dolutegravir was administered orally at up to 1,000 mg per kg daily to pregnant rats and rabbits on gestation Days 6 to 17 and 6 to 18, respectively, and to rats on gestation Day 6 to lactation/post-partum Day 20. No adverse effects on embryo-fetal (rats and rabbits) or pre/post-natal (rats) development were observed at up to the highest dose tested.). During organogenesis, systemic exposures (AUC) to dolutegravir in rabbits were less than the exposure in humans at the MRHD and in rats were approximately 27 times the exposure in humans at the MRHD. In the rat pre/post-natal development study, decreased body weight of the developing offspring was observed during lactation at a maternally toxic dose (approximately 27 times human exposure at the MRHD). ).
Breast-feeding: Lamivudine/Tenofovir Disoproxil Fumarate: In animal studies it has been shown that tenofovir is excreted into milk. It is not known whether tenofovir is excreted in human milk. Lamivudine is excreted into the breast milk of lactating mothers.
Current recommendations on HIV and breastfeeding (e.g. those from the WHO) should be consulted before advising patients on this matter. Preferred options may vary depending on the local circumstances.
Dolutegravir: Risk Summary: It is not known whether Dolutegravir is present in human breast milk, affects human milk production, or has effects on the breastfed infant. When administered to lactating rats, dolutegravir was present in milk (see Data).
Because of the potential for (1) HIV-1 transmission (in HIV-negative infants), (2) developing viral resistance (in HIV-positive infants), and (3) adverse reactions in a breastfed infant similar to those seen in adults, instruct mothers not to breastfeed if they are receiving Dolutegravir.
Data: Animal Data: Dolutegravir was the primary drug-related component excreted into the milk of lactating rats following a single oral dose of 50 mg per kg on lactation Day 10, with milk concentrations of up to approximately 1.3 times that of maternal plasma concentrations observed 8 hours postdose.
Fertility: Dolutegravir: Females and Males of Reproductive Potential: Pregnancy Testing: Perform pregnancy testing in adolescents and adults of childbearing potential before initiation of Dolutegravir.
Contraception: Adolescents and adults of childbearing potential should avoid use of Dolutegravir at the time of conception through the first trimester of pregnancy because of the potential risk of neural tube defects. Advise adolescents and adults of childbearing potential who are taking Dolutegravir to consistently use effective contraception.