Pregnancy & Lactation : הריון/הנקה

4.6     Fertility, pregnancy and lactation

Contraception in males and females
Barrier contraception should always be used in combination with other methods of contraception (for example, oral or other hormonal contraceptives, see section 4.5). Because of the long half-life of efavirenz, use of adequate contraceptive measures for 12 weeks after discontinuation of efavirenz is recommended.

Pregnancy
Efavirenz should not be used during pregnancy, unless the patient’s clinical condition requires such treatment. Women of childbearing potential should undergo pregnancy testing before initiation of efavirenz (see section 5.3).

There have been seven retrospective reports of findings consistent with neural tube defects, including meningomyelocele, all in mothers exposed to efavirenz-containing regimens (excluding any efavirenz containing fixed-dose combination tablets) in the first trimester. Two additional cases (1 prospective and 1 retrospective) including events consistent with neural tube defects have been reported with a fixed-dose combination tablet containing efavirenz, emtricitabine, and tenofovir disoproxil. A causal relationship of these events to the use of efavirenz has not been established, and the denominator is unknown. As neural tube defects occur within the first 4 weeks of foetal development (at which time neural tubes are sealed), this potential risk would concern women exposed to efavirenz during the first trimester of pregnancy.
As of July 2013, the Antiretroviral Pregnancy Registry (APR) has received prospective reports of 904 pregnancies with first trimester exposure to efavirenz-containing regimens, resulting in 766 live births. One child was reported to have a neural tube defect, and the frequency and pattern of other birth defects were similar to those seen in children exposed to non-efavirenz-containing regimens, as well as those in HIV negative controls. The incidence of neural tube defects in the general population ranges from 0.5-1 case per 1,000 live births.
Malformations have been observed in foetuses from efavirenz-treated monkeys (see section 5.3).

Breast-feeding

Efavirenz has been shown to be excreted in human milk. There is insufficient information on the effects of efavirenz in newborns/infants. Risk to the infant can not be excluded. Breast-feeding should be discontinued during treatment with efavirenz. It is recommended that HIV infected women do not breast feed their infants under any circumstances in order to avoid transmission of HIV.

Fertility
The effect of efavirenz on male and female fertility in rats has only been evaluated at doses that achieved systemic drug exposures equivalent to or below those achieved in humans given recommended doses of efavirenz. In these studies, efavirenz did not impair mating or fertility of male or female rats (doses up to 100 mg/kg/bid), and did not affect sperm or offspring of treated male rats (doses up to 200 mg/bid). The reproductive performance of offspring born to female rats given efavirenz was not affected.