Pregnancy & Lactation : הריון/הנקה

4.6    Fertility, pregnancy and lactation

Pregnancy

As a general rule, when deciding to use antiretroviral agents for the treatment of HIV infection in pregnant women and consequently for reducing the risk of HIV vertical transmission to the newborn, the animal data as well as the clinical experience in pregnant women should be taken into account.

Animal studies with abacavir have shown toxicity to the developing embryo and foetus in rats, but not in rabbits. Animal studies with lamivudine showed an increase in early embryonic deaths in rabbits but not in rats. (see section 5.3). The active ingredients of ABACAVIR LAMIVUDINE TARO may inhibit cellular DNA replication and abacavir has been shown to be carcinogenic in animal models (see section 5.3). The clinical relevance of these findings is unknown. Placental transfer of abacavir and lamivudine has been shown to occur in humans.
In pregnant women treated with abacavir, more than 800 outcomes after first trimester exposure and more than 1000 outcomes after second and third trimester exposure indicate no malformative and foetal/neonatal effect. In pregnant women treated with lamivudine, more than 1000 outcomes from first trimester and more than 1000 outcomes from second and third trimester exposure indicate no malformative and foeto/neonatal effect. There are no data on the use of ABACAVIR LAMIVUDINE TARO in pregnancy, however the malformative risk is unlikely in humans based on those data.

For patients co-infected with hepatitis who are being treated with a lamivudine containing medicinal product such as ABACAVIR LAMIVUDINE TARO and subsequently become pregnant, consideration should be given to the possibility of a recurrence of hepatitis on discontinuation of lamivudine.

Mitochondrial dysfunction
Nucleoside and nucleotide analogues have been demonstrated in vitro and in vivo to cause a variable degree of mitochondrial damage. There have been reports of mitochondrial dysfunction in HIV- negative infants exposed in utero and/or post-natally to nucleoside analogues (see section 4.4).

Breast-feeding

Abacavir and its metabolites are excreted into the milk of lactating rats. Abacavir is also excreted into human milk.

Based on more than 200 mother/child pairs treated for HIV, serum concentrations of lamivudine in breastfed infants of mothers treated for HIV are very low (<4% of maternal serum concentrations) and progressively decrease to undetectable levels when breastfed infants reach 24 weeks of age. There are no data available on the safety of abacavir and lamivudine when administered to babies less than three months old.

It is recommended that women living with HIV do not breast-feed their infants in order to avoid transmission of HIV.

Fertility

Studies in animals showed that neither abacavir nor lamivudine had any effect on fertility (see section 5.3).