Pregnancy & Lactation : הריון/הנקה

4.6     Fertility, pregnancy and lactation

Women of childbearing potential
Women of childbearing potential should use appropriate contraceptive measures during treatment (see section 4.3).

Pregnancy

Atherosclerosis is a chronic process, and ordinarily discontinuation of lipid-lowering drugs during pregnancy should have little impact on the long-term risk associated with primary hypercholesterolaemia.

ATOZET
ATOZET is contraindicated during pregnancy (see section 4.3). No clinical data are available on the use of ATOZET during pregnancy. ATOZET should not be used in women who are pregnant, trying to become pregnant or suspect they are pregnant. Treatment with ATOZET should be suspended for the duration of pregnancy or until it has been determined that the woman is not pregnant (see section 4.3).

The co-administration of ezetimibe and atorvastatin in pregnant rats indicated that there was a test article-related increase in the skeletal variation “reduced ossification of the sternebrae” in the high dose ezetimibe/atorvastatin group. This may be related to the observed decrease in foetal body weights. In pregnant rabbits a low incidence of skeletal deformities (fused sternebrae, fused caudal vertebrae and asymmetrical sternebrae variation) were observed.

Atorvastatin
Safety in pregnant women has not been established. No controlled clinical trials with atorvastatin have been conducted in pregnant women. Rare reports of congenital anomalies following intrauterine exposure to HMG-CoA reductase inhibitors have been received. Animal studies have shown toxicity to reproduction (see section 5.3). Maternal treatment with atorvastatin may reduce the foetal levels of mevalonate which is a precursor of cholesterol biosynthesis.

Ezetimibe
No clinical data are available on the use of ezetimibe during pregnancy. Animal studies on the use of ezetimibe in monotherapy have shown no evidence of direct or indirect harmful effects on pregnancy, embryofoetal development, birth or postnatal development (see section 5.3).

Breast-feeding
ATOZET is contraindicated during breast-feeding. Because of the potential for serious adverse reactions, women taking ATOZET should not breast-feed their infants. Studies on rats have shown that ezetimibe is secreted into breast milk. In rats, plasma concentrations of atorvastatin and its active metabolites are similar to those in milk. It is not known if the active components of ATOZET are secreted into human breast milk (see section 4.3).

Fertility
No fertility studies were conducted with ATOZET.

Atorvastatin
In animal studies atorvastatin had no effect on male or female fertility.
Ezetimibe
Ezetimibe had no effect on the fertility of male or female rats.