Pregnancy & Lactation : הריון/הנקה

4.6   Fertility, pregnancy and lactation
Pregnancy

There are no adequate or well-controlled clinical studies in pregnant women using ciclosporin. There is a moderate amount of data on the use of ciclosporin in pregnant patients from post-marketing experience, including transplantation registries and published literature with majority of cases available from transplant recipients. Pregnant women receiving immunosuppressive therapies after transplantation, including ciclosporin and ciclosporin-containing regimens, are at risk of premature delivery (<37 weeks).


Embryo-foetal developmental (EFD) studies in rats and rabbits with ciclosporin have shown embryofoetal toxicity at dose levels below the maximum recommended human dose (MRHD) based on body surface area (BSA) (see section 5.3).

Sandimmun Neoral should not be used during pregnancy unless the potential benefit to the mother outweighs the potential risk to the foetus. The ethanol content of the Sandimmun Neoral formulations should also be taken into account in pregnant women (see section 4.4).

Published data from the National Transplantation Pregnancy Registry (NTPR), described pregnancy outcomes in female kidney (482), liver (97), and heart (43) transplant recipients receiving ciclosporin.
The data indicated successful pregnancies with a live birth rate of 76% and 76.9%, and 64% in kidney, liver, and heart transplant recipients, respectively. Premature delivery (< 37 weeks) was reported in 52%, 35%, and 35% of kidney, liver, and heart transplant recipients, respectively.

The rates of miscarriages and major birth defects were reported to be comparable to the rates observed in the general population. A potential direct effect of ciclosporin on maternal hypertension, preeclampsia, infections or diabetes could not be excluded given the limitations inherent to registries and post-marketing safety reporting.

A limited number of observations in children exposed to ciclosporin in utero are available, up to an age of approximately 7 years. Renal function and blood pressure in these children were normal.

Breast-feeding
Ciclosporin is transferred into breast milk. Mothers receiving treatment with Sandimmun Neoral should not breast-feed because of the potential of Sandimmun Neoral to cause serious adverse drug reactions in breast-fed newborns/infants. A decision should be made whether to abstain from breast-feeding or to abstain from using the medicinal drug, taking into account the benefit of breastfeeding for the newborn/infant and the importance of the medicinal product to the mother.

Limited data showed that the milk to maternal blood concentration ratio of ciclosporin was in the range of 0.17 to 1.4. Based on the infant milk intake, the highest estimated ciclosporin dose ingested by fully breastfed infant was approximately 2% of maternal weight-adjusted dose.

The ethanol content of the Sandimmun Neoral formulations should also be taken into account in women who are breast-feeding (see section 4.4).

Fertility
There is limited data on the effect of Sandimmun Neoral on human fertility (see section 5.3). No adverse effects on fertility were observed in male and female rats up to 15 mg/kg/day (below MRHD based on BSA) (see section 5.3).