TRILEPTAL

OXCARBAZEPINE SANDOZ is indicated in the treatment of partial epileptic seizures with or without secondary generalization.

OXCARBAZEPINE SANDOZ is indicated as monotherapy or in association with another anti-epileptic treatment in adults and children from 6 years of age.

Women of childbearing potential and contraceptive measures

Oxcarbazepine may lead to ineffectiveness of contraceptives containing ethinylestradiol (EE) and levonorgestrel (LNG) (see sections 4.4 and 4.5). Women of childbearing potential should be informed to use a highly effective method of contraception (preferably non-hormonal, for example an intrauterine implant) during treatment with oxcarbazepine.

Pregnancy

Risks related to epilepsy and anti-epileptics in general

In women treated for epilepsy, an increase in the number of malformations has been observed mainly in cases of polytherapy, particularly if it includes valproate.

Furthermore, an effective anti-epileptic drug should not be discontinued because worsening of the disease can be harmful to both the mother and the foetus.

Risks related to oxcarbazepine

There is a moderate amount of data in pregnant women (300-1000 from pregnancy). However, data concerning congenital malformations related to oxcarbazepine are limited. Available data have not shown an increase in the overall rate of malformations with oxcarbazepine compared to the rate observed in the general population (2-3 %). Nevertheless, the relevant data were still limited, a moderate teratogenic risk cannot be completely excluded. The results of studies concerning the risk of neurodevelopmental disorders in children exposed to oxcarbazepine during pregnancy are contradictory and a risk cannot be excluded. Data from an observational registry study conducted in the Nordic countries suggest an increased risk of small weight for gestational age (PAG children, defined as having a birth weight below the 10th percentile of normal weight for their sex and gestational age) in children having prenatal exposure to oxcarbazepine. The risk of PAG in children born to women with epilepsy receiving oxcarbazepine was 15.2 %, compared to a rate of 10.9 % in children born to women with epilepsy not taking anticonvulsant drugs.

Given these data:

· in case of pregnancy or if pregnancy is planned: the use of the product should be carefully reassessed. The minimum effective dose will be prescribed and preferably monotherapy will be used at least during the first trimester of pregnancy,

· during pregnancy, an effective anti-epileptic treatment with oxcarbazepine should not be interrupted, as the worsening of the disease is harmful to both the mother and the foetus.

Monitoring and prevention

Some anti-epileptic drugs may contribute to folate deficiency, a possible cause of foetal abnormalities. Folate supplementation is recommended before and during pregnancy. Given that the efficacy of this measure has not been demonstrated, specific prenatal diagnosis should be offered to women whether they are supplemented with folate or not.

Data from a limited number of women show that the plasma level of the active metabolite of oxcarbazepine, the 10-monohydroxy derivative (DMH), may progressively decrease during pregnancy. It is recommended to closely monitor the clinical response in women receiving oxcarbazepine during pregnancy to ensure that seizure control is maintained. Plasma measurement of DMH may be necessary. If doses have been increased during pregnancy, plasma measurement of DMH in the postpartum period may be necessary for monitoring.

In the newborn

Hemorrhagic syndromes have been reported in newborns with hepatic inducing anti-epileptic drugs. As a precautionary measure, vitamin K1 should be administered preventively during the last weeks of pregnancy as well as to the newborn.

Breastfeeding

Oxcarbazepine and its active metabolite (DMH) are present in breast milk. Limited data indicate that plasma concentrations of DMH in breastfed infants are 0,2 - 0,8 μg/mL, which corresponds to a maximum of 5 % of the maternal plasma concentration of DMH. Although exposure appears low, a risk to the infant cannot be excluded. Therefore, the decision to breastfeed or not during oxcarbazepine treatment should take into account both the benefits of breastfeeding and the potential risk of side effects in the infant. If breastfed, the infant should be monitored for any adverse effect such as somnolence and low weight gain.

Fertility

No clinical data relating to fertility are available.

In rats, oxcarbazepine showed no effect on fertility. Effects on reproductive parameters were observed in female rats at DMH doses comparable to doses in humans (see section 5.3).