TRILEPTAL

OXCARBAZEPINE VIATRIS is indicated for the treatment of partial epileptic seizures with or without subsequently generalized tonic-clonic seizures.

OXCARBAZEPINE VIATRIS 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 a loss of the therapeutic effect of oral contraceptive medicines containing ethinylestradiol (EE) and levonorgestrel (LNG) (see sections 4.4 and 4.5). Women of childbearing potential should be advised to use a highly effective contraceptive method (preferably non-hormonal; e.g., an intrauterine device) during treatment with oxcarbazepine.

Pregnancy

Risk related to epilepsy and antiepileptics in general

In the treated population, an increase in the number of malformations has been observed with polytherapy; particularly when these polytherapies included valproate.

Furthermore, effective antiepileptic treatment must not be interrupted, as the worsening of the disease is detrimental to both the mother and the fetus.

Risk related to oxcarbazepine

There is a moderate amount of data in pregnant women (300 to 1 000 pregnancy outcomes). However, data regarding the link 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, with this amount of data, a moderate teratogenic risk cannot be completely excluded. Results of studies regarding the risk of neurodevelopmental disorders in children exposed to oxcarbazepine during pregnancy are conflicting and a risk cannot be excluded.

Given these data

· If a woman taking oxcarbazepine becomes pregnant or is planning to become pregnant, the use of the product should be carefully re-evaluated. The minimum effective dose will be prescribed and preferably monotherapy will be used at least during the first trimester of pregnancy;

· During pregnancy, effective antiepileptic treatment with oxcarbazepine must not be interrupted, as the worsening of the disease is detrimental to both the mother and the fetus.

Data from an observational registry study conducted in the Nordic countries suggest an increased risk of small for gestational age (SGA infants, defined as having a birth weight below the 10th percentile of the normal weight for their sex and gestational age) in children with prenatal exposure to oxcarbazepine.

The risk of SGA in children born to epileptic women receiving oxcarbazepine was 15.2 %, compared to a rate of 10.9 % in children born to epileptic women not taking anticonvulsant medicines.

Monitoring and prevention

Some antiepileptic medicines may contribute to folic acid deficiency, a possible cause of fetal abnormalities. Folic acid supplementation is recommended before and during pregnancy. Given that the effectiveness of this measure is not proven, a specific prenatal diagnosis should be offered even to women supplemented with folic acid.

Data from a limited number of women show that the plasma level of the active metabolite of oxcarbazepine, the 10-monohydroxy derivative (MHD), may decrease gradually 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 level monitoring of MHD may be necessary. If doses have been increased during pregnancy, plasma level monitoring of MHD in the postpartum period may be necessary for surveillance.

In the newborn

Hemorrhagic syndromes have been reported in newborns with hepatic enzyme-inducing antiepileptic 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 human 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 DMH concentration. Although exposure appears to be low, a risk to the infant cannot be excluded. Therefore, the decision whether or not to breastfeed during oxcarbazepine treatment must 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 effects such as somnolence and poor weight gain.

Fertility

There are no data relating to fertility in humans. In rats, oxcarbazepine had no effects on fertility. Effects on reproductive parameters were observed in female rats with DMH at doses comparable to those used in humans (see section 5.3).