ALZIM LP

Epilepsies

In adults

· either as monotherapy;

· or in association with another anti-epileptic treatment;

· treatment of partial epilepsies with or without secondary generalization;

· treatment of generalized epilepsies: tonic-clonic seizures.

In children

· either as monotherapy;

· or in association with another anti-epileptic treatment;

· treatment of partial epilepsies with or without secondary generalization;

· treatment of generalized epilepsies: tonic-clonic seizures.

Psychiatry

· Prevention of relapses in the context of bipolar disorders, notably in patients presenting with relative resistance, contraindications or intolerance to lithium.

· Treatment of manic or hypomanic states.

Pain

· Treatment of trigeminal and glossopharyngeal neuralgias.

· Treatment of neuropathic pain in adults.

Pregnancy

Risk related to antiepileptic drugs in general

Specialized medical advice regarding the potential risks to the fetus caused by both epileptic seizures and antiepileptic treatment should be given to all women of childbearing potential taking antiepileptic treatment, particularly to women planning a pregnancy and to pregnant women.

Abrupt discontinuation of antiepileptic drug treatment should be avoided as it may lead to seizures that could have serious consequences for the woman and the unborn child.

Monotherapy should be preferred for the treatment of epilepsy during pregnancy, as far as possible. Indeed, polytherapy with antiepileptic drugs may be associated with a higher risk of congenital malformations than monotherapy; this risk varies according to the co-administered antiepileptic drugs.

Risks related to carbamazepine

In humans, carbamazepine crosses the placenta. Prenatal exposure to carbamazepine may increase the risks of congenital malformations and other adverse developmental effects. In humans, exposure to carbamazepine during pregnancy is associated with a frequency of major congenital malformations 2 to 3 times higher than that of the general population, which is 2 to 3 %. The most frequently encountered malformations are neural tube defects (spina bifida), craniofacial defects (including cleft lip/palate), cardiovascular malformations, hypospadias, digital hypoplasia, microcephaly and other anomalies involving different organs have been reported in children of women treated with carbamazepine during pregnancy. Data from an observational study based on population registries conducted in the Nordic countries suggest an increased risk of children born small for gestational age (SGA; defined as a birth weight below the 10th percentile for sex and gestational age) after prenatal exposure to carbamazepine. The risk of SGA in children of epileptic women treated with carbamazepine was 12.8 %, compared to 10.9 % in children of epileptic women not receiving antiepileptic treatment. Specialized prenatal monitoring for these malformations and growth retardation is recommended.

Neurodevelopmental disorders have been reported in children born to epileptic women taking carbamazepine alone or in combination with other antiepileptic drugs during pregnancy. Studies regarding the risk of neurodevelopmental disorders in children exposed to carbamazepine during pregnancy are contradictory and do not allow a risk to be excluded.

Carbamazepine should not be used during pregnancy, unless the benefit is judged to outweigh the risks after a careful examination of available therapeutic alternatives. The woman must be fully informed and understand the risks related to taking carbamazepine during pregnancy.

Available data suggest that the risk of malformation associated with carbamazepine may be dose-dependent. If, based on a careful assessment of risks and benefits, no therapeutic alternative is appropriate, and treatment with carbamazepine is continued, monotherapy and the lowest effective dose of carbamazepine should be used and monitoring of plasma levels is recommended. The plasma concentration could be maintained in the lower part of the therapeutic range from 4 to 12 microgrammes/mL, provided that seizure control is maintained.

It has been reported that some antiepileptic drugs, such as carbamazepine, decrease serum folate levels. This deficiency may contribute to the increased incidence of congenital malformations in the offspring of treated epileptic women. Folic acid supplementation is recommended before and during pregnancy. In order to prevent bleeding disorders in the offspring, it has also been recommended to administer vitamin K1 to the mother during the last weeks of pregnancy, as well as to the newborn.

If a woman is planning a pregnancy, every effort must be made to switch to an appropriate alternative treatment before conception and before discontinuation of contraception. If a woman becomes pregnant while taking carbamazepine, she must be referred to a specialist to re-evaluate the treatment with carbamazepine and to consider therapeutic alternatives.

Children and female adolescents, women of childbearing potential

Carbamazepine must not be used in women of childbearing potential unless the potential benefit is judged to be greater than the risks after a careful examination of available therapeutic alternatives. The woman must be fully informed and understand the risk of potential harm to the fetus if carbamazepine is taken during pregnancy and, consequently, the importance of planning a pregnancy. A pregnancy test in women of childbearing potential should be considered before starting treatment with carbamazepine.

At the initiation of treatment, and once a year, the physician ensures that treatment with carbamazepine is the best option for the patient and signs with her a shared information form.

Women of childbearing potential must use effective contraception during treatment and for two weeks after stopping treatment. Due to the enzyme-inducing effect of carbamazepine, treatment with TEGRETOL may lead to failure of hormonal contraceptives (see section 4.5).

Consequently, women of childbearing potential must be advised on the use of other effective contraceptive methods. At least one effective method of contraception (such as an intrauterine device) or two complementary forms of contraception, including a mechanical method of contraception (for example a condom), must be used. Individual conditions must be evaluated in each case, involving the patient in the discussion, when choosing the method of contraception.

Prescribers must ensure that parents / guardians of female children and adolescents treated with carbamazépine understand the need to contact a specialist as soon as the first menstruation occurs (menarche). The patient and her parents / guardians must then receive complete information on the risks associated with in utero exposure to carbamazépine and on the need to use highly effective contraception as soon as necessary. The need to continue treatment with carbamazépine must be re-evaluated and therapeutic alternatives must also be considered.

Before delivery / In the newborn:

Enzyme-inducing antiepileptic drugs can sometimes cause in the newborn of a treated mother:

· a hemorrhagic syndrome that may occur during delivery or in the first days of life. Prevention with oral vitamine K1 in the mother in the month preceding delivery and administration of parenteral vitamine K1 (IM or slow IV) at birth to the newborn seem effective. A normal hemostasis assessment in the mother does not rule out hemostasis abnormalities in the newborn.

· disturbances of phosphocalcic metabolism and bone mineralization, which supplementation of the mother with vitamine D during the 3rd trimester seems to be able to prevent.

Postnatal follow-up / In the child: in case of exposure during pregnancy, close monitoring of the child's neurobehavioral development must be established and appropriate care must be implemented as soon as possible if necessary.

Breastfeeding

Breastfeeding is not recommended due to the significant passage of carbamazépine into breast milk and the possibility of the occurrence of hepatic disorders in breastfed newborns.

Fertility

Not applicable.

TEGRETOL L.P. 200 mg, scored film-coated prolonged-release tablet has a moderate influence on the ability to drive vehicles and use machines.

Attention is drawn, particularly in vehicle drivers and machine users, to the risks associated with epileptic seizures, as well as the following adverse effects: dizziness, drowsiness, sensations of vertigo, ataxia, accommodation disorders, diplopia and blurred vision, associated with the use of carbamazepine.