Epilim/Epilim Chrono Warnings

Pancreatitis: Pancreatitis, which may be severe and result in fatalities, has been very rarely reported. Patients experiencing nausea, vomiting or acute abdominal pain should have a prompt medical evaluation (including measurement of serum amylase). Young children are at particular risk; this risk decreases with increasing age. Severe seizures and severe neurological impairment with combination of anticonvulsant therapy may be risk factors. Hepatic failure with pancreatitis increases the risk of fatal outcome. In case of pancreatitis, Epilim should be discontinued.
Female children, Women of childbearing potential, Pregnancy: Pregnancy Prevention Programme: Valproate has a high teratogenic potential and children exposed in utero to valproate have a high risk for congenital malformations and neurodevelopmental disorders.
Epilim is contraindicated in the following situations: In pregnancy unless there is no suitable alternative treatment for epilepsy indication; In pregnancy for bipolar disorder indication; In women of childbearing potential unless conditions as follows are fulfilled.
Conditions of Pregnancy Prevention Programme: The prescriber must ensure that: Individual circumstances should be evaluated in each case. Involving the patient in the discussion to guarantee her engagement, discuss therapeutic options and ensure her understanding of the risks and the measures needed to minimise the risks.
The potential for pregnancy is assessed for all female patients.
The patient has understood and acknowledged the risks of congenital malformations and neurodevelopmental disorders including the magnitude of these risks for children exposed to valproate in utero.
The patient understands the need to undergo pregnancy testing prior to initiation of treatment and during treatment, as needed.
The patient is counselled regarding contraception, and that the patient is capable of complying with the need to use effective contraception (for further details refer to contraception as follows), without interruption during the entire duration of treatment with valproate.
The patient understands the need for regular (at least annual) review of treatment by a specialist experienced in the management of epilepsy.
The patient understands the need to consult her physician as soon as she is planning pregnancy to ensure timely discussion and switching to alternative treatment options prior to conception and before contraception is discontinued.
The patient understands the need to urgently consult her physician in case of pregnancy.
The patient has received the Patient Guide.
The patient has acknowledged that she has understood the hazards and necessary precautions associated with valproate use (Annual Risk Acknowledgement Form).
These conditions also concern women who are not currently sexually active unless the prescriber considers that there are compelling reasons to indicate that there is no risk of pregnancy.
Female children: The prescriber must ensure that: The parents/caregivers of female children understand the need to contact the specialist once the female child using valproate experiences menarche.
The parents/caregivers of female children who have experienced menarche are provided with comprehensive information about the risks of congenital malformations and neurodevelopmental disorders including the magnitude of these risks for children exposed to valproate in utero.
In patients who have experienced menarche, the prescribing specialist must annually reassess the need for valproate therapy and consider alternative treatment options. If valproate is the only suitable treatment, the need for using effective contraception and all other conditions of the pregnancy prevention programme should be discussed. Every effort should be made by the specialist to switch female children to alternative treatment before they reach adulthood.
Pregnancy test: Pregnancy must be excluded before the start of treatment with valproate. Treatment with valproate must not be initiated in women of childbearing potential without a negative pregnancy test (plasma pregnancy test) result, confirmed by a healthcare provider, to rule out unintended use in pregnancy.
Contraception: Women of childbearing potential who are prescribed valproate must use effective contraception without interruption during the entire duration of treatment with valproate. These patients must be provided with comprehensive information on pregnancy prevention and should be referred for contraceptive advice if they are not using effective contraception. At least one effective method of contraception (preferably a user independent form such as an intra-uterine device or implant) or two complementary forms of contraception including a barrier method should be used. Individual circumstances should be evaluated in each case when choosing the contraception method, involving the patient in the discussion to guarantee her engagement and compliance with the chosen measures. Even if she has amenorrhea she must follow all the advice on effective contraception.
Oestrogen-containing products: Concomitant use with oestrogen-containing products, including oestrogen-containing hormonal contraceptives, may potentially result in decreased valproate efficacy. Prescribers should monitor clinical response (seizure control) when initiating or discontinuing oestrogen-containing products.
On the opposite, valproate does not reduce efficacy of hormonal contraceptives.
Annual treatment reviews by a specialist: The specialist should review at least annually whether valproate is the most suitable treatment for the patient. The specialist should discuss the Annual Risk Acknowledgement Form at initiation and during each annual review and ensure that the patient has understood its content.
Pregnancy planning: If a woman is planning to become pregnant, a specialist experienced in the management of epilepsy must reassess valproate therapy and consider alternative treatment options. Every effort should be made to switch to appropriate alternative treatment prior to conception and before contraception is discontinued. If switching is not possible, the woman should receive further counselling regarding the risks of valproate for the unborn child to support her informed decision-making regarding family planning.
In case of pregnancy: If a woman using valproate becomes pregnant, she must be immediately referred to a specialist to re-evaluate treatment with valproate and consider alternative treatment options. Patients with valproate-exposed pregnancy and their partners should be referred to a specialist experienced in prenatal medicine for evaluation and counselling regarding the exposed pregnancy.
Pharmacists must ensure that: The Patient Card is provided with every valproate dispensation and that patients understand its content.
Patients are advised not to stop valproate medication and to immediately contact a specialist in case of planned or suspected pregnancy.
Educational materials: In order to assist healthcare professionals and patients in avoiding exposure to valproate during pregnancy, the Marketing Authorisation Holder has provided educational materials to reinforce the warnings, provide guidance regarding the use of valproate in women of childbearing potential and provide details of the Pregnancy Prevention Programme. A Patient Guide and Patient Card should be provided to all women of childbearing potential using valproate.
An Annual Risk Acknowledgement Form needs to be used at the time of treatment initiation and during each annual review of valproate treatment by the specialist.
Valproate therapy should only be continued after a reassessment of the benefits and risks of the treatment with valproate for the patient by a specialist experienced in the management of epilepsy.