Epilepsy and Women Quick Reference Guide

Transcription

1 Quality in Practice Committee Epilepsy and Women Quick Reference Guide AUTHORS Dr Niamh Moran and Dr Toiréas Moriarty EDITED 2016 Dr Miriam Daly Based on original document Guidelines on the Management of Epilepsy in General Practice, Dr Ray O Connor, 2002

2 DISCLAIMER AND WAIVER OF LIABILITY Whilst every effort has been made by the Quality in Practice Committee to ensure the accuracy of the information and material contained in this document, errors or omissions may occur in the content. This guidance represents the view of the ICGP which was arrived at after careful consideration of the evidence available at time of publication. This quality of care may be dependent on the appropriate allocation of resources to practices involved in its delivery. Resource allocation by the state is variable depending on geographical location and individual practice circumstances. There are constraints in following the guidelines where the resources are not available to action certain aspects of the guidelines. Therefore, individual healthcare professionals will have to decide what is achievable within their resources particularly for vulnerable patient groups. The guide does not however override the individual responsibility of healthcare professionals to make decisions appropriate to the circumstances of individual patients in consultation with the patient and/or guardian or carer. Guidelines are not policy documents. Feedback from local faculty and individual members on ease of implementation of these guidelines is welcomed. EVIDENCE-BASED MEDICINE Evidence-based medicine is the conscientious, explicit and judicious use of current best evidence in making decisions about the care of individual patients. In this document you will see that evidence and recommendations are graded according to levels of evidence (Levels 1 5) and grades of recommendations (Grades A-C) respectively. This grading system is an adaptation of the revised Oxford Centre 2011 Levels of Evidence. LEVELS OF EVIDENCE Level 1: Evidence obtained from systematic review of randomised trials Level 2: Evidence obtained from at least one randomised trial Level 3: Evidence obtained from at least one nonrandomised controlled cohort/follow-up study Level 4: Evidence obtained from at least one case-series, case-control or historically controlled study Level 5: Evidence obtained from mechanism-based reasoning GRADES OF RECOMMENDATIONS A: Requires at least one randomised controlled trial as part of a body of literature of overall good quality and consistency addressing the specific recommendation. (Evidence levels 1, 2) B: Requires the availability of well-conducted clinical studies but no randomised clinical trials on the topic of recommendation. (Evidence levels 3, 4). C: Requires evidence obtained from expert committee reports or opinions and/or clinical experience of respected authorities. Indicates an absence of directly applicable clinical studies of good quality. (Evidence level 5). ICGP QUALITY IN PRACTICE COMMITTEE 2016 Dr Paul Armstrong, Dr Patricia Carmody, Dr Regina Codd, Dr Harry Comber, Dr Mary Kearney, Dr Niamh Moran, Dr Brian Osborne, Dr Maria O Mahony, Dr Ben Parmeter, Dr Philip Sheeran Purcell, Dr Patrick Redmond ACKNOWLEDGMENTS QIP Committee would like to thank Cora Flynn, RANP Epilepsy and Dr Colin Doherty, Consultant Neurologist St James Hospital Dublin who carried out an external review of this document. Correspondence to: QRGfeedback@icgp.ie Original Publication: 2002 Next Review Date: 2019

3 QUALITY IN PRACTICE COMMITTEE Epilepsy and Women Quick Reference Guide TABLE OF CONTENTS 1. Introduction 1 Background 1 Aims of the document 1 2. Catamenial epilepsy 1 3. Contraception 1 What are enzyme inducing AEDs? 2 Advice for women taking enzyme inducing AEDs 2 Emergency contraception 3 4. Pre Conception/Fertility 3 Pre pregnancy counselling 3 Important note regarding sodium valproate 4 5. Epilepsy and pregnancy 5 Effect of pregnancy on epilepsy 5 Effect of epilepsy on pregnancy 5 What to do when a WWE presents in early pregnancy to her GP 6 7. Postpartum management considerations 7 Breastfeeding and epilepsy 7 Advice for new parents with epilepsy 7 8. Menopause 8 9. Bone health 8 References 9 Appendix 1 Valproate patient information leaflet 11 Appendix 2 Adult service epilepsy phone support (2016) 15

4 QUALITY IN PRACTICE COMMITTEE Epilepsy and Women Quick Reference Guide 1 1. Introduction Background GPs need to be aware of the particular issues that women with epilepsy (WWE) will face at different times throughout their reproductive life, including epilepsy occurring around the menstrual cycle, issues around contraception choices, issues during pregnancy, changes in epilepsy in the menopause and the effect of AEDs on bone mineral density. When GPs are seeing women patients about their epilepsy they should raise the relevant women s health issues. Most importantly they should discuss and provide information regarding pregnancy and contraception at every visit in women of child bearing potential. Discussion should include the risks of unplanned pregnancy to the woman and the foetus and why women with epilepsy need to plan their pregnancy. Aims of the document The aim of this document is to inform GPs how the care of women with epilepsy differs from women without epilepsy and guide best practice management of these patients. 2. Catamenial epilepsy Catamenial (menstrual) epilepsy refers to a pattern of seizure clustering that is related to the menstrual cycle. Catamenial seizures are uncommon and occur in approximately 10% of WWE. Depending on the study method the reported incidence of catamenial epilepsy varies from 10 78%. (1) If there is a suggestion of a cyclical occurrence GPs should encourage women to keep careful menstrual cycle and seizure diaries to help facilitate diagnosis because management options differ to non-menstrual epilepsy. Management options include cyclical use of Clobazam 3 days prior to menses and 3 days during menses and hormonal therapy. 3. Contraception Key points: WWE should be offered an effective contraception at every possible opportunity. AEDs that induce liver enzymes do not reduce the efficacy of DMPA, Levonorgestrel releasing intrauterine system (Lng IUS), Copper intrauterine device (Cu IUD) or barrier methods therefore these are the best contraceptive options for WWE. If not taking an enzyme inducing AED: Avoid lamotrigine with COCP (COCP can reduce levels of lamotrigine (level 2 grade b), (2) and seizure frequency may increase) otherwise no restrictions apply.

5 QUALITY IN PRACTICE COMMITTEE Epilepsy and Women Quick Reference Guide 2 What are enzyme inducing AEDs? The hepatic cytochrome P450 system is the primary metabolic pathway of the sex steroid hormones. AEDS which have a side-effect of increasing the speed of this metabolic pathway are known as enzyme inducers. They cause a more rapid clearance of sex hormones and may allow for ovulation in women taking these mediations and some hormonal forms of contraception as outlined below. The following antiepileptic medicines are liver enzyme inducers: Carbamazepine (Tegretol), Oxcarbazepine (Trileptal, Phenobarbital (Phenobarbitone), Phenytoin (Epanutin), Topiramate (Topamax), Eslicarbazepine (Zebinix), Primidone The other antiepileptic medicines, including Sodium Valproate (Epilim), lamotrigine (Lamictal) Levetiracetam (Keppra), Zonisamide (Zonergran), Lacosamide (vimpat) Ethosuximide (Zarontin), are not liver enzyme inducers. Advice for women taking enzyme inducing AEDs Women on enzyme inducing drugs should be advised to use a reliable contraceptive method that is not affected by enzyme inducers. The best contraceptive options for women on enzyme inducers are DMPA, Cu IUD or Lng IUS. (level 5 grade c) (3) If a GP does not offer insertion of IUS/ IUD in their practice, they should refer to a GP colleague who does offer this service. The progesterone implant, progesterone only pills and the combined transdermal contraceptive patch are not recommended and should not be offered. AEDs that induce liver enzymes may reduce contraceptive efficacy of combined oral contraceptive pills, this is because there are interactions between COCP and enzyme inducers increases the rate of metabolism of both oestrogen and progesterone, thereby lowering the blood concentrations of these drugs. If a woman is starting an enzyme inducing drug and is already on the COC and wants to continue on her COC, she should be advised to use an additional method such as condoms with the COC. To minimise the risk of contraceptive failure the Faculty of Sexual and Reproductive Health recommend extended regimen, tricycling and shortened pill free interval. Women may also be offered an increased dose of COC containing at least 50mcg EE (e.g. a 30mcg COC plus a 20mcg COC). However, the use of two COC, tricycling, / extended regimens/ shortened interval, are outside the product licence for COCs and there is no evidence that such practice is effective in women using enzyme inducing drugs. A woman should be informed of this by her GP. If breakthrough bleeding occurs (and all other causes are ruled out) it is recommended that the dose of ethinylestradiol is increased by increments of 10 micrograms up to a maximum of 70 micrograms daily [unlicensed use], or to use additional precautions, or to change to a method unaffected by enzyme-inducing drugs. For more detailed guidance on best practice the Faculty of Sexual and Reproductive Health (FRSH) guidance (3) can be accessed here (level5 grade c)

6 QUALITY IN PRACTICE COMMITTEE Epilepsy and Women Quick Reference Guide 3 Emergency contraception Women who require emergency contraception while using enzyme inducing AEDs should be advised that an intrauterine device (copper IUD) is the preferred option. GPs who do not insert these devices should refer to a GP who does. The FSRH state that those who prefer to use oral-progesterone only emergency contraception may be advised to double the dose of levonorgestrel. However, the medication SPC for Levonelle does not recommend doubling up of their product. There is no evidence to confirm that this increase dose is actually required. Efficacy of ellipristal acetate is reduced by enzyme inducing AEDs and its use is not recommended in women on enzyme inducing AEDs. The SPC for levonelle and ella One do not recommend use in women using enzyme inducing AEDs. 4. Pre Conception/Fertility Key point: There is decreased fertility in WWE and women should be counselled regarding this. (level5 grade c) Preconception information should be offered to WWE (level 5 grade c) All WWE from menarche to menopause should be prescribed Folic Acid 5mg as soon as AEDs are commenced. (level 5 grade c) Fertility in WWE can be reduced by 20% to 40% when compared to women without seizures (4,5). (level 2 grade c) The low fertility rates may be intrinsic to the disease and/or secondary to antiepileptic drugs (5). A common cause of infertility is polycystic ovarian syndrome (PCOS) (4,5). PCOS is more common in patients with primary generalised epilepsy (6,7,8,9) and patients on sodium valproate have a higher risk of developing PCOS especially when taken prior to age 26 (10). (level 4 grade b) Pre pregnancy counselling Pre pregnancy counselling is of utmost importance for women with epilepsy. WWE should be advised that if they wish to become pregnant in the future, they should be referred by their GP to a neurology service for preconception counselling at least one year before becoming pregnant. If changes to medications are to be made then they can be made pre conceptually. All WWE on AEDs of child bearing potential should be prescribed Folic Acid 5mgs per day (11,12,13,14) unless contraindicated (there is evidence to suggest that Folic acid should be best avoided in those with a history of bowel cancer due to the potential for tumour reactivation). (15) WWE should be counselled re the advisability of attempting to defer pregnancy until seizure free for at least six months. Research suggests that if

7 QUALITY IN PRACTICE COMMITTEE Epilepsy and Women Quick Reference Guide 4 a woman remains seizure free for a year pre-pregnancy then her seizures are less likely to recur during her pregnancy (16). Some women require anticonvulsant drugs continuously. For these every effort should be made to control their epilepsy using a single drug at the lowest dose possible (17). Valproic acid (11% physical malformation risk) and carbamazepine are associated with a higher incidence of neural tube defects than in the general population approximately 1% 2% and 0.5% 1% respectively (18). Patients should be referred for medication review. IMPORTANT NOTE REGARDING SODIUM VALPROATE The European Medicines Agency (EMA) Pharmacovigilance and Risk Assessment Committee (PRAC) has recommended strengthening the restrictions on the use of valproate medicines due to the risk of malformations and developmental problems in children exposed to valproate in the womb. Recent studies have shown that the risk of developmental problems is up to 30 to 40% in pre-school children exposed to valproate in the womb. Data also shows that children exposed to valproate in the womb are at increased risk of autistic spectrum disorder in the order of around 3 times higher than in the general population. It has also been shown that children exposed to valproate in the womb are at an approximately 11% risk of malformations at birth (such as neural tube defects and cleft palate) compared to a 2 to 3% risk in the general population. (19). Therefore, it has been concluded that Sodium valproate should not be used to treat epilepsy in girls or women who are pregnant or who could become pregnant unless other treatments are ineffective or not tolerated. (level 5 grade c) (19) Women who have been prescribed valproate should not stop taking their medicine without first consulting their doctor. Women for whom valproate is the only option after trying other treatments, should use effective contraception. GP s should inform all females prescribed valproate of these risks. In Appendix 1 there is a valproate patient information leaflet which has been developed by the HSE Epilepsy Clinical Care Programme and the HPRA. Given the current emerging evidence, from a General Practice perspective, it would be advisable that women of child bearing potential on sodium valproate should be referred to a specialist for a medication review.

8 QUALITY IN PRACTICE COMMITTEE Epilepsy and Women Quick Reference Guide 5 5. Epilepsy and pregnancy Key points: Seizure frequency increases during pregnancy in up to a third of women (20). Maternal Death rate is ten times higher in women with epilepsy than in women without. GPs should Reassure WWE that the majority of WWE have uncomplicated pregnancies, normal deliveries and healthy babies and that AEDs should not be stopped unless advised to do so. (level 2 nvds) GPs should play a role in the education of women with epilepsy regarding the importance of pregnancy planning, medication adherence, drug level monitoring where appropriate and ensuring referral to a neurologist. Effect of pregnancy on epilepsy An increase in plasma volume, altered protein binding and altered drug clearance in pregnancy may result in decreased bioavailability of anticonvulsant. It has been recommended that drug levels are measured at the very start of pregnancy to establish a baseline (21). Most women on lamotrigine and levetiracetam will require an increase dose in pregnancy. In about one third of WWE seizure frequency increases during pregnancy. The discontinuation of AEDs may increase the risk of seizures, which can be harmful to both the mother and foetus. In 1% 2% of women with epilepsy, tonic-clonic seizures develop during labour (22). Eclampsia should be outruled. Effect of epilepsy on pregnancy Increase in seizure frequency can be due to changes in drug absorption of AED s but a contributing factor is poor adherence to treatment due to concern about the adverse effects of the medication on the foetus (17). The risks of uncontrolled seizures should be explained to women with epilepsy so that they remain adherent to their medication regime. The maternal death rate is 10 times higher in women with epilepsy as compared to women without. The risk is thought to be due to an increased rate of seizures due to either sub-therapeutic AED levels or a change in medication (1). There were two maternal deaths in Ireland in the period in WWE (23). Whilst the relative risk of death in WWE is increased and GPs need to be mindful of this in their consultations with WWE, the absolute risk of maternal death remains very small. Therefore, in order to help alleviate the anxiety that often causes them to stop their prescribed AEDs, WWE need to be reassured that the majority of mothers have uncomplicated pregnancies, normal deliveries and healthy babies.

9 QUALITY IN PRACTICE COMMITTEE Epilepsy and Women Quick Reference Guide 6 What to do when a WWE presents in early pregnancy to her GP Refer to obstetric service early. (Contact details for specialised Epilepsy Nurses whom GPs can contact for information regarding referral etc. is provided in Appendix 2) Prescribe 5mg folic acid if not already on it and not contraindicated and advise to stay on for duration of pregnancy. Advise her to continue taking her AED as prescribed and inform her of the dangers of discontinuing an AED during pregnancy. Reassure her that the majority of mothers have uncomplicated pregnancies, normal deliveries and give birth to healthy babies and that AEDs should be taken as prescribed Encourage to register the pregnancy with The UK and Ireland Epilepsy and Pregnancy Register or Freephone ) Advise regarding triggers for seizures such as vomiting, changes in metabolism due to pregnancy, sleep deprivation and non-compliance with medications for epilepsy. (15) Advise WWE to carry their own supply of AEDS and buccal midazolam if prescribed, and to take them as normal throughout antenatal admissions/ labour/post-natal period etc. (Since changes in brand of AED can potentially affect seizure control). (15) Offer/remind WWE of practical advice for example that showering is preferable to bathing and to keep the bathroom door unlocked. Give contact details for Epilepsy Ireland for more practical advice and support, including access to the support of an Epilepsy Nurse Specialist. ( / Phone: ) Advise women to expect that the Obstetric service will arrange an anomaly scan at between weeks. It is also recommended that a cardiac anomaly scan is carried out at 24 weeks if the mother is taking Carbamazepine, Valproate or Phenytoin. (15) Women experiencing hyperemesis may require PRN clobazam along with other supportive treatment.

10 QUALITY IN PRACTICE COMMITTEE Epilepsy and Women Quick Reference Guide 7 7. Postpartum management considerations Key Points: WWE should be offered an effective contraception at every possible opportunity. Women should be advised to attend for pre-natal counselling at least one year prior to their next pregnancy. Women should be prescribed folic acid 5mg and advised to stay on this unless contraindicated. In those women where the anticonvulsant dose was increased during pregnancy, the dose should be reduced gradually over the first few weeks post-partum to the pre-pregnancy dose to avoid rebound toxicity (17). Perinatal mortality is increased by fold in the offspring of women with epilepsy (17). The reasons for this are unclear, but do not appear to be influenced by maternal seizure rates or anticonvulsant therapy (17). Vitamin K metabolism: Enzyme inducing anticonvulsants can deplete vitamin K dependent clotting factors, and neonatal haemorrhage can result. Vitamin K 1mg should be given intramuscularly to the neonate to prevent this. Neonatal withdrawal symptoms and signs: Phenobarbitone, primidone and benzodiazepines remain in the neonatal circulation for several days. They may cause sedation and possibly symptoms of neonatal withdrawal (17). Breastfeeding and epilepsy Key Points: Most AEDs are not contra indicated in breastfeeding and most women with epilepsy should be encouraged to breastfeed unless they experience extreme exhaustion and an exacerbation of seizures, likewise if the baby is very sleepy this may need to be reviewed individually. (In each case GPs should consult individual drug advice in the SPC and the BNF.) Women should be advised re possible breastfeeding related sleep deprivation as a potential trigger for seizures. Advice for new parents with epilepsy Information should be given to all parents about safety precautions to be taken when caring for the baby. Appendix D of the NICE Guidelines on Epilepsy entitled Information for Women with Epilepsy contains practical safety advice regarding feeding, bathing, carrying newborns etc. Available here.

11 QUALITY IN PRACTICE COMMITTEE Epilepsy and Women Quick Reference Guide 8 8. Menopause Reported seizures may become more frequent in 40% during the menopause but 27% report an improvement (24). Hormone Replacement Therapy may exacerbate seizures (25) especially in women with a history of catamenial epilepsy. GPs should identify their WWE who are approaching menopause and should discuss this at their next scheduled visit. Women should be given information about possible changes to their epilepsy during the menopause. Women approaching menopause should be offered to be referred to the local neurology service. 9. Bone health Women with epilepsy are at an increased risk of fractures, falls, osteoporosis, and osteopenia (26). (level 3 grade b) This is due to seizure trauma, reduced coordination with some AED and the adverse effects of AED on vitamin D, bone metabolism and turnover. Long term treatment with carbamazepine, phenytoin, primidone and sodium valproate is associated with loss of bone mineral density and fracture. GPs should inform women who are on or who have been on AEDs that they are more prone to osteoporosis and a risk assessment for osteoporosis should be carried out. Based on the risk assessment women should be offered a DXA scan if indicated. Dietary and exercise advice should be given. Women with low dietary calcium intake should be prescribed a calcium and vitamin D supplement.

12 QUALITY IN PRACTICE COMMITTEE Epilepsy and Women Quick Reference Guide 9 References 1. Duncan S, Read CL, Brodie MJ. How common is catamenial epilepsy? Epilepsia. 1993;34: [PubMed] 2. Stodieck SRG, Schwenkhagen AM. Lamotrigine plasma levels and combined monophasic oral contraceptives or a contraceptive vaginal ring, a prospective evaluation in 30 women. Epilepsia 2004;45(suppl7): Faculty of Sexual and Reproductive Healthcare Clinical Effectiveness Unit. CEU Statement (January 2010) Antiepileptic Drugs and Contraception. London: FSRH 4. Dansky V, Andermann E, Andermann F. Marriage and fertility in epileptic patients. Epilepsia. 1980;21: Wallace H, Shorvon S, Tallis R. Age specific incidence and prevalence rates of treated epilepsy in an unselected population of 2,052,922 and age-specific fertility rates of women with epilepsy. Lancet. 1998;352: [PubMed] 6. Morrell MJ, Montouris G. Reproductive disturbances in patients with epilepsy. Cleve Clin J Med. 2004;71(suppl 2):S19 S24. [PubMed] 7. Knochenhauser ES, Key TJ, Kashar-Miller M. Prevalence of polycystic ovary syndrome in unselected black and white women of the southeastern united states: a prospective study. J Clin Endocrinol Metab. 1998;83: et al. [PubMed] 8. Herzog AG, Schachter SC. Valproate and the polycystic ovarian syndrome: final thoughts. Epilepsia. 2001;42: [PubMed] 9. Bilo L, Meo R, Nappi C. Reproductive endocrine disorders in women with primary generalized epilepsy. Epilepsia. 1988;29: et al. [PubMed] 10. Isojärvi JI, Laatikainen TJ, Pakarinen AJ, Juntunen KT, Myllylä VV. Polycystic ovaries and hyperandrogenism in women taking valproate for epilepsy. N Engl J Med Nov 4; 329(19): Sander JWA, O Donoghue MF. Epilepsy: getting the diagnosis right. BMJ 1997; 314: Morrow JI. Epilepsy: treatment and prognosis. Medicine 1996: Stephen LJ, Brodie MJ. New drug treatment for epilepsy. Prescribers Journal 1998; 38(2): Dichter MA, Brodie MJ. New antiepileptic drugs. NEJM 1996; 334(24): HSE SOP Effective management of Women with Epilepsy in the non-acute setting (unpublished) 16. Feely M. Drug treatment of epilepsy. BMJ 1999; 318: Byrne B. Epilepsy and pregnancy. IMJ 1997; 90(5): Brodie MJ, Dichter MA. Antiepileptic drugs. NEJM 1996; 334(3): PRAC recommends strengthening the restrictions on the use of valproate in women and girls. European Medicines Agency, / 2014

13 QUALITY IN PRACTICE COMMITTEE Epilepsy and Women Quick Reference Guide Chadwick DM. Overuse of monitoring blood concentrations of antiepileptic drugs. BMJ 1987; 294: O Brien MD, Gilmore White S. Epilepsy and pregnancy. BMJ 1993; 307: Epilepsy and pregnancy. Drug Ther Bull 1994; 32(7): MDEReportForTheTriennium pdf 24. Abbasi F1, Krumholz A, Kittner SJ, Langenberg P. Effects of menopause on seizures in women with epilepsy. Epilepsia Feb;40(2): Harden CL1, Herzog AG, Nikolov BG, Koppel BS, Christos PJ, Fowler K, Labar DR, Hauser WA. Hormone replacement therapy in women with epilepsy: a randomized, double-blind, placebo-controlled study. Epilepsia Sep;47(9): Souverein PC, Webb DJ, Petri H, Weil J, Van Staa TP, Egberts T. Incidence of fractures among epilepsy patients: a population-based retrospective cohort study in the General Practice Research Database. Epilepsia Feb; 46(2):

14 QUALITY IN PRACTICE COMMITTEE Epilepsy and Women Quick Reference Guide 11 Appendix 1 Valproate patient information leaflet Information booklet This booklet is for any female patients who are taking any medicine containing valproate. This booklet contains key information about the risks of valproate in pregnancy. It is important that you read this booklet even if you have been taking valproate for a while because it contains the most up to date information on your medicine. Keep this booklet as you may need to refer to it again in the future and it should be read along with the information provided by the company with your medication. This message is supported by the National Clinical Programmes for Epilepsy, Mental Health and Medicines Management. The following support groups provide information about epilepsy and bipolar disorder: / Tel / Tel VALPROATE is subject to additional monitoring and any side effects you may get should be reported to your doctor, pharmacist or nurse and also to the Health Products Regulatory Authority via HPRA Pharmacovigilance, Earlsfort Terrace, Dublin 2; Tel Website: medsafety@hpra.ie VALPROATE VALPROATE is a medicine which is used to treat epilepsy and bipolar disorder. If you are a female capable of becoming pregnant your doctor should only prescribe valproate for you if nothing else works for you. This booklet is for FEMALES taking any medicine that contains VALPROATE and it contains important information about the risks to be aware of if your doctor has recommended valproate as the best treatment for you.

15 QUALITY IN PRACTICE COMMITTEE Epilepsy and Women Quick Reference Guide 12 What are the risks of taking VALPROATE during PREGNANCY? Taking VAPLROATE during pregnancy can harm your unborn baby. The risks are higher with valproate than with other medicines used to treat epilepsy. There are risks to your baby at any dose of valproate and the higher the dose the higher the risk. The risks include causing birth defects and problems with development and learning. The next page explains the problems that your child could have. Birth defects If you take valproate while you are pregnant, you have a higher risk than other women of having a child with birth defects. In women who take valproate while pregnant, around 10 babies in every 100 will have a birth defect. Birth defects seen in children of mothers who take valproate during pregnancy include: Spina bifida (when the bones of the spine do not develop properly) Facial and skull malformations (including cleft lip and palate, where the upper lip or facial bones are split) Malformations of the limbs, heart, kidney, urinary tract and sexual organs. Ask your doctor about taking folic acid when trying for a baby. Folic acid can lower the general risk of spina bifida and early miscarriage that exists with all pregnancies. However, it is unlikely that it will reduce the risk of birth defects associated with valproate use.

16 QUALITY IN PRACTICE COMMITTEE Epilepsy and Women Quick Reference Guide 13 Developmental disorders If you take valproate while you are pregnant, it could affect your child s development as they grow up. In women who take valproate while pregnant, about children in every 100 may have developmental problems. The long-term effects are not known. The effects on development can include: Being late to learn to walk and talk Lower intelligence that other children of the same age Poor speech and language skills Memory problems Children exposed to valproate in the womb are more likely to have autism or autistic spectrum disorders. There is also some evidence that these children may be more likely to be at risk of developing symptoms of attention deficit hyperactivity disorder (ADHD). What does this mean for me? I am starting treatment with valproate When you first start valproate your doctor should explain all the known risks and why they feel that valproate is the right medicine for you. If you are too young to become pregnant, it is still important that you and your parents know what to do when you are old enough to have children. If you are old enough to become pregnant, make sure you are using an effective method of contraception throughout your treatment. It is important to make sure you don t have an unplanned pregnancy. I am taking valproate and NOT planning pregnancy If you are taking VALPROATE and don t plan to have a baby, make sure you always use an effective method of contraception. You should discuss this with your doctor. Tell your doctor at once if you think you might be pregnant or if you become pregnant. It is important that you do not stop taking your medication until you have discussed this with your doctor.

17 QUALITY IN PRACTICE COMMITTEE Epilepsy and Women Quick Reference Guide 14 I am taking valproate and planning a pregnancy If you are planning a baby, DO NOT STOP taking VALPROATE or stop using contraception until you and your doctor have decided what can be done to reduce the risks to you and your baby s health. Your doctor may need to change your dose or switch you to another medicine well in advance of you becoming pregnant to ensure your medical condition is stable. Ask your doctor about taking folic acid. Taking folic acid is generally recommended for anyone trying to have a baby as it can reduce the risk of spina bifida in all pregnancies. However, it is unlikely to reduce the risk of birth defects from VALPROATE. I am taking valproate and have become pregnant Babies born to mothers who have been treated with valproate during pregnancy are at a higher risk of birth defects and early developmental disorders Tell your doctor if you think you might be pregnant or if you become pregnant to discuss your options. DO NOT STOP taking VALPROATE without speaking to your doctor first as it may be dangerous for both you and your baby. Things to remember when taking VALPROATE VALPROATE is an effective medicine used to treat epilepsy and bipolar disorder VALPROATE can seriously harm an unborn child when taken during pregnancy and should not be taken by females unless no other treatment works for their condition When taking VALPROATE a reliable contraception should ALWAYS be used so an unplanned pregnancy does not occur Talk to your doctor if you are thinking about having a baby and do NOT stop using contraception until you have done so and your doctor has considered your options. Tell your doctor at once if you think you may be pregnant or know you are pregnant. NEVER stop taking VALPROATE unless your doctor tells you to as your condition may become worse.

18 QUALITY IN PRACTICE COMMITTEE Epilepsy and Women Quick Reference Guide 15 Appendix 2 Adult service epilepsy phone support (2016) SERVICE HOSPITAL REGION PHONE NO NOTE Beaumont NA Hospital Epilepsy Phone Service Epilepsy Telemetry Service (24 Hour VEEG) Epilepsy Surgery Nurse Service Community Epilepsy Nurse Service Epilepsy Nurse Service Epilepsy Nurse Service Epilepsy Nurse Service Epilepsy Nurse Service Epilepsy Nurse Service Epilepsy Nurse Service Epilepsy Telemetry Service (24 Hour VEEG) Epilepsy Nurse Service Beaumont Hospital Beaumont Hospital Beaumont Hospital/ Epilepsy Ireland Mater Hospital St James s Hospital Tallaght Hospital UCGH Limerick Cork Cork University Hospital Sligo DNE Open Monday Friday 8am 2pm (ex BH) Available to Beaumont Hospital Patients only All Ireland NA Available nationally to anyone referred for VEEG@ Beaumont Hospital All Ireland NA Available nationally to anyone referred for epilepsy surgery/vns inc battery Beaumont Hospital DNE NA Available nationally for telephone queries Home visits to Beaumont Hospital patients DNE Ext 4172 NA Available to Mater Hospital Patients only DML epilepsy@ stjames.ie DML Not available Wednesdays West Galway Limerick Regional Cork University Hospital Available to St James s Hospital Patients only Pts NA Available to University Hospital Galway Patients only NA Available to University Hospital Galway Patients only Tues Thur 9 1pm Available to Cork University Hospital Patients only All Ireland NA Available nationally to anyone referred for VEEG@ CUH Letterkenny and Sligo Regional Monday, Wednesday and Friday from to Pregnancy Register Available to patients of Sligo/ Letterkenny Epilepsy service only

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