Dravet syndrome

Prescribing Notes:

• All children with complex epilepsies should be managed in tertiary epilepsy clinics or have ongoing management with a tertiary epilepsy specialist.
• Prior to starting valproate, 2 specialists should independently consider and document that there is no other effective or tolerated treatment for all patients (male and female) aged under 55 years, or there are compelling reasons that the reproductive risks do not apply. 
• For more information, refer to "Prescribing Valproate to female patients under 18 years of age" and "BPEG/OPEN UK/RCPCH on Prescribing Valproate" from the British Paediatric Neurology Associated in collaboration with Royal College of Paediatrics and Child Health available from the British Paediatric Neurology Association website.
• Liver dysfunction, particularly hepatic encephalopathy, has been associated with valproate especially in children under 3 years of age. See BNFc.
• Prolonged release formulations of sodium valproate such as m/r capsules and m/r granules may be useful when patients are unable to tolerate m/r tablets or large volumes of oral solution. The contents of the capsules or granules may be mixed with cold food or drink and swallowed without chewing.
• Young females of childbearing potential should discuss with a specialist the impact of both epilepsy and treatment (in particular those taking sodium valproate and topiramate) on the outcome of pregnancy. Note some antiepileptics may affect the efficacy of hormonal contraception. Advice on interactions is available in BNF or Faculty for Sexual and Reproductive Health.
• Valproate should never be started in any females unless alternative treatments are not suitable, including in young females below the age of puberty.
• Valproate must not be used in any females able to have children unless patient has a pregnancy prevention programme in place. This includes the completion of a signed risk acknowledgement form for female patients starting valproate and at annual review.
• A retrospective observational study has indicated a possible association between valproate use in males around the time of conception and an increased risk of neurodevelopmental disorders in their children. As a precaution male patients taking valproate and their partners are recommended to use effective contraception during valproate treatment and for at least 3 months after stopping valproate. Where the decision is taken to initiate valproate in male patients, a signed risk acknowledgement form for male patients must be completed.  
• Females with childbearing potential must use highly effective contraception if they are able to become pregnant.
• Valproate is contra-indicated for epilepsy during pregnancy unless there is no other effective treatment available.
• See MHRA guidance valproate safety measures.
• To obtain risk materials including pregnancy prevention materials for a specific brand of valproate or topiramate, see external links to the eMC (SPC & patient leaflets) found next to the medicines choices above or access the eMC website valproate search or eMC website topiramate search and click on "Risk Materials" next to that medicine.
• Topiramate is contraindicated in pregnancy and in any individual of childbearing potential unless the conditions of a Pregnancy Prevention Programme are fulfilled. This follows a review by the MHRA which concluded that the use of topiramate during pregnancy is associated with significant harm to the unborn child. Harms included a higher risk of congenital malformation, low birth weight and a potential increased risk of intellectual disability, autistic spectrum disorder and attention deficit hyperactivity disorder in children of mothers taking topiramate during pregnancy. 
• See MHRA guidance topiramate safety measures. 
• The MHRA has recommended that children and their parents or carers should be advised to seek medical advice if any mood changes, distressing thoughts, or feelings about suicide or self-harming develop, and that the child should be referred for appropriate treatment if necessary. They should also be advised not to stop or switch antiepileptic treatment and to seek advice from a healthcare professional if concerned.
• The stiripentol sachet formulation and capsules are not bioequivalent and any switch of formulations should be done under medical supervision.
• Carbamazepine, gabapentin, lacosamide, lamotrigine, oxcarbazepine, phenobarbital, pregabalin, tiagabine, or vigabatrin should be avoided in children with Dravet syndrome.
• The Commission on Human Medicines (CHM) has issued advice on prescribing of antiepileptic drugs (AEDs). These drugs have been classified into three categories to help prescribers and patients decide whether it is necessary to maintain continuity of supply of a specific manufacturer’s product. Further details can be found on the MHRA website See ‘Antiepileptic drugs: new advice on switching between different manufacturers’ products’:
  
  • Category 1 – Phenytoin, carbamazepine, phenobarbital, primidone – maintain patient on a specific manufacturer’s product.
  • Category 2 – Valproate, lamotrigine, perampanel, retigabine, rufinamide, clobazam, clonazepam, oxcarbazepine, eslicarbazepine, zonisamide, topiramate – the need for continued supply of a particular manufacturer’s product should be based on clinical judgement and consultation with patient and/or carer taking into account factors such as seizure frequency and treatment.
  • Category 3 – Levetiracetam, lacosamide, tiagabine, gabapentin, pregabalin, ethosuximide, vigabatrin – usually unnecessary to ensure that patients are maintained on a specific manufacturer’s product unless there are specific concerns such as patient anxiety, and risk of confusion or dosing errors.