4.8.1 Control of epilepsy
All patients with epilepsy need specialist assessment, generally before therapy is started. Use of newer agents should follow NICE guidance.
Updated advice on brand prescribing in the treatment of epilepsy (Nov 2013)/Drug Safety Update November 2017
The Medicines and Healthcare Products Regulatory Agency (MHRA) has issued new guidance to prescribers, pharmacists and patients in relation to anti-epileptic drugs (AEDs). This follows a review by the Commission on Human Medicines (CHM) which looked at the evidence on patients switching between different manufacturers' products of particular AEDs. CHM concluded that whilst there was no clear evidence of harm associated with switching products, an effect in some drugs, for some drugs, could not be completely ruled out.
The potential effects of switching may include a loss of seizure control or the occurrence of side effects, or both. These risks can be associated with switching between a branded originator and a generic product, and between different generic products.
CHM advised that AEDs could be classified into three categories. These categories aim to help prescribers and patients whether it is necessary to maintain continuity of supply of a specific manufacturer's product
Category 1 |
For these drugs doctors are advised to ensure that their patient is maintained on a specific manufacturer's product. |
The AEDs in this category are: phenytoin, carbamazepine, phenobarbital, primidone |
Category 2 |
For these drugs 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 history. |
The AEDs in this category are: valproate, lamotrigine, perampanel, retigabine, rufinamide, clobazam, clonazepam, oxcarbazepine, eslicarbazepine, zonisamide, topiramate.
Category 3 |
For these drugs it is 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. |
The AEDs in this category are: levetiracetam, lacosamide, tigabine, gabapentin, pregabalin, ethosuximide, vigabatrin |
When evaluating whether continuity of supply should be maintained for category 2 or 3 medicines, it would be appropriate to consider: | | > perception by patients of differences in supply, for example differences in product presentations | > co-morbid autism, mental health issues or special education needs. | | It is clinically appropriate to maintain an individual on a specific manufacturers' product, prescribe either by specifying brand prescribe either by specifying brand name or by using the generic drug name and name of manufacturer. | | |
The newer antiepileptic drugs gabapentin, lamotrigine, levetiracetam, topiramate and zonisamide, within their licensed indications, are recommended for the management of epilepsy in people who have not benefited from |
treatment with the older antiepileptic drugs such as carbamazepine or sodium valproate, or for whom the older |
antiepileptic drugs are unsuitable because: |
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- there are contraindications to the drugs
- they could interact with other drugs the person is taking (notably oral contraceptives)
- they are already known to be poorly tolerated by the individual
- the person is a woman of childbearing potential
Careful adjustment of dose is needed, starting low and increasing gradually until seizures are controlled or there are adverse effects. Therapy with two or more antiepileptics concurrently should only be used when monotherapy with several alternative drugs has proved ineffective.
Valproate is associated with a dose-dependent risk of abnormal pregnancy outcomes, whether taken alone or in combination with other medicines. Data suggest that when valproate is taken for epilepsy with other medicines, the risk of abnormal pregnancy outcomes is greater than when valproate is taken alone.
The risk of congenital malformations is approximately 10 % while studies in preschool children exposed in utero to valproate show that up to 30-40% experience delays in their early development.
Given these risks, valproate for the treatment of epilepsy or bipolar disorder should not be used during pregnancy and in women of child-bearing potential unless clearly necessary ie in situations where other treatments are ineffective or not tolerated.
Carefully balance the benefits of valproate treatment against the risks when prescribing valproate for the first time, at routine treatment reviews, when a female child reaches puberty and when a woman plans a pregnancy or becomes pregnant. If you decide to prescribe valproate to a woman of child-bearing potential, she must use effective contraception during treatment and be fully informed of the risks for the unborn child if she becomes pregnant during treatment with valproate.
Older anti-epileptics |
AMBER Carbamazepine (Tegretol®) | tablets 100mg, 200mg, 400mg to reach stable dose | then convert to tablets m/r 200mg, 400mg | liquid 100mg/5mL | suppositories 125 mg | |
AMBER Clobazam (only for epilepsy, endorse script SLS) | tablets 10mg | |
AMBER Clonazepam (Rivotril®) tablets 500mcg | Clonazepam 0.5mg/5mL oral suspension (Rosemont) | |
AMBER Ethosuximide capsules 250mg (Epesri®) [PRESCRIBE BY BRAND] | AMBER Oral solution SF 250mg/5mL [paediatric use only] | |
AMBER Phenytoin (Epanutin®) | tablets chewable 50mg | suspension 30mg/5mL | |
AMBER Phenytoin Sodium (Flynn Hardcaps®) | capsules 25mg, 50mg, 100mg | |
AMBER Sodium valproate (Epilim®) | tablets e/c 200mg, 500mg | tablets m/r 200mg, 300mg, 500mg | tablets crushable 100mg | liquid 200 mg/5mL | RED Sodium Valproate injection 400mg | |
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Episenta® | Episenta® capsules (prolonged release sodium valproate) are also available for use, and are especially helpful for those | patients with swallowing difficulties. They are given once daily, as capsules or sachets which can be opened and put on | soft food if required, without chewing. Like other valproate preparations when used for epilepsy, they should be | prescribed by brand name. | |
AMBER Sodium valproate (Episenta ® ) | capsules m/r 150mg, 300mg | AMBER Phenobarbital | tablets 15mg, 30mg, 60mg | |
RED Phenobarbital elixir [all strengths] |
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Newer anti-epileptics |
AMBER Gabapentin | AMBER Lamotrigine (Lamictal®) | tablets 25mg, 50mg | AMBER Levetiracetam (prescribe generically) | tablets 250mg, 500mg, 1g | oral solution (sugar free) 100mg/mL | RED Levetiracetam Conc for solution for injection 500mg/5ml [Keppra®] [Epilepsy] | AMBER Levetiracetam Conc for solution for injection 500mg/5ml [Keppra®] Specialist Palliative Care use | | A list of Community Pharmacies who stock specialist palliative care drugs can be accessed here | |
AMBER Topiramate | tablets 25mg, 50mg, 100mg, 200mg | sprinkle capsules 15mg, 25mg, 50mg | Topiramate oral suspension 20mg/mL - paediatric use only [Rosemont pharmaceuticals] | AMBER Zonisamide (Zonegran®) | capsules 25mg, 50mg, 100mg | AMBER Zonisamide oral solution 100mg/5mL [paediatric use only] | AMBER Lacosamide (Vimpat®) | tablets 50mg, 100mg, 150mg 200mg | syrup 10mg/mL | RED intravenous infusion 10mg/mL | AMBER Oxcarbazepine (Trileptal®) | tablets f/c 150mg . 300mg, 400mg | suspension 300mg/5mL | |
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Brivaracetam | Adjunctive therapy in the treatment of partial-onset seizures with or without secondary generalisation in adult, | adolescent and children from 4 years of age with epilepsy. | AMBER Brivaracetam (Briviact®) | tablets 10mg, 25mg, 50mg, 75mg, 100mg | oral solution 10mg/1ml | | Please note: Unlicensed use in children under the age of 4 years - initiated on advise of specialist or tertiary centre. | RED Brivaracetam (Briviact®) | tablets 10mg, 25mg, 50mg, 75mg, 100mg | oral solution 10mg/1ml | | | |
ED Cenobamate [Ontozry®: tablets 100mg, 150mg, 25mg, 50mg] | NICE TA753 Recommended as an option for treating focal onset seizures with or without secondary seizures in | adults with drug-resistant epilepsy that has not been adequately controlled with at least w anti-seizure | medicines. It is only recommended if: | > it is used as an add-on treatment, after at least 1 other add-on treatment has not controlled | seizures, and | > treatment is started in a tertiary epilepsy service | |
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RED Cannabidiol with clobazam [Epidyolex®] NHS England Commissioned | NICE TA614 - Cannabidiol with clobazam is recommended as an option for treating seizures associated with Dravet | syndrome in people aged 2 years and older, only if: | > the frequency of convulsions is checked every 6 months, and cannabidiol is topped if the frequency has | not fallen by at least 30% compared with the 6 months before starting treatment. | > the company provides cannabidiol according to the commercial arrangement | |
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Eslicarbazepine actetate | For adjunctive therapy in adults with focal (partial onset) seizures with or without secondary generalisation, only for | refractory patients in whom standard adjunctive treatment is inefffective or not tolerated. | Treatment should only be considered following referral to or discussion with a tertiary care specialist | | |
AMBER Eslicarbazepine acetate (Zebininx®) | tablets 800mg |
Perampanel | For use only as an option when other treatment options recommended by NICE CG137 have been tried or fully | considered in the treatment of partial-onset seizures with or without secondarily generalised seizures in people with | epilepsy aged 12 years and over. | |
AMBER Perampanel (Fycompa®) | tablets f/c 2 mg, 4 mg, 6 mg, 8 mg,10 mg, 12 mg |
Rufinamide | Rufinamide should only be initiated or recommended by a specialist in the management of Lennox-Gastaut Syndrome | (LGS) and other forms of epilepsy, after which prescribing may be passed to the primary care prescriber. Adequate | advice on dose titration should be provided in every case. | It should be used as a fourth line adjunctive therapy, usually in a combination with one or more of the following | medicines; sodium valproate (unlicensed), topiramate or lamotrigine. | Women of child-bearing potential taking rufinamide should be advised to use two forms of safe and effective contraception. | Hypersensitivity syndrome - Serious hypersensitivity syndrome has developed especially in children and upon initiation | of therapy; consider withdrawal if rash or signs or symptoms of hypersensitivity syndrome develop. Warn patients to | seek immediate medical attention if signs or symptoms of hypersensitivity develop. | |
AMBER Rufinamide (Inovelon®) | tablets 100mg, 200mg, 400mg | Infantile Spasms | AMBER Vigabatrin sachets 500mg Stiripentol to treat Dravet Syndrome in combination with Sodium Valproate and clobazam. | For use under specialist advice only | RED Stiripentol (Diacomit®) | 250mg, 500mg capsules | Stiripentol as adjunctive therapy of refractory generalised tonic-clonic seizures in patients over the age of 18 years | who were previously diagnosed with severe myoclonic epilepsy in infancy (Dravet syndrome) whose seizures are not | adequately controlledwith clobazam and valproate. | RED* Stiripentol (Diacomit®) | 250mg, 500mg capsules | | * Red Traffic Light (for all ages) for continuation of treatment of patients who have previously received the drug during | childhood under the NHSE standard contract for paediatric neurosciences - neurology. | NOT to be newly initiated in adults. | Medicine to be supplied by the hospital for the duration of the treatment course. | Primary care initiaion or continuation of treatment is not recommended. | | | |
4.8.2 Drugs used in status epilepticus | Guidelines for the management of status epilepticus - see Appendix 2 | | Lorazepam is the drug of choice for initial use. | RED Clonazepam (specialist use) | injection 1mg/1mL | GREEN Diazepam | injection (emulsion) 5mg/mL | rectal tubes 5mg, 10mg | RED Lorazepam injection 4mg/mL | AMBER Midazolam buccal liquid 5mg/mL (Buccolam®) Prefilled oral syringes, sugar free | AMBER *Midazolam maleate oromucosal solution 10mg/mL (Epistatus®) Pre-filled oral syringe SF [1mL] | *(licensed for use in children and adolescents aged 10 to less than 18 years) | | | Transfer to new Licensed Buccal Midazolam 5mg/ml (Buccolam▼): Guidance for Practitioners is available here | RED Paraldehyde injection (intramuscular or rectal use) | RED Phenytoin sodium injection 250mg/5mL | | | |
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All material in this section is aimed at health care professionals, but is information currently held in the |
public domain, members of the public seeking advice on medicine-related matters are advised to speak |
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Email: info.elmmb@nhs.net |
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