4.8 Antiepileptics

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

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:

> 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.

Sodium Valproate - Risk of abnormal pregnancy outcomes- MHRA alert Jan 2015

https://www.gov.uk/drug-safety-update/medicines-related-to-valproate-risk-of-abnormal-pregnancy-outcomes

Link to Valproate Safety Implementation Group (VSIG)

[link to resources and recent updates]

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]

oral syrup 250mg/5mL (Emeside®) [paediatric use only] [PRESCRIBE BY BRAND]

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

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]

Newer anti-epileptics

AMBER Gabapentin Capsules 100mg, 300mg, 400mg

AMBER Lamotrigine tablets 25mg, 50mg, 100mg

AMBER Lamotrigine chewable/dispersible tablets 2mg, 5mg, 25mg,100mg (paediatric use only)

AMBER Levetiracetam (prescribe generically):

tablets 250mg, 500mg, 1g

oral solution (sugar free) 100mg/mlL

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 [generic prescribing only]

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 Lacosamide Intravenous infusion 10mg/mL

AMBER Oxcarbazepine (Trileptal®)

tablets f/c 150mg . 300mg, 400mg

suspension 300mg/5mL

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

AMBER Brivaracetam (Briviact®)

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

RED Brivaracetam (Briviact®)

oral solution 10mg/1ml

RED Cannabidiol with clobazam [Epidyolex®]

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 convulsive seizures 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 NHS England Commisioned

NICE TA615 - Cannabidiol with clobazam is recommended as an option for treating seizures associated with Lennox-Gastaut syndrome in people aged 2 years and older, only if:

> the frequency of drop seizures is checked every 6 months, and cannabidiol is stopped 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 NHS England Commisioned

RED 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

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 treating Dravet Syndrome in combination with Sodium Valproate and clobazam. For use under specialist advice only

RED Stiripentol (Diacomit®)

250mg, 500mg capsules

Stirpentol 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 controlled

with 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 initiation or continuation of treatment is not recommended.

Fenfluramine for treating seizures associated with Dravet syndrome

NICE TA808 Fenfluramine is recommended as an add-on to other ant-seizure medicines for treating seizures associated with

Dravet syndrome in people aged 2 years and older, only if:

> seizures have not been controlled after trying 2 or more antiseizure medicines

> the frequency of convulsive seizures is checked every 6 months, and fenfluramine is stopped if it has not fallen by

at least 30% compared with the 6 months before starting treatment

> the company provides fenfluramine according to the commercial arrangement.

RED Fenfluramine [Fintepla] 2.2mg/mL oral solution

NHS England Commissioned

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)

AMBER *Midazolam maleate oromucosal solution 10mg/mL (Epistatus®) Pre-filled syringe [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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public seeking advice on medicine-related matters are advised to speak with their GP, pharmacist, nurse or contact NHS111 Service

Email: info.elmmb@nhs.net