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4.8 Antiepileptics

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 resources ]
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 (Zarontin®)  
                  capsules 250mg
                  syrup 250mg/5mL
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 (Lamictal®) tablets 25mg, 50mg        
AMBER     Levetiracetam (prescribe generically):
                   tablets 250mg, 500mg, 1g 
                   oral solution (sugar free) 100mg/mlL
AMBER     Topiramate (Topamax®):
                  tablets 25mg, 50mg, 100mg, 200mg
                  sprinkle capsules 15mg, 25mg, 50mg
AMBER     Zonisamide (Zonegran®) 
                  capsules 25mg, 50mg, 100mg
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
 
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
 
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 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) 
 AMBER     *Midazolam maleate oromucosal solution 10mg/mL  (Epistatus®)
   *(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
 
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