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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 
  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 
        > 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 
  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
  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® 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 
  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
  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
    AMBER      Perampanel (Fycompa®) 
                       tablets f/c 2 mg, 4 mg, 6 mg, 8 mg,10 mg, 12 mg 
  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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