4.8.1 Control of the epilepsies

MHRA Drug Safety Update (November 2017): Antiepileptic drugs: updated advice on switching between different manufacturers' products

Different antiepileptic drugs vary considerably in their characteristics, which influences the risk of whether switching between different manufacturers' products of a particular drug may cause adverse effects or loss of seizure control

Antiepileptic drugs have been divided into three risk-based categories to help healthcare professionals decide whether it is necessary to maintain continuity of supply of a specific manufacturer's product. These categories are listed below:

  • Category 1: Phenytoin, carbamazepine, phenobarbital, primidone. For these drugs, doctors are advised to ensure that their patient is maintained on a specific manufacturer's product
  • Category 2: Valproate, lamotrigine, perampanel, rufinamide, clobazam, clonazepam, oxcarbazepine, eslicarbazepine, zonisamide, topiramate. For these drugs, the need for continued supply of a particular manufacturer's product should be based on clinical judgement and consultation with the patient and/or carer taking into account factors such as seizure frequency and treatment history
  • Category 3: Levetiracetam, lacosamide, tiagabine, gabapentin, pregabalin, ethosuximide, vigabatrin, brivaracetam. 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
Brivaracetam
  • Tablets 10mg, 25mg, 50mg, 75mg, 100mg (25mg-100mg twice daily = £129.64)
  • Oral solution 10mg/ml (25mg-100mg twice daily = £54.05-£216.22)
  • Solution for injection/infusion 10mg/ml (£22.28 per 5ml vial)

Indication

Notes

  1. In clinical studies, there was no observed benefit of brivaracetam versus placebo in patients taking levetiracetam concurrently.
  2. MHRA Category 3: It is usually unnecessary to ensure that patients are maintained on a specific manufacturer's product unless there are specific reasons such as patient anxiety and risk of confusion or dosing errors
  3. The routine commissioning of brivaracetam as an adjunctive treatment for partial-onset (focal) seizures is accepted in Devon (see Commissioning Policy for more details).
Carbamazepine
  • Tegretol® Tablet 100mg, 200mg, 400mg (£3.83 = 200mg x 84)
  • Tegretol® m/r tablet 200mg, 400mg (£5.20 = 56 x 200mg)
  • Tegretol® liquid sugar free 20mg/ml (£6.12 = 300ml)
  • Carbamazepine Essential Pharma® suppository 125mg, 250mg (£8.03 = 125mg x 5)

Indications

Notes

  1. Prescribe by brand. MHRA Category 1: Doctors are advised to ensure that their patient is maintained on a specific manufacturer's product.
  2. Prescribing by brand name is not needed when prescribing for non-epilepsy conditions
Eslicarbazepine acetate
  • Zebinix® tablets 800mg (£136.00 x 30 tablets)

Indications

Notes

  1. MHRA Category 2: The need for continued supply of a particular manufacturer's product should be based on clinical judgement and consultation with the patient and/or carer taking into account factors such as seizure frequency and treatment history. If the patient is stable on a particular generic preparation there is no requirement to switch to branded prescribing
Ethosuximide
  • Capsules 250mg (£173.00 = 56 capsules)

Indications

Notes

  1. MHRA Category 3: It is usually unnecessary to ensure that patients are maintained on a specific manufacturer's product unless there are specific reasons such as patient anxiety and risk of confusion or dosing errors
Gabapentin
  • Capsules 100mg, 300mg, 400mg (£3.24 = 400mg x 100)

Indications

Notes

  1. MHRA Category 3: It is usually unnecessary to ensure that patients are maintained on a specific manufacturer's product unless there are specific reasons such as patient anxiety and risk of confusion or dosing errors
  2. MHRA Drug Safety Update (October 2017): Be aware of risk of CNS depression, including severe respiratory depression, with gabapentin, and consider whether dose adjustments might be necessary in patients at higher risk of respiratory depression, including:
    1. Elderly people
    2. Patients with compromised respiratory function
    3. Patients with respiratory or neurological disease
    4. Patients with renal impairment
    5. Patients taking other CNS depressants
  3. MHRA Drug Safety Update (April 2019): Pregabalin (Lyrica), gabapentin (Neurontin) and risk of abuse and dependence
    1. evaluate patients carefully for a history of drug abuse and dependence before prescribing pregabalin and gabapentin
    2. observe patients on pregabalin and gabapentin for possible signs of abuse and dependence, for example, drug-seeking behaviour, dose escalation, and development of tolerance
    3. ensure patients are aware of the risk of potentially fatal interactions with other medicines that cause CNS depression, particularly opioid medicines, and with alcohol
Lacosamide
  • Tablets 50mg, 100mg, 150mg, 200mg (£8.77 = 200mg x 56)
  • Syrup 10mg/1ml (£25.74 (200ml)

Indications

Notes

  1. MHRA Category 3: It is usually unnecessary to ensure that patients are maintained on a specific manufacturer's product unless there are specific reasons such as patient anxiety and risk of confusion or dosing errors
Lamotrigine
  • Generic lamotrigine tablet 25mg, 50mg, 100mg, 200mg (£1.25 = 200mg daily)
  • Generic lamotrigine dispersible tablet 2mg, 5mg, 25mg, 100mg (£3.57 = 200mg daily)
  • Lamictal® tablet 25mg, 50mg, 100mg, 200mg (£58.68 = 200mg daily)
  • Lamictal® dispersible tablet 2mg, 5mg, 25mg, 100mg (£69.04 = 200mg daily)

Indications

Notes

  1. The CSM has advised prescribers to be alert for symptoms and signs suggestive of bone-marrow failure such as anaemia, bruising or infection. Aplastic anaemia, bone-marrow depression and pancytopenia have been associated rarely with lamotrigine.
  2. MHRA Category 2: In the treatment of epilepsy the need for continued supply of a particular manufacturer's product should be based on clinical judgement and consultation with the patient and/or carer taking into account factors such as seizure frequency and treatment history. If the patient is stable on a particular generic preparation there is no requirement to switch to branded prescribing. Prescribing by brand name is not needed when prescribing for non-epilepsy conditions
Levetiracetam
  • Tablets 250mg 500mg, 750mg, 1000mg (£5.50 = 1g x 60 tablets)
  • Oral solution sugar free 100mg/ml (£5.33 = 300ml)
  • Granules sugar free, sachet 250mg, 500mg, 1g (£76.27 = 1g x 60 sachets)

Indications

Notes

  1. MHRA Category 3: It is usually unnecessary to ensure that patients are maintained on a specific manufacturer's product unless there are specific reasons such as patient anxiety and risk of confusion or dosing errors
  2. Levetiracetam granules are included for use in paediatric patients who cannot take the tablets and cannot tolerate the oral solution.
Oxcarbazepine
  • Trileptal® tablets 150mg, 300mg, 600mg (£48.96 = 600mg x 50 tablets)

Indications

Notes

  1. MHRA Category 2: The need for continued supply of a particular manufacturer's product should be based on clinical judgement and consultation with the patient and/or carer taking into account factors such as seizure frequency and treatment history. If the patient is stable on a particular generic preparation there is no requirement to switch to branded prescribing.
Perampanel
  • Fycompa® tablets 2mg, 4mg, 6mg, 8mg, 10mg, 12mg (£140.00 = 28 tablets)

Indications

Notes

  1. Perampanel prescribing must only be passed onto primary care once the patient is titrated and established on a stabilised dose.
  2. MHRA Category 2: The need for continued supply of a particular manufacturer's product should be based on clinical judgement and consultation with the patient and/or carer taking into account factors such as seizure frequency and treatment history. If the patient is stable on a particular generic preparation there is no requirement to switch to branded prescribing.
Phenytoin Sodium Flynn

(Phenytoin)

  • Hard capsules 25mg, 50mg, 100mg, 300mg (£54.00 = 100mg x 84 capsules)

Indications

Notes

  1. Phenytoin has been identified as a drug where particular care needs to be exercised on initiation of therapy. Prescribers who are unfamiliar with the prescribing of this drug are strongly advised to read the full SPC. See NPSA Rapid Response Report Preventing fatalities from medication loading doses (Nov 2010)
  2. Prescribe by brand. MHRA Category 1: Doctors are advised to ensure that their patient is maintained on a specific manufacturer's product.
Pregabalin
  • Capsules 25mg, 50mg, 75mg, 100mg, 150mg, 200mg, 225mg, 300mg (£0.54 per capsule across all strengths)
  • Oral solution 20mg/ml (£99.48 = 473ml)

Indications

Notes

  1. Pregabalin capsules have a flat pricing structure so it is most cost-effective to prescribe the least number of capsules to form the required dose and to prescribe twice daily instead of three times daily
  2. Oral solution is only included for people with swallowing difficulties
  3. Public Health England: Practitioners should prescribe pregabalin and gabapentin appropriately to minimise the risks of misuse and dependence, and should be able to identify and manage problems of misuse if they arise. Most patients who are given these drugs will use their medicines appropriately without misuse. Further information see here
  4. MHRA Category 3: It is usually unnecessary to ensure that patients are maintained on a specific manufacturer's product unless there are specific reasons such as patient anxiety and risk of confusion or dosing errors.
  5. MHRA Drug Safety Update (April 2019): Pregabalin (Lyrica), gabapentin (Neurontin) and risk of abuse and dependence
    1. evaluate patients carefully for a history of drug abuse and dependence before prescribing pregabalin and gabapentin
    2. observe patients on pregabalin and gabapentin for possible signs of abuse and dependence, for example, drug-seeking behaviour, dose escalation, and development of tolerance
    3. ensure patients are aware of the risk of potentially fatal interactions with other medicines that cause CNS depression, particularly opioid medicines, and with alcohol
Sodium valproate
  • Generic sodium valproate enteric coated tablets 200mg, 500mg (£4.93 = 500mg twice daily)
  • Generic sodium valproate liquid sugar free 200mg/5ml (£5.01 = 300ml)
  • Epilim® liquid sugar free 200mg/5ml (£9.33 = 300ml)
  • Epilim® Crushable tablet 100mg (£5.60 = 100)
  • Epilim® enteric coated tablets 200mg, 500mg (£10.78 = 500mg twice daily)
  • Episenta® modified release capsules 150mg, 300mg (£3.64 = 300mg/day)
  • Episenta® modified release granules 500mg, 1g (£11.48 = 1g/day)

Indications

Notes

  1. Sodium valproate is not licensed for the treatment of manic episodes associated with bipolar disorder
  2. Episenta® m/r capsules and granules are included for use in paediatric patients who are not able to swallow sodium valproate tablets and other patients with swallowing difficulties
  3. MHRA Category 2: The need for continued supply of a particular manufacturer's product should be based on clinical judgement and consultation with the patient and/or carer taking into account factors such as seizure frequency and treatment history. If the patient is stable on a particular generic preparation there is no requirement to switch to branded prescribing.
  4. Specific information to support adherence to the Valproate Pregnancy Prevention Programme during the Covid-19 pandemic can be found here.
  5. MHRA Drug Safety Update (April 2018): Valproate medicines (Epilim▼, Depakote▼): contraindicated in women and girls of childbearing potential unless conditions of Pregnancy Prevention Programme are met and only if other treatments are ineffective or not tolerated, as judged by an experienced specialist
    1. GPs must identify and recall all women and girls who may be of childbearing potential, provide the Patient Guide and check they have been reviewed by a specialist in the last year and are on highly effective contraception
    2. Specialists must book in review appointments at least annually with women and girls under the Pregnancy Prevention Programme and re-evaluate treatment as necessary; explain clearly the conditions as outlined in the supporting materials; and complete and sign the Risk Acknowledgement Form—copies of the form must be given to the patient or patient/caregiver/responsible person and sent to their GP
    3. Use of valproate in pregnancy is contraindicated for bipolar disorder and must only be considered for epilepsy if there is no suitable alternative treatment
  6. The Medicines and Healthcare Products Regulatory Agency's (MHRA) Toolkit (Pregnancy Prevention Programme) on the risks of valproate medicines in female patients, provides resources to ensure female patients are better informed about the risks of taking valproate medicines during pregnancy.
  7. See resources for: contraception for drugs with teratogenic potential, and prescribing in pregnancy and lactation
Tiagabine
  • Tablets 5mg, 10mg, 15mg (£156.13 = 15mg x 100 tablets)

Indications

Notes

  1. MHRA Category 3: It is usually unnecessary to ensure that patients are maintained on a specific manufacturer's product unless there are specific reasons such as patient anxiety and risk of confusion or dosing errors.
Topiramate
  • Generic topiramate tablets 25mg, 50mg, 100mg, 200mg (£13.07 = 400mg daily)
  • Topamax® tablet 25mg, 50mg, 100mg, 200mg (£102.88 = 400mg daily)
  • Topamax Sprinkle® capsules 15mg, 25mg, 50mg (£34.02 = 100mg daily)

Indications

Notes

  1. Topiramate has been associated with acute myopia with secondary angle-closure glaucoma, typically occurring within 1 month of starting treatment. Choroidal effusions resulting in anterior displacement of the lens and iria have also been reported. The CSM advises that if raised intra-ocular pressure occurs to seek specialist ophthalmological advice, to use appropriate measures to reduce intra-ocular pressure and to stop topiramate as rapidly as possible.
  2. MHRA Category 2: In the treatment of epilepsy the need for continued supply of a particular manufacturer's product should be based on clinical judgement and consultation with the patient and/or carer taking into account factors such as seizure frequency and treatment history. If the patient is stable on a particular generic preparation there is no requirement to switch to branded prescribing. Prescribing by brand name is not needed when prescribing for non-epilepsy conditions.
  3. See resources for: contraception for drugs with teratogenic potential, and prescribing in pregnancy and lactation
Vigabatrin
  • Tablets 500mg (£44.41 = 100 tablets)
  • Granules for oral solution 500mg (£24.60 = 50 sachets)

Indications

Notes

  1. Vigabatrin is associated with visual field defects. The onset of symptoms varies from 1 month to several years after starting. In most cases, visual field defects have persisted despite discontinuation, and further deterioration after discontinuation cannot be excluded
  2. Patients should undergo visual field testing and assessment of visual acuity before treatment and at 6-month intervals for the whole duration of treatment
  3. Patients and their carers should be warned to report any new visual symptoms that develop and those with symptoms should be referred for an urgent ophthalmological opinion. Gradual withdrawal of vigabatrin should be considered
  4. MHRA Drug Safety Update (2014) Vigabatrin for infantile spasms: risk of movement disorders and MRI abnormalities
  5. MHRA Category 3: It is usually unnecessary to ensure that patients are maintained on a specific manufacturer's product unless there are specific reasons such as patient anxiety and risk of confusion or dosing errors.
Zonisamide
  • Zonegran® capsules 25mg, 50mg, 100mg (£94.08 = 300mg daily)

Indications

Notes

  1. MHRA Category 2: The need for continued supply of a particular manufacturer's product should be based on clinical judgement and consultation with the patient and/or carer taking into account factors such as seizure frequency and treatment history. If the patient is stable on a particular generic preparation there is no requirement to switch to branded prescribing.

Barbiturates

Phenobarbital
  • Tablets 15mg, 30mg, 60mg (£6.03 = 60mg x 28 tablets)

Indications

Notes

  1. Prescribe by brand. MHRA Category 1: Doctors are advised to ensure that their patient is maintained on a specific manufacturer's product.

Benzodiazepines

MHRA Drug Safety Update (March 2020): Benzodiazepines and opioids: reminder of risk of potentially fatal respiratory depression.

  • benzodiazepines (and benzodiazepine-like drugs) and opioid medicines (opioids) can both cause respiratory depression; when used together, additive effects on the central nervous system increase the risks of sedation, respiratory depression, coma, and death
Clobazam
  • Tablets 10mg (£3.42 = 30)

Indications

Notes

  1. MHRA Category 2: The need for continued supply of a particular manufacturer's product should be based on clinical judgement and consultation with the patient and/or carer taking into account factors such as seizure frequency and treatment history. If the patient is stable on a particular generic preparation there is no requirement to switch to branded prescribing.
Clonazepam
  • Tablet 500 microgram, 2mg (£31.49 = 2mg x 100 tablets)

Indications

Notes

  1. MHRA Category 2: The need for continued supply of a particular manufacturer's product should be based on clinical judgement and consultation with the patient and/or carer taking into account factors such as seizure frequency and treatment history. If the patient is stable on a particular generic preparation there is no requirement to switch to branded prescribing.

Other antiepileptics

Cannabidiol
  • Oral solution 100mg/ml

Notes

  1. NICE TA614: Cannabidiol (Epidyolex) with clobazam is recommended as an option for treating seizures associated with Dravet syndrome in people aged 2 years and older, only when the criteria of the NICE TA are met (December 2019)
  2. NICE TA615: Cannabidiol (Epidyolex) with clobazam is recommended as an option for treating seizures associated with Lennox–Gastaut syndrome in people aged 2 years and older, only when the criteria of the NICE TA are met (December 2019)

 

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