4.8.1 Control of the epilepsies

MHRA Antiepileptic drugs: advice on switching between different manufacturers' products for a particular drug (November 2013)

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. 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
  • Briviact® tablets 10mg, 25mg, 50mg, 75mg, 100mg (25mg-100mg twice daily = £129.64)
  • Briviact® oral solution 10mg/ml (25mg-100mg twice daily = £54.05-£216.22)
  • Briviact® 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. The routine commissioning of brivaracetam as an adjunctive treatment for partial-onset (focal) seizures has been 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® liquidSF 100mg/ml (£6.12 = 300ml)
  • Carbamazepine Essential Pharma® suppository 125mg, 250mg (£8.03 = 125mg x 5)

Indications

Notes

  1. MHRA: 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: 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
  • Capsule 250mg (£173.00 = 56 capsules)
  • Syrup 250mg/5ml (£173.00 = 200ml)

Indications

Notes

  1. MHRA: 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
Gabapentin
  • Capsule 100mg, 300mg, 400mg (£3.24 = 100 x 400mg)
  • Tablets 600mg, 800mg (£29.06 = 100 x 800mg)
  • Liquid 50mg/ml

Indications

Notes

  1. MHRA: 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
  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
Lacosamide
  • Tablets 50mg, 100mg, 150mg, 200mg (£8.77 = 200mg x 56 tablets)
  • Syrup 10mg/1ml (£25.74 = 200ml)
  • Intravenous infusion 10mg/ml 200mg vial

Indications

Notes

  1. MHRA: 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
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

  • Epilepsy
  • Prevention of depressive episodes associated with bipolar disorder

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: 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
  3. Prescribing by brand name is not needed when prescribing for non-epilepsy conditions.
Levetiracetam
  • Tablets 250mg, 500mg, 750mg, 1g (£5.50 = 1g x 60 tablets)
  • Oral solutionSF 100mg/ml (£5.33 = 300ml)
  • GranulesSF sachet 250mg, 500mg, 1g (£76.27 = 1g x 60 sachets)
  • Concentrate for I/V infusion 100mg/ml 5ml vial

Indications

Notes

  1. MHRA: 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
  2. Levetiracetam granules are included for use in paediatric patients who cannot swallow the tablets, and cannot tolerate the oral solution.
Oxcarbazepine
  • Trileptal® tablets 150mg, 300mg, 600mg (£48.96 = 600mg x 50 tablets)
  • Trileptal® oral suspensionSF 300mg/5ml (£48.96 = 250ml)

Indications

Notes

  1. MHRA: 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: 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
  • Phenytoin sodium Flynn hard capsule 25mg, 50mg, 100mg, 300mg (£54.00 = 100mg x 84 capsules)
  • Phenytoin sodium tablets 100mg (£23.00 = 28 tablets)
  • Epanutin® infatabs chewable tablet 50mg (scored) (£13.18 = 200)
  • Epanutin® suspension 30mg in 5ml (£4.27 = 500ml)
  • Intravenous injection 250mg/5ml
  • Suspension 90mg in 5ml (unlicensed preparation)

Indications

  • Epilepsy
  • Trigeminal neuralgia if carbamazepine inappropriate
  • Status epilepticus

Notes

  1. Phenytoin has a narrow therapeutic index and the relationship between dose and plasma concentration is non-linear; a small dose increase in some patients may produce large rises in plasma concentration with acute toxic side effects.
  2. 90mg of phenytoin (chewable tablets or suspension) is considered to be equivalent to 100mg of phenytoin sodium (capsules or tablets), so care is needed if patients are transferred from one preparation to another.
  3. MHRA: doctors are advised to ensure that their patient is maintained on a specific manufacturer's product
  4. Prescribing by brand name is not needed when prescribing for non-epilepsy conditions
Pregabalin
  • Capsules 25mg, 50mg, 75mg, 100mg, 150mg, 200mg, 225mg, 300mg (£2.29 = 150mg twice daily)
  • 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: For epilepsy treatment 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.
Rufinamide
  • Inovelon® tablet 100mg, 200mg, 400mg (£102.96 = 400mg x 60 tablets)

Indications

Notes

  1. MHRA: 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.
Sodium valproate
  • Generic sodium valproate e/c tablets 200mg, 500mg (£4.93 = 500mg twice daily)
  • Generic sodium valproate liquidSF 200mg/5ml (£5.01 = 300ml)
  • Epilim® liquidSF 200mg/5ml (£9.33 = 300mg)
  • Epilim® Crushable tablet 100mg (£5.60 = 100)
  • Epilim® e/c tablets 200mg, 500mg (£10.78 = 500mg twice daily)
  • Epilim Chrono® m/r tablet 200mg, 300mg, 500mg (£16.30 = 500mg twice daily)
  • Episenta® m/r capsules 150mg, 300mg (£13.00 = 300mg x 100)
  • Episenta® m/r granules 500mg, 1g (£41.00 = 1g x 100 sachets)
  • Intravenous injection 400mg

Indications

Notes

  1. Episenta® has been included for patients with swallowing difficulties
  2. MHRA: 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.
  3. Prescribing by brand name is not needed when prescribing for non-epilepsy conditions
  4. MHRA Drug Safety Update (February 2016): Valproate and risk of abnormal pregnancy outcomes: new communication materials. MHRA Drug Safety Update (April 2017): Valproate and developmental disorders: new alert asking for patient review and further consideration of risk minimisation measures.
    1. ensure women and girls taking valproate medicines understand the 30–40% risk of neurodevelopmental disorders and 10% risk of birth defects and are using effective contraception
    2. valproate should not be prescribed to female children, female adolescents, women of childbearing potential or pregnant women unless other treatments are ineffective or not tolerated; migraine is not a licensed indication
    3. valproate use in women and girls of childbearing potential must be initiated and supervised by a specialist experienced in managing epilepsy or bipolar disorder
    4. 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
    5. you must ensure that all female patients are informed of and understand:
      1. risks associated with valproate during pregnancy
      2. need to use effective contraception
      3. need for regular review of treatment
      4. the need to rapidly consult if she is planning a pregnancy or becomes pregnant
  5. Patient Safety Alert to further highlight risks to the unborn child and support the safety of girls and women taking valproate
  6. The Medicines and Healthcare Products Regulatory Agency's (MHRA) Toolkit 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.
Tiagabine
  • Tablets 5mg, 10mg, 15mg (£156.13 = 15mg x 100 tablets)

Indications

Notes

  1. MHRA: 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
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: 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.
  3. Prescribing by brand name is not needed when prescribing for non-epilepsy conditions.
Zonisamide
  • Zonegran® capsules 25mg, 50mg, 100mg (£94.08 = 300mg daily)

Indications

Notes

  1. MHRA: 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.
Vigabatrin
  • Tablet 500mg
  • PowderSF 500mg

Notes

  1. Vigabatrin is associated with irreversible retinal toxicity in many patients. 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. Product literature advises visual field testing before treatment and at 6-month intervals. Patients 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.
  2. Subsequently, its indications are limited for use in combination therapy only when all other antiepileptic drug combination therapy has proved ineffective or poorly tolerated. It may only be used for monotherapy in infantile spasms (West's syndrome), where it remains first-line therapy. It should only be initiated by an epilepsy specialist.

Barbiturates

Phenobarbital
  • Tablets 15mg, 30mg, 60mg (£6.03 = 60mg x 28 tablets)
  • Elixir 15mg/5ml, contains alcohol (£83.00 = 500ml)
  • Oral solution 50mg/5ml, alcohol free (unlicensed preparation)
  • Injection 30mg/1ml, 200mg/ml

Indications

Notes

  1. Phenobarbital is included in the formulary for patients currently taking this drug. It is not expected that there will be any new initiations of treatment.
  2. MHRA: doctors are advised to ensure that their patient is maintained on a specific manufacturer's product

Benzodiazepines

Clobazam
  • Tablet 10mg (£3.42 = 30)
  • Oral suspension 5mg/5ml (£90.00 = 150ml)

Indications

Notes

  1. MHRA: 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)
  • Intravenous injection 1mg/ml or infusion of 1mg
  • Liquid 250 micrograms/ml (unlicensed preparation)

Indications

Notes

  1. MHRA: 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 drugs

Acetazolamide (section 11.6), a carbonic anhydrase inhibitor, has a specific role in treating epilepsy associated with menstruation. It can also be used with other antiepileptics for refractory tonic-clonic, absence, and focal seizures. It is occasionally helpful in atypical absence, atonic, and tonic seizures.

 

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