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4.8 Antiepileptics

.Click here for theNICE Clinical Guideline CG137: The epilepsies: the diagnosis and management of the epilepsies in adults and children in primary and secondary care


Antiepileptic drugs: new MHRA advice on switching

Different antiepileptic drugs (AEDs) 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. The MHRA have divided AEDs 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. Phenytoin, primidone, carbamazepine, and phenobaribital are classified as category 1, the most important group to maintain consistent product supply.  If it is felt desirable for a patient to be maintained on a specific manufacturer’s product, this should be prescribed either by specifying a brand name, or by using the generic drug name and name of the manufacturer.

For further information: See MHRA Drug Safety Update

Carbamazepine tablets, MR tablets, liquid, suppositories (MHRA Category 1)
Diazepam tablets, syrup, emulsion injection, rectal solution, suppositories
Phenytoin capsules, infatabs, tablets, syrup, injection (MHRA Category 1); see note
Phenobarbital tablets, elixir, injection (MHRA Category 1)
Sodium valproate tablets, chrono tablets, MR capsules, liquid, injection - see note
Brivaracetam  tablets – see note
Clobazam tablets, oral liquid suspension (paediatrics only) – see note
Clonazepam tablets, syrup, injection
Eslicarbazepine tablets RED drug
Ethosuximide capsules, syrup (first line option for absence seizures)
Gabapentin capsules, tablets - for neuropathic pain only
Lacosamide tablets, syrup, intravenous infusion
Lamotrigine tablets, dispersible tablets
Levetiracetam tablets, oral solution
Lorazepam injection
Midazolam (Epistatus) buccal liquid (unlicensed) - use in < 3 months only BROWN drug
Midazolam (Buccalam) oromucosal solution (licensed for use in children from 3 months) GREEN drug
Perampanel tablets RED drug
Pregabalin capsules - neurologist use only for add on therapy in partial seizures or use by the pain clinic for neuropathic pain in patients where gabapentin is effective but not tolerated
Paraldehyde in olive oil enema (unlicensed product)
Oxcarbazepine tablets - neurologist use only in patients intolerant of carbamazepine
Rufinamide tablets - severe resistant epilepsy, including Lennox-Gastaut syndrome
Vigabatrin tablets, sachets click here for shared care
Topiramate tablets, sprinkle capsules
Tiagabine tablets - specialist initiation only for refractory partial epilepsy
Zonisamide capsules


Pharmacokinetics of drugs requiring therapeutic drug monitoring


1. Injectable phenytoin is used to slow and stabilise erratic electrical brain activity in status epilepticus, a life-threatening medical emergency. Phenytoin is a particularly complicated drug to use. It has a narrow therapeutic index, meaning that there is little difference between the effective dose and a larger dose that can cause harm. A loading dose, to quickly raise the amount of the drug in the body, is recommended for injectable phenytoin. The BNF recommends a loading dose of 20mg/kg, given at a maximum rate of 50mg/minute. After dilution, iv phenytoin should be given via a 0.22-0.5 micron in-line filter. Further information on prescribing, preparation, administration and monitoring is available in the BNF. A UKMi Q&A “How can we minimise the risks to patients when using intravenous phenytoin in status epilepticus (SE)?” is also available here..

A NHS Improvement ‘Patient Safety Alert’ has been produced: “Risk of death and severe harm from error with injectable phenytoin” (November 2016): available here. Also, local poster available here.

2. When prescribing phenytoin suspension, remember that 90mg (15mls) of suspension is approximatley equivalent in therapeutic effect to 100mg of phenytoin sodium in capsule or tablet form.

3. Paraldehyde in olive oil enema is for refractory status epilepticus in children - care needs to be taken with dosing.

4. Vigabatrin for infantile spasms: risk of movement disorders and MRI abnormalities:

Movement disorders have been reported in patients treated with vigabatrin for infantile spasms. If new movement disorders occur during treatment with vigabatrin, consideration should be given to dose reduction or a gradual
discontinuation of treatment in consultation with specialist advice. Cases of abnormal brain MRI findings have been reported, in particular in young infants treated for infantile spasms with high doses (≥125 mg/kg/day) of vigabatrin. The clinical significance of these findings is currently unknown.

5. Sodium valproate MR (Episenta) capsules are listed for paediatric use only. The capsules can be opened and the contents mixed with soft food e.g. yoghurt. As the granules are modified release, this preparation can be given as a single daily dose.

Sodium valproate - FOR FEMALES OF CHILD-BEARING POTENTIAL: Initiate under specialist advice ONLY when other medication ineffective/not-tolerated. Pregnancy prevention programme required. Refer new/existing patients if they haven’t been seen by a specialist within 12 months. Link to Pregnancy Prevention Programme resource materials. 

Sodium valproate should not be used during pregnancy and in women of childbearing potential unless clearly necessary (high risk of neurodevelopmental delay and congenital malformations in children following maternal use). See  DSU January 2015February 2016 and April 2017

An MHRA toolkit for prescribing of valproate in females outlining the risks of use in pregnancy  is available.

6. Retigabine is restricted to last-line use in resistant partial onset seizures with or without secondary generalisation in patients aged 18 years or older, where other treatments or combinations have proved inadequate or have not been tolerated. This is due to reports of pigment changes of ocular tissues, including the retina. Comprehensive ophthalmic examination should be done at the start of treatment and at least every 6 months thereafter. See DSU July 2013.

7. Brivaracetam is reserved for specialist epilepsy service use only, for patients who have responded to levetiracetam but have developed unacceptable non-psychotic behavioural side effects severely affecting quality of life. It is NOT appropriate for patients in whom there has been an inadequate response to levetiracetam.

8. Clobazam is approved by NICE for use in various epilepsies.

9.Gabapentin has been associated with a rare risk of severe respiratory depression even without concomitant opioid medicines. Patients with compromised respiratory function, respiratory or neurological disease, renal impairment, concomitant use of central nervous system (CNS) depressants, and elderly people might be at higher risk of experiencing severe respiratory depression. Dose adjustments might be necessary in these patients (link to DSU)

10.Patients who are receiving benzodiazepines for extended periods of time should be reviewed by their prescribers on a regular basis so that their suitability for long term prescribing can be assessed. When withdrawing benzodiazepines the patient should be monitored closely during this period. Advice on withdrawing patients from benzodiazepines is available on the CKS website.  

 Link to BNF section: 4.8 Antiepileptic drugs