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4.8.1 Control of epilepsy

AEDs 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. Please refer to MHRA

(a) Pharmacological treatment of focal seizures, evolving / not evolving to bilateral tonic clonic seizure (previously termed with and without secondary generalisation)
ChoiceDrug
1st choiceLamotrigine tablets 25mg, 50mg, 100mg, 200mg
2nd choiceLevetiracetam tablets f/c 250mg, 500mg, 750mg, 1g; oral solution 100mg/ml
Or
Oxcarbazepine tablets 150mg, 300mg, 600mg
Or

Carbamazepine m/r tablets 200mg, 400mg; Carbamazepine liquid 100mg/5ml; Carbamazepine suppositories 125mg, 250mg

Prescribe By Brand Name

Or

Sodium valproate tablets e/c 200mg, 500mg; m/r 200mg, 300mg, 500mg; oral solution 200mg/5ml

(Valproate must not be started in new patients (male or female) < 55 years, unless two specialists independently consider and document that there is no other effective or tolerated treatment, or there are compelling reasons that the reproductive risks do not apply. Any use of valproate in women of childbearing potential who cannot be treated with other medicines must be in accordance with the Pregnancy Prevention Programme. See MHRA.)

(b) Pharmacological treatment of generalised (tonic-clonic, absence, myoclonic, tonic, clonic, atonic) and unclassified seizures
ChoiceDrug
1st choiceLamotrigine tablets 25mg, 50mg, 100mg, 200mg
Or

Sodium valproate tablets e/c 200mg, 500mg; m/r 200mg, 300mg, 500mg; oral solution 200mg/5ml

(Valproate must not be started in new patients (male or female) < 55 years, unless two specialists independently consider and document that there is no other effective or tolerated treatment, or there are compelling reasons that the reproductive risks do not apply. Any use of valproate in women of childbearing potential who cannot be treated with other medicines must be in accordance with the Pregnancy Prevention Programme. See MHRA.)

2nd choiceLevetiracetam tablets f/c 250mg, 500mg, 750mg, 1g; oral solution 100mg/ml
Or

Topiramate tablets 25mg, 50mg, 100mg, 200mg

(Topiramate is contraindicated in pregnancy and in women of childbearing potential unless the conditions of a Pregnancy Prevention Programme are fulfilled. See MHRA.)

Prescribing Notes

General Information

  • Refer to NICE CG137 ‘The epilepsies: diagnosis and management of the epilepsies in adults and children in primary and secondary care.’
  • The table above provides details on selected first and second choices, please refer to NICE CG137 for the full range of treatment options.
  • The AED treatment strategy should be individualised according to the seizure type, epilepsy syndrome, co-medication, co-morbidity, the young person or adult’s lifestyle and the preferences of the person and their family and/or carers as appropriate.
  • Sudden Unexpected Death in Epilepsy (SUDEP) risk can be actively reduced by identifying high risk individuals in primary care; such as those who pick up prescriptions erratically, alcohol or substance misuse, convulsive seizures, drug-resistant epilepsy (not seizure free after two appropriately selected, well tolerated drugs, at top dose range).
  • Many AEDs are hepatic enzyme-inducing agents, in particular carbamazepine, phenytoin, phenobarbital, oxcarbazepine, eslicarbazepine acetate and topiramate. Hepatic enzyme-inducing agents interact with a range of medicines, including:
    • AEDs which induce hepatic enzymes may impair the efficacy of oral contraceptives; see BNF for details
    • Sudden withdrawal of these drugs may decrease the rate at which warfarin is metabolized and put a patient taking a combination of these drugs at an increased risk of bleeding
  • AEDs use can have adverse effects on bone. Patients should be given dietary and lifestyle advice on minimising the risk of osteoporosis and vitamin D supplementation should be considered for at risk patients.  See MHRA for further details on risks associated with the different AEDs.
  • Liquid formulations and dispersible or chewable tablets are more expensive than standard tablets. Standard tablet formulations (m/r or e/c included) should be prescribed where possible.
  • Patients taking multiple tablets of lamotrigine (generic or Lamictal®) should be reviewed to consider switching to the equivalent dose of higher strength tablets e.g. 100mg x 2 tablets to 200mg x 1 tablet. Only switch patients that are stable on an established effective dose that controls seizures.
  • If using carbamazepine, offer controlled-release carbamazepine preparations as they are better tolerated.
Initiation of pharmacological treatment
  • AED therapy should only be started once the diagnosis of epilepsy is confirmed, except in exceptional circumstances.
  • In considering patients with suspected seizures; the appropriate pathway is either via ED, via local first seizure clinic, or via named neurologist who may have them under review.
  • Valproate must not be started in new patients (male or female) younger than 55 years, unless two specialists independently consider and document that there is no other effective or tolerated treatment, or there are compelling reasons that the reproductive risks do not apply. For the majority of patients, other effective treatment options are available. See MHRA and ‘Women and girls of childbearing’ potential below.
  • Routine plasma drug level monitoring is generally unnecessary unless side-effects/toxicity are suspected or non-compliance is suspected.
  • Abnormal blood parameters occur with a number of AEDs. Routine bloods should be checked at baseline, after initiation of a new AED and periodically thereafter (every 1-2 years).
  • Gradual withdrawal of antiepileptic drugs can be considered with caution, for some patients, after a prolonged period of seizure freedom (at least 2 years) but note implications for driving. Specialist advice should always be sought to estimate the individual risk of seizure recurrence on withdrawal of AED treatment.
Women and girls of childbearing potential
  • Refer to the Epilepsy Action Women and Epilepsy guidance for advice on topics including contraception and pre-pregnancy planning.
  • The dose of AED may need to be adjusted in women who commence or stop oral contraceptives – see FSRH website.
  • Certain AEDs carry a risk of teratogenicity. Never stop AEDs acutely upon finding out a woman is pregnant; specialist discussion is required. Teratogenic risk is dependent on several factors, most notably dose and AED choice. Hence the importance of appropriate contraception –see FSRH website.
  • Antiepileptic drugs in pregnancy – updated MHRA advice confirms that lamotrigine (Lamictal) and levetiracetam are safer to use during pregnancy than other antiepileptics. Refer to MHRA and Epilepsy medicines and pregnancy leaflet for full details.
  • Use of valproate in women and girls of childbearing potential who cannot be treated with other medicines must be in accordance with the Pregnancy Prevention Programme. See MHRA and ‘Initiation of pharmacological treatment’ above.
  • Topiramate is contraindicated in pregnancy and in women of childbearing potential unless the conditions of a Pregnancy Prevention Programme are fulfilled. See MHRA.
AED polytherapy
  • If a patient is still having ongoing seizures discuss with the specialist epilepsy team.

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