Also see SIGN Guideline Number 70 Diagnosis and management of epilepsy in adults.
Carbamazepine (tablets, m/r tablets, liquid, suppositories) is recommended for the treatment of many seizure types. Therapy should be initiated at low doses and increased slowly to the optimum dose.
Sodium valproate (tablets, e/c tablets, m/r tablets, capsules, liquid, syrup, injection) is recommended for the treatment of many seizure types. Therapy should be initiated at low dose and increased by 200mg every three days as required.
Phenytoin (tablets, capsules, suspension, injection) is an adjunct where control is difficult to obtain. It is no longer used first-line because of its narrow therapeutic range, saturation kinetics and side-effects. Therapy should be initiated once daily and increased slowly. Where doses of greater than 300mg/day are required, they should be increased in 25mg increments.
Phenobarbital/phenobarbitone (tablets, elixir, injection) tends only to be used to continue treatment. It is no longer used first line. Withdrawing barbiturate treatment is difficult and should only be attempted with specialist advice. It is a Controlled Drug but is exempt from the legal requirement that the prescription should be written in the doctor's own handwriting (this exemption does not apply to the date).
Lamotrigine (tablets, dispersible tablets) is licensed for the treatment of many seizure types. It is used either as monotherapy or as an adjunct to treatment with other antiepileptic drugs. Lamotrigine use has been associated with serious blood disorders and skin reactions, see BNF for details of CSM advice.
Levetiracetam (tablets, oral solution) may be initiated by physicians who have appropriate experience in the treatment of epilepsy as adjunctive therapy in the treatment of partial seizures with or without secondary generalisation.
Update October 2007 - Levetiracetam (Keppra®) in the treatment of - partial onset seizures in children with epilepsy [SMC 394/07], - myoclonic seizures in adults and adolescents from 12 years of age with juvenile myoclonic epilepsy [SMC 395/07], - primary generalised tonic-clonic seizures in adults and adolescents from 12 years of age with generalised idiopathic epilepsy [SMC 396/07], - partial onset seizures in patients from 16 years of age with newly diagnosed epilepsy [SMC 397/07]. Levetiracetam will not be included in Grampian Joint Formulary for these indications however patients currently receiving treatment should NOT HAVE their therapy changed if it is proving clinically effective.
Clonazepam (tablets, injection) is occasionally prescribed but its effectiveness may reduce after weeks or months of continuous use. It is a second-line drug and should usually only be prescribed on the recommendation of a consultant.
Clobazam (tablets) is like clonazepam and may be used as adjunctive therapy. It is only prescribable for epilepsy and the prescription must be endorsed 'SLB'.
The following drugs are all prescribed on specialist advice in resistant cases:
Lacosamide (tablets and syrup, Vimpat®) SMC 532/09
Vigabatrin (tablets, powder)
Major status epilepticus should be treated initially with intravenous lorazepam. Intravenous diazepam may also be used, but lorazepam has a longer duration of antiepileptic action. Due to the risk of respiratory depression following intravenous administration, resuscitation equipment should ideally be available. Where this is not the case, small doses should be given or consideration should be given to diazepam being administered as a rectal solution.
Phenytoin sodium may be given by slow intravenous injection with ECG monitoring followed by the maintenance dosage.
Paraldehyde given intramuscularly or rectally may be used if other preparations are ineffective or where respiratory depression must be avoided. Note: avoid contact with rubber and plastics.
PRESCRIBING POINTS FOR ANTIEPILEPTICS
- Routine plasma drug level monitoring is generally unnecessary except with phenytoin dosage adjustments. Exceptions are where toxicity is suspected or where there are suspected compliance problems.
- Folate deficiency can occur with long-term phenytoin and other antiepileptic treatments.
- All commonly used antiepileptic drugs carry a risk of teratogenicity. Women should be advised to obtain medical advice before a planned pregnancy.
- To counteract the risk of neural tube defects adequate folate supplements are advised for women before and during pregnancy. Women who are taking antiepileptic drugs need individual counselling before starting folic acid.
- Controversy still persists over the evidence for differences between the bioavailability of phenytoin sodium tablets and capsules. Hospitals in Grampian currently dispense Epanutin® if capsules are required, and some clinics prefer patients to remain on the same brand whenever possible. Consistent dispensing is the most important consideration - different preparations of phenytoin, sodium valproate and carbamazepine may vary in bioavailability and are not interchangeable and should be prescribed by brand name.
- Suspension of phenytoin 90mg in 15mL may be considered to be equivalent in therapeutic effect to tablets or capsules containing phenytoin sodium 100mg. Care should be taken if making changes. For this reason the suspension of phenytoin should be avoided whenever possible.
- Epanutin Infatabs® contain phenytoin 50mg as opposed to phenytoin sodium. Care should be taken if changing to tablets or capsules containing phenytoin sodium.
- Carbamazepine may be rarely associated with mild leucopenia.
- Sodium valproate can cause transient increases in liver function tests. This is not usually sinister. There have rarely been cases of liver failure. The risk is greatest at 2 to 12 weeks after starting therapy. The BNF currently recommends that liver function should be monitored for the first 6 months of therapy in those patients most at risk, that is, children and those with a history of liver disease.
- Intravenous phenytoin or sodium valproate may be used to initiate maintenance therapy in a clinical emergency.
- Modified-release formulations of carbamazepine and sodium valproate provide more uniform plasma concentrations and are to be preferred for maintenance therapy.
- When diazepam is given intravenously there may be a high risk of venous thrombophlebitis. This is minimised by using an emulsion formulation (Diazemuls®).