Drug Safety Update
February 2021: Pregabalin (Lyrica): reports of severe respiratory depression
January 2021: Antiepileptic drugs in pregnancy: updated advice following comprehensive safety review
May 2020: Valproate Pregnancy Prevention Programme: temporary advice for management during coronavirus (COVID-19)
 February 2020: Valproate (Epilim▼, Depakote▼) pregnancy prevention programme: updated educational materials
 April 2019: Valproate medicines and serious harms in pregnancy: new Annual Risk Acknowledgement Form and clinical guidance from professional bodies to support compliance with the Pregnancy Prevention Programme
 April 2019: Pregabalin (Lyrica), gabapentin (Neurontin) and risk of abuse and dependence: new scheduling requirements from 1 April
 March 2019: Medicines with teratogenic potential: what is effective contraception and how often is pregnancy testing needed?
 December 2018:Valproate medicines: are you acting in compliance with the pregnancy prevention measures?
 September 2018: Valproate Pregnancy Prevention Programme: actions required now from GPs, specialists, and dispensers
May 2018: Valproate medicines (Epilimâ–¼, Depakoteâ–¼): Pregnancy Prevention Programme materials online
April 2018: Valproate medicines (Epilimâ–¼, Depakoteâ–¼): contraindicated in women and girls of childbearing potential unless conditions of Pregnancy Prevention Programme are met
November 2017: Antiepileptic drugs: updated advice on switching between different manufacturers’ products
 October 2017: Gabapentin (Neurontin): risk of severe respiratory depression
 November 2016: Patient Safety Alert: Risk of death or severe harm from error with injectable phenytoin
 December 2012: Carbamazepine, oxcarbazepine and eslicarbazepine potential risk of serious skin reactions
 April 2009: Antiepileptics adverse effects on bone (carbamazepine, phenytoin, primidone and sodium valproate)
 August 2008: Antiepileptics risk of suicidal thoughts and behaviour
April 2008: Carbamazepine: genetic testing recommended in some Asian populations
- Higher risk of carbamazepine-induced Stevens -Johnson syndrome in some Asian populations. Also see December 2012 update above
 November 2007: Herbal ingredient St John's Wort may interact with antiepileptics
- This should not be taken concurrently.Â
Drug Level Monitoring is useful for both checking compliance and for checking therapeutic levels particularly for phenytoin.
Drug Interactions are common between antiepileptics and other drugs particularly those which are hepatically metabolised. Interactions should be checked when prescribing a new drug for patients on antiepileptics.
It is important to avoid switching brands for some anti-epileptics - see BNF.
Neuropathic pain may be treated using antiepileptics particularly gabapentin and pregabalin. See local guidelines.
Phenytoin
- has a narrow therapeutic index and the relationship between the dose and plasma concentration is non-linear. Dose adjustments should be made in small increments of 25mg if the level is near the end of the therapeutic range (eg for dose increases above 300mg daily)
- 90 mg of phenytoin (chewable tablets or suspension) is equivalent to 100mg of phenytoin sodium (capsules or tablets) so care is needed if transferring from one formulation to another.
- IV phenytoin the dosage should be divided and given 8 hourly rather than once daily to avoid toxic levels developing.
Sodium valproate
- must no longer be used in women and girls of childbearing potential unless a Pregnancy Prevention Programme is in place. All prescribers that are initiating valproate should complete the Risk Acknowledgement Form and keep a copy in the patient's healthcare records as a permanent record of your discussion.
Brivaracetam (Briviact)
- within its licensed indications is for restricted use for refractory patients who remain uncontrolled with or are intolerant to other adjunctive anti-epileptic medicines. Levetiracetam should be tried as an option prior to prescribing brivaracetam.
Perampanel (Fycompa)
- is available for the adjunctive treatment of focal seizures. An overview of the evidence supporting the use of perampanel is available on the NICE website .Â
Levetiracetam
- when used in palliative care levetiracetam may be given as a subcutaneous injection. (unlicensed route of administration).
Topiramate
- caution in women of child-bearing potential or pregnancy - risk of fetal malformations and can impair the effectiveness of hormonal contraceptives (see BNF).
