Perampanel


  Issues for Surgery


Precipitation of rebound seizures or status epilepticus if omitted.


  Advice in the Perioperative period


Elective and Emergency Surgery

Continue.

Patients should be advised to take their regular medications on the day of surgery1, 2, 3.

Abrupt withdrawal of any anticonvulsant drug should be avoided1.

Confirm with the patient if they need to be maintained on a specific manufacturer’s product (see Further Information).

Post-operative Advice

Regular dosing of the patient’s usual oral medication should be re-established as early as possible post-operatively2, 3.

Perampanel is only available as oral preparations. If patients cannot resume their usual oral medication post-operatively, the advice of a Neurologist should be sought to determine the most appropriate antiepileptic preparation, dose, route and frequency to be used.


  Interaction(s) with Common Anaesthetic Agents


For general information regarding the use of anaesthetic agents in patients with epilepsy – see Antiepileptics – A General Overview.

Central Nervous System (CNS) Depression (also see under Interaction(s) with other Common Medicines used in the Perioperative Period)

Perampanel has CNS depressant effects which may be additive with other medicines that also have CNS depressant effects such as1: -

  • benzodiazepines
  • inhalational anaesthetics and intravenous anaesthetics
  • local anaesthetics
  • opioids*

*NB: Tramadol should be avoided in patients with a history of epilepsy due to an increase in seizure risk1.

(Consult British National Formulary for available drugs in each class)

Midazolam

The manufacturers note perampanel 6mg daily decreased the area under curve for midazolam by 13% (due to perampanel effects on CYP3A substrates), whilst this is unlikely to be clinically significant, they advise a larger decrease in midazolam exposure cannot be ruled out with higher perampanel doses4, 5.


  Interaction(s) with other Common Medicines used in the Perioperative Period


CNS Depression (also see under Interaction(s) with Common Anaesthetic Agents for information on opioids)

Perampanel has CNS depressant effects which may be additive with antiemetics that also have CNS depressant effects such as cyclizine, droperidol and prochlorperazine*1.

*NB: see Antiepileptics – A General Overview

Antimicrobials

Clarithromycin is predicted to slightly increase the exposure to perampanel1, 4. Until more is known monitor for perampanel adverse effects (dizziness, blurred vision, gait disturbances) and reduce the dose of perampanel according to clinical need4.

Whilst single surgical prophylactic doses should not pose a problem, continued post-operative treatment may require close monitoring. Consult current product literature.


  Further Information


MHRA/CHM Advice: Antiepileptic Drugs: updated advice on switching between different manufacturer’s products (November 2017)1

Perampanel is a category 2 antiepileptic, hence 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 treatment history, and potential implications to the patient having a breakthrough seizure. Non-clinical factors such as patient anxiety, confusion, potential for dosing errors should also be considered (For more information see Antiepileptics – A General Overview).


  References


  1. Joint Formulary Committee. British National Formulary (online) London: BMJ Group and Pharmaceutical Press http://www.medicinescomplete.com [Accessed 30th June 2019]
  2. Perks A, Cheema S, Mohanraj R. Anaesthesia and epilepsy. BJA: British Journal of Anaesthesia. 2012; 108(4):562-571
  3. Carter EL, Adapa RM. Adult epilepsy and anaesthesia. BJA Education. 2015; 15(3):111-117
  4. Summary of Product Characteristics – Fycompa® (perampanel) 10mg film-coated tablets. Eisai Ltd. Accessed via www.medicines.org.uk 20/07/2019 [date of revision of the text March 2019]
  5. Baxter K, Preston CL (eds), Stockley’s Drug Interactions (online) London: Pharmaceutical Press. http://www.medicinescomplete.com [Accessed on 30th September 2019]