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Perampanel

 

Usage

  • Perampanel is a relatively new anti-convulsant. It can be used to treat partial onset seizures and generalised seizures.
  • The PBS indication is for adjunctive treatment by a neurologist of focal onset seizures and for generalised seizures in children > 12 years who have not been satisfactorily controlled by at least 2 other anti-epileptic drugs. Refer to PBS for specific requirements and current updates. 
  • Perampanel is a non-competitive AMPA antagonist that works by blocking excitatory neurotransmission. It does not share a mechanism of action with any other anti-epileptic drug.
  • Several drug interactions have been noted with perampanel (see Drug Interactions below).

 

Side effects

Common side effects:

  • Irritability
  • Dizziness
  • Somnolence
  • Fatigue
  • Headache
  • Nausea
  • Blurred vision
  • Weight gain
  • Gait disturbance
  • Vertigo

 

Other notable side effects:

  • Psychiatric and behavioural problems with aggression, irritability and homicidal ideation, threats and physical assault. Current data suggests the risk is greatest during the titration period or at higher doses.
  • Suicidal ideation is reported in around 1 in 500 people taking Perampanel.
  • All anticonvulsants are potentially teratogenic and this is often dose related (see section: Pregnancy and AEDs)
  • For a complete list of adverse effects, appropriate formularies should be consulted

 

Dosing

  • The initiation and escalation dose depends upon age, weight, syndrome, seizure frequency and intensity, and side effect profile.
  • Unfortunately, a one dose regime does not fit all. A Paediatric Neurologist should be consulted if there is uncertainty.

 

A commonly used regime is below:

  • Initial dose: 2mg daily
  • Reasonable maintenance dose is 4-8mg od (Max dose 12mg) depending on efficacy and tolerability. Slow titrations are advised, with a minimum of 2 weeks between dose increases of 2mgs.
  • Perampanel should be taken once daily at bedtime.
  • These dosages are only a guideline and appropriate formularies should be consulted as needed

 

 

Preparations

  • Tablets: 2mg, 4mg, 6mg, 8mg, 10mg, 12mg
  • Tablets can be chewed or crushed and added to food or liquid

 

Drug Interactions

  • Carbamazepine, oxcarbazepine, phenytoin and topiramate, may result in decreased plasma levels of perampanel. Similarly, other CYP3A4 inducing drugs such as rifampicin and St John’s Wort are not recommended to be used in conjunction with Perampanel.
  • Perampanel can increase the concentration of oxcarbazepine.
  • Perampanel can decrease levels of carbamazepine, clobazam, lamotrigine, midazolam, and valproate.
  • Perampanel can potentially decrease efficacy of progestative oral contraceptives, leading to consideration of additional non-hormonal methods of contraception.
  • Inhibitors of CYP3A4 drug metabolism including ketoconazole or grapefruit juice may cause modest increases in perampanel concentrations. 

 

 

Precautions

  • Renal impairment: Limited data. Advised not to use in moderate or severe renal impairment.
  • Hepatic impairment: Limited data. Advised not to use in severe hepatic impairment and use with caution in mild-moderate impairment (maximum dose 4-6mg). See product information.

 

Weaning

  • When ceasing Perampanel it is important to withdraw slowly to minimize the potential of increased seizure frequency.

 

Pregnancy

  • There is limited data of the safety of Perampanel in pregnancy.
  • Usage in pregnancy needs to be discussed with a neurologist.

 

 

 

MIMS

PBS

 

Parent Handout

 

 

 

This page was created on the 8/11/2018.