Perampanel | Epilepsy clinician handbook
- Perampanel is a relatively new anti-seizure medication.
- It can be used to treat both focal 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-seizure medications. 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.
Possible side effects
- Somnolence, fatigue
- Irritability
- Dizziness, vertigo
- Anger, anxiety, aggression
- Headache
- Nausea
- Blurred vision
- Weight gain (common)
- Gait disturbance
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 anti-seizure medications are potentially teratogenic and this is often dose related.
- For a complete list of adverse effects, appropriate formularies should be consulted.
Interactions and precautions
- 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: Perampanel metabolites are partially renally excreted. Limited data. Advised not to use in moderate or severe renal impairment.
- Hepatic impairment: Limited data. Peramapanel is extensively metabolised by the liver. 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.