Perampanel oral
- Drugs List
- Therapeutic Indications
- Dosage
- Contraindications
- Precautions and Warnings
- Pregnancy and Lactation
- Side Effects
- Monograph
Presentation
Oral formulations of perampanel.
Drugs List
Therapeutic Indications
Uses
Epilepsy - primary generalised tonic-clonic seizures - adjunctive
Epilepsy-partial seizures with/without secondary generalisation-adjunctive
Perampanel is indicated for the adjunctive treatment of partial-onset seizures (POS) with or without secondary generalised seizures in patients from 4 years of age and older.
Perampanel is indicated for the adjunctive treatment of primary generalised tonic-clonic (PGTC) seizures in patients from 7 years of age and older with idiopathic generalised epilepsy.
Dosage
Perampanel must be titrated according to individual patient response, in order to optimise the balance between efficacy and tolerability.
Perampanel should be taken once daily before bedtime.
Adults
Adjunctive treatment for partial seizures with/without secondary generalisation
Initial dose: 2mg per day.
Increased thereafter by 2mg, every 2 weeks. A faster titration is required in patients taking concomitant enzyme inducers (see additional dosage information).
Maintenance dose: 4mg to 8mg per day.
Depending upon individual clinical response and tolerability at a dose of 8mg per day, the dose may be further increased by increments of 2mg per day to 12mg per day.
Adjunctive treatment for primary generalised tonic-clonic seizures
Initial dose: 2mg per day.
Increased thereafter by 2mg, every 2 weeks. A faster titration is required in patients taking concomitant enzyme inducers (see additional dosing information)
Maintenance dose: 8mg per day.
Depending upon individual clinical response and tolerability at a dose of 8mg per day, the dose may be further increased to 12mg per day.
Children
Adjunctive treatment for partial seizures with/without secondary generalisation
Children above 12 years:
(see Dosage; Adults)
Children aged 4 to 11 years weighing 30kg or more:
Initial dose: 2mg per day.
Increased thereafter by 2mg, either weekly or every 2 weeks as per half-life considerations.
Maintenance dose: 4mg to 8mg per day. Depending upon individual clinical response and tolerability at a dose of 8mg per day, the dose may be further increased by increments of 2mg per day to 12mg per day.
Children aged 4 to 11 years weighing 20 to 30kg:
Initial dose: 1mg per day.
Increased thereafter by 1mg, either weekly or every 2 weeks as per half-life considerations.
Maintenance dose: 4mg to 6mg per day. Depending upon individual clinical response and tolerability at a dose of 6mg per day, the dose may be further increased by 1mg to 8mg per day.
Children aged 4 to 11 years weighing less than 20kg:
Initial dose: 1mg per day.
Increased thereafter by 1mg, either weekly or every 2 weeks as per half-life considerations.
Maintenance dose: 2mg to 4mg per day. Depending upon individual clinical response and tolerability at a dose of 4mg per day, the dose may be further increased by 0.5mg to 6mg per day.
Adjunctive treatment for primary generalised tonic-clonic seizures
Children above 12 years:
(see Dosage; Adults)
Children aged 7 to 11 years weighing 30kg or more:
Initial dose: 2mg per day.
Increased thereafter by 2mg, either weekly or every 2 weeks as per half-life considerations.
Maintenance dose: 4mg to 8mg per day. Depending upon individual clinical response and tolerability at a dose of 8mg per day, the dose may be further increased by 2mg to 12mg per day.
Children aged 7 to 11 years weighing 20 to 30kg:
Initial dose: 1mg per day.
Increased thereafter by 1mg, either weekly or every 2 weeks as per half-life considerations.
Maintenance dose: 4mg to 6mg per day. Depending upon individual clinical response and tolerability at a dose of 6mg per day, the dose may be further increased by 1mg to 8mg per day.
Children aged 7 to 11 years weighing less than 20kg:
Initial dose: 1mg per day.
Increased thereafter by 1mg, either weekly or every 2 weeks as per half-life considerations.
Maintenance dose: 2mg to 4mg per day. Depending upon individual clinical response and tolerability at a dose of 4mg per day, the dose may be further increased by 0.5mg to 6mg per day.
Patients with Hepatic Impairment
Mild or moderate hepatic impairment
Initial dose: 2mg
Increased thereafter by 2mg not less than every 2 weeks, based on tolerability and effectiveness. Maximum dose 8mg per day.
Additional Dosage Information
Switching between tablets and oral liquid
The manufacturer advises caution when switching between formulations.
Concomitant CYP3A inducing antiepileptic drugs
Combination with CYP3A enzyme inducing anti-epileptic drugs may reduce the response rate of perampanel. As such, during initiation, doses must be titrated at weekly intervals. Patients switching to or from a concomitant enzyme inducer or inhibitor during perampanel therapy should be closely monitored. Dose adjustments may be required. The manufacturers indicate particular effect has been noted during combination with phenytoin, carbamazepine and oxcarbazepine.
Missed doses
If a single dose is missed, wait and take the next dose as scheduled.
If more than one dose is missed for a continuous period of less than 5 half-lives (3 weeks for patients not taking perampanel metabolism-inducing drugs, 1 week for patients who are taking perampanel metabolism-inducing drugs) consider restarting treatment from the last dose level.
If a patient has discontinued perampanel for a continuous period of more than 5 half-lives, initial dosing recommendations given above should be followed.
Contraindications
Children under 4 years
Breastfeeding
Haemodialysis
Moderate renal impairment
Pregnancy
Severe hepatic impairment
Precautions and Warnings
Children under 12 years
Elderly
Females of childbearing potential
Suicidal ideation
Galactosaemia
Glucose-galactose malabsorption syndrome
Hereditary fructose intolerance
History of drug misuse
Lactose intolerance
Mild hepatic impairment
Advise ability to drive/operate machinery may be affected by side effects
Consider prescribing by manufacturer to ensure seizure control maintenance
May precipitate or aggravate absence and myoclonic seizures
Presentations with sorbitol unsuitable in hereditary fructose intolerance
Some formulations contain lactose
Where treatment is interrupted review dose before restarting
Consider monitoring hepatic enzymes
Monitor closely for skin reactions
Monitor for signs of suicide ideation or behaviour
Potential for drug abuse
Advise patient to seek medical advice if severe skin reaction occurs
Advise patients/carers to seek medical advice if changes in behaviour/mood
Consider dose reduction/discontinuation where aggressive behaviour persists
Progressive withdrawal recommended
Discontinue and do not restart if severe cutaneous adverse reactions occur
Not licensed for all indications in all age groups
Advise patient not to take St John's wort concurrently
Advise that effects are potentiated by CNS depressants (including alcohol)
Advise patient grapefruit products may increase plasma level
Female: Effect of hormonal contraceptive may be reduced
Female: Ensure adequate contraception during treatment
Female: Non-hormonal contraception advised in addition to hormonal
Advise patient of increased risk of falls
Advise patient/carers to report signs of suicide ideation or behaviour
Antiepileptic treatment is associated with a small increased risk of suicidal thoughts and behaviour; available data suggest that the increased risk applies to all antiepileptics and is seen as early as one week after starting treatment. Patients (and carers of patients) should be alert to any mood changes, distressing thoughts, or feelings about suicide or harming themselves at any point during treatment. They should be advised to seek medical advice if they develop such thoughts or behaviour, and should be referred for appropriate treatment if necessary.
The available evidence does not define whether the risk of suicidal thoughts and behaviour differs between antiepileptics. Patients should not stop or switch treatment on the basis of this information and without speaking to a healthcare professional.
Severe cutaneous adverse reactions (SCARs) including drug reaction with eosinophilia, systemic symptoms (DRESS) and Stevens-Johnson syndrome (SJS) have been associated with perampanel treatment. Monitor patients for skin reactions and ensure patients are aware of the signs and symptoms. If signs and symptoms suggestive of these reactions appear, perampanel should be stopped immediately and an alternative treatment considered (as appropriate). If the patient presents a serious reaction such as DRESS or SJS with the use of perampanel, treatment with perampanel must not be restarted in this patient at any time.
Pregnancy and Lactation
Pregnancy
Perampanel is contraindicated during pregnancy.
The manufacturer does not recommend using perampanel during pregnancy. At the time of writing there are limited amounts of published data regarding the use of perampanel in pregnancy, animal studies do not indicate any teratogenic effects, but embryotoxicity was observed in toxic doses.
Lactation
Perampanel is contraindicated during breastfeeding.
The manufacturer advises that the patient either discontinues perampanel or discontinues breastfeeding. It is not known whether perampanel is excreted in human milk, and therefore a risk to the neonate cannot be excluded. Animal studies have shown excretion of perampanel and/or its metabolites in milk.
LactMed (2020) indicates that if perampanel is needed by the mother, it is not necessarily a reason to discontinue breastfeeding, but monitor the infant for drowsiness, agitation, adequate weight gain, and developmental milestones, especially in younger, exclusively breastfed infants and when using combination of drugs.
Side Effects
Aggression
Agitation
Anger
Anxiety
Ataxia
Back pain
Blurred vision
Confusion
Decreased appetite
Diplopia
Dizziness
Drug rash with eosinophilia and systemic symptoms (DRESS)
Dysarthria
Falls
Fatigue
Gait abnormality
Hepatotoxicity
Increased appetite
Irritability
Loss of balance
Nausea
Severe cutaneous adverse reactions
Somnolence
Stevens-Johnson syndrome
Suicidal tendencies
Vertigo
Weight gain
Overdosage
It is strongly recommended that the UK National Poisons Information Service be consulted on cases of suspected or actual overdose where there is doubt over the degree of risk or about appropriate management.
The following number will direct the caller to the relevant local centre (0844) 892 0111
Information may be obtained if you have access to ToxBase the primary clinical toxicology database of the National Poisons Information Service. This is available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).
Further Information
Last Full Review Date: February 2021
Reference Sources
Summary of Product Characteristics: Fycompa 2mg film-coated tablets. Eisai Ltd. Revised November 2020.
Summary of Product Characteristics: Fycompa 4mg film-coated tablets. Eisai Ltd. Revised November 2020.
Summary of Product Characteristics: Fycompa 6mg film-coated tablets. Eisai Ltd. Revised November 2020.
Summary of Product Characteristics: Fycompa 8mg film-coated tablets. Eisai Ltd. Revised November 2020.
Summary of Product Characteristics: Fycompa 10mg film-coated tablets. Eisai Ltd. Revised November 2020.
Summary of Product Characteristics: Fycompa 12mg film-coated tablets. Eisai Ltd. Revised November 2020.
Summary of Product Characteristics: Fycompa 0.5mg/ml oral suspension. Eisai Ltd. Revised November 2020.
NICE Evidence Services Available at: www.nice.org.uk Last accessed: 04 February 2021
US National Library of Medicine. Toxicology Data Network. Drugs and Lactation Database (LactMed).
Available at: https://www.ncbi.nlm.nih.gov/books/NBK501922/
Perampanel Last revised: 21 September 2020
Last accessed: 08 February 2021
Medscape UK | Univadis prescription drug monographs & interactions are based on FDB Multilex Content
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