Special Warning : אזהרת שימוש

4.4   Special warnings and precautions for use

Suicidal ideation
Suicidal ideation and behaviour have been reported in patients treated with anti-epileptic medicinal products in several indications. A meta-analysis of randomised placebo-controlled trials of anti-epileptic medicinal products has also shown a small increased risk of suicidal ideation and behaviour. The mechanism of this risk is not known and the available data do not exclude the possibility of an increased risk for perampanel.
Therefore, patients (children, adolescents, and adults) should be monitored for signs of suicidal ideation and behaviours and appropriate treatment should be considered. Patients (and caregivers of patients) should be advised to seek medical advice should signs of suicidal ideation or behaviour emerge.

Severe cutaneous adverse reactions (SCARs)

Severe cutaneous adverse reactions (SCARs) including drug reaction with eosinophilia and systemic symptoms (DRESS), and Stevens - Johnson Syndrome (SJS), which can be life- threatening or fatal, have been reported (frequency unknown; see section 4.8) in association with perampanel treatment.


At the time of prescription patients should be advised of the signs and symptoms and monitored closely for skin reactions.

Symptoms of DRESS include typically, although not exclusively, fever, rash associated with other organ system involvement, lymphadenopathy, liver function tests abnormalities and eosinophilia. It is important to note that early manifestations of hypersensitivity, such as fever or lymphadenopathy, may be present even though rash is not evident.

Symptoms of SJS include typically although not exclusively, skin detachment (epidermal necrosis/blister) < 10%, erythematous skin (confluent), rapid progression, painful atypical target-like lesions and/or purpuric macules in wide dissemination or large erythema (confluent), bullous/erosive involvement of more than 2 mucous membranes.

If signs and symptoms suggestive of these reactions appear, perampanel should be withdrawn immediately and an alternative treatment considered (as appropriate).

If the patient has developed a serious reaction such as SJS or DRESS with the use of perampanel, treatment with perampanel must not be restarted in this patient at any time.

Absence and myoclonic seizures
Absence and myoclonic seizures are two common generalised seizure types that frequently occur in IGE patients. Other AEDs are known to induce or aggravate these seizure types.
Patients with myoclonic seizures and absence seizures should be monitored while on Fycompa.

Nervous system disorders
Perampanel may cause dizziness and somnolence and therefore may influence the ability to drive or use machines (see section 4.7).

Hormonal contraceptives
At doses of 12 mg/day Fycompa may decrease the effectiveness of progestative-containing hormonal contraceptives; in this circumstance additional non-hormonal forms of contraception are recommended when using Fycompa (see section 4.5).


Falls
There appears to be an increased risk of falls, particularly in the elderly; the underlying reason is unclear.

Aggression, psychotic disorder

Aggressive, hostile , and abnormal behaviours have been reported in patients receiving perampanel therapy. In perampanel-treated patients in clinical trials, aggression, anger, irritability, and psychotic disorder were reported more frequently at higher doses. Most of the reported events were either mild or moderate and patients recovered either spontaneously or with dose adjustment. However, thoughts of harming others, physical assault or threatening behaviour were observed in some patients (< 1% in perampanel clinical trials). Homicidal ideation has been reported in patients. Patients and caregivers should be counselled to alert a healthcare professional immediately if significant changes in mood or patterns of behaviour are noted. The dosage of perampanel should be reduced if such symptoms occur and discontinuation should be considered if symptoms are severe (see section 4.2).

Abuse potential
Caution should be exercised in patients with a history of substance abuse and the patient should be monitored for symptoms of perampanel abuse.

Concomitant CYP 3A inducing anti-epileptic medicinal products

Response rates after addition of perampanel at fixed doses were less when patients received concomitant CYP3A enzyme-inducing anti-epileptic medicinal products (carbamazepine, phenytoin, oxcarbazepine) as compared to response rates in patients who received concomitant non-enzyme–inducing anti-epileptic medicinal products. Patient’s response should be monitored when they are switching from concomitant non-inducer anti-epileptic medicinal products to enzyme inducing medicinal products and vice versa. Depending upon individual clinical response and tolerability, the dose may be increased or decreased 2 mg at a time (see section 4.2).
Other concomitant (non- anti-epileptic) cytochrome P450 inducing or inhibiting medicinal products
Patients should be closely monitored for tolerability and clinical response when adding or removing cytochrome P450 inducers or inhibitors, since perampanel plasma levels can be decreased or increased; the dose of perampanel may need to be adjusted accordingly.

Hepatotoxicity
Cases of hepatotoxicity (mainly hepatic enzyme increased) with perampanel in combination with other antiepileptic drugs have been reported. If hepatic enzymes elevation is observed, monitoring of liver function should be considered.

Excipients
Fructose intolerance
Fycompa Oral suspension contains sorbitol (E420), each mL of Fycompa contains 175 mg sorbitol.
Patients with hereditary fructose intolerance (HFI) should not take this medicinal product.

Caution should be exercised when combining Fycompa oral suspension with other antiepileptic medications containing sorbitol, since a combined intake of over 1 gram of sorbitol may affect absorption of some drugs.

Benzoic Acid (E210) and Sodium Benzoate (E211)
Fycompa contains benzoic acid (E210) and sodium benzoate (E211), each mL of Fycompa contains <0.005 mg benzoic acid and 1.1 mg sodium benzoate.

Benzoic acid and benzoates can displace bilirubin from albumin. Increase in bilirubinaemia following its displacement from albumin may increase neonatal jaundice which may develop into kernicterus.

Lactose intolerance
Fycompa film-coated tablets contains lactose, therefore patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.

Effects on Driving

4.7   Effects on ability to drive and use machines

Fycompa has moderate influence on the ability to drive and use machines.
Perampanel may cause dizziness and somnolence and therefore may influence the ability to drive or use machines. Patients are advised not to drive a vehicle, operate complex machinery or engage in other potentially hazardous activities until it is known whether perampanel affects their ability to perform these tasks (see sections 4.4 and 4.5).