Vancouver follow-up: Eisai benefits for your patients

Dear [HCP Name],
See how Eisai can help you make a difference for your patients. Get more information about BANZEL^® (rufinamide), FYCOMPA^® (perampanel), and Eisai reimbursement services below.

For the adjunctive treatment of seizures associated with LGS in children and adults

Add BANZEL for powerful, broad spectrum efficacy in total seizure reduction

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Indication
BANZEL is indicated for adjunctive treatment of seizures associated with Lennox-Gastaut Syndrome (LGS) in pediatric patients 1 year of age and older, and in adults.

Important Safety Information

Contraindication
BANZEL is contraindicated in patients with Familial Short QT syndrome.

Warnings:
AEDs increase the risk of suicidal thoughts or behavior in patients. Patients, their caregivers, and families should be informed of the risk and advised to monitor and report any emergence or worsening of depression, suicidal thoughts or behavior, or any unusual changes in mood or behavior, or thoughts of self-harm. If these symptoms occur, consider if it may be related to the AED or illness because epilepsy itself can increase these risks.

Use of BANZEL has been associated with central nervous system–related adverse reactions, such as somnolence or fatigue, coordination abnormalities, dizziness, gait disturbances, and ataxia.

Precautions:
Formal cardiac ECG studies demonstrated shortening of the QT interval (mean = 20 msec, for doses ≥ 2400 mg twice daily) with BANZEL. Caution should be used when administering BANZEL with other drugs that shorten the QT interval.

Multi-organ hypersensitivity syndrome has been reported in association with BANZEL therapy. In clinical trials, hypersensitivity reactions occurred in children less than 12 years of age and within 4 weeks of starting BANZEL therapy. In addition, rare cases of Drug Reaction with Eosinophilia and Systemic Symptoms and Stevens-Johnson syndrome have been reported in association with rufinamide therapy post marketing. If any of these reactions are suspected, BANZEL should be discontinued and alternative treatment started. All patients who develop a rash while taking BANZEL must be closely supervised.

As with all AEDs, BANZEL should be gradually withdrawn to minimize the risk of increased seizure frequency.

See additional Important Safety Information below and full US Prescribing Information for BANZEL.

BANZEL HAS DEMONSTRATED POWERFUL, BROAD SPECTRUM EFFICACY IN THE REDUCTION OF TOTAL SEIZURES

Total Seizure

32.7% median reduction of total seizures in the BANZEL group vs 11.7% for placebo (P<0.002)^*1,2

Drop Attacks

42.5% median reduction in tonic-atonic seizures (drop attacks) in the BANZEL group vs 1.4% increase for placebo (P<0.0001)^*1,2

A 12-week, randomized, double-blind, multicenter, placebo-controlled, parallel-group trial to assess the effectiveness of BANZEL to reduce inadequately controlled seizures associated with LGS in patients (N=138, intent to treat) being treated with 1-3 concomitant stable-dose AEDs. These were primary efficacy endpoints in the pivotal trial.^1,2,5

For your patients with primary generalized tonic-clonic (PGTC) seizures

Experience the strength of FYCOMPA

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Indication
FYCOMPA^® (perampanel) is indicated as adjunctive therapy for the treatment of partial-onset seizures with or without secondarily generalized seizures and primary generalized tonic-clonic seizures in patients with epilepsy 12 years of age and older.

WARNING: SERIOUS PSYCHIATRIC AND BEHAVIORAL REACTIONS

•	Serious or life-threatening psychiatric and behavioral adverse reactions including aggression, hostility, irritability, anger, and homicidal ideation and threats have been reported in patients taking FYCOMPA
•	These reactions occurred in patients with and without prior psychiatric history, prior aggressive behavior, or concomitant use of medications associated with hostility and aggression
•	Advise patients and caregivers to contact a healthcare provider immediately if any of these reactions or changes in mood, behavior, or personality that are not typical for the patient are observed while taking FYCOMPA or after discontinuing FYCOMPA
•	Closely monitor patients particularly during the titration period and at higher doses
•	FYCOMPA should be reduced if these symptoms occur and should be discontinued immediately if symptoms are severe or are worsening

See Important Safety Information below and full US Prescribing Information for FYCOMPA.

FYCOMPA HAS DEMONSTRATED A 76% REDUCTION IN PGTC SEIZURE FREQUENCY VS PLACEBO (38%) (P<0.0001)^†3,4

64% of patients experienced a 50% or greater reduction in seizure frequency vs placebo (40%) (P<0.0019)^4,5

48% of patients on FYCOMPA exhibited a 75% to 100% reduction in PGTC seizure frequency vs placebo (24%)^3,5

31%^‡ of patients in the FYCOMPA group achieved 100% reduction of PGTC seizures vs placebo (24%)^4,5

•	50% to <75%: FYCOMPA 16% of patients, placebo 16% of patients
•	25% to <50%: FYCOMPA 15% of patients, placebo 20% of patients
•	0 to <25%: FYCOMPA 11% of patients, placebo 12% of patients
•	Seizure frequency increase: FYCOMPA 10% of patients, placebo 28% of patients

†	Phase 3 study design: Multicenter, randomized, double-blind, placebo-controlled, parallel-group study on effectiveness of FYCOMPA as adjunctive therapy in patients 12 years of age and older. The total treatment period was 17 weeks (4: titration; 13: maintenance). Inclusion criteria included taking 1 to 3 concomitant AEDs at baseline and ≥3 PGTC seizures experienced in 8-week baseline period.³
‡	N=25. This was a prespecified exploratory endpoint.

The Eisai Assistance Program offers access and coverage support for BANZEL and FYCOMPA.

BANZEL Important Safety Information (cont.)

Adverse Reactions:

In the pooled, double-blind, adjunctive therapy studies in adults and pediatric patients ages 4 and older, the most commonly observed (≥10%) adverse reactions with BANZEL vs placebo, respectively, were headache (25% vs 20%), dizziness (17% vs 10%), fatigue (15% vs 9%), somnolence (13% vs 9%), and nausea (11% vs 7%).

In a multicenter, parallel group, open-label study in pediatric patients (1 year to less than 4 years of age) the most commonly observed (≥10%) adverse reactions and with a higher frequency with BANZEL vs any other AED, respectively, were vomiting (24% vs 9%), somnolence (16% vs 0%), constipation (12% vs 9%), cough (12% vs 9%), bronchitis (12% vs 0%), rash (12% vs 9%), and decreased appetite (12% vs 9%).

See full Prescribing Information for BANZEL.

FYCOMPA Important Safety Information (cont.)

SERIOUS PSYCHIATRIC AND BEHAVIORAL REACTIONS
In the partial-onset seizures clinical trials, hostility- and aggression-related adverse reactions occurred in 12% and 20% of patients randomized to receive FYCOMPA at doses of 8 mg and 12 mg per day, respectively, compared to 6% of patients in the placebo group. These effects were dose-related and generally appeared within the first 6 weeks of treatment, although new events continued to be observed through more than 37 weeks. These effects in FYCOMPA-treated patients led to dose reduction, interruption, and discontinuation more frequently than placebo-treated patients. The combination of alcohol and FYCOMPA significantly worsened mood and increased anger. Homicidal ideation and/or threat have also been reported postmarketing in patients treated with FYCOMPA. Patients taking FYCOMPA should avoid the use of alcohol. Patients, their caregivers, and families should be informed that FYCOMPA may increase the risk of psychiatric events. Patients should be monitored during treatment and for at least one month after the last dose of FYCOMPA, and especially when taking higher doses and during the initial few weeks of drug therapy (titration period) or at other times of dose increases. Similar serious psychiatric and behavioral events were observed in the primary generalized tonic-clonic (PGTC) seizure clinical trial.

Suicidal Behavior and Ideation
Antiepileptic drugs (AEDs), including FYCOMPA, increase the risk of suicidal thoughts or behavior in patients. Anyone considering prescribing FYCOMPA or any other AED must balance the risk of suicidal thoughts or behavior with the risk of untreated illness. Epilepsy and many other illnesses for which AEDs are prescribed are themselves associated with morbidity and mortality and an increased risk of suicidal thoughts and behavior. Patients, their caregivers, and families should be informed of the risk and advised to monitor and immediately report the emergence or worsening of depression, suicidal thoughts or behavior, thoughts about self-harm and/or any unusual changes in mood or behavior. Should suicidal thoughts and behavior emerge during treatment, consider whether the emergence of these symptoms in any given patient may be related to the illness being treated.

Dizziness and Gait Disturbance
FYCOMPA caused dose-related increases in events related to dizziness and disturbance in gait or coordination. Dizziness and vertigo were reported in 35% and 47% of patients in the partial-onset seizure trials randomized to receive FYCOMPA at doses of 8 mg and 12 mg per day, respectively, compared to 10% of placebo-treated patients. Gait disturbance related events were reported in 12% and 16% of patients in the partial-onset seizure clinical trials randomized to receive FYCOMPA at doses of 8 mg and 12 mg per day, respectively, compared to 2% of placebo-treated patients. These adverse reactions occurred mostly during the titration phase. These adverse reactions were also observed in the PGTC seizure clinical trial.

Somnolence and Fatigue
FYCOMPA caused dose-dependent increases in somnolence and fatigue-related events. Somnolence was reported in 16% and 18% of patients in the partial-onset seizure trials randomized to receive FYCOMPA at doses of 8 mg and 12 mg per day, respectively, compared to 7% of placebo patients. Fatigue-related events were reported in 12% and 15% of patients in the partial-onset seizure trials randomized to receive FYCOMPA at doses of 8 mg and 12 mg per day, respectively, compared to 5% of placebo patients. These adverse reactions occurred mostly during the titration phase. These adverse reactions were also observed in the PGTC seizure clinical trial. Patients should be advised against engaging in hazardous activities requiring mental alertness, such as operating motor vehicles or dangerous machinery, until the effect of FYCOMPA is known.

Falls
Falls were reported in 5% and 10% of patients in the partial-onset seizure clinical trials randomized to receive FYCOMPA at doses of 8 mg and 12 mg per day, respectively, compared to 3% of placebo-treated patients.

Withdrawal of AEDs
A gradual withdrawal is generally recommended with AEDs to minimize the potential of increased seizure frequency, but if withdrawal is a response to adverse events, prompt withdrawal can be considered.

Most Common Adverse Reactions
The most common adverse reactions in patients receiving FYCOMPA (≥5% and ≥1% higher than placebo) include dizziness, somnolence, fatigue, irritability, falls, nausea, weight gain, vertigo, ataxia, headache, vomiting, contusion, abdominal pain, and anxiety.

Drug Interactions
FYCOMPA may decrease the efficacy of contraceptives containing levonorgestrel. Plasma levels of FYCOMPA were decreased when administered with carbamazepine, phenytoin, or oxcarbazepine. Concomitant use of FYCOMPA with other strong CYP3A inducers (e.g., rifampin, St. John’s wort) should be avoided. Multiple dosing of FYCOMPA 12 mg per day enhanced the effects of alcohol on vigilance and alertness, and increased levels of anger, confusion, and depression. These effects may also be seen when FYCOMPA is used in combination with other CNS depressants.

Pregnancy and Lactation
Physicians are advised to recommend that pregnant patients taking FYCOMPA enroll in the North American Antiepileptic Drug (NAAED) Pregnancy Registry. Caution should be exercised when FYCOMPA is administered to pregnant or nursing women as there are no adequate data on the developmental risk associated with use in pregnant women, and no data on the presence of perampanel in human milk, the effects on the breastfed child, or the effects of the drug on milk production.

Hepatic and Renal Impairment
Use in patients with severe hepatic or severe renal impairment is not recommended. Dosage adjustments are recommended in patients with mild or moderate hepatic impairment. Use with caution in patients with moderate renal impairment.

Drug Abuse and Dependence
FYCOMPA is a Schedule III controlled substance and has the potential to be abused and lead to drug dependence.

You are encouraged to report side effects of prescription drugs to the FDA. Visit www.fda.gov/medwatch or call 1‑800‑FDA‑1088.

Sincerely,
Eisai Epilepsy

References: 1. Glauser et al. Rufinamide for generalized seizures associated with Lennox-Gastaut syndrome. Neurology. 2008;70(21):19‌50-19‌58. 2. BANZEL^® (rufinamide) prescribing information, Eisai Inc. 3. FYCOMPA US Prescribing Information. Woodcliff Lake, NJ: Eisai Inc. 4. French JA, Krauss GL, Wechsler RT, et al. Perampanel for tonic-clonic seizures in idiopathic generalized epilepsy: a randomized trial. Neurology. 2015;85(11):950-957. 5. Data on file. Eisai Inc., Woodcliff Lake, NJ.

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