(bright music)

 

- Hello and welcome.

 

My name is Sarah, and today I'm joined by 2 national experts:

Dr. Eric Piña-Garza, Professor of Neurology and Pediatrics, and Director of Pediatric Epilepsy at Children's Hospital at Centennial Medical Center in Nashville, Tennessee;

 

and Nurse Practitioner, Patricia Dean, Epilepsy Program Specialist in the Comprehensive Epilepsy Center at Nicklaus Children's Hospital in Miami, Florida.

 

In this video, we will review broad-spectrum treatment with FYCOMPA (perampanel), which may offer convulsive seizure freedom for patients with primarily generalized tonic-clonic seizures.

 

Welcome, both of you. So happy you could join us today.

 

- Thank you.

 

- Happy to be here.

 

Before we begin, let's take a moment to review

some important safety information about FYCOMPA.

 

INDICATION.

FYCOMPA (perampanel) is indicated in patients with epilepsy aged four years and older

for partial-onset seizures (POS) with or without secondarily generalized seizures

and adjunctive therapy for patients aged 12 years and older

for primary generalized tonic-clonic (PGTC) seizures.

 

IMPORTANT SAFETY INFORMATION.

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.

 

Please see full important safety information at the end of this video.

 

- Now, Dr. Piña-Garza, would you like to begin by reviewing our patient case?

 

- Yes, thank you.

 

This case is based on an actual patient from my practice but identifying details have been changed.

 

Aaron is a 22-year-old college student.He maintains a healthy lifestyle and balances school with college baseball.

 

He is single, with no children. He has no history of smoking or drug use, although he admits rare social alcohol use.

 

Aaron has a history of epilepsy since age 13. There is no family history of epilepsy and no other current medical issues or diagnosis.

 

As mentioned, Aaron's first seizure occurred at age 13. He experienced 3 unprovoked episodes of general clonic activity lasting about 3 to 5 minutes each.

 

They were followed by psychomotor slowing, but he was asymptomatic between the events.

 

At the time, he was living with his biological family and had limited psychosocial stressors.

 

He was taken to the emergency room where initial work-up showed an normal MRI.

 

The patient was referred to a neurologist, who ran a routine EEG.

 

The initial 23-hour video-EEG came back normal. Aaron was placed on levetiracetam 1500 mg ER daily and given a rescue medication for seizure clusters or prolonged seizures.

 

Unfortunately, Aaron's seizures continued to occur, even after raising the dose of levetiracetam to 2250 mg daily.

 

After a 7-minute seizure with prolonged postictal psychomotor slowing,Aaron visited the ER.

 

He was then admitted by the hospitalist due to the prolonged nature of his seizures and unknown etiology.

 

A second EEG showed bursts of 4.5 Hzs generalized polyspikes and P3 sharp waves (fragments vs comorbid focal epilepsy), which led to a more precise diagnosis of primary generalized epilepsy.

 

My treatment goal for Aaron is to ultimately achieve seizure freedom.

 

To achieve this, he needs additional therapy despite high doses of levetiracetam.

 

Aaron is mostly compliant with medication but sometimes has an erratic schedule with his baseball travel.

 

I was also concerned about the impact of epilepsy on Aaron's schooling and want to avoid a medication that could suppress cognition while choosing a treatment that is straightforward and easy to use to avoid challenges with adherence.

 

I consider FYCOMPA as an appropriate option. I explained to Aaron and his parents that the long half-life of FYCOMPA means that his blood levels of FYCOMPA will remain relatively unchanged in the event of a missed dose.

 

Together, we discussed the boxed warning and reviewed the adverse event profile of FYCOMPA, and I gave the family time to make a decision.

 

Aaron chose to begin treatment with FYCOMPA.

Per the prescribing information, FYCOMPA was initiated at 2 mg and then titrated up to 4 mg once daily in addition to levetiracetam.

 

Aaron demonstrated good control with minimal side effects.

However, after 18 months on this regimen, Aaron experienced a brief seizure after missing medications and then one a week later while treatment was resumed.

 

In response, I raised his dose of FYCOMPA to 6 mg daily.

Overall, Aaron has remained seizure-free when fully adherent to treatment but has had a couple of seizures after missing doses.

 

I raised his dose to 8 mg and then 10 mg daily, hoping that the higher level, if tolerated, could be maintained even after missing a dose or 2.

 

With the combination of levetiracetam 2250 mg + FYCOMPA 10 mg daily, Aaron has remained seizure-free for the past 3 years.

 

He continues to live independently in the dormitory at college and plays on the baseball team.

Aaron still has rescue medication in the event of a seizure, but he has learned to be adherent to treatment and enjoys the freedom associated with good control of his epilepsy.

 

- Thank you, Dr. Piña-Garza.

Would you like to share anything else about your clinical decision-making in this patient case?

 

- My main clinical consideration for a patient like Aaron,and for any patient that I see, is to offer them seizure freedom.

 

It cannot be accomplished for every patient, but it is always my goal.

 

When we aim for seizure freedom, we are generally able to accomplish the best possible control for a given patient.

 

Ideally, we do this without the patient experiencing many side effects.

I look to offer patients like Aaron a treatment that is safe, well-tolerated,and offers the possibility of seizure freedom, like FYCOMPA.

 

In many patients, especially in the adult population, the first EEG does not sufficiently establish whether they are having primary generalized seizures or secondary generalized seizures.

 

In fact, Aaron's first EEG was normal.

 

Some medications for focal epilepsy may not cover generalized epilepsy well, and some can even enhance the absence or myoclonic seizures we see in generalized epilepsy.

 

Therefore, having the option of a broad-spectrum drug like FYCOMPA is important for patients like Aaron.

 

- Thank you for that excellent review.

Ms. Dean, what would you like to add from your perspective?

 

- I agree with Dr. Piña-Garza's treatment choices for Aaron.

Our ultimate treatment goal is to achieve seizure freedom while minimizing adverse effects.

 

FYCOMPA is my go-to medication for generalized seizures. It's necessary to counsel patients like Aaron about the importance of remembering to take his medication.

 

Because of the half-life of FYCOMPA, if he misses one dose he can wait until the next day to take his next dose.

 

But ultimately, we want to encourage him to do whatever he needs to remember to take his medication.

 

At 22, Aaron is at an age where patients are usually busy with their lives and medication adherence may not be top-of-mind, especially if they haven't had any seizures in a while.

 

- Thank you for those insights.

Let's continue by reviewing the pivotal data for FYCOMPA in primarily generalized tonic-clonic seizures.

Ms. Dean, could you please review the study design for us?

 

- Certainly, the efficacy and safety of FYCOMPA in primary generalized tonic-clonic seizures were evaluated in a randomized double-blind, placebo-controlled, multicenter phase 3 trial.

 

The design of the FYCOMPA pivotal trials was consistent with the design of other epilepsy studies.

 

The study included patients with 3 or more primary generalized tonic-clonic seizures over 8 weeks at baseline, despite taking 1 to 3 other anti-seizure medications.

 

During the 4-week titration period, patients were titrated up to a dose of 8 mg daily or the highest tolerated dose, and they entered the maintenance period at the last dose achieved during titration.

 

Although dose adjustment was not recommended during the 13-week maintenance period, patients with inadequate seizure control could have their dose increased by one 2-mg increment up to a maximum daily dose of 8 mg, depending on the investigator's clinical judgment.

 

Patients who experience intolerable adverse events could have their dose decreased by one 2-mg increment.

 

- Thank you for that thorough review, Ms. Dean.

Dr. Piña-Garza, would you please continue by discussing the results of the FYCOMPA pivotal trial?

 

- Of course, the primary endpoint of the study was median reduction in primary generalized tonic-clonic seizure frequency per 28 days.

 

There was a 76% median reduction in the FYCOMPA group, vs 30% reduction with placebo.

 

For the secondary endpoint of responder rate, 64% of patients taking FYCOMPA during the maintenance phase exhibited a 50% to 100% reduction in primary generalized tonic-clonic seizure frequency vs 40% for those taking placebo.

 

The proportions of patients exhibiting primary generalized tonic-clonic seizure frequency reductions are outlined in the table shown here.

 

Given this population, it's challenging for trials to show patients achieving seizure freedom.

However, nearly 1 in 3 patients with generalized tonic-clonic seizures taking FYCOMPA during the 13-week maintenance phase, a total of 31%, were convulsive seizure free vs placebo.

 

It is important to note that this was an exploratory endpoint of the study.

 

- Thank you, Dr. Piña-Garza.

Ms. Dean, would you please continue by reviewing the safety results of this FYCOMPA pivotal trial?

 

- My pleasure. In this pivotal trial, the FYCOMPA safety profile in primary generalized tonic-clonic seizures as adjunctive therapy was consistent with that in partial-onset seizures.

 

The table shown here lists adverse reactions reported in at least 4% of patients receiving FYCOMPA 8 mg/day and more frequently than in the placebo group.

 

Discontinuation due to adverse reactions occurred in 11.1% of patients taking FYCOMPA and 6.1% of the patients taking placebo.

 

The adverse reactions most commonly leading to discontinuation of FYCOMPA were vomiting and dizziness.

 

I find the adverse event profile of FYCOMPA to be similar to many other anti-seizure medications.

 

Headache, fatigue, and dizziness were the most common adverse events reported in the pivotal trial, and it is important to inform patients that these might occur.

 

I find that unwanted effects like these most often occur when a patient first starts FYCOMPA, and they often go away as the patient continues the treatment journey.

 

- When I consider the pivotal trial data, I often expect that my patients will experience even more treatment success than the positive outcomes reported in the clinical trial.

 

A clinical trial has a protocol that requires medication to be titrated at an established rate.

 

But in clinical practice, you have the option to titrate based on tolerability, current medications,and other patient factors.

 

So, in theory, tolerability should be better.The clinical trials give us information that we can use to achieve even better patient management.

 

- Thanks, both of you, for that excellent review of the data.

Let's continue by discussing how the pharmacokinetic profile of FYCOMPA can help inform treatment choices.

Dr. Piña-Garza, could you please begin?

 

- I would be happy to.

FYCOMPA has a long half-life of up to 105 hours.If a patient misses a dose,plasma levels remain relatively stable, possibly limiting the occurrence of a breakthrough seizure associated with the missed dose.

 

The long half-life of FYCOMPA means that when a patient misses a dose, their plasma levels remain relatively unchanged.

 

Patients who missed a dose should resume dosing the following day at their prescribed dose.

 

Patients should contact their healthcare provider if more than 1 day of dosing is missed.

 

The time to maximum serum concentration of FYCOMPA ranges between 0.5 to 2.5 hours under fasted conditions.

Steady state is reached in about 2-3 weeks.

 

- For a patient of Aaron's age, it can be especially helpful that,if he misses a dose, the long half-life of FYCOMPA can be beneficial.

 

We want to make patients' lives easier in any way we can and help to ease the burden that they carry.

 

- Thank you both for your excellent insights so far.

Let's wrap up this roundtable by discussing the dosing recommendations for FYCOMPA and their implications for patient treatment.

Ms. Dean, would you please begin?

 

- I'd be happy to.

FYCOMPA should be administered once daily at bedtime.When titrating FYCOMPA, I start low and go slow.

 

The dosing is easy:

start patients at 2 mg and titrate slowly, increasing to 4 mg at 1 to 2 weeks.

 

Then, assess at 4 mg and adjust as necessary, modifying the dose as needed based on clinical response and tolerability.

 

The dose can be increased based on clinical response and tolerability by increments of 2 mg once daily,no more frequently than at weekly intervals.

 

Most of my patients end up taking between 4 mg and 10 mg, which speaks to the efficacy of FYCOMPA.

 

- It is also important to individualize titration.

In patients who are more vulnerable, such as geriatric patients, you may consider waiting as long as 3 weeks between dose increases.

 

There are certain situations in which a patient may be having a lot of seizures, and in those cases, I may consider titrating more quickly.

I explain to the patient that they may experience more somnolence and dizziness, but we could try increasing their dose weekly to achieve control more quickly.

 

My strategy may change based on the patient situation, but, overall, I follow the guidance from the FYCOMPA Prescribing Information.

 

- This has been an excellent review.

I can't thank you both enough for joining me today to discuss FYCOMPA.

 

And I would like to thank those of you watching, as well.

 

But before we end, please stay tuned for some additional important safety information.

IMPORTANT SAFETY INFORMATION.

 

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.

 

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.

 

Homicidal ideation and/or threat have also been reported postmarketing in patients treated with FYCOMPA.

 

The combination of alcohol and FYCOMPA significantly worsened mood and increased anger.

 

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.

 

Anti-epileptic 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-treated 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-treated 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.

 

Patients should be carefully observed for signs of central nervous system (CNS) depression when FYCOMPA is used with other drugs with sedative properties because of potential additive effects.

 

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.

 

DRUG REACTION WITH EOSINOPHILIA AND SYSTEMIC SYMPTOMS (DRESS).

 

DRESS, also known as multiorgan hypersensitivity, has been reported in patients taking AEDs, including FYCOMPA.

 

DRESS may be fatal or life-threatening.

 

DRESS typically, although not exclusively, presents with fever, rash, lymphadenopathy, and/or facial swelling, in association with other organ system involvement.

 

If signs or symptoms are present, immediately evaluate the patient and discontinue FYCOMPA if an alternative etiology for signs or symptoms cannot be established.

 

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 COMMONN ADVERSE REACTIONS.

 

The most common adverse reactions in patients age 12 years and older receiving FYCOMPA (greater than or equal to 5%,and greater than or equal to 1% higher than placebo) include dizziness, somnolence, fatigue, irritability, falls,nausea, weight gain, vertigo, ataxia, headache, vomiting, contusion, abdominal pain, and anxiety.

 

Adverse reactions in patients 4 to less than 12 years were generally similar to patients aged 12 years and older.

 

DRUG INTERACTIONS.

 

FYCOMPA may decrease the efficacy of contraceptives containing levonorgestrel.

 

Plasma levels of perampanel were decreased when administered with known moderate and strong CYP3A4 inducers,including, carbamazepine, phenytoin, or oxcarbazepine.

 

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 seenvwhen FYCOMPA is used in combinationv with other CNS depressants.

 

PREGNANCY AND LACTATION.

 

Physicians are advised to recommend that pregnant patients taking FYCOMPA enrolled 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 DEPENCENCE.

 

FYCOMPA is a Schedule III controlled substance and has the potential to be abused and lead to drug dependence and withdrawal symptoms including anxiety, nervousness, irritability,fatigue, asthenia, mood swings, and insomnia.

 

INDICATION.

 

FYCOMPA (perampanel) is indicated in patients with epilepsy aged 4 years and older for partial-onset seizures (POS) with or without secondarily generalized seizures,and adjunctive therapy for patients aged 12 years and older for primary generalized tonic-clonic (PGTC) seizures.

 

View the prescribing information linked on this site.

 

(light music)