[Music]
CHEZ: Hi, I’m Dr Michael Chez.
GUPTA: And I’m Dr Ajay Gupta.
CHEZ: Dr Gupta and I have known each other for a long time, and together we have about 60 years of experience treating children with epilepsy.
GUPTA: Today we’re going to talk about why controlling epilepsy in children is so important.
CHEZ: Then we’ll review the clinical profile of FYCOMPA, or perampanel, and discuss why we believe it’s a good treatment option for many of our pediatric patients.
CHEZ: Most cases of epilepsy begin in children (and then there’s also another peak in elderly adults), and if seizures are not well-controlled, they can substantially affect development and have ripple effects throughout a child’s life.
GUPTA: So it’s critical to identify epilepsy, accurately diagnose the seizure type and the disease state, and effectively treat epilepsy in children as early as possible.
CHEZ: Dr Gupta, what do you look for in an antiseizure medication for your pediatric patients?
GUPTA: Well, this is a very important question. I think there are many considerations. The most important one to me is making an accurate diagnosis of seizure type, using EEG to correctly diagnose the electro-clinical syndrome whenever possible, and factor in the etiology when necessary.
Then, I look at the indications for the medication and in what age groups it is approved. I obviously consider the efficacy and safety profile, including interactions with other medications. I look at the mechanism of action of the drug and how it may differ from that of other antiseizure medications that the patient may already be taking. And I also consider available formulations (such as an oral suspension), and ease of dosing, as well as pharmacokinetic properties, such as the half-life of the drug.
CHEZ: I think that’s a great list and a great transition into our overview of FYCOMPA for the treatment of pediatric patients with partial-onset seizures and primary generalized tonic-clonic seizures.
CHEZ: We’ll start with a brief overview of FYCOMPA’s pivotal trials.
For an in-depth presentation of FYCOMPA pivotal trial data, please explore the other videos available at FYCOMPAonDemand.com.
GUPTA: First, we’ll look at the pivotal trials for FYCOMPA in patients with partial-onset seizures with or without secondary generalization not adequately controlled with 1 to 3 concomitant antiseizure medications. Three randomized, double-blind, placebo-controlled, multicenter trials were conducted.
These studies enrolled patients 12 years of age and older.
The primary outcome in those studies was the median percent change in the seizure frequency per 28 days during the treatment period as well as compared to the baseline period.
GUPTA: In 2018, the FDA expanded FYCOMPA’s indication for partial-onset seizures to pediatric patients 4 years and older.
This expansion was supported by efficacy that was extrapolated from the three pivotal trials and safety findings from two studies in patients 4 to less than 12 years of age.
CHEZ: Now let’s look at FYCOMPA as an adjunctive therapy for patients with primary generalized tonic-clonic seizures.
A multicenter, randomized, double-blind, placebo-controlled study was conducted. Patients were 12 years of age or older.
Efficacy was analyzed in 162 patients, 81 of whom received FYCOMPA and had at least one post-treatment seizure assessment.
GUPTA: This is the summary of the adverse reactions seen in the partial-onset seizure pivotal trials.
The safety profile of FYCOMPA in patients with primary generalized tonic-clonic seizures was consistent with these findings.
CHEZ: Adverse reactions seen in patients ages 4 to 12 years were generally similar to what was seen in patients who were 12 and older.
CHEZ: In two studies in pediatric patients 4 to <12 years of age with epilepsy, 225 patients received FYCOMPA, with 110 patients exposed for at least 6 months, and 21 patients for at least 1 year.
GUPTA: Dr Chez, we should also discuss the Boxed WARNING regarding serious psychiatric and behavioral reactions, which was summarized at the beginning of the video.
How do you discuss the Boxed Warning with parents and other caregivers?
CHEZ: That’s a great question. I like to speak to it very directly. I explain to parents that it’s a rare but potentially very serious side effect. I note that we will titrate the medication slowly and watch closely for side effects. I also emphasize that it’s important for them to quickly report to me any concerning changes of behavior in their child.
GUPTA: And I always start the discussion by explaining why I think FYCOMPA might be a good choice for the child. So the parents understand the potential benefits that we are balancing with the potential risks.
CHEZ: That’s a great point, and before we move on from the safety discussion, I wanted to mention an interesting study that looked at the effects of long-term FYCOMPA treatment on cognition in adolescents.
For those interested in this topic, check out the video about it on FYCOMPAonDemand.com.
GUPTA: Yes, I believe it’s an important topic.
Now let’s talk about some of the other properties of FYCOMPA that make it a good choice to help control seizures for many of our pediatric patients.
CHEZ: Yes, let’s look at the dosing of FYCOMPA.
It’s dosed once-daily at bedtime, and it can be dosed the same in pediatric patients as well as in adults. No weight-based dosing is needed, so as our patients grow we don’t necessarily have to change the dosing regimen.
And it’s available both in tablets—a small pill—and as an oral suspension, which can especially be valuable for our pediatric patients who may not be able to swallow pills.
GUPTA: I like that the dosing is not weight-based because that’s one less thing to have to think about. FYCOMPA is dosed in children the same as it is in younger and older and adults.
And the ability to dose once daily makes it easier for parents and caregivers of school-age children.
CHEZ: Yes, we should point out that it’s the long half-life of FYCOMPA that makes once-daily dosing possible. It has a unique half-life is actually about 105 hours. Such a long half-life is not typical for antiseizure medications.
GUPTA: That long half-life gives me a measure of comfort when I think about the busy lives of my patients and their families.
As shown here, if one daily dose is missed, plasma levels of FYCOMPA remain relatively stable. So, I believe there is low risk for the patient having a breakthrough seizure because of a single missed dose with FYCOMPA.
CHEZ: Dr Gupta, you started this video by listing a variety of factors you consider when selecting an antiseizure medication for a child with epilepsy in your practice.
We haven’t had time for a complete review of the profile of FYCOMPA, but I think several properties of the medication stand out to me when I think about the patients in my practice.
GUPTA: I fully agree.
To me, one of the key attributes of FYCOMPA is its broad spectrum. FYCOMPA offers potential seizure control across convulsive and nonconvulsive seizures, including partial onset-seizures with secondarily generalized tonic-clonic seizures, primary generalized tonic-clonic seizures, and simple and complex partial seizures.
That broad-spectrum, coupled with the long half-life and lack of weight-based dosing, make FYCOMPA an easy-to-use and an appealing option.
CHEZ: Yes, now let’s please stay tuned for additional Important Safety Information for FYCOMPA.
[NARRATOR]
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 led to dose reduction, interruption, and discontinuation.
The combination of alcohol and FYCOMPA significantly worsened mood and increased anger. Patients 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 with FYCOMPA, especially when taking higher doses.
Antiepileptic drugs, including FYCOMPA, 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 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.
FYCOMPA caused dose-related increases in events related to dizziness and disturbance in gait or coordination, especially during the titration phase.
FYCOMPA caused dose-dependent increases in somnolence and fatigue-related events, especially during the titration phase.
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 depression when FYCOMPA is used with other drugs with sedative properties because of potential additive effects.
Falls were more common in patients taking FYCOMPA at doses of 8 mg and 12 mg versus placebo.
Drug reaction with eosinophilia and systemic symptoms, or DRESS, also known as multiorgan hypersensitivity, has been reported in patients taking AEDs, including FYCOMPA. DRESS may be fatal or life-threatening.
Evaluate your patients if these signs or symptoms are present.
A gradual withdrawal is generally recommended with AEDs to minimize the potential of increased seizure frequency.
The most common adverse reactions include dizziness, somnolence, fatigue, irritability, falls, nausea, weight gain, vertigo, ataxia, headache, vomiting, contusion, abdominal pain, and anxiety.
FYCOMPA may decrease the efficacy of contraceptives containing levonorgestrel.
Plasma levels of perampanel were decreased when administered with moderate and strong CYP3A4 inducers.
FYCOMPA may enhance the effects of alcohol on vigilance, alertness, anger, confusion, and depression.
These effects may also be seen when FYCOMPA is used in combination with other CNS depressants.
Caution should be exercised when FYCOMPA is administered to pregnant or nursing women.
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.
FYCOMPA is a Schedule III controlled substance and has the potential to be abused and lead to drug dependence and withdrawal symptoms.
Thanks for watching. To learn more about FYCOMPA, visit FYCOMPAonDemand.com.
