Hi, I'm Jessica Bishop, a physician assistant practicing at an epilepsy and neurology clinic in Boise, Idaho. I see many patients with epilepsy, and I am a patient myself. I'm also involved in clinical research on epilepsy treatments.
I prescribe FYCOMPA or parampanel for many of my patients with epilepsy because of its efficacy and safety profile, long half-life, and once-daily dosing. But the decision to prescribe FYCOMPA is not the physicians alone. It must be made in conjunction with the patient.
To help inform the decision, we must clearly explain the efficacy and safety profile of the medication, including the box warning regarding serious psychiatric and behavioral reactions. This way, when the patient goes home and does their own research on FYCOMPA, they'll understand our rationale for prescribing it. In part one of this video, you'll see an excerpt of a hypothetical discussion with a patient discussing FYCOMPA and specifically the boxed warning.
In part two, I'll review the data behind the box warning. The patient I'll be speaking with today is Amanda. She's a 23-year-old woman who works as a graphic designer and teaches night classes at her local community college.
Although Amanda has tried two different anti-seizure medications, she still has inadequate seizure control. Today, she and I will discuss FYCOMPA and why it might be a good choice for her. So, based on what you've told me today and your medical history, I believe FYCOMPA might be a good option.
FYCOMPA is an anti-seizure medication that targets a receptor in the brain called AMPA that's involved in seizures. As with many other anti-seizure medications, the way FYCOMPA works is not fully understood, but it has been proven effective for people with partial onset seizures, with or without secondary generalized seizures, as well as with primary generalized seizures. Okay, that sounds promising.
How often do I need to take it? You take FYCOMPA just once a day. The pill is small, so it's convenient to take. I'd start you on a low dose and increase it over time.
We're aiming for the dose that helps control your seizures with the fewest side effects. Also, FYCOMPA has a long half-life, which means it stays in your system for a while. So, if you happen to miss a dose, you should still have adequate levels of FYCOMPA in the bloodstream.
Oh, that's good. Can you tell me more about the kinds of side effects I might have? Yes, we'll talk more about the overall safety profile of FYCOMPA. We'll also need to discuss potential mood or behavioral issues with FYCOMPA that are important to understand.
What kind of behavioral issues? Let me summarize the box warning from the product label for you, and then we'll talk about it. The box warning outlines how some people might have experienced serious or life-threatening psychiatric and behavioral adverse reactions while taking FYCOMPA. This has happened in people with and without a history of psychiatric problems, aggressive behavior, or regardless that they were using medications associated with hostility and aggression while taking FYCOMPA.
People should contact their healthcare provider immediately if they notice any of these reactions or changes in mood, behavior, or personality that are not typical for them while taking FYCOMPA or after stopping treatment with FYCOMPA. Later, we will review the complete boxed warning. Okay.
I know this information may be concerning to you. My goal is to help you become seizure-free with minimal medication side effects. What do I need to do if I have these kinds of mood or behavior issues? Great question.
I will keep in close contact with you and your family to ensure that you aren't having any troublesome side effects. If you do have any change in mood or behavior, please reach out to my office right away. Some side effects we can work through by lowering the medication dose, but others may require us to discontinue treatment immediately.
In what situations would you cut back on the dose versus stopping the medication altogether? It really depends on the severity of your side effects and your comfort level. We'll look at the risk versus benefit of the medication to ensure you're getting the best possible outcome. That makes me feel better.
Thank you. It's also important that you attend all of your follow-up visits. Don't worry.
I will. I'm a stickler about keeping appointments. Great.
As I mentioned before, we can start with a low dose of FYCOMPA and go slowly. For some people, a low dose will work, and if dose increases are needed, we will do them slowly and gradually based on your response and how you're tolerating the medication. If the medication isn't working for you, we'll try something else.
We won't just keep raising the dose because you're more likely to get side effects at higher doses. Okay. That sounds good.
I also need to advise you that you should avoid the use of alcohol while taking FYCOMPA. The combination of alcohol and FYCOMPA significantly worsened mood and increased anger. Also, the medication may increase impairing effects of alcohol.
That won't be a problem for me. I don't drink. That's even better.
You may also feel increased impairment if you take other drugs that depress the central nervous system while you're taking FYCOMPA, which I don't think you are at the moment. Nope. Just my seizure medicines.
So you believe that starting FYCOMPA is the right next step for me? I do. Based on your diagnosis, previous treatments, and goals, I think it makes sense. Remember that I prescribe medications every day, and I'm constantly making assessments about their safety and effectiveness.
As a person with epilepsy myself, I wouldn't recommend a medication that I wouldn't be comfortable taking. Okay. That's really good to know.
I understand that the potential risks of treatment can be a little scary, but so can the consequences of uncontrolled epilepsy. I know. I think about that a lot.
One more thing. Here's the medication guide for FYCOMPA. Let's review this together before we finalize our shared decision about FYCOMPA.
Now let's look at some of the data behind the box warning for FYCOMPA. The data I'll present related to the box warning were described by Ettinger and colleagues and published in the journal Epilepsia in 2015. This post hoc analysis of pooled safety data from clinical studies of FYCOMPA examined psychiatric and behavioral treatment emergent adverse events, or TEAEs, classified according to Medical Dictionary for Regulatory Activities, or MEDRA, terms.
Patients used for the safety analysis included parampanel treated patients with partial seizures, as well as non-epilepsy patients from phase two and phase three double blind and open label extension studies. Note that this post hoc analysis of TEAEs suggestive of hostility aggression is based on classification of event reports in the clinical studies, which were not designed to specifically target behavioral abnormalities and did not use validated measures or specific scales or assessments for this purpose. Specific assessments on levels of hostility, aggression, or psychiatric behavior were not performed at baseline or during the phase three studies.
Here are some of the hostility and aggression related events that were observed during FYCOMPA phase three double blind partial onset seizure clinical trials. The chart shows events that occurred in more than three patients in the total population, so events occurring in fewer patients are not included. It should be noted that in these studies, FYCOMPA was titrated weekly in two milligram per day increments up to the randomized dose.
Patients experiencing intolerable adverse events could defer up titration or have their dose reduced. These data show elevated rates of treatment emergent adverse events suggestive of hostility and aggression in patients receiving FYCOMPA compared to those receiving placebo. During the phase three double blind partial onset seizure trials, 0.7% of patients receiving placebo and 1.6% of patients receiving FYCOMPA discontinued due to any hostility and aggression related adverse reaction.
Let's discuss some important details regarding the hostility and aggression related adverse events that occurred in the partial onset seizure double blind phase three studies. Note that a patient with two or more adverse events with the same preferred term is counted only once for that preferred term. The most common hostility and aggression related adverse event was irritability.
The incidence was higher with eight milligram and 12 milligram doses of FYCOMPA. These effects were dose related and generally paired within the first six weeks of treatment, although new events continue to be observed through more than 37 weeks. The patient should be monitored during treatment, particularly during titration when taking higher doses and at times of dose increases.
The dose of FYCOMPA should be reduced or discontinued if hostility and aggression related symptoms occur. Patients should also be monitored for at least one month after the last dose of FYCOMPA. In the partial seizure and non-epilepsy trials, 6 or 0.1% of the 4,368 patients treated with FYCOMPA were categorized as having homicidal ideation and or threat.
Patients categorized as exhibiting homicidal ideation and or threat were described as having worsening or intermittent aggressive behavior disorder, aggressive behavior, and anger outbursts as well as homicidal ideation. Event onset for four of these patients occurred during the open label extension phase of the clinical studies. For two patients, event onset was during the double-blind phase of the clinical trials.
Two of the six patients had a history of aggression and aggressive behavior, and another three patients had previously reported psychiatric history. All of the events occurred at a time when the dose of FYCOMPA was between 6 and 12 milligrams. Patient ages ranged from 13 to 57 years old with three male and three female patients.
All six patients who experienced homicidal ideation and or threat recovered. Two after FYCOMPA was withdrawn, two after the dose was reduced, and two with no change in the dose. Now, please stay tuned for additional important safety information for FYCOMPA.
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 milligrams and 12 milligrams per day, respectively, compared to 6% of patients in the placebo group. These effects were dose-related and generally appeared within the first six 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. Anti-epileptic 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 multi-organ 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 parampanel 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. For more information about FYCOMPA, please see the full prescribing information including boxed warning at FYCOMPA.com.hcp
