Hi, I’m Dr. Matthew Holtzman from Wayne Neurology in Wayne, Michigan. Today I’m going to present a case study from my clinical practice.
This real-world case describes the first-line use of FYCOMPA in a patient with convulsive seizures—specifically, a newly diagnosed patient who has partial-onset seizures with secondary generalization.
Note that FYCOMPA is indicated in patients with epilepsy aged 4 years and older for partial-onset seizures with or without secondarily generalized seizures.
FYCOMPA is also indicated as adjunctive therapy for patients aged 12 years and older for primary generalized tonic-clonic seizures.
Please stay tuned for additional Important Safety Information, including complete Boxed WARNING relating to serious or life-threatening psychiatric and behavioral adverse reactions.
Now let’s take a look at this patient. She is a 28-year-old woman with no prior significant medical history.
She denied smoking and use of illicit substances. She did report occasional alcohol use.
Regarding her seizure history, the patient experienced 2 unprovoked partial-onset seizures with secondary generalization approximately 2 months apart. Her EEG and MRI results were unremarkable. After the second seizure, she was prescribed levetiracetam by the emergency room physician and instructed to follow up with neurology.
Several weeks later, she was seen in the clinic. Her dose of levetiracetam was 250 mg in the morning and 500 mg at bedtime.
She had not experienced any seizures since beginning levetiracetam, but she experienced difficulty tolerating the medication. Additionally, she did not like taking the medication twice daily and preferred a once-daily option.
Her EEG at this follow-up visit showed a fairly organized 9-Hz rhythmic waveform background while awake, symmetrically distributed over both posterior quadrants and reactive to eye opening.
A moderate amount of sharp waves was seen at T3 during recording. No buildup was seen during the hyperventilation period.
Mild bilateral photic drive was detected on photic stimulation, and sleep stages I and II were seen.
My impression was that of an abnormal EEG while awake and asleep. Sharp waves in the left temporal region were considered epileptiform in nature and were consistent with a lesion in the left temporal region, which might be epileptogenic in nature.
The treatment goals for this patient were to maintain seizure freedom with a once-daily medication that balanced safety with efficacy. The patient was particularly concerned about experiencing agitation or anger.
She also indicated that she did not want to undergo frequent blood draws for medication monitoring.
I presented several medication options to this patient. We made a shared decision to start FYCOMPA because it is administered once daily at bedtime and does not require drug-level monitoring.
We reviewed the Medication Guide together and both felt that the documented side-effect profile of FYCOMPA, which I reviewed with her, was acceptable.
So I started her on FYCOMPA 2 mg once daily at bedtime for 2 weeks, and instructed her to increase the dose to 4 mg once daily at bedtime after that if she was tolerating the medication.
I also instructed her to avoid alcohol while taking FYCOMPA and advised her to contact the office if she experienced a seizure or side effects.
I also encouraged the patient to enlist a caregiver to help her monitor any behavioral changes or psychiatric side effects.
I closely monitored her for somnolence, agitation, ataxia, and other neurologic side effects.
She did not report any side effects during the titration period or the initial 4-mg period. Once she reached the 4 mg dose of FYCOMPA, levetiracetam was discontinued.
I’d like to point out that the recommended maintenance dose range for FYCOMPA for partial-onset seizures is 8 mg to 12 mg once daily, although some patients with partial-onset seizures may respond to a dose of 4 mg daily.
I’m pleased to report that, at 6 months of follow-up, this patient remained convulsive seizure free.
She does experience occasional morning somnolence, but does not report any anxiety or anger.
She is able to continue working now that she is seizure free, and was able to return to driving after 6 consecutive months of seizure freedom.
Throughout treatment, I will continue to monitor for efficacy and tolerability.
Lastly, here, keep in mind that the treatment plan and results I have just described are specific to this particular patient, and other patients may have different outcomes.
Let us now review the study data that looked at FYCOMPA monotherapy in newly diagnosed or untreated patients, similar to the patient case we just reviewed.
The FREEDOM study is a 26-week, multicenter, uncontrolled, open-label study conducted in Japan and South Korea, which assessed the first-line use of FYCOMPA in newly diagnosed or untreated patients with epilepsy who have partial-onset seizures with or without secondary generalization.
The objective of this study was to evaluate the seizure-freedom rate during a 26-week maintenance phase. The evaluation criteria focused on the efficacy and safety of FYCOMPA used as monotherapy in new-onset or untreated patients with partial-onset seizures, including secondarily generalized seizures.
In this study, 96% of the patients were newly diagnosed with epilepsy. These patients presented with the seizure types seen here. The majority of patients presented with complex partial seizures with secondary generalization.
Seventy-three patients entered the 4-mg maintenance period and had at least 1 postdose primary efficacy measurement. These patients had experienced a median baseline seizure frequency of 2 seizures per 12 weeks.
Following a 28-day pretreatment phase, the patients were started on 2 mg of FYCOMPA for 2 weeks, and then titrated to 4 mg of FYCOMPA for 4 weeks.
They then began a 26-week maintenance phase during which they were monitored for seizure freedom. If a seizure occurred during this 26-week maintenance phase, the patients were titrated to 6 mg once daily, and then to 8 mg once daily.
During the 26-week maintenance phase, the majority of the newly diagnosed or untreated patients with partial-onset seizures were seizure free. In the open-label analysis, 63% of patients with partial-onset seizures achieved seizure freedom with FYCOMPA 4 mg. Of the patients with secondarily generalized seizures at baseline, 65% achieved seizure freedom.
It’s important to note that this was an open-label study without blinding, randomization, or a control arm. Appropriate multiplicity adjustments were not applied and the information presented here is descriptive.
Here you see the adverse events at 26 weeks that occurred in at least 5% of patients taking 4 mg of FYCOMPA.
Psychiatric disorders reported at 4 mg/day included irritability (2.9%), affect lability (1.5%), depression (1.5%), and insomnia (1.5%).
It’s important to note that of the 22 patients who discontinued treatment during the 4-mg treatment phase, 8 patients or 9% discontinued due to an adverse event. Additional reasons for discontinuation can be seen here.
I’m encouraged to see additional data that supports why we may want to pause at 4 mg and assess for efficacy and safety in partial-onset seizure patients. It’s important to know that some patients may respond to 4 mg.
Here you can see the dosing information for FYCOMPA. Please take a moment to review FYCOMPA’s recommended dosing.
If you need more time, feel free to pause the presentation or see FYCOMPA’s prescribing information provided with this presentation.
Now let’s review the important safety information. This is information I always discuss with my patients when initiating FYCOMPA.
FYCOMPA has a boxed warning for 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, irrespective of prior psychiatric history, prior aggressive behavior, or concomitant use of medications associated with hostility and aggression.
Monitor patients for these reactions as well as for changes in mood, behavior, or personality that are not typical for the patient, 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.
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 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 reactions with eosinophilia and systemic symptoms, also known as multiorgan hypersensitivity, have 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.
Please see the Full Prescribing Information for FYCOMPA, including the Boxed Warning regarding SERIOUS PSYCHIATRIC AND BEHAVIORAL REACTIONS or visit FYCOMPA.com/hcp.
I’m glad to have had the opportunity to share this patient’s case with you. I’m pleased to see monotherapy data for FYCOMPA in patients with newly diagnosed partial-onset seizures, including those with convulsive seizures.
For more information about FYCOMPA and the FREEDOM study, please review the other materials on this site and FYCOMPA.com/hcp.
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