An outpatient drug-use evaluation of perampanel from a pediatric medical center
W. Blake Hays, PharmD Candidate 2016, Joshua Courter, PharmD
Background
Methods
Results (continued)
• Perampanel (Fycompa TM) is a non-competitive AMPA
receptor antagonist on the postsynaptic neuron.
Retrospective chart review from July 2014 to May 2015. A total of
8 patients were evaluated in the study.
Table 2: Dosing Information
• Perampanel is FDA approved for:
• Adjunctive therapy for the treatment of partial-onset
seizures with or without secondarily generalized
seizures in patients with epilepsy aged 12 years or older
Group Comparison
< 12 Years
> 12 Years
5.3 ± 1.2
5 ± 3.3
0.27 ± 0.05
0.12 ± 0.09
3±2
7 ± 3.5
0.2 ± 0.11
0.16 ± 0.09
Once daily
21 (91.3%)
20 (57.1%)
Twice daily
2 (8.7%)
15 (42.9%)
Initial daily dose (mg), Mean ± SD
Study Population
Initial daily dose (MKD), Mean ± SD
Maximum tolerated daily dose (mg), Mean ± SD
Patients receiving perampanel as an outpatient prescription from
CCHMC.
Maximum tolerated daily dose (MKD), Mean ± SD
Administration frequency, n (%)
Medication Profile:
• Available formulation: Oral tablet (2,4,6,8,10,12 mg)
• Recommended dosing: Initiate at 2 mg daily and
increase dose by 2 mg per day no more frequently than
weekly
• Pharmacokinetic background:
Outcome Variables
Primary Outcome:
• Intolerance of perampanel dose, characterized by an adverse
drug reaction resulting in a dose reduction.
Secondary Outcomes:
• Milligram per kilogram dosage strengths related to intolerances
• Incidence of prescribing of once daily vs. twice daily dosing
Table 3: Dose Reductions
Age in years
Reason for dose
n
at dose
reduction
reduction
• Absorption: Rapid and complete with
negligible first-pass metabolism
• Protein binding: 95% to 96%
• Metabolism: Primary oxidation by CYP3A4/5
with sequential glucuronidation
GI disturbances
1
13
Agitation
1
9
Other – unspecified 1
7
Daily dose at the time of
reduction, mg (MKD)
Dosing
schedule
12 (0.324)
8 (0.349)
6 (0.261)
6 (0.261)
4 (0.174)
Twice daily
Once daily
Once daily
Once daily
Once daily
* Patients had multiple dose reductions
Results
Conclusions
Figure 1: Patient Allocation
• Half-life elimination: 105 hours
8 patients evaluated
• Time to peak concentration: Median range of
0.5 hours – 2.5 hours
Further studies of perampanel in pediatric patients less than 12 years of
age are needed to obtain dosing recommendations.
•
Perampanel is being prescribed on a twice daily dosing schedule, while
this is not supported by the medication’s pharmacokinetic profile.
•
Traditional dosing of perampanel may not be the safest in pediatric
patients as it does not take the size of the patient into account.
5 patients age 12 years or
older
3 patients less than 12
years of age
• Common side effects: Dizziness, somnolence,
headache, irritability, fatigue
•
Limitations
Problem
The use of perampanel at Cincinnati Children’s Hospital
Medical Center (CCHMC) is increasing in pediatric patients
less than the age of 12 years. Perampanel has not been
studied in this patient population and therefore, lacks
validated dosing recommendations.
Objective
This study was designed to analyze dosing regimens and
tolerance of perampanel in the outpatient setting from a
pediatric medical center.
Table 1: Patient Demographics
Group Comparison
Total Patients, n
< 12 Years
> 12 Years
3
5
Mean age, years
6.3
17.2
Mean weight, kg
19.9
48.6
Male
2 (66%)
3 (60%)
Female
1 (33%)
2 (40%)
3 (100%)
5 (100%)
•
Due to the small study population, results were not able to be
statistically validated.
•
With this being an outpatient evaluation of perampanel, proper patient
compliance could not be guaranteed.
•
Documentation of adverse events were based on self-reporting from
patients and their parents/guardians
Gender, n (%)
Race, n (%)
Caucasian
Disclosure: Authors have no conflicts of interest
References
1. Fycompa (perampanel) prescribing information, 2015, Eisai Inc: Woodcliff Lake, NJ.
2. French JA, Krauss GL, Steinhoff BL, et al. Adjunctive perampanel for refractory partial-onset seizures:
Randomized phase III study 304. Neurology. 2012; 79:589-596.
3. French JA, Krauss GL, Steinhoff BL, et al. Evaluation of adjunctive perampanel in patients with refractory
partial-onset seizures: Results of randomized global phase III study 305. Epilepsia. 2013; 54(1):117–125.
4. Kraus GL, Serratos JM, Villanueva V, et al. Adjunctive perampanel for refractory partial-onset seizures:
Randomized phase III study 306. Neurology. 2012; 78:1408-1415.