Home' Australian Pharmacist : Australian Pharmacist February 2016 Contents Australian Pharmacist February 2016 I ©Pharmaceutical Society of Australia Ltd. 63
CONTINUING PROFESSIONAL DEVELOPMENT
Adverse e ects
Most adverse effects appear to be
dose-related.23 In the phase III trials,
the adverse reactions most commonly
leading to discontinuation were
dizziness and somnolence.15 (See Table
2 for more information on adverse effects
in the phase III trials). In extension
study 30721, the most frequently
reported adverse events (>10%) were
dizziness, somnolence, headache,
fatigue, irritability and weight gain.15
(See 'Precautions' section for more
information regarding psychiatric
Perampanel is metabolised by
CYP3A4/5, and inducers of these
enzymes (e.g. carbamazepine,
oxcarbazepine, phenytoin, St John's
wort, rifampicin) can reduce its serum
levels and efficacy. Patients taking these
combinations should be monitored
for seizure breakthrough and have
their dose of perampanel increased if
necessary.11,13--15,23 (See also Table 3).
CYP3A4/5 inhibitors may increase
perampanel serum levels and the risk
of adverse effects. They include triazole
antifungal agents (e.g. fluconazole,
posaconazole), HIV-protease inhibitors
(e.g. atazanavir, fosamprenavir, indinavir,
ritonavir, saquinavir), HCV-protease
inhibitors (e.g. boceprevir), and
Perampanel 12 mg daily decreases
levonorgestrel serum levels by 40%,
and may reduce the efficacy of oral
contraceptives. Although doses below
12 mg do not affect levonorgestrel
concentration, women of childbearing
age taking perampanel should be
advised to use an alternative, reliable
contraceptive method (e.g. an IUD).11,23
As is the case with all AEDs, perampanel
should be used with caution with
medicines that lower the seizure
threshold. These include antipsychotics,
antidepressants, quinolone antibiotics,
donepezil, galantamine, rivastigmine,
pizotifen, and bupropion.23
• Prescribed dose to be taken once daily
at bedtime, without regard to food.
• Perampanel can cause dizziness,
drowsiness and balance disturbances,
and increase the risk of falls.
• Advise patients/caregivers to monitor
for psychiatric/behavioural reactions
and suicidal thoughts/behaviour.
• Alcohol can worsen sedative,
cognitive and behavioural side effects
and should be avoided.
• Perampanel should not be stopped
abruptly, unless advised by a doctor.
1. Shih JJ, Tatum WO, Rudzinski LA. New drug classes for the
treatment of partial onset epilepsy: focus on perampanel.
Ther Clin Risk Manag 2013;9:285--93. At: www.ncbi.nlm.nih.
2. Facts and statistics about epilepsy. Epilepsy Action Australia.
3. Bromfield EB, Cavazos JE, Sirven JI, eds. An Introduction to
Epilepsy. Chapter 1: basic mechanisms underlying seizures
and epilepsy. West Hartford (CT): American Epilepsy
Society; 2006. At: www.ncbi.nlm.nih.gov/books/NBK2510/
4. Cruciani R. Neurotransmission [revised December 2009].
In: Porter RS, ed. The Merck manual online. 2015. At: www.
5. Barnes J. Essential biological psychology. Chapter 1.
Neurons, neurotransmission and communication. Sage
publications 2013. At: https://au.sagepub.com/sites/
6. Rogawski MA. Revisiting AMPA receptors as an antiepileptic
drug target, Epilepsy Currents 2011;11(2):56--63. At: www.
7. Brunton LL, Parker KL eds. Goodman and Gilman's manual
of pharmacology and therapeutics. McGraw-Hill, 2008.
8. Adamolekun B. Seizure disorders. 2013. The Merck manual
online. At: www.merckmanuals.com/professional/
9. Scheffer IE, Berkovic SF, Capovilla G, et al. The organization
of the epilepsies: report of the ILAE Commission on
Classification and Terminology. International League
Against Epilepsy, 2013. At: www.ilae.org/Visitors/Centre/
Table 3. Interactions between perampanel and other AEDs11,13
Influence of AED on perampanel
Influence of perampanel on AED
Carbamazepine 67% decrease
Oxcarbazepine 50% decrease
Phenobarbitone No influence
"AS IS THE CASE WITH ALL AEDS, PERAMPANEL SHOULD
BE USED WITH CAUTION WITH MEDICINES THAT LOWER
THE SEIZURE THRESHOLD."
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