|Drug class||Anticonvulsant (AMPA receptor blocker)|
|Side effects||Sleepiness, irritability, nausea, weight gain, poor coordination, abuse|
|Typical dose||8 to 12 mg per day|
|Metabolism||Hepatic, mostly via CYP3A4 and/or CYP3A5|
|Elimination half-life||105 hours, 295 hours (moderate hepatic impairment)|
|Excretion||70% faeces, 30% urine|
|Chemical and physical data|
|Molar mass||349.393 g·mol−1|
|3D model (JSmol)|
|(what is this?)|
Perampanel, sold under the brand name Fycompa, is a medication used to treat partial seizures and generalized tonic-clonic seizures. It maybe used in addition to other medications or by itself. It is taken by mouth.
Common side effects include sleepiness, irritability, nausea, weight gain, and poor coordination. Other side effects may include homicidal or suicidal thoughts, drug reaction with eosinophilia and systemic symptoms (DRESS), and abuse. It also reduced the effectiveness of birth control containing levonorgestrel. Use during pregnancy may harm the baby. It works by blocking the AMPA receptor.
Perampanel was approved for medical use in the United States and Europe in 2012. In the United Kingdom 4 weeks of medication costs the NHS about £140 as of 2021. This amount in the United States costs about 1,000 USD. It is a Schedule III controlled substance by the Drug Enforcement Administration.
A 2016 review found it effective for both indications but due to the newness of the drug was unable to describe its optimal role in the treatment of epilepsy relative to other drugs. A 2014 review of the probability of added benefit of perampanel to the standard of care was unable to come to any conclusions, as no trial conducted by Eisai compared perampanel to a drug within the standard of care, but only to placebo.
Its optimal role in the treatment of epilepsy relative to other drugs was not clear.
It is started at 2 mg per day and gradually increased to 8 to 12 mg per day.
People with severe liver impairment or severe kidney disease, including those on dialysis, should not take perampanel.
Perampanel's label has a black box warning noting that some people taking the drug have undergone serious psychiatric and behavioral changes. These events occurred in people who had no history of such issues, as well as people who had such a history. The psychiatric changes included mood changes like euphoric mood, anger, irritability, aggression, belligerence, agitation, and anxiety, as well as psychosis (acute psychosis, hallucinations, delusions, paranoia) and delirium (delirium, confusional state, disorientation, memory impairment). Behavioral changes included physical assault and homicidal ideation and/or threats.
Other serious side effects include suicidal thoughts or behavior (like all anti-epileptic drugs), dizziness and gait disturbance, somnolence and fatigue, risk of falls, and increased risk of seizures if the drug is quickly withdrawn.
In clinical trials, dizziness, somnolence, vertigo, aggression, anger, loss of coordination, blurred vision, irritability, and slurred speech were the side effects that most commonly led people to leave the trial.
Perampanel is liable to be abused; very high doses produced euphoria responses similar to ketamine, although subjects liked it less and had experienced it more negatively than ketamine; it produced dissociative effects similar to ketamine. It is designated as a Schedule III controlled substance by the Drug Enforcement Administration. A study of dependence in rats found withdrawal symptoms when the drug was removed; dependence in humans wasn't studied well enough to make generalizations as of April 2016. There is limited experience with overdose.
Perampanel reduced the effectiveness of levonorgestrel oral contraceptives by about 40%. Other antieptilectic drugs that induce cytochrome P450, including carbamazepine, phenytoin, and oxcarbazepine decrease the effectiveness of perampanel by 50-67%. Use of perampanel with strong CYP3A inducers like rifampin or St. John's wort is not recommended. Use of perampanel with CNS depressants like alcohol may increase the effect of the CNS depressant.
Whole-cell voltage clamp studies have demonstrated that perampanel is a negative allosteric AMPA receptor antagonist. Perampanel caused a slow (τ∼1 s at 3 μM), concentration-dependent inhibition of AMPA receptor currents. The rates of block and unblock of AMPA receptor currents were 1.5 × 105 M−1 s−1 and 0.58 s−1, respectively. Perampanel did not affect NMDA receptor currents. The extent of block (IC50, 0.56 μM) was similar at all agonist concentrations, demonstrating a noncompetitive blocking action. Parampanel did affect AMPA receptor desensitization, or the ratio of peak to late response to rapid application of AMPA. Perampanel is a selective negative allosteric AMPA receptor antagonist of high-affinity and slow blocking kinetics, and is not use-dependent.
Perampanel has a prolonged terminal half-life in humans of approximately 105 hours. The drug is 95% bound to plasma protein. Its primary route of metabolism is by CYP3A4. It does not induce P450 enzymes. About 70% of the dose is excreted in the feces and 30% in the urine; less than 2% of the dose is excreted unchanged into the urine.
The tablets contain lactose monohydrate, low substituted hydroxypropyl cellulose, povidone, microcrystalline cellulose, magnesium stearate, hypromellose, polyethylene glycol, talc, and titanium dioxide in addition to the API; the oral suspension contains sorbitol, microcrystalline cellulose, carboxymethylcellulose sodium, poloxamer, simethicone, citric acid, sodium benzoate and purified water in addition to the API.
It was approved for marketing under the brand name Fycompa by the European Medicines Agency (EMA) in July 2012, and as of July 2016, was approved as an adjunct treatment of partial-onset seizures with or without secondarily generalised seizures in people with epilepsy older than twelve years and as an adjunct treatment of primary generalised tonic-clonic seizures for people older than twelve years who have idiopathic generalised epilepsy.
It was first approved by the FDA under the same brand name in October 2012, and then in June 2015, for the same uses as those in the European Union; it was one of four new drugs for epilepsy approved between 2010 and 2016, along with clobazam (Onfi), ezogabine (Potiga), and eslicarbazepine (Aptiom).
As of August 2016 perampanel had been studied and development discontinued in migraine, multiple sclerosis, neuropathic pain, and Parkinson's disease.
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