Perampanel

Drug Information: Perampanel

Perampanel is a non-competitive AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid) receptor antagonist used as an adjunctive treatment for partial-onset seizures with or without secondarily generalized seizures in patients with epilepsy aged 4 years and older, and for the treatment of primary generalized tonic-clonic seizures in patients with epilepsy aged 12 years and older. By selectively targeting AMPA receptors, Perampanel modulates excitatory neurotransmission in the brain, helping to reduce the frequency and severity of seizures. It is available in oral tablet form and must be taken as prescribed by a healthcare professional.

Category

Neurological Drugs – Anticonvulsant

Mechanism of Action

Perampanel is a highly selective, non-competitive antagonist of the AMPA receptor, which is the primary glutamate receptor in the brain responsible for fast excitatory synaptic transmission. Glutamate, the major excitatory neurotransmitter in the central nervous system, binds to AMPA receptors, leading to an influx of sodium ions and subsequent neuronal depolarization. This depolarization is crucial for the initiation and propagation of action potentials, which underlie many neurological processes, including seizure activity.

By blocking the AMPA receptor, perampanel reduces the excitatory drive in the brain, thereby decreasing the likelihood of seizure generation and spread. Unlike some other anticonvulsants that target voltage-gated ion channels or GABAergic neurotransmission, perampanel directly modulates glutamatergic neurotransmission. The non-competitive nature of its antagonism means that perampanel binds to a site on the AMPA receptor distinct from the glutamate binding site, modulating the receptor’s function without directly competing with glutamate. This results in a unique mechanism of action that can be particularly effective in patients who do not respond adequately to other anticonvulsant medications.

The specific binding site of perampanel is located on the GluA2 subunit of the AMPA receptor. GluA2 subunits are crucial for regulating the calcium permeability of the receptor. By interacting with this subunit, perampanel can indirectly influence calcium signaling within neurons, further contributing to its anticonvulsant effect. The clinical significance of this unique mechanism of action is evidenced by perampanel’s efficacy in treating both partial-onset and generalized tonic-clonic seizures, making it a valuable therapeutic option for a broad range of epilepsy syndromes.

Clinical Uses

Perampanel is primarily used as an adjunctive treatment for seizures in patients with epilepsy. Specifically, it is approved for the treatment of partial-onset seizures with or without secondarily generalized seizures in patients aged 4 years and older. It is also indicated for the treatment of primary generalized tonic-clonic seizures in patients with epilepsy aged 12 years and older. Clinical trials have demonstrated its effectiveness in reducing the frequency of these seizure types when added to other antiepileptic medications. The medication has also been investigated, and in some cases used off-label, for other neurological conditions involving neuronal excitability, but its primary and approved use remains within the treatment of epilepsy. Its unique mechanism of action, targeting AMPA receptors, makes it a valuable option for patients who may not adequately respond to traditional antiepileptic drugs that work through different mechanisms, such as modulating GABAergic transmission or affecting voltage-gated ion channels.

Dosage

Adults: The typical starting dose of perampanel is 2 mg orally once daily at bedtime. The dose may be increased based on individual response and tolerability, typically in increments of 2 mg, no more frequently than every 1-2 weeks. The maintenance dose usually ranges from 4 mg to 8 mg once daily, though some patients may require up to 12 mg per day.

Pediatrics (4 years and older for partial-onset seizures; 12 years and older for generalized tonic-clonic seizures): The starting dose is also 2 mg orally once daily at bedtime. Dosage adjustments are similar to adults, based on response and tolerability. Consult a pediatric neurologist or epileptologist for specific dosing recommendations.

Route of Administration: Oral (tablet). It’s crucial to follow the prescribed dosing schedule and instructions provided by a healthcare professional.

Indications

* Adjunctive treatment of partial-onset seizures with or without secondarily generalized seizures in patients with epilepsy (4 years and older).
* Adjunctive treatment of primary generalized tonic-clonic seizures in patients with epilepsy (12 years and older).

Contraindications

* Significant hypersensitivity to perampanel or any of its ingredients.
* Severe hepatic impairment (Child-Pugh Class C) – Dosage adjustments are needed for mild to moderate hepatic impairment.
* Severe Renal Impairment or End-Stage Renal Disease not undergoing Hemodialysis.
* Concurrent use with strong CYP3A4 inducers may reduce perampanel’s effectiveness. Dosage adjustments may be necessary.
* Caution should be exercised in patients with a history of psychiatric events or aggression.

FAQ

Q: What is Perampanel used for?

A: Perampanel is used as an add-on medication to treat partial-onset seizures and primary generalized tonic-clonic seizures in people with epilepsy.

Q: How does Perampanel work?

A: It works by blocking AMPA receptors in the brain, reducing the over-excitation of nerve cells that can lead to seizures.

Q: What are the common side effects of Perampanel?

A: Common side effects can include dizziness, sleepiness, irritability, aggression, falls, and difficulty with coordination.

Q: Can Perampanel be taken with other medications?

A: Perampanel can interact with other medications, especially those that affect liver enzymes. It’s important to tell your doctor about all the medications you are taking.

Q: What should I do if I miss a dose of Perampanel?

A: If you miss a dose, take it as soon as you remember. However, if it is almost time for your next dose, skip the missed dose and continue with your regular schedule. Do not double the dose to catch up.

Q: Can I drink alcohol while taking Perampanel?

A: Alcohol can increase the side effects of Perampanel, such as dizziness and sleepiness. It is best to avoid alcohol while taking this medication.

Q: How long does it take for Perampanel to start working?

A: It may take several weeks to months to see the full effects of Perampanel. It is important to continue taking the medication as prescribed by your doctor, even if you don’t notice an immediate improvement.

Q: Is Perampanel safe during pregnancy or breastfeeding?

A: Perampanel should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. It is not recommended to breastfeed while taking perampanel due to the potential for adverse effects in the infant. Consult your doctor for personalized advice.