Afalino12.5 mg

Approved Indication

Afalino is FDA-approved as adjunctive (add-on) treatment of focal (partial-onset) seizures in adult patients. It is used together with other antiseizure medications, not as a first-line monotherapy.

• Established use: Add-on therapy for focal-onset seizures, with or without secondary generalization, in adults whose seizures are not adequately controlled by other antiepileptic drugs (AEDs).
• Adjunct requirement: Afalino is studied and approved only as adjunctive therapy; it must be added to an existing antiseizure regimen rather than used alone.
• Not established: Safety and effectiveness of Afalino have not been established for primary generalized seizures, monotherapy use, or in pediatric patients.

Use of Afalino should be initiated and supervised by a physician experienced in the treatment of epilepsy.

Cenobamate is available as oral tablets in multiple strengths (typically 12.5 mg, 25 mg, 50 mg, 100 mg, 150 mg, and 200 mg) to allow for the gradual dose-titration schedule required for this medicine. Each tablet contains Cenobamate as the sole active pharmaceutical ingredient, along with standard pharmaceutical excipients.

Afalino is a tetrazole-alkyl-carbamate-derivative anticonvulsant (antiepileptic drug, AED) approved for adjunctive treatment of focal-onset seizures in adults. It is believed to reduce seizure activity through a dual mechanism: inhibition of the persistent (late) sodium current and positive allosteric modulation of GABA-A receptors.

Afalino carries boxed warnings for a serious hypersensitivity reaction (DRESS) and for dose-dependent shortening of the QT interval, both of which require careful patient selection, a slow dose-titration schedule, and ongoing monitoring. Because of these risks, Afalino is generally reserved for patients whose focal seizures remain uncontrolled despite other antiseizure therapies.

Anticonvulsant / Antiepileptic drug (AED) - tetrazole alkyl carbamate derivative; Afalino is chemically and mechanistically distinct from older AED classes.

Mechanism of Action

The precise mechanism by which Cenobamate exerts its antiseizure effect is not fully established, but is believed to involve two complementary actions:

• Inhibition of the persistent (late) sodium current: Cenobamate preferentially reduces the persistent component of the voltage-gated sodium current, which is thought to contribute to sustained neuronal hyperexcitability in seizure activity, more than it affects the transient sodium current.
• Positive allosteric modulation of GABA-A receptors: Cenobamate enhances inhibitory neurotransmission by acting at a site on the GABA-A receptor distinct from the benzodiazepine binding site.

Pharmacokinetics

Cenobamate is well absorbed orally, is extensively metabolized in the liver (primarily via UGT2B7 and UGT2B4 glucuronidation, with minor CYP2E1, CYP2A6, and CYP2B6 involvement), and has a long elimination half-life (roughly 50-60 hours at steady state), which supports once-daily dosing after titration. Cenobamate is also a clinically significant inducer of CYP3A4/2B6 and inhibitor of CYP2B6/2C19, underlying its notable drug-interaction profile.

Afalino is taken by mouth once daily, with or without food. Tablets should be swallowed whole; do not stop, skip, or change the dose of Afalino without consulting a physician, given the importance of the titration schedule and the risk of withdrawal seizures with abrupt discontinuation. If a dose is missed, take it as soon as remembered unless it is close to the next scheduled dose; do not double the dose.

Clinically Significant Drug Interactions

Afalino affects, and is affected by, several cytochrome P450 (CYP) and UGT enzyme pathways, requiring careful medication review before and during treatment.

• Phenytoin: Afalino substantially increases phenytoin plasma concentrations (by up to 70-84%); phenytoin dose reduction (up to 50%) is typically required, with monitoring of phenytoin levels.
• Carbamazepine: Afalino reduces carbamazepine concentrations; carbamazepine dose adjustment may be needed, and carbamazepine (a CYP3A4 inducer) can also lower Afalino levels.
• Lamotrigine: Afalino reduces lamotrigine concentrations; a lamotrigine dose increase may be required to maintain seizure control.
• CYP2C19 substrates (e.g., omeprazole, clobazam): Afalino inhibits CYP2C19, increasing exposure to these drugs (e.g., omeprazole levels increased 83-107%); dose reduction of the CYP2C19 substrate may be needed.
• CYP3A4/CYP2B6 substrates: Afalino induces these enzymes, which can reduce the effectiveness of drugs metabolized through them, requiring dose increases of the affected medication.
• Hormonal contraceptives: Afalino may reduce the efficacy of hormonal contraceptives through CYP3A4 induction; patients should be advised to use an alternative or additional non-hormonal method of contraception during treatment with Afalino.
• Other CNS depressants (alcohol, benzodiazepines, opioids): Additive sedation and CNS depression may occur when combined with Afalino; concurrent use should be approached with caution.
• Other QT-shortening drugs: Combining Afalino with other agents known to shorten the QT interval should be avoided or undertaken with caution and cardiac monitoring (see Precautions and Warnings).

A full medication review, including other antiseizure drugs and hormonal contraceptives, is recommended before starting Afalino and whenever other medications are added or stopped.

Common Side Effects

• Somnolence and sedation
• Dizziness
• Fatigue
• Diplopia (double vision)
• Headache
• Balance and gait disturbances (ataxia)
• Nausea/vomiting
• Blurred vision

Serious Side Effects

Afalino carries a boxed warning for DRESS (drug reaction with eosinophilia and systemic symptoms), a rare but potentially fatal hypersensitivity reaction, and for dose-dependent QT interval shortening; see Precautions and Warnings for full details on recognizing and managing these risks. Suicidal thoughts or behavior have also been reported, consistent with other antiepileptic drugs.

Patients should seek prompt medical attention for fever, rash, swollen lymph nodes, facial swelling, unusual bruising, or signs of organ involvement while taking Afalino.

Pregnancy

There are no adequate and well-controlled studies of Afalino use in pregnant women. Animal reproduction studies have shown increased embryo-fetal mortality and decreased fetal/offspring body weight at maternally toxic doses. Afalino should be used during pregnancy only if the potential benefit to the mother clearly justifies the potential risk to the fetus, and only under close physician supervision. Patients who become pregnant while taking Afalino are encouraged to enroll in an antiepileptic drug pregnancy registry, and should consult their physician before stopping or changing treatment, since uncontrolled seizures also pose risks to mother and fetus.

Lactation

It is not known whether Afalino passes into human breast milk. Because of the potential for adverse effects in a breastfed infant, a decision should be made, in consultation with a physician, whether to discontinue breastfeeding or discontinue Afalino, taking into account the importance of the medicine to the mother.

Boxed Warning: DRESS (Drug Reaction with Eosinophilia and Systemic Symptoms)

Afalino can cause DRESS, a serious and potentially fatal multi-organ hypersensitivity reaction, including at least one reported fatality when the drug was titrated more rapidly than recommended. Strict adherence to the slow, multi-week dose-titration schedule described in Dosage and Administration is essential and non-negotiable to reduce this risk; it is a distinguishing safety feature of Afalino's dosing compared with many other anticonvulsants. Signs of DRESS include fever, rash, lymphadenopathy (swollen lymph nodes), facial swelling, and evidence of organ involvement (e.g., liver, kidney). If DRESS is suspected, Afalino must be discontinued immediately and the patient evaluated urgently, as this reaction can be fatal if treatment continues.

Boxed Warning: QT Interval Shortening

Afalino causes dose-dependent shortening of the QT interval, a distinctive risk for this medicine. This is contraindicated in patients with familial Short QT syndrome (see Contraindications) because of increased risk of ventricular arrhythmias. Caution is needed when combining Afalino with other drugs known to shorten the QT interval, and an ECG should be considered in patients with relevant cardiac risk factors.

Central Nervous System (CNS) Effects

Afalino commonly causes somnolence, dizziness, and fatigue, particularly during dose titration. Patients should avoid driving, operating heavy machinery, or performing other hazardous tasks that require full alertness until they know how Afalino affects them.

Suicidal Thoughts and Behavior

Like other antiepileptic drugs, Afalino may increase the risk of suicidal thoughts or behavior. Patients, families, and caregivers should be alert to mood changes, depression, or unusual behavior and report these to a physician promptly.

Withdrawal Seizures

Abrupt discontinuation of Afalino can precipitate withdrawal seizures or increase seizure frequency. When Afalino needs to be stopped, the dose should be tapered gradually under medical supervision rather than stopped suddenly.

Drug Interactions

Afalino has clinically significant CYP450-mediated interactions with other antiseizure medications and with hormonal contraceptives (which may become less effective); a careful medication review is required before and during therapy (see Interaction).

Hepatic and Renal Impairment

Dose adjustment is required in hepatic and renal impairment; Afalino is not recommended in severe hepatic impairment or end-stage renal disease (see Dosage and Administration).

Limited clinical experience with Afalino overdose is available. Expected effects of overdose include exaggerated somnolence, dizziness, ataxia, and other CNS depression, and there may be effects on cardiac conduction (QT shortening) given the drug's known pharmacology. There is no specific antidote for Afalino overdose.

If overdose with Afalino is suspected, seek immediate medical attention or contact emergency services / a poison control center right away. Treatment should be supportive, with monitoring of vital signs, cardiac rhythm, and level of consciousness in a medical facility; do not attempt to manage a suspected overdose at home.

Store at room temperature (below 30°C), away from light and moisture. Keep out of reach of children.

Pediatric Patients

Safety and effectiveness of Afalino have not been established in patients younger than 18 years.

Elderly Patients

Clinical studies of Afalino did not include sufficient numbers of patients aged 65 and over to determine whether they respond differently from younger patients. Elderly patients may be more sensitive to CNS side effects such as somnolence and dizziness; dose selection should be cautious.

Renal Impairment

Use with caution; dose adjustment may be needed. Not recommended in end-stage renal disease/dialysis (see Dosage and Administration).

Hepatic Impairment

Maximum dose is limited in mild-to-moderate impairment; not recommended in severe hepatic impairment (see Dosage and Administration).

Pregnancy and Lactation

See Pregnancy and Lactation for detailed guidance.

Afalino is intended for long-term, ongoing use in the management of focal seizures, as epilepsy is typically a chronic condition. Reaching the recommended maintenance dose requires approximately 10-11 weeks of gradual titration, and treatment is then continued indefinitely as directed by the treating physician, based on seizure control and tolerability. If discontinuation is ever needed, Afalino must be tapered gradually rather than stopped abruptly, to reduce the risk of withdrawal seizures.

Anticonvulsants; Antiepileptic Drugs (AEDs); Tetrazole alkyl carbamate derivatives. Cenobamate is used for the adjunctive treatment of focal-onset seizures.

Cenobamate is believed to act through two complementary mechanisms: it preferentially inhibits the persistent (late) component of the voltage-gated sodium current in neurons, reducing sustained neuronal excitability, and it acts as a positive allosteric modulator at the GABA-A receptor, enhancing inhibitory neurotransmission at a site distinct from the benzodiazepine binding site. Together, these actions are thought to underlie the antiseizure effect of Cenobamate in focal-onset seizures.

The safety and effectiveness of Afalino have not been established in pediatric patients (younger than 18 years of age). Afalino should not be used in children outside of a clinical trial setting until further data are available. Pediatric patients with epilepsy should be managed with antiseizure medications that have established pediatric safety and dosing data.