FDA Expands APTIOM Indication Through Extrapolation for Partial-Onset Seizures

The US Food and Drug Administration approved eslicarbazepine acetate (APTIOM) on Sept. 13, for the treatment of partial-onset seizures in patients 4 years and older based on extrapolation of adult data.

This supports of pediatric indication is based on extrapolating adult efficacy for treatment of partial onset-seizures to pediatric patients 4 years and older in an adjunctive treatment scenario. This allows a dosing regimen that could provide similar exposures, at levels demonstrated to be effective in adults, in pediatric subjects 4 years and older to eslicarbazepine exposure in adult subjects with partial-onset seizures.

“Despite being the most common seizure type in patients with epilepsy, there continues to be a critical need for new therapeutic options for partial-onset seizures, especially for children and adolescents,” Steven Wolf, MD, Director of Pediatric Epilepsy, associate professor of neurology, Mount Sinai Health System said.

Additionally, efficacy for partial onset-seizures in a monotherapy treatment scenario was determined based on inference of efficacy in an adjunctive treatment scenario.

This monotherapy indication support pathway for partial-onset seizures is based on extrapolation of pharmacokinetic information deemed adequate to demonstrate that the proposed dosages of a drug, when used as monotherapy, can be expected to result in exposures similar to those safe and effective when the drug is used as an adjunctive treatment therapy. This requires assessment of possible drug-drug interactions (inhibition or induction) which may alter the metabolism of the drug.

Inferences of adult adjunctive efficacy to pediatric adjunctive efficacy, and adjunctive efficacy to monotherapy efficacy relied on population pharmacokinetic analyses of adult and pediatric patient data with partial-onset seizures from phase 2a and phase 3 trials.

Recommended dosage regimen for APTIOM varies based on age, weight and renal function.

The approved recommended initial dosage for adults 18 years and older is 400 mg orally once daily. For some patients, treatment may be initiated at 800 mg orally once daily if the need for seizure reduction outweighs an increased risk of adverse effects.

For patients on APTIOM monotherapy, the 800 mg once daily maintenance dose should be generally considered in patients unable to tolerate a 12,000-mg daily dose. Those on APTIOM adjunctive therapy, the 1,600 daily dose should be considered in patients who didn’t achieve a satisfactory response with a 1,200 mg daily dose.

Dosage for pediatric patients 4—17 years of age is based on body weight. Increase dosage no more frequently than once per week based on clinical response and tolerability.

APTIOM is a once-daily medication immediate release antiepileptic drug (AED) that can be taken whole or crushed, with or without food.

Serious adverse effects associated with APTIOM are suicidal behavior and ideation, serious dermatologic reactions, drug reaction with eosinophilia and systemic symptoms (DRESS)/multiorgan hypersensitivity, anaphylactic reactions and angioedema, hyponatremia, drug induced liver injury, neurologic and hematologic adverse effects.

Side effects are similar in pediatric patients and most commonly include dizziness, somnolence, nausea, headache, diplopia, vomiting, fatigue, vertigo, ataxia, blurred vision and tremor.

A press release was made available.