Zonisamide Oral Suspension FDA-Approved for Partial Seizures in Epilepsy

Author(s):

Previously used to treat conditions such as temporal lobe epilepsy and focal impaired awareness, the FDA approved a new oral suspension of zonisamide, an antiseizure medication on the market for over 2 decades.

James Wheless, MD

Originally approved in the US in 2000, the FDA has cleared a new oral suspension of zonisamide (Azurity Pharmaceuticals), marketed as Zonisade, for the treatment of partial seizures in adults and pediatrics aged 16 years and older with epilepsy.¹

The recommended initial dose of zonisamide is 100 mg daily, although dosage may be increased to 100 mg daily every 2 weeks, based on clinical response and tolerability, to 400 mg daily. Those who tolerate a 400-mg daily dose and require further reduction of seizures may increase their dosage to a maximum of 600 mg daily. Additionally, the drug is contraindicated in patients who have demonstrated hypersensitivity to sulfonamides or zonisamide.²

"The provider community continues to seek reliable formulations of medicines that may reduce the epilepsy patient and caregiver burden and help improve treatment adherence,” James Wheless, MD, chair, Pediatric Neurology, University of Tennessee Health Science Center, said in a statement.¹ “Zonisade addresses an important unmet need in patients who have difficulty swallowing or who are unable or unwilling to take tablets."

Designed as a carbonic anhydrase inhibitor, the efficacy and tolerability of the oral suspension had been previously established in 3 double-blind, placebo-controlled, multicenter trials. The first study, which featured 203 patients with partial-onset seizures, showed statistically significant treatment differences favoring zonisamide across 100-, 200-, and 400-mg daily dose levels. In the second and third studies, both showed statistically significant differences favoring doses of 400 mg to 600 mg daily, with no apparent difference between once daily and twice daily dosing. Additionally, analysis of the first 4 weeks of treatment during titration showed statistically significant differences from placebo in those on zonisamide doses between 100 mg and 400 mg.²

"Zonisade is the first and only FDA-approved oral liquid formulation of zonisamide, and it offers healthcare providers an important new treatment option for their patients with epilepsy," Richard Blackburn, chief executive officer, Azurity Pharmaceuticals, said in a statement.¹ "We are excited about this approval as we continue to grow our portfolio of liquid medications that meet the individual needs of certain patients."

Zonisamide was first used in Japan in 1972 to treat psychiatric diseases and has been widely used to treat epilepsy in Japan and Korea since at least 1990. It received FDA approval in 2000 as an adjunctive therapy to treat partial seizures in adults, however, there have been several clinical studies showing efficacy and benefits in pediatric populations as well. More specifically, the generic drug has treated conditions such as temporal lobe epilepsy, focal impaired awareness or complex partial seizures, refractory seizures, secondarily generalized seizures or bilateral tonic clonic seizures, and focal aware or simple partial seizures.

There are risks to taking treatment, as zonisamide may cause metabolic acidosis and increase the risk of hyperammonemia and kidney stone formulation. No specific antidotes for zonisamide overdosage are available; however, due to the low protein binding of the medication, renal dialysis may be effective. The effectiveness of renal dialysis to treat overdose has not been formally studied and a poison control center should be contacted for more information on the management of zonisamide overdosage.²

"Delivering new treatment formulations is important to help ensure diverse epilepsy populations can access the medication for management of their epilepsy because it offers greater flexibility and customization in dosing,” Beth Dean, chief executive officer, CURE Epilepsy, said in a statement. “The FDA approval and availability of Zonisade is a welcomed advancement for patients and their families who may be seeking a liquid formulation alternative to treat epilepsy."¹

REFERENCES
1. Azurity Pharmaceuticals, INC. announces FDA approval of Zonisade (zonisamide oral suspension). News release. Azurity Pharmaceuticals. July 18, 2022. Accessed July 18, 2022. https://www.prnewswire.com/news-releases/azurity-pharmaceuticals-inc-announces-fda-approval-of-zonisade-zonisamide-oral-suspension-301587834.html
2. Zonisade prescribing information. Azurity Pharmaceuticals. https://azurity.com/wp-content/uploads/2022/07/ZONISADE-Prescribing-Information-rev-07.22.pdf. Updated July 2022. Accessed July 18, 2022.