Zonisamide

Zonisamide

Zonisamide is an antiepileptic drug used primarily for the treatment of epilepsy. It belongs to a class of medications known as sulfonamides and has a unique mechanism of action that distinguishes it from other antiepileptic drugs. Zonisamide is effective in managing partial seizures, with or without secondary generalization, in adults and children.

Mechanism of Action

Zonisamide works by inhibiting sodium and calcium channels, which decreases neuronal hyperexcitability. It is also thought to have an effect on neurotransmitter release, further contributing to its antiepileptic properties. The exact mechanism, however, is not fully understood.

Pharmacokinetics

After oral administration, zonisamide is well absorbed from the gastrointestinal tract. It has a bioavailability of nearly 100% and reaches peak plasma concentrations within 2 to 5 hours. Zonisamide is primarily metabolized in the liver and has a half-life of approximately 60 hours, allowing for once or twice daily dosing. It is excreted both in urine and feces.

Indications

Zonisamide is indicated for the treatment of partial seizures in adults and children. It can be used as monotherapy or in combination with other antiepileptic drugs.

Adverse Effects

Common adverse effects of zonisamide include drowsiness, dizziness, headache, and nausea. Less frequently, it may cause cognitive impairment, kidney stones, weight loss, and hypersensitivity reactions. Due to its sulfonamide structure, zonisamide carries a risk of serious skin reactions, such as Stevens-Johnson syndrome.

Contraindications

Zonisamide is contraindicated in patients with a known hypersensitivity to sulfonamides. Caution is advised in patients with renal or hepatic impairment, as well as in those with a history of kidney stones.

Drug Interactions

Zonisamide's plasma concentration can be affected by other drugs. Enzyme inducers, such as phenytoin and carbamazepine, can decrease zonisamide levels, while enzyme inhibitors like ketoconazole can increase its levels. Additionally, zonisamide can increase the levels of other antiepileptic drugs, such as phenytoin and carbamazepine.

Dosage and Administration

The starting dose of zonisamide is typically low, gradually increasing to the optimal dose. For adults, the initial dose is usually 100 mg daily, with increments of 100 mg every two weeks, up to a usual maintenance dose of 300 to 500 mg daily. In children, dosing is based on body weight.

Pharmacological Properties

Zonisamide's unique pharmacological properties, including its broad spectrum of antiepileptic activity and favorable pharmacokinetic profile, make it a valuable option in the treatment of epilepsy.

Conclusion

Zonisamide is an effective and generally well-tolerated antiepileptic drug with a unique mechanism of action. Its role in the management of partial seizures, both as monotherapy and as part of combination therapy, is well established. However, like all medications, it must be used cautiously, considering potential adverse effects and interactions with other drugs.

• Dailymed label info on Zonisamide
• FDA Zonisamide