Zonisamide

Indications

Zonisamide is used for: Adjunct in partial seizures, Monotherapy for partial seizures with or without secondary generalisation

Adult Dose

Oral Adjunct in partial seizures Adult: Initially, 50 mg daily in 2 divided doses, increase to 100 mg daily after 1 wk. Thereafter, may further increase dose at wkly intervals in increments of up to 100 mg. Usual maintenance dose: 300-500 mg daily, some patients may respond to lower doses. Child: ?6 yr Initially, 1 mg/kg once daily for 1 wk, may increase by increments of 1 mg/kg at wkly interval. Usual maintenance dose: 20-55 kg: 6-8 mg/kg once daily; >55 kg: 300-500 mg once daily, some may respond to lower dose. Monotherapy for partial seizures with or without secondary generalisation Adult: In patients w/ newly diagnosed epilepsy: Initially, 100 mg once daily, increase to 200 mg once daily after 2 wk. May further increase by increments of 100 mg at intervals of at least 2 wk. Usual maintenance dose: 300 mg once daily, up to 500 mg daily. Hepatic impairment: Mild to moderate: Slower dosage titration may be needed. Severe: Not recommended.

Child Dose

Oral Adjunct in partial seizures Child: >6 yr Initially, 1 mg/kg once daily for 1 wk, may increase by increments of 1 mg/kg at wkly interval. Usual maintenance dose: 20-55 kg: 6-8 mg/kg once daily; >55 kg: 300-500 mg once daily, some may respond to lower dose.

Renal Dose

Renal impairment: GFR ?50 mL/min: Slower dosage titration may be needed. GFR <50 mL/min: Not recommended.

Administration

May be taken with or without food.

Contra Indications

Hypersensitivity to zonisamide or sulfonamides

Precautions

Patient at risk of nephrolithiasis. Avoid abrupt withdrawal. Renal or hepatic impairment. Childn. Pregnancy and lactation. Patient Counselling Increase fluid intake (i.e. 6-8 glasses of water/day) to reduce risk of renal stone. This drug may cause drowsiness or difficulty w/ concentration, if affected, do not drive or operate machinery. Increase in suicidal ideation may occur with use. Monitoring Parameters Monitor metabolic profile specifically BUN, serum creatinine; serum bicarbonate, body temp, suicidality, decreased sweating. Lactation: Unknown; avoid during breastfeeding

Pregnancy-Lactation

Interactions

Reduced plasma concentration w/ phenytoin, phenobarbital, carbamazepine. Increased risk of metabolic acidosis w/ carbonic anhydrase inhibitors (e.g. acetazolamide).

Adverse Effects

Side effects of Zonisamide : >10% Somnolence (17%) Anorexia (13%) Dizziness (13%) 1-10% Headache (10%) Nausea (9%) Agitation (9%) Abdominal pain (6%) Ataxia (6%) Confusion (6%) Depression (6%) Diplopia (6%) Insomnia (6%) Diarrhea (5%) Speech disorder (5%) Flu-like symptoms (4%) Kidney stones (4%) Nystagmus (4%) Paresthesia (4%) Dysgeusia (3%) Weight loss (3%) Anxiety (3%) Rash (3%) Constipation (2%) Rhinitis (2%) Xerostomia (2%)

Mechanism of Action

Zonisamide is a benzisoxazole derivative anticonvulsant containing sulfonamide. It may act on voltage sensitive Na and Ca channels, thereby affecting neuronal firing, hence reducing the spread of seizure discharges. It may modulate GABA-mediated neuronal inhibition.