ZONISAMIDE

ZONISAMIDE (zon-i'sa-mide) Zonegran Classifications: anticonvulsant; sulfonamide; Therapeutic: anticonvulsant; sulfonamide Pregnancy Category: C

Availability

25 mg, 50 mg, 100 mg capsules

Action

A broad-spectrum anticonvulsant that facilitates dopaminergic and serotonergic neurotransmission but does not potentiate the activity of gamma-aminobutyric acid (GABA) in the synapses of the neurons.

Therapeutic Effect

Suppresses focal spike discharges and electroshock seizures. Effective against a variety of seizure types.

Uses

Adjunctive therapy for partial seizures in adults.

Unlabeled Uses

Bipolar disorder.

Contraindications

Hypersensitivity to sulfonamides or zonisamide; pregnancy (category C), lactation; children <16 y.

Cautious Use

Renal or hepatic insufficiency, dehydration, hypovolemia; renal impairment; concomitant administration of drugs that induce or inhibit CYP3A4; older adults.

Route & Dosage

Partial Seizures Adult: PO Start at 100 mg q.d., may increase after 2 wk to 200 mg/d, may then increase q2wk, if necessary (max: 400 mg/d in 1–2 divided doses)

Administration

Oral

• Do not crush or break capsules; ensure capsules are swallowed whole with adequate fluid.
• Withdraw drug gradually when discontinued to minimize seizure potential.
• Store at 25° C (77° F); room temperature permitted. Protect from light and moisture.

Adverse Effects (≥1%)

Body as a Whole: Flu-like syndrome, weight loss. CNS: Agitation, irritability, anxiety, ataxia, confusion, depression, difficulty concentrating, difficulty with memory, dizziness, fatigue, headache, insomnia, mental slowing, nervousness, nystagmus, paresthesia, schizophrenic behavior, somnolence, tiredness, tremor, convulsion, abnormal gait, hyperesthesia, incoordination. GI: Abdominal pain, anorexia, constipation, diarrhea, dyspepsia, nausea, dry mouth, flatulence, gingivitis, gum hyperplasia, gastritis, stomatitis, cholelithiasis, glossitis, melena, rectal hemorrhage, ulcerative stomatitis, ulcer, dysphagia. Metabolic: Oligohidrosis, sometimes resulting in heat stroke and hyperthermia in children. Respiratory: Rhinitis, pharyngitis, cough. Skin: Ecchymosis, rash, pruritus. Special Senses: Difficulties in verbal expression, diplopia, speech abnormalities, taste perversion, amblyopia, tinnitus. Urogenital: Kidney stones.

Interactions

Drug: Phenytoin, carbamazepine, phenobarbital, valproic acid may decrease half-life of zonisamide.

Pharmacokinetics

Peak: 2–6 h. Distribution: 40% protein bound, extensively binds to erythrocytes. Metabolism: Acetylated in liver by CYP3A4. Elimination: Primarily in urine. Half-Life: 63–105 h.

Nursing Implications

Assessment & Drug Effects

• Withhold drug and notify physician if an unexplained rash or S&S of hypersensitivity appear (see Appendix F).
• Monitor for and report S&S of CNS impairment (somnolence, excessive fatigue, cognitive deficits, speech or language problems, incoordination, gait disturbances); oligohidrosis (lack of sweating) and hyperthermia in pediatric patients.
• Lab tests: Periodic BUN and serum creatinine, and CBC with differential.

Patient & Family Education

• Do not abruptly stop taking this medication.
• Increase daily fluid intake to minimize risk of renal stones. Notify physician immediately of S&S of renal stones: sudden back or abdominal pain, and blood in urine.
• Report any of the following: dizziness, excess drowsiness, frequent headaches, malaise, double vision, lack of coordination, persistent nausea, sore throat, fever, mouth ulcers, or easy bruising.
• Exercise special caution with concurrent use of alcohol or CNS depressants.
• Do not drive or engage in other potentially hazardous activities until response to drug is known.

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Common adverse effects in italic, life-threatening effects underlined; generic names in bold; classifications in SMALL CAPS; Canadian drug name; Prototype drug