zonisamide
Zonegran

Available forms
Available by prescription only
Capsules: 100 mg

 Adjunct therapy for partial seizures in adults with epilepsy. Adults older than age 16: Initially, 100 mg P.O. as a single daily dose for 2 weeks. After 2 weeks, may increase to 200 mg daily for at least 2 weeks. May be increased to 300 mg and 400 mg P.O. daily, with dose stable for at least 2 weeks to achieve steady state at each level. Doses can be given once or twice daily except for the daily dose of 100 mg at start of therapy. Can be taken with or without food.
≡ Dosage adjustment. Use cautiously in patients with hepatic and renal disease; they may need slower adjustment and more frequent monitoring. If glomerular filtration rate is less than 50 ml/minute, don’t give drug.

Pharmacodynamics
Antiseizure action: Unknown, but drug is thought to produce antiseizure effects through action at the sodium and calcium channels, thereby stabilizing neuronal membranes and suppressing neuronal hypersynchronization. Other models suggest that synaptically driven electrical activity is suppressed without potentiation of synaptic activity by gamma-aminobutyric acid. Drug also may facilitate dopaminergic and serotonergic neurotransmission.

Pharmacokinetics
Absorption: Food delays but doesn’t alter bioavailability.
Distribution: Extensively binds to erythrocytes. Drug is about 40% bound to plasma proteins. Protein-binding is unaffected in the presence of therapeutic levels of phenytoin, phenobarbital, or carbamazepine.
Metabolism: Metabolized by cytochrome P-450 3A4. Clearance increases in patients who are receiving enzyme-inducing drugs.
Excretion: Excreted mainly in urine as parent drug and as glucuronide of a metabolite. Half-life of zonisamide in plasma is about 63 hours.

Contraindications and precautions
Contraindicated in patients hypersensitive to sulfonamides or zonisamide. Use cautiously in patients with renal and hepatic dysfunction. If glomerular filtration rate is less than 50 ml/minute, don’t give drug.

Interactions
Drug-drug. Drugs that induce or inhibit CYP3A4: May alter zonisamide levels. Monitor patient.

Adverse reactions
CNS: headache, dizziness, ataxia, asthenia, nystagmus, paresthesia, confusion, difficulty with concentration or memory, mental slowing, agitation, irritability, depression, insomnia, anxiety, nervousness, schizophrenic or schizophreniform behavior, somnolence, fatigue, tiredness, speech abnormalities, difficulty with verbal expression, tremor, seizures, abnormal gait, hyperesthesia, lack of coordination.
EENT: diplopia, rhinitis, pharyngitis, amblyopia, tinnitus.
GI: taste perversion, anorexia, nausea, diarrhea, dyspepsia, constipation, dry mouth, abdominal pain, vomiting.
Hematologic: ecchymoses.
Metabolic: weight loss.
Respiratory: increased cough.
Skin: rash, pruritus.
Other: flu syndrome, accidental injury.

Effects on lab test results
• May increase BUN and creatinine levels.

Overdose and treatment
Overdose probably would cause CNS signs and symptoms, although information is limited.
 No antidote is available. After a suspected overdose, induce emesis or perform gastric lavage with precautions to protect the airway. Provide supportive care and frequent monitoring of vital signs. Dialysis may not be effective. Contact a poison control center for information on managing zonisamide overdose.

Special considerations
• Consider discontinuing zonisamide in patients who develop an unexplained rash.
• Monitor patient for symptoms of hypersensitivity.
• Monitor body temperature, especially in the summer, because decreased sweating and increased body temperature has occurred (especially in patients age 17 and younger), causing heatstroke and dehydration.
• Abrupt withdrawal of zonisamide may increase frequency of seizures or status epilepticus; reduce dose or discontinue drug gradually.
• Increase fluid intake and urine output to help prevent kidney stones, especially in patients with predisposing factors.
• Monitor renal function periodically. If patient develops acute renal failure or a clinically significant sustained increase in creatinine or BUN levels, discontinue drug.
Breast-feeding patients
• It isn’t known if drug appears in breast milk. A decision should be made to discontinue breast-feeding or drug, taking into account the importance of the drug to the mother. Use in breast-feeding women only if benefits outweigh risks.
Pediatric patients
• Pediatric patients are at an increased risk for zonisamide-associated oligohidrosis and hyperthermia. Monitor this age-group closely for evidence of decreased sweating and increased body temperature.
• Safety and efficacy in children younger than age 16 haven’t been established.
Geriatric patients
• Use cautiously, and start at lower end of dosage range.

Patient education
• Tell patient to take drug with or without food. Caution against biting or breaking the capsule.
• Urge patient to immediately report rash, fever, sore throat, mouth sores, easy bruising easily, sudden back pain, abdominal pain, pain when urinating, bloody or dark urine, decreased sweating, increased body temperature, depression, or speech or language problems.
• Caution patient to avoid hazardous activities until drug effects are known because drug can cause drowsiness.
• Warn patient not to stop taking drug without medical approval.
• Urge patient to drink six to eight glasses of water daily to help reduce the risk of kidney stones.
• Tell women to report planned, suspected, or known pregnancy during therapy. Also, tell them to report an intention to breast-feed.
• Urge women of childbearing potential to use contraception while taking this drug.

Reactions may be common, uncommon, life-threatening, or COMMON AND LIFE THREATENING.
◆ Canada only
◇ Unlabeled clinical use