Pronunciation:

(zoe NIS a mide)

U.S. Brand Names:

Generic Available:

Canadian Brand Names:

Use:

Use - Unlabeled/Investigational:

Pregnancy Risk Factor:

Pregnancy Implications:

Lactation:

Contraindications:

Warnings/Precautions:

Decreased sweating (oligohydrosis) and hyperthermia requiring hospitalization have been reported in children. Discontinue zonisamide in patients who develop acute renal failure or a significant sustained increase in creatinine/BUN concentration. Kidney stones have been reported. Use cautiously in patients with renal or hepatic dysfunction. Significant CNS effects include psychiatric symptoms, psychomotor slowing, and fatigue or somnolence. Fatigue and somnolence occur within the first month of treatment, most commonly at doses of 300-500 mg/day. Abrupt withdrawal may precipitate seizures; discontinue or reduce doses gradually. Safety and efficacy in children <16 years of age has not been established.

Adverse Reactions:

>10%:

Central nervous system: Somnolence (17%), dizziness (13%)

Gastrointestinal: Anorexia (13%)

1% to 10%:

Central nervous system: Headache (10%), agitation/irritability (9%), fatigue (8%), tiredness (7%), ataxia (6%), confusion (6%), decreased concentration (6%), memory impairment (6%), depression (6%), insomnia (6%), speech disorders (5%), mental slowing (4%), anxiety (3%), nervousness (2%), schizophrenic/schizophreniform behavior (2%), difficulty in verbal expression (2%), status epilepticus (1%), tremor (1%), convulsion (1%), hyperesthesia (1%), incoordination (1%)

Dermatologic: Rash (3%), bruising (2%), pruritus (1%)

Gastrointestinal: Nausea (9%), abdominal pain (6%), diarrhea (5%), dyspepsia (3%), weight loss (3%), constipation (2%), dry mouth (2%), taste perversion (2%), vomiting (1%)

Neuromuscular & skeletal: Paresthesia (4%), weakness (1%), abnormal gait (1%)

Ocular: Diplopia (6%), nystagmus (4%), amblyopia (1%)

Otic: Tinnitus (1%)

Respiratory: Rhinitis (2%), pharyngitis (1%), increased cough (1%)

Miscellaneous: Flu-like syndrome (4%) accidental injury (1%)

<1%: Flank pain, malaise, abnormal dreams, vertigo, movement disorder, hypotonia, euphoria, chest pain, facial edema, palpitation, tachycardia, vascular insufficiency, hyper-/hypotension, syncope, bradycardia, peripheral edema, edema, cerebrovascular accident, maculopapular rash, acne, alopecia, dry skin, eczema, urticaria, hirsutism, pustular rash, vesiculobullous rash, dehydration, decreased libido, amenorrhea, flatulence, gingivitis, gum hyperplasia, gastritis, gastroenteritis, stomatitis, glossitis, melena, ulcerative stomatitis, gastroduodenal ulcer, dysphagia, weight gain, urinary frequency, dysuria, urinary incontinence, impotence, urinary retention, urinary urgency, polyuria, nocturia, rectal hemorrhage, gum hemorrhage, leukopenia, anemia, cholelithiasis, thrombophlebitis, neck rigidity, leg cramps, myalgia, myasthenia, arthralgia, arthritis, hypertonia, neuropathy, twitching, hyperkinesia, dysarthria, peripheral neuritis, paresthesia, increased reflexes, allergic reaction, lymphadenopathy, immunodeficiency, thirst, diaphoresis, parosmia, conjunctivitis, visual field defect, glaucoma, deafness, hematuria, dyspnea, dystonia, encephalopathy, atrial fibrillation, heart failure, ventricular extrasystoles, petechia, hypoglycemia, hyponatremia, gynecomastia, mastitis, menorrhagia, cholangitis, hematemesis, colitis, duodenitis, esophagitis, fecal incontinence, mouth ulceration, enuresis, bladder pain, bladder calculus, thrombocytopenia, microcytic anemia, cholecystitis, cholestatic jaundice, increased AST (SGOT), increased ALT (SGPT), circumoral paresthesia, dyskinesia, facial paralysis, hypokinesia, myoclonus, lupus erythematosus, increased lactic dehydrogenase, oculogyric crisis, photophobia, iritis, albuminuria, pulmonary embolus, apnea, hemoptysis

Postmarketing and/or case reports: Agranulocytosis, aplastic anemia, BUN increased, hyperthermia, kidney stones, oligohydrosis, serum creatinine increased, serum alkaline phosphatase increased, Stevens-Johnson syndrome, toxic epidermal necrolysis

Overdosage/Toxicology:

Drug Interactions:

CNS depressants: Sedative effects may be additive with other CNS depressants; monitor for increased effect; includes barbiturates, benzodiazepines, narcotic analgesics, ethanol, and other sedative agents.

CYP3A4 inducers: CYP3A4 inducers may decrease the levels/effects of zonisamide. Example inducers include aminoglutethimide, carbamazepine, nafcillin, nevirapine, phenobarbital, phenytoin, and rifamycins.

CYP3A4 inhibitors: May increase the levels/effects of zonisamide. Example inhibitors include azole antifungals, ciprofloxacin, clarithromycin, diclofenac, doxycycline, erythromycin, imatinib, isoniazid, nefazodone, nicardipine, propofol, protease inhibitors, quinidine, and verapamil.

Ethanol/Nutrition/Herb Interactions:

Ethanol: Avoid ethanol (may increase CNS depression).

Food: Food delays time to maximum concentration, but does not affect bioavailability.

Stability:

Mechanism of Action:

Pharmacodynamics/Kinetics:

Distribution: Vd: 1.45 L/kg

Protein binding: 40%

Metabolism: Hepatic via CYP3A4; forms N-acetyl zonisamide and 2-sulfamoylacetyl phenol (SMAP)

Half-life elimination: 63 hours

Time to peak: 2-6 hours

Excretion: Urine (62%, 35% as unchanged drug, 65% as metabolites); feces (3%)

Dosage:

Children >16 years and Adults:

Adjunctive treatment of partial seizures: Initial: 100 mg/day; dose may be increased to 200 mg/day after 2 weeks. Further dosage increases to 300 mg/day and 400 mg/day can then be made with a minimum of 2 weeks between adjustments, in order to reach steady state at each dosage level. Doses of up to 600 mg/day have been studied, however, there is no evidence of increased response with doses above 400 mg/day.

Mania (unlabeled use): Initial: 100-200 mg/day; maximum: 600 mg/day (Kanba, 1994)

Elderly: Data from clinical trials is insufficient for patients >65 years; begin dosing at the low end of the dosing range.

Dosage adjustment in renal/hepatic impairment: Slower titration and frequent monitoring are indicated in patients with renal or hepatic disease. There is insufficient experience regarding dosing/toxicity in patients with estimated GFR <50 mL/minute. Marked renal impairment (Clcr<20 mL/minute) was associated with a 35% increase in AUC.

Administration:

Monitoring Parameters:

Dietary Considerations:

Patient Education:

Dental Health: Effects on Dental Treatment:

Dental Health: Vasoconstrictor/Local Anesthetic Precautions:

Dosage Forms:

International Brand Names: