Dosing and uses of Zonegran (zonisamide)
Adult dosage forms and strengths
capsule
- 25mg
- 50mg
- 100mg
Partial Seizures
Initial: 100 mg PO qDay
Titrate up by 100 mg increments q2Week to no more than 600 mg PO qDay (may divide q12hr after 1st week)
Weight Loss (Off-label)
100 mg increments q2Week to no more than 600 mg PO qDay (may divide q12hr after first week); use 600 mg/day in patients who have not lost at least 5% of their initial body weight
Dosing Modifications
Renal impairment: Slower titration and more frequent monitoring advised; not recommended if patient's glomerular filtration rate is less than 50 mL/min
Hepatic impairment: Slower titration and more frequent monitoring advised
Pediatric dosage forms and strengths
capsule
- 25mg
- 50mg
- 100mg
<16 years
Not recommended
>16 years
Partial seizures
- Same as in adults
Geriatric dosage forms and strengths
Administer as in adults; initiate dosing at the lower end of the dosing range
Zonegran (zonisamide) adverse (side) effects
>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%)
Postmarketing Reports
Acute pancreatitis
Rhabdomyolysis
Creatine phosphokinase increased
Warnings
Contraindications
Hypersensitivity to zonisamide or sulfonamides
Cautions
Maintain fluid intake due to risk of kidney stone formation
Discontinue treatment if significant sustained increase in creatinine occurs
Risk of serious skin reactions; consider discontinuation in patients who develop unexplained rash
Sedation may occur
Slowing and fatigue may occur within first month of treatment
Risk of rare, but potentially fatal, anaphylactic reactions (including blood dyscrasias and skin reactions)
Risk of metabolic acidosis
Use appropriate precautions for handling and disposaL
Increase in suicidal ideation may occur with use; see FDA Warning on potential suicidal behavior
Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS), also known as multi-organ hypersensitivity reported; early manifestations of hypersensitivity (e.g., fever, lymphadenopathy) may be present even though rash not evident; if such signs or symptoms present, evaluate immediately; discontinue therapy if an alternative etiology for signs or symptoms cannot be established
Pregnancy and lactation
Pregnancy category: C
Lactation: Unknown; avoid during breastfeeding
Pregnancy categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.
C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.
D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.
X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.
NA: Information not available.
Pharmacology of Zonegran (zonisamide)
Mechanism of action
Unknown; benzisoxazole compound; more active against tonic phase than it is against clonic phase; may stabilize neuronal membranes by acting at sodium and calcium channels; does not affect GABA activity
It has some weak carbonic anhydrase inhibitor activity
Absorption
Peak plasma time: 2-6 hr (concentration: 2-5 mcg/mL)
Distribution
Protein bound: 40%
Vd: 1.45 L/kg
Metabolism
Hepatic; through CYP3A4
Elimination
Half-life: 63 hr
Renal clearance: 3.5 mL/min
Total body clearance: 0.30-0.35 mL/min/kg
Excretion: Urine (62%); feces (3%)
