zonisamide ZONEGRAN
Class: AED/Mood StabilizerFDA Indications: Adjunct Therapy For Partial Seizures In Adults With Epilepsy
Off-Label Use: Binge Eating Disorder, Migraines, Parkinson's Disease, Neuropathic Pain, Mood Stabilization, Lewy Body Dementia
Prescribing
Forms: 25, 50, 100mg capsuleDose Range: 100-600 mg/day
Starting: 100 mg qd, ↑ to 200 mg qd after 2 weeks, then ↑ by 100mg/d q2 weeks if necessary
Stopping: Taper; can be epileptogenic on withdrawal
Precautions
Contraindications: Allergy to sulfonamidesSerious Side Effects: Stevens-Johnson syndrome (46 per million patient-years of exposure), rash (~2%), carbonic anhydrase inhibition can cause kidney stones
Side Effects: sedation/somnolence, depression, difficulty concentrating, agitation, irritability, dizziness, ataxia, psychomotor slowing, headache, nausea, anorexia, abdominal pain, vomiting
Pharmacodynamics
1° MOA: Blockade of both sodium and T-type calcium channelsPharmacokinetics
t½: 63 (50-70)° TMAX: 2-6°Substrate of: 3A4, 2D6, renal
Inhibits: ∅ ; Induces: ∅
Active Metabolites: ∅
DDIs
- - 3A4 inhibitors can ↑ levels; likewise, 3A4 inducers can ↓ levels
- - theoretically, may interact with carbonic anhydrase inhibitors & ↑ risk of kidney stones
Misc
- - weight gain is rare, with some reports of weight loss in epilepsy trials
- - sedation can be significant
- - off-label use for mood stabilization not well supported by literature
- - there is increasing evidence for a role in the treatment of both motor and nonmotor symptoms in Parkinson's Disease
Special Populations
Category C—Limited Human Data — Animal Data Suggest High Risk
Limited Human Data — Potential Toxicity
Elderly patients may be more susceptible to adverse effects
Predominantly renally cleared, use with caution; marked renal impairment (CrCl < 20 mL/min) was associated with an increase in AUC by 35%
The pharmacokinetics of zonisamide in patients with impaired liver function have not been studied
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