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zonisamide (Zonegran)

Tradename: Zonegran. Indications: 1) adjunctive therapy for partial seizures 2) treatment of generalized seizures [6] 3) adjunctive therapy for Parkinson's disease 4) adjunctive therapy for diffuse lewy body disease with parkinsonism [9] Contraindications: - allergy to sulfonamides Dosage: 25-100 mg QD Take with copious fluids to reduce risk of nephrolithiasis * dosage adjustment in liver failure uncertain [6] Dosage adjustment in renal failure: - none - supplemental dose after dialysis uncertain [6] Pharmacokinetics: - metabolized in the liver by cyt P450 3A4 - cleared renally [6] Monitor: - renal function periodically [7] - serum bicarbonate baseline & periodically (may cause metabolic acidosis) [7] Adverse effects: 1) allergy to sulfa a) toxic skin reactions b) agranulocytosis 2) rash [6] 3) fatigue [2] 4) sedation [6] 5) paresthesias [2] 6) cognitive impairment [2,8] affecting verbal fluency - less so than topiramate [8] - does not worsen cognitive function in patients with parkinsonism associated with diffuse lewy body disease [9] 7) visual impairment [2], visual field defect [6] 8) metabolic acidosis [5] 9) nephrolithiasis [6] 10) anorexia, weight loss [6] 11) increased risk of nephrolithiasis [6] 12) depression [6] 13) psychosis [6] - does not worsen psychiatric symptoms in patients with parkinsonism associated with diffuse lewy body disease [9] Drug interactions: 1) any drug that inhibits cyt P450 3A4 may increase levels of zonisamide 2) any drug that induces cyt P450 3A4 may diminish levels of zonisamide Laboratory: - zonisamide in serum - zonisamide/creatinine in urine

Interactions

drug interactions drug adverse effects (more general classes) monitor with anticonvulsants

Related

cytochrome P450 3A4 (cytochrome P450 C3, nifedipine oxidase, P450-PCN1, NF-25, CYP3A4) seizure; epileptic seizure

General

anticonvulsant sulfonamide

Properties

MISC-INFO: elimination route LIVER

Database Correlations

PUBCHEM cid=5734

References

  1. Prescriber's Letter 7(5):28, May 2000
  2. Prescriber's Letter 13(3): 2006 Cytochrome P450 drug interactions Detail-Document#: 220233 (subscription needed) http://www.prescribersletter.com
  3. Prescriber's Letter 10(6):32 2003
  4. Murata M, Hasegawa K, Kanazawa I; The Japan Zonisamide on PD Study Group. Zonisamide improves motor function in Parkinson disease: a randomized, double-blind study. Neurology. 2007 Jan 2;68(1):45-50. PMID: 17200492
  5. FDA Medwatch http://www.fda.gov/medwatch/safety/2009/safety09.htm#Zonisamide
  6. Medical Knowledge Self Assessment Program (MKSAP) 15, 16, 17, 18. American College of Physicians, Philadelphia 2009, 2012, 2015, 2018.
  7. Prescriber's Letter 17(7): 2010 Recommended Lab Monitoring for Common Medications Detail-Document#: 260704 (subscription needed) http://www.prescribersletter.com
  8. Wandschneider B et al. Effect of topiramate and zonisamide on fMRI cognitive networks. Neurology 2017 Feb 17 PMID: 28213372
  9. Murata M, Odawara T, Hasegawa K et al. Adjunct zonisamide to levodopa for DLB parkinsonism: A randomized, double-blind phase 2 study. Neurology 2018 Jan 24 PMID: 29367449 Free PMC Article http://n.neurology.org/content/90/8/e664