Zonisamide

Aka: Zonisamide, Zonegran

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II. Indications

  1. Adjunctive management of Partial Seizures
  2. Add to primary antiepileptic regimens
    1. Carbamazepine
    2. Phenytoin
    3. Valproate
  3. Other potential uses currently being researched
    1. Myoclonic Seizures
    2. Infantile Spasm
    3. Atypical Absence Seizure
    4. Generalized Tonic Clonic Seizures

III. Contraindications

  1. Sulfonamide Allergy
  2. Pregnancy (Teratogenic in animals)

IV. Mechanism

  1. Anticonvulsant
  2. Sulfonamide derivative
  3. Blocks CNS Sodium and Calcium channels and stabilizes Neuron membranes, preventing hypersynchronization
  4. Also binds GABA Receptor ionophore complex, but does not appear to potentiate GABA activity at Synapse
  5. Facilitates the Neurotransmitters Dopamine and Serotonin

V. Dosing: Adults (and age >16 years)

  1. Initial: 100 mg orally daily for at least 2 weeks
  2. Increase: 100 mg every two weeks as needed
  3. Target: 400 mg/day divided once to twice daily
  4. Maximum: 600 mg/day (but doses above 400 mg/day do not appear to offer benefit)
  5. Caution: Increase more slowly in Renal Insufficiency and hepatic dysfunction

VI. Pharmacokinetics

  1. Weak carbonic anhydrase inhibitor
  2. Sulfonamide that blocks Sodium and Calcium channels
    1. Increases Dopaminergic transmission
    2. Increases serotonergic transmission
  3. Metabolized by CYP3A4
    1. Drug levels affected by Phenytoin, Carbamazepine, Phenobarbital, Valproic Acid
  4. Half-Life: 60 hours

VII. Drug Interactions

  1. Increased Zonisamide clearance with CYP3A4 inducers
    1. Phenytoin
    2. Carbamazepine
    3. Phenobarbital
  2. Concurrent carbonic anhydrase inhibitor (Topamax)
    1. Increased Nephrolithiasis risk

VIII. Adverse effects

  1. Common
    1. Dizziness
    2. Ataxia
    3. Somnolence
    4. Nausea
    5. Anorexia
    6. Abdominal Pain
    7. Insomnia
    8. Impaired cognition
      1. Confusion
      2. Decreased concentration
      3. Speech problems
  2. Serious
    1. Psychosis
    2. Stevens Johnson Syndrome
    3. Toxic Epidermal Necrolysis
    4. Fulminant hepatic necrosis
    5. Narrow Angle Glaucoma (IOP may increase during first month of use)
  3. Childhood Adverse Effects
    1. Oligohydrosis
    2. Hyperthermia (and Heat Stroke)
  4. Other
    1. Nephrolithiasis (associated with Metabolic Acidosis)

IX. Safety

  1. Unknown Safety in Pregnancy (but Teratogenic in animals)
  2. Unknown Safety in Lactation

X. Resources

  1. Zonisamide (DailyMed)
    1. https://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=d12de43e-3ac3-4335-bc85-70d7366a91eb

XI. References

  1. Padgett (1997) Epilepsia 38(suppl 8):107 [PubMed]
  2. Schmidt (1993) Epilepsy Res 15:67 [PubMed]
  3. Wallace (1998) Epilepsy Res 29:147 [PubMed]
  4. Yagi (2000) Neurology 54(Suppl 3):A195 [PubMed]
  5. Yanai (1999) Brain Dev 21:157 [PubMed]
  6. (2000) Med Lett Drugs Ther 42(1089):93-4 [PubMed]

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Related Studies

Cost: Medications

zonisamide (on 12/21/2022 at Medicaid.Gov Survey of pharmacy drug pricing)
ZONISAMIDE 100 MG CAPSULE Generic $0.12 each
ZONISAMIDE 25 MG CAPSULE Generic $0.08 each
ZONISAMIDE 50 MG CAPSULE Generic $0.09 each
FPNotebook does not benefit financially from showing this medication data or their pharmacy links. This information is provided only to help medical providers and their patients see relative costs. Insurance plans negotiate lower medication prices with suppliers. Prices shown here are out of pocket, non-negotiated rates. See Needy Meds for financial assistance information. GoodRx is another tool for finding lower drug prices.

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