Zonisamide

What is Zonisamide

Zonisamide is a sulfonamide anticonvulsant. It is a derivative of a series of compounds known as benzisoxazoles.

The pharmacological profile is similar to that of carbamazepine and phenytoin; however, no comparative double-blind trials have been published.

Zonisamide showed a significant reduction in seizure frequency as compared to placebo.

No less than 28% of patients achieved a >= 50% reduction in seizure frequency during three multicenter, placebo-controlled, double blind, 3-month clinical trials (two in the US, one in Europe).

Zonisamide appears to possess more than one mechanism of action which may make it effective in a broader range of seizures. Central nervous system adverse reactions (e.g., ataxia, psychosis, speech impairment, etc.) are common and can limit the usefulness of the drug in some patients.

Zonisamide is approved for adjunctive treatment of partial seizures in adults 16 years and older with epilepsy.

Although not approved for use in children in the US, the drug is often used ‘off-label’ in children; the drug is approved for use in children in Japan where it has been marketed since 1989. FDA approval for zonisamide was granted in March 2000.

Brand Name

Zonegran

Indications & Dosage

  • partial seizures

For use as adjunctive therapy in the treatment of partial seizures

Side Effects

  1. abdominal pain
  2. acne vulgaris
  3. agitation
  4. agranulocytosis
  5. alopecia
  6. amblyopia
  7. amenorrhea
  8. anemia
  9. anhidrosis
  10. anorexia
  11. anxiety
  12. aplastic anemia
  13. apnea
  14. arthralgia
  15. asthenia
  16. ataxia
  17. atopic dermatitis
  18. atrial fibrillation
  19. azotemia
  20. bradycardia
  21. chest pain (unspecified)
  22. cholangitis
  23. cholecystitis
  24. cholelithiasis
  25. colitis
  26. confusion
  27. conjunctivitis
  28. constipation
  29. cough
  30. dehydration
  31. depression
  32. diarrhea
  33. diplopia
  34. dizziness
  35. drowsiness
  36. Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS)
  37. dysarthria
  38. dysgeusia
  39. dyskinesia
  40. dyspepsia
  41. dysphagia
  42. dyspnea
  43. dystonic reaction
  44. dysuria
  45. ecchymosis
  46. edema
  47. encephalopathy
  48. esophagitis
  49. euphoria
  50. fatigue
  51. fecal incontinence
  52. flank pain
  53. flatulence
  54. gastritis
  55. gingival hyperplasia
  56. gingivitis
  57. glossitis
  58. gynecomastia
  59. hallucinations
  60. headache
  61. hearing loss
  62. heart failure
  63. heat intolerance
  64. hematemesis
  65. hematuria
  66. hemoptysis
  67. hepatic necrosis
  68. hirsutism
  69. hyperammonemia
  70. hyperesthesia
  71. hyperhidrosis
  72. hyperkinesis
  73. hyperreflexia
  74. hypertension
  75. hyperthermia
  76. hypertonia
  77. hypoglycemia
  78. hyponatremia
  79. hypotension
  80. hypotonia
  81. impotence (erectile dysfunction)
  82. increased urinary frequency
  83. influenza
  84. insomnia
  85. iritis
  86. irritability
  87. jaundice
  88. leukopenia
  89. libido decrease
  90. lupus-like symptoms
  91. lymphadenopathy
  92. maculopapular rash
  93. malaise
  94. melena
  95. memory impairment
  96. menorrhagia
  97. metabolic acidosis
  98. muscle cramps
  99. myalgia
  100. myasthenia
  101. myoclonia
  102. myopia
  103. nausea
  104. nephrolithiasis
  105. neuritis
  106. nocturia
  107. nystagmus
  108. ocular hypertension
  109. oligohidrosis
  110. oral ulceration
  111. osteomalacia
  112. palpitations
  113. pancreatitis
  114. paresthesias
  115. parosmia
  116. peptic ulcer
  117. peripheral edema
  118. peripheral neuropathy
  119. petechiae
  120. pharyngitis
  121. photophobia
  122. polyuria
  123. proteinuria
  124. pruritus
  125. psychosis
  126. pulmonary embolism
  127. rash
  128. renal failure (unspecified)
  129. rhabdomyolysis
  130. rhinitis
  131. seizures
  132. sinus tachycardia
  133. Stevens-Johnson syndrome
  134. stomatitis
  135. stroke
  136. suicidal ideation
  137. syncope
  138. teratogenesis
  139. thrombocytopenia
  140. tinnitus
  141. toxic epidermal necrolysis
  142. tremor
  143. urinary incontinence
  144. urinary retention
  145. urinary urgency
  146. urticaria
  147. vertigo
  148. vomiting
  149. weight gain
  150. weight loss
  151. xerosis
  152. xerostomia

Monitoring Parameters

  • serum bicarbonate
  • serum creatinine/BUN

Contraindications

  • abrupt discontinuation
  • ambient temperature increase
  • anticholinergic medications
  • breast-feeding
  • children
  • depression
  • diarrhea
  • driving or operating machinery
  • geriatric
  • hepatic disease
  • infants
  • metabolic acidosis
  • mitochondrial disease
  • neonates
  • pregnancy
  • pulmonary disease
  • renal disease
  • renal failure
  • renal impairment
  • status epilepticus
  • suicidal ideation
  • sulfonamide hypersensitivity

Interactions

  • Acetaminophen; Butalbital
  • Acetaminophen; Butalbital; Caffeine
  • Acetaminophen; Butalbital; Caffeine; Codeine
  • Acetazolamide
  • Afatinib
  • Aliskiren
  • Aliskiren; Amlodipine
  • Aliskiren; Amlodipine; Hydrochlorothiazide, HCTZ
  • Aliskiren; Hydrochlorothiazide, HCTZ
  • Aliskiren; Valsartan
  • Alogliptin; Metformin
  • Alprazolam
  • Amitriptyline
  • Amitriptyline; Chlordiazepoxide
  • Amlodipine; Atorvastatin
  • Amobarbital
  • Amoxicillin; Clarithromycin; Lansoprazole
  • Amoxicillin; Clarithromycin; Omeprazole
  • Amphetamines
  • Anticholinergics
  • Apalutamide
  • Apixaban
  • Aprepitant, Fosaprepitant
  • Aripiprazole
  • Asenapine
  • Asparaginase Erwinia chrysanthemi
  • Aspirin, ASA; Butalbital; Caffeine
  • Aspirin, ASA; Butalbital; Caffeine; Codeine
  • Atorvastatin
  • Atorvastatin; Ezetimibe
  • Atropine
  • Atropine; Benzoic Acid; Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate
  • Atropine; Difenoxin
  • Atropine; Diphenoxylate
  • Atropine; Edrophonium
  • Atropine; Hyoscyamine; Phenobarbital; Scopolamine
  • atypical antipsychotic
  • Barbiturates
  • Belladonna Alkaloids; Ergotamine; Phenobarbital
  • Belladonna; Opium
  • Benzoic Acid; Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate
  • Benztropine
  • Betrixaban
  • Boceprevir
  • Bosentan
  • Brexpiprazole
  • Budesonide
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  • Bupropion
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  • Butabarbital
  • Canagliflozin; Metformin
  • Carbamazepine
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  • Cariprazine
  • Carvedilol
  • Chlordiazepoxide; Clidinium
  • Chlorpromazine
  • Clarithromycin
  • Clomipramine
  • Clozapine
  • Cobimetinib
  • Codeine; Phenylephrine; Promethazine
  • Codeine; Promethazine
  • Colchicine
  • Colchicine; Probenecid
  • Colesevelam
  • Cyclosporine
  • Dabigatran
  • Dapagliflozin; Metformin
  • Dapagliflozin; Saxagliptin
  • Dasabuvir; Ombitasvir; Paritaprevir; Ritonavir
  • Desipramine
  • Dexamethasone
  • Dextromethorphan; Promethazine
  • Dextromethorphan; Quinidine
  • Dichlorphenamide
  • Dicyclomine
  • Digoxin
  • Docetaxel
  • Doravirine; Lamivudine; Tenofovir disoproxil fumarate
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  • Doxorubicin
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  • Drospirenone; Ethinyl Estradiol; Levomefolate
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  • Eletriptan
  • Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Disoproxil Fumarate
  • Empagliflozin; Linagliptin; Metformin
  • Empagliflozin; Metformin
  • Emtricitabine; Rilpivirine; Tenofovir disoproxil fumarate
  • Emtricitabine; Tenofovir disoproxil fumarate
  • Enzalutamide
  • Ertugliflozin; Metformin
  • Erythromycin
  • Erythromycin; Sulfisoxazole
  • Ethinyl Estradiol
  • Ethinyl Estradiol; Desogestrel
  • Ethinyl Estradiol; Ethynodiol Diacetate
  • Ethinyl Estradiol; Etonogestrel
  • Ethinyl Estradiol; Levonorgestrel
  • Ethinyl Estradiol; Levonorgestrel; Ferrous bisglycinate
  • Ethinyl Estradiol; Levonorgestrel; Folic Acid; Levomefolate
  • Ethinyl Estradiol; Norelgestromin
  • Ethinyl Estradiol; Norethindrone
  • Ethinyl Estradiol; Norethindrone Acetate
  • Ethinyl Estradiol; Norethindrone Acetate; Ferrous fumarate
  • Ethinyl Estradiol; Norethindrone; Ferrous fumarate
  • Ethinyl Estradiol; Norgestimate
  • Ethinyl Estradiol; Norgestrel
  • Ethotoin
  • Felbamate
  • Flavoxate
  • Fluoxetine; Olanzapine
  • Fluphenazine
  • Fosamprenavir
  • Fosphenytoin
  • Glecaprevir; Pibrentasvir
  • Glipizide; Metformin
  • Glyburide
  • Glyburide; Metformin
  • Glycopyrrolate
  • Glycopyrrolate; Formoterol
  • Haloperidol
  • Homatropine; Hydrocodone
  • Hydroxychloroquine
  • Hyoscyamine
  • Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate; Sodium Biphosphate
  • Idelalisib
  • Iloperidone
  • Imipramine
  • Indacaterol; Glycopyrrolate
  • Indinavir
  • Isavuconazonium
  • Isocarboxazid
  • Isoniazid, INH; Pyrazinamide, PZA; Rifampin
  • Isoniazid, INH; Rifampin
  • Itraconazole
  • L-Asparaginase Escherichia coli
  • Lacosamide
  • Lamivudine; Tenofovir Disoproxil Fumarate
  • Lapatinib
  • Ledipasvir; Sofosbuvir
  • Lefamulin
  • Linagliptin; Metformin
  • Loperamide
  • Loperamide; Simethicone
  • Lopinavir; Ritonavir
  • Loxapine
  • Lumacaftor; Ivacaftor
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  • Lumateperone
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  • Maprotiline
  • Maraviroc
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  • Mepenzolate
  • Meperidine; Promethazine
  • Mephobarbital
  • Mesoridazine
  • Metformin
  • Metformin; Pioglitazone
  • Metformin; Repaglinide
  • Metformin; Rosiglitazone
  • Metformin; Saxagliptin
  • Metformin; Sitagliptin
  • Methadone
  • Methazolamide
  • Methenamine; Sodium Acid Phosphate; Methylene Blue; Hyoscyamine
  • Methohexital
  • Methscopolamine
  • Mitomycin
  • Mitotane
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  • Morphine
  • Morphine; Naltrexone
  • Nelfinavir
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  • Nortriptyline
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  • Phenelzine
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  • Phenothiazines
  • Phentermine; Topiramate
  • Phenylephrine; Promethazine
  • Phenytoin
  • Pimozide
  • Posaconazole
  • Primidone
  • Prochlorperazine
  • Promethazine
  • Propantheline
  • Protriptyline
  • Quetiapine
  • Quinidine
  • Quinine
  • Rabeprazole
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