Zonisamideside effects

The following clinically signification adverse reactions are described elsewhere in the labeling:

Potentially Fatal Reactions to Sulfonamides

Serious Skin Reactions

Serious Hematologic Events

Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS)/Multi-Organ Hypersensitivity

Oligohidrosis and Hyperthermia in Pediatric Patients

Acute Myopia and Secondary Angle Closure Glaucoma

Suicidal Behavior and Ideation

Metabolic Acidosis

Seizures on Withdrawal of Antiepileptic Drugs

Teratogenicity

Cognitive/Neuropsychiatric Adverse Reactions

Hyperammonemia and Encephalopathy

Kidney Stones

Effect on Renal Function

Status Epilepticus The most common adverse reactions with ZONISADE (an incidence at least 4% greater than placebo) in controlled clinical trials and shown in descending order of frequency were somnolence, anorexia, dizziness, ataxia, agitation/irritability, and difficulty with memory and/or concentration. To report SUSPECTED ADVERSE REACTIONS, contact Azurity Pharmaceuticals, Inc., at 1-800-461-7449 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

6.1 Clinical

Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. Adverse Reactions in Placebo-Controlled Trials with Zonisamide Capsules The most common adverse reactions with zonisamide capsules (an incidence at least 4% greater than placebo) in controlled clinical trials and shown in descending order of frequency were somnolence, anorexia, dizziness, ataxia, agitation/irritability, and difficulty with memory and/or concentration. In controlled clinical trials, 12% of patients receiving zonisamide as adjunctive therapy discontinued because of an adverse reaction compared to 6% receiving placebo. Approximately 21% of the 1,336 patients with epilepsy who received zonisamide in clinical studies discontinued treatment because of an adverse reaction. The most common adverse reactions leading to discontinuation were somnolence, fatigue and/or ataxia (6%), anorexia (3%), difficulty concentrating (2%), difficulty with memory, mental slowing, nausea/vomiting (2%), and weight loss (1%). Many of these adverse reactions were dose-related. Table 2 lists adverse reactions that occurred in at least 2% of patients treated with zonisamide capsules in controlled clinical trials that were numerically more common in the zonisamide group. In these studies, either zonisamide or placebo was added to the patient's current AED therapy. Table 2. Adverse Reactions that Occurred in at least 2% of Patients Treated with Zonisamide Capsules and More Frequently than in Patients who Received Placebo in Placebo-Controlled, Adjunctive Trials BODY SYSTEM/Adverse Reaction Zonisamide Capsules (n=269) % Placebo (n=230) % BODY AS A WHOLE Headache 10 8 Abdominal Pain 6 3 Flu Syndrome 4 3 DIGESTIVE Anorexia 13 6 Nausea 9 6 Diarrhea 5 2 Dyspepsia 3 1 Constipation 2 1 Dry Mouth 2 1 HEMATOLOGIC AND LYMPHATIC Ecchymosis 2 1 METABOLIC AND NUTRITIONAL Weight Loss 3 2 NERVOUS SYSTEM Dizziness 13 7 Ataxia 6 1 Nystagmus 4 2 Paresthesia 4 1 NEUROPSYCHIATRIC AND COGNITIVE DYSFUNCTION-ALTERED COGNITIVE FUNCTION Confusion 6 3 Difficulty Concentrating 6 2 Difficulty with Memory 6 2 Mental Slowing 4 2 NEUROPSYCHIATRIC AND COGNITIVE DYSFUNCTION-BEHAVIORAL ABNORMALITIES (NON-PSYCHOSIS-RELATED) Agitation/Irritability 9 4 Depression 6 3 Insomnia 6 3 Anxiety 3 2 Nervousness 2 1 NEUROPSYCHIATRIC AND COGNITIVE DYSFUNCTION-BEHAVIORAL ABNORMALITIES (PSYCHOSIS-RELATED) Schizophrenic/Schizophreniform Behavior 2 0 NEUROPSYCHIATRIC AND COGNITIVE DYSFUNCTION-CNS DEPRESSION Somnolence 17 7 Fatigue 8 6 Tiredness 7 5 NEUROPSYCHIATRIC AND COGNITIVE DYSFUNCTION-SPEECH AND LANGUAGE ABNORMALITIES Speech Abnormalities 5 2 Difficulties in Verbal Expression 2 <1 RESPIRATORY Rhinitis 2 1 SKIN AND APPENDAGES Rash 3 2 SPECIAL SENSES Diplopia 6 3 Taste Perversion 2 0 Laboratory Tests Zonisamide increases serum chloride and alkaline phosphatase and decreases serum bicarbonate, phosphorus, calcium, and albumin. Other Adverse Reactions in Clinical Trials of Zonisamide Capsules Zonisamide capsules have been administered to 1,598 individuals during all clinical trials, only some of which were placebo-controlled. The frequencies represent the proportion of the 1,598 individuals exposed to zonisamide capsules who experienced an event on at least one occasion. All events are included except those already listed in the previous table or discussed in, trivial events, those too general to be informative, and those not reasonably associated with zonisamide. Events are further classified within each category and listed in order of decreasing frequency as follows: frequent occurring in at least 1:100 patients; infrequent occurring in 1:100 to 1:1000 patients; rare occurring in fewer than 1:1000 patients.

Body as a Whole: Frequent: Accidental injury, asthenia.

Infrequent: Chest pain, flank pain, malaise, allergic reaction, face edema, neck rigidity.

Rare: Lupus erythematosus.

Cardiovascular: Infrequent: Palpitation, tachycardia, vascular insufficiency, hypotension, hypertension, thrombophlebitis, syncope, bradycardia.

Rare: Atrial fibrillation, heart failure, pulmonary embolus, ventricular extrasystoles.

Digestive: Frequent: Vomiting.

Infrequent: Flatulence, gingivitis, gum hyperplasia, gastritis, gastroenteritis, stomatitis, cholelithiasis, glossitis, melena, rectal hemorrhage, ulcerative stomatitis, gastro-duodenal ulcer, dysphagia, gum hemorrhage.

Rare: Cholangitis, hematemesis, cholecystitis, cholestatic jaundice, colitis, duodenitis, esophagitis, fecal incontinence, mouth ulceration.

Hematologic and Lymphatic: Infrequent: Leukopenia, anemia, immunodeficiency, lymphadenopathy.

Rare: Thrombocytopenia, microcytic anemia, petechia.

Metabolic and Nutritional: Infrequent: Peripheral edema, weight gain, edema, thirst, dehydration.

Rare: Hypoglycemia, hyponatremia, lactic dehydrogenase increased, SGOT increased, SGPT increased.

Musculoskeletal: Infrequent: Leg cramps, myalgia, myasthenia, arthralgia, arthritis.

Nervous System: Frequent: Tremor, convulsion, abnormal gait, hyperesthesia, incoordination.

Infrequent: Hypertonia, twitching, abnormal dreams, vertigo, libido decreased, neuropathy, hyperkinesia, movement disorder, dysarthria, cerebrovascular accident, hypotonia, peripheral neuritis, reflexes increased.

Rare: Dyskinesia, dystonia, encephalopathy, facial paralysis, hypokinesia, hyperesthesia, myoclonus, oculogyric crisis. Behavioral Abnormalities –Non-Psychosis-Related: Infrequent: Euphoria.

Respiratory: Frequent: Pharyngitis, cough increased.

Infrequent: Dyspnea.

Rare: Apnea, hemoptysis.

Skin and Appendages: Frequent: Pruritus.

Infrequent: Maculopapular rash, acne, alopecia, dry skin, sweating, eczema, urticaria, hirsutism, pustular rash, vesiculobullous rash.

Special Senses: Frequent: Amblyopia, tinnitus.

Infrequent: Conjunctivitis, parosmia, deafness, visual field defect, glaucoma.

Rare: Photophobia, iritis.

Urogenital: Infrequent: Urinary frequency, dysuria, urinary incontinence, hematuria, impotence, urinary retention, urinary urgency, amenorrhea, polyuria, nocturia.

Rare: Albuminuria, enuresis, bladder pain, bladder calculus, gynecomastia, mastitis, menorrhagia.

6.2 Postmarketing

Experience The following serious adverse reactions have been reported since approval and use of zonisamide worldwide. These reactions are reported voluntarily from a population of uncertain size; therefore, it is not possible to estimate their frequency or establish a causal relationship to drug exposure. Acute pancreatitis, rhabdomyolysis, increased creatine phosphokinase, and drug reaction with eosinophilia and systemic symptoms (DRESS), acute myopia and secondary angle closure glaucoma, and hyperammonemia and encephalopathy.