ZONEGRAN SIDE EFFECTS
- Generic Name: zonisamide
- Brand Name: Zonegran
- Drug Class: Anticonvulsants, Other
SIDE EFFECTS
The most common adverse reactions with ZONEGRAN (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 ZONEGRAN as adjunctive therapy discontinued due to an adverse reaction compared to 6% receiving placebo. Approximately 21% of the 1,336 patients with epilepsy who received ZONEGRAN 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.
Adverse Reaction Incidence In Controlled Clinical Trials
Table 1 lists adverse reactions that occurred in at least 2% of patients treated with ZONEGRAN in controlled clinical trials that were numerically more common in the ZONEGRAN group. In these studies, either ZONEGRAN or placebo was added to the patient’s current AED therapy.
Table 1. Adverse Reactions in Placebo-Controlled, Add-On Trials (Events that occurred in at least 2% of ZONEGRAN-treated patients and occurred more frequently in ZONEGRAN-treated than placebo-treated patients)
| BODY SYSTEM/ PREFERRED TERM |
ZONEGRAN (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 |
| HEMATOLOGIS 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-PSYCHOSISRELATED) | ||
| 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 |
Other Adverse Reactions In Clinical Trials
ZONEGRAN has 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 ZONEGRAN who experienced an event on at least one occasion. All events are included except those already listed in the previous table or discussed in WARNINGS or PRECAUTIONS, trivial events, those too general to be informative, and those not reasonably associated with ZONEGRAN.
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.
Post Marketing Experience
The following serious adverse reactions have been reported since approval and use of ZONEGRAN 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, drug reaction with eosinophilia and systemic symptoms (DRESS), acute myopia and secondary angle closure glaucoma, and hyperammonemia and encephalopathy.
SRC: NLM .