Zonisamide

SECTION 2: Hazards identification

CANADIAN

Potential Acute Health Effects

SWALLOWED ■ Accidental ingestion of the material may be harmful; animal experiments indicate that ingestion of less than 150 gram may be fatal or may produce serious damage to the health of the individual. ■ Antiepileptic drugs (AEDs) act as anticonvulsants and increase the risk of suicidal thoughts or behavior in patients taking these drugs for any indication. Persons exposed to AEDs for any indication should be monitored for the emergence or worsening of depression, suicidal thoughts or behavior, and/or any unusual changes in mood or behavior (such as anxiety, agitation, hostility, pressured/rapid speech). The increased risk of suicidal thoughts or behavior with AEDs was observed as early as one week after starting drug treatment with AEDs and persisted for the duration of treatment assessed. Because most trials included in the analysis did not extend beyond 24 weeks, the risk of suicidal thoughts or behavior beyond 24 weeks could not be assessed. The finding of increased risk with AEDs of varying mechanisms of action and across a range of indications suggests that the risk applies to all AEDs used for any indication. The risk did not vary substantially by age (5-100 years) in the clinical trials analysed. The relative risk for suicidal thoughts or behavior was higher in clinical trials for epilepsy than in clinical trials for psychiatric or other conditions, but the absolute risk differences were similar for the epilepsy and psychiatric indications. ■ Sulfonamides and their derivatives can cause extensive kidney damage, and destroy red blood cells. Overdose may cause an accumulation of acid in the blood or a diminished blood sugar level with confusion and coma resulting. Predisposed persons can develop hypersensitivity reactions, including for topical application. Deaths have occurred due to hypersensitivity, anemia, imbalances in blood cell distribution and kidney and liver damage. 2-5 grams can be fatal. Sulfonamides cross the placental barrier, are excreted in the breast milk and may produce adverse effects in the fetus/ embryo and newborn, including loss of certain white blood cells causing immune function deficiency, anemia, jaundice and kernicterus. EYE ■ There is some evidence to suggest that this material can causeeye irritation and damage in some persons. ■ Eye drops with sulfonamides can cause local irritation, sensations of burning and stinging, blurred vision and loss of depth perception. The conjunctiva and cornea may become inflamed, and the cornea and lens may become clouded. SKIN ■ Skin contact is not thought to produce harmful health effects (as classified using animal models). Systemic harm, however, has been identified following exposure of animals by at least one other route and the material may still produce health damage following entry through wounds, lesions or abrasions. Good hygiene practice requires that exposure be kept to a minimum and that suitable gloves be used in an occupational setting. ■ Open cuts, abraded or irritated skin should not be exposed to this material. ■ Entry into the blood-stream, through, for example, cuts, abrasions or lesions, may produce systemic injury with harmful effects. Examine the skin prior to the use of the material and ensure that any external damage is suitably protected. INHALED ■ The material is not thought to produce either adverse health effects or irritation of the respiratory tract following inhalation (as classified using animal models). Nevertheless, adverse effects have been produced following exposure of animals by at least one other route and good hygiene practice requires that exposure be kept to a minimum and that suitable control measures be used in an occupational setting. ■ Persons with impaired respiratory function, airway diseases and conditions such as emphysema or chronic bronchitis, may incur further disability if excessive concentrations of particulate are inhaled.

Potential chronic health

Results in experiments suggest that this material may cause disorders in the development of the embryo or fetus, even when no signs of poisoning show in the mother. There has been some concern that this material can cause cancer or mutations but there is not enough data to make an assessment. There is some evidence to provide a presumption that human exposure to the material may result in impaired fertility on the basis of: some evidence in animal studies of impaired fertility in the absence of toxic effects, or evidence of impaired fertility occurring at around the same dose levels as other toxic effects but which is not a secondary non-specific consequence of other toxic effects. Prolonged oral treatment with sulfonamides has caused nausea, vomiting, diarrhea, abdominal pain, loss of appetite, inflammation of the mouth cavity, impaired folic acid absorption, exacerbation of porphyria, acidosis, liver damage with impaired blood clotting, jaundice and inflammation of the pancreas. Effects on the kidney include blood and crystals in the urine, painful and frequent urination or lack of urine with nitrogen retention. Nervous system symptoms include headache, drowsiness, trouble sleeping, dizziness, ringing in the ears, hearing loss, depression, hallucinations, inco-ordination, paralysis of muscles, numbness in the extremities, spinal cord damage and inflammation, convulsions and unconsciousness. Effects on the blood includes a change in blood cell distribution with loss of white blood cells and platelets, and anemia, which Africans seem to be more prone to developing than Europeans. Cyanosis can occur owing to complexes being formed by hemoglobin. Eye effects include inflamed cornea and conjunctiva with eyelid swelling and in severe cases, fear of the light. Allergies and cross- sensitivity is common, and can cause itches, wheals and sometimes a severe red rash with blisters that is often fatal. This class of drugs can scar the cornea and conjunctiva, swelling around the eyes, painful and inflamed joints, reduced sperm counts, pneumonia, fever, chills, hair loss, inflammation of vessels, lupus, reduced lung function, infertility, hypothyroidism and goiter, and increased urinary output. More seriously, the lungs may become permanently scarred and there may be irreversible damage to the nervous system and muscles. Inflammation of the skin has occurred after the drug is ingested and has traveled through the bloodstream. Skin effects often occur when there has been exposure in conjunction with UV light. Clothed areas are initially less likely to be affected but may be in later stages. Rarely there may be persistence of inflammation on light contact even after the drug has been removed. Long term exposure to high dust concentrations may cause changes in lung function i.e. pneumoconiosis; caused by particles less than 0.5 micron penetrating and remaining in the lung. Prime symptom is breathlessness; lung shadows show on X-ray.