Acetazolamide ER Capsules

SECTION 2: Hazards identification

Component Exposure Limit CAS No. Principle Component Acetazolamide Not Available 59-66-5 Inactive Ingredients Not Available 9004-34-6 Microcrystalline Cellulose Not Available 68585-47-1 Sodium Lauryl Sulfate Ammonio Methacrylate Copolymer Not Found 33434-24-1, 110-44-1, 67-56-1 Dispersion Type A/B Not Found 110-44-1 Sorbic Acid Not Found 67-56-1 Methanol Not Found 14807-96-6 Talc, Lo Micron

Health hazards

Information Dose and Administration Glaucoma The recommended dosage is 1 capsule (500 mg) two times a day. Usually 1 capsule is administered in the morning and 1 capsule in the evening. It may be necessary to adjust the dose, but it has usually been found that dosage in excess of 2 capsules (1 g) does not produce an increased effect. The dosage should be adjusted with careful individual attention both to symptomatology and intraocular tension. In all cases, continuous supervision by a physician is advisable. In those unusual instances where adequate control is not obtained by the twice- a-day administration of acetazolamide extended-release capsules, the desired control may be established by means of acetazolamide (tablets or parenteral). Use tablets or parenteral in accordance with the more frequent dosage schedules recommended for these dosage forms, such as 250 mg every four hours, or an initial dose of 500 mg followed by 250 mg or 125 mg every four hours, depending on the case in question. Acute Mountain Sickness Dosage is 500 mg to 1000 mg daily, in divided doses using tablets or extended- release capsules as appropriate. In circumstances of rapid ascent, such as in rescue or military operations, the higher dose level of 1000 mg is recommended. It is preferable to initiate dosing 24 to 48 hours before ascent and to continue for 48 hours while at high altitude, or longer as necessary to control symptoms Adverse events Body as a whole: Headache, malaise, fatigue, fever, pain at injection site, flushing, growth retardation in children, flaccid paralysis, anaphylaxis. Digestive: Gastrointestinal disturbances such as nausea, vomiting, diarrhea. Hematological/Lymphatic: Blood dyscrasias such as aplastic anemia, agranulocytosis, leukopenia, thrombocytopenic purpura, melena. Hepato-biliary disorders: Abnormal liver function, cholestatic jaundice, hepatic insufficiency, fulminant hepatic necrosis Metabolic/Nutritional: Metabolic acidosis, electrolyte imbalance, including hypokalemia, hyponatremia, osteomalacia with long-term phenytoin therapy, loss of appetite, taste alteration, hyper/hypoglycemia Nervous: Drowsiness, paresthesia (including numbness and tingling of extremities and face), depression, excitement, ataxia, confusion, convulsions dizziness Skin: Allergic skin reactions including urticaria, photosensitivity, Stevens-Johnson syndrome, toxic epidermal necrolysis Special senses: Hearing disturbances, tinnitus, transient myopia Urogenital: Crystalluria, increased risk of nephrolithiasis with long-term therapy, hematuria, glycosuria, renal failure polyuria Contraindications Acetazolamide ER Capsules is contraindicated in patients with: Hypersensitivity to acetazolamide or any excipients in the formulation. Since acetazolamide is a sulfonamide derivative, cross sensitivity between acetazolamide, sulfonamides and other sulfonamide derivatives is possible. Acetazolamide therapy is contraindicated in situations in which sodium and/or potassium blood serum levels are depressed, in cases of marked kidney and liver disease or dysfunction, in suprarenal gland failure, and in hyperchloremic acidosis. It is contraindicated in patients with cirrhosis because of the risk of development of hepatic encephalopathy. Long-term administration of acetazolamide is contraindicated in patients with chronic non-congestive angle-closure glaucoma since it may permit organic closure of the angle to occur while the worsening glaucoma is masked by lowered intraocular pressure Pregnancy Comments

Teratogenic Effects

Acetazolamide, administered orally or parenterally, has been shown to be teratogenic (defects of the limbs) in mice, rats, hamsters, and rabbits. There are no adequate and well-controlled studies in pregnant women. Acetazolamide should be used in pregnancy only if the potential benefit justifies the potential risk to the fetus Nursing Mothers: Because of the potential for serious adverse reactions in nursing infants from acetazolamide, a decision should be made whether to discontinue nursing or to discontinue the drug taking into account the importance of the drug to the mother. Acetazolamide should only be used by nursing women if the potential benefit justifies the potential risk to the child Pregnancy Category Pregnancy Category C: . Section 4. First aid measures General Ingestion: If ingestion occurs, induce vomiting immediately and seek medical attention immediately. Never induce committing on an unconscious person. Overdose in humans is unlikely to occur since Acetazolamide is remarkably non-toxic as shown in animal testing. Overdose Treatment No specific antidote is known. Treatment should be symptomatic and supportive. Electrolyte imbalance, development of an acidotic state, and central nervous system effects might be expected to occur. Serum electrolyte levels (particularly potassium) and blood pH levels should be monitored. Supportive measures are required to restore electrolyte and pH balance. The acidotic state can usually be corrected by the administration of bicarbonate. Despite its high intraerythrocytic distribution and plasma protein binding properties, acetazolamide may be dialyzable. This may be particularly important in the management of Acetazolamide overdosage when complicated by the presence of renal failure Fire – fighting measures Flash point Not Found Upper Flammable Not Found Limit Auto-Ignition Not Found Lower Flammable Not Found Temperature Limit Extinguishing Water Spray, dry Fire and Explosion This material is assumed to be Media chemical, carbon dioxide Hazard combustible. or foam as appropriate for As with all dry powders it is surrounding fire and advisable to ground mechanical material. equipment in contact with the dry material to dissipate the potential build up of static electricity Fire Fighting As with all fires, evacuate personnel to a safe area. Fire fighter should use self- contained Procedure breathing equipment and protective clothing. Section 6. Storage / Spill / Disposal Measures

Storage

Store at 20° to 25°C (68° to 77°F) Dispense in well-closed containers Spill Response Small Spill: Use appropriate tools to put the spilled solid in a convenient waste disposal container. Finish cleaning by spreading water on the contaminated surface and dispose of according to local and regional authority requirements Large Spill Use a shovel to put the material into a convenient waste disposal container. Finish cleaning by spreading water on the contaminated surface and allow to evacuate through the sanitary system

Disposal

Dispose the waste in accordance with all applicable Federal, State and local laws Section 7. Exposure controls and personal protection Engineering Controls Use process enclosures, local exhaust ventilation, or other engineering controls to keep airborne levels below recommended exposure limits. If user operations generate dust, fume or mist, use ventilation to keep exposure to airborne contaminants below the exposure limit. Personal Protection Safety glasses. Lab coat. Dust respirator. Be sure to use an approved/certified respirator or equivalent. Gloves. Personal Protection in Case of a Large Spill Splash goggles. Full suit. Dust respirator. Boots. Gloves. A self contained breathing apparatus should be used to avoid inhalation of the product. Suggested protective clothing might not be sufficient; consult a specialist BEFORE handling this product. Exposure Limits: Not available. Section 8. Physical and chemical properties Appearance • Hard Gelatin Capsules, Cap Orange Opaque/Body White Opaque, Cap Imprinted EP in Black Ink and Body Imprinted 107 in Black Ink. Filled with white to off-white pellets. Solubility in water Practically in soluble in Odour Odourless water Boiling point No Data Available Melting Point No Data Available Evaporation rate No Data Available Vapour density No Data Available Reactivity in water No Data Available Evaporation rate No Data Available Percentage Volatile No Data Available Specific gravity No Data Available by volume Vapour pressure No Data Available

Physical hazards

Condition to Avoid exposure to extreme Stable Stable under normal ambient and avoid heat, light and moisture. anticipated storage and handling conditions. Decomposition No Data Available Hazardous No data available. Products Reaction Incompatibilities No data available. Section 10. Toxicological information General Handling of formulated product is not expected to cause any toxicological affects. The data pertains to the ingredient in formulations, rather than this specific formulation. Other Carcinogenesis, Mutagenesis, Impairment of Fertility Long-term studies in animals to evaluate the carcinogenic potential of acetazolamide has not been conducted. In a bacterial mutagenicity assay, acetazolamide was not mutagenic when evaluated with and without metabolic activation. The drug had no effect on fertility when administered in the diet to male and female rats at a daily intake of up to 4 times the recommended human dose of 1000 mg in a 50 kg individual. Section 11. Ecological information No data available on Ecotoxicity