Acetazolamide

U.S. BRAND NAMES — Diamox® Sequels®
PHARMACOLOGIC CATEGORY Anticonvulsant, MiscellaneousCarbonic Anhydrase InhibitorDiuretic, Carbonic Anhydrase InhibitorOphthalmic Agent, Antiglaucoma
DOSING: ADULTS — Note: I.M. administration is not recommended.
Glaucoma: Chronic simple (open-angle): Oral: 250 mg 1-4 times/day or 500 mg extended release capsule twice daily Secondary, acute (closed-angle): I.V.: 250-500 mg, may repeat in 2-4 hours to a maximum of 1 g/day
Edema: Oral, I.V.: 250-375 mg once daily
Epilepsy: Oral: 8-30 mg/kg/day in 1-4 divided doses, not to exceed 1 g/day. Note: Extended release capsule is not recommended for treatment of epilepsy.
Metabolic alkalosis (unlabeled use): I.V. 250 mg every 6 hours for 4 doses or 500 mg single dose; reassess need based upon acid-base status
Mountain sickness: Oral: 250 mg every 8-12 hours (or 500 mg extended release capsules every 12-24 hours). Therapy should begin 24-48 hours before and continue during ascent and for at least 48 hours after arrival at the high altitude. Note: In situations of rapid ascent (such as rescue or military operations), 1000 mg/day is recommended.
Urine alkalinization (unlabeled use): Oral: 5 mg/kg/dose repeated 2-3 times over 24 hours
Respiratory stimulant in COPD (unlabeled use): Oral, I.V.: 250 mg twice daily
DOSING: PEDIATRIC — Note: I.M. administration is not recommended.
(For additional information see "Acetazolamide: Pediatric drug information")
Glaucoma: Oral: 8-30 mg/kg/day or 300-900 mg/m2/day divided every 8 hours I.V.: 20-40 mg/kg/24 hours divided every 6 hours, not to exceed 1 g/day
Edema: Oral, I.V.: 5 mg/kg or 150 mg/m2 once every day
Epilepsy: Oral: Refer to adult dosing.
DOSING: ELDERLY — Oral: Initial: 250 mg once or twice daily; use lowest effective dose possible.
DOSING: RENAL IMPAIRMENT Clcr 10-50 mL/minute: Administer every 12 hours.
Clcr <10 mL/minute: Avoid use (ineffective).
Moderately dialyzable (20% to 50%)
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Capsule, extended release: Diamox® Sequels®: 500 mg
Injection, powder for reconstitution: 500 mg
Tablet: 125 mg, 250 mg
DOSAGE FORMS: CONCISE Capsule, extended release: Diamox® Sequels®: 500 mg
Injection, powder for reconstitution: 500 mg
Tablet: 125 mg, 250 mg
GENERIC EQUIVALENT AVAILABLE — Yes: Injection, tablet
ADMINISTRATION Oral: May cause an alteration in taste, especially carbonated beverages. Short-acting tablets may be crushed and suspended in cherry or chocolate syrup to disguise the bitter taste of the drug; do not use fruit juices. Alternatively, submerge tablet in 10 mL of hot water and add 10 mL honey or syrup.
I.M.: I.M. administration is painful because of the alkaline pH of the drug; use by this route is not recommended.
COMPATIBILITY — Stable in dextran 6% in D5W, dextran 6% in NS, D5LR, D5NS, D51/2NS, D51/4NS, D5W, D10W, LR, NS, 1/2NS.
Y-site administration: Variable (consult detailed reference): Diltiazem, TPN.
Compatibility when admixed: Compatible: Cimetidine, ranitidine. Incompatible: Multivitamins.
USE — Treatment of glaucoma (chronic simple open-angle, secondary glaucoma, preoperatively in acute angle-closure); drug-induced edema or edema due to congestive heart failure (adjunctive therapy); centrencephalic epilepsies (immediate release dosage form); prevention or amelioration of symptoms associated with acute mountain sickness
USE - UNLABELED / INVESTIGATIONAL — Urine alkalinization; respiratory stimulant in COPD; metabolic alkalosis
ADVERSE REACTIONS SIGNIFICANT — Frequency not defined.
Cardiovascular: Flushing
Central nervous system: Ataxia, confusion, convulsions, depression, dizziness, drowsiness, excitement, fatigue, fever, headache, malaise
Dermatologic: Allergic skin reactions, photosensitivity, Stevens-Johnson syndrome, toxic epidermal necrolysis, urticaria
Endocrine & metabolic: Electrolyte imbalance, growth retardation (children), hyperglycemia, hypoglycemia, hypokalemia, hyponatremia, metabolic acidosis
Gastrointestinal: Appetite decreased, diarrhea, melena, nausea, taste alteration, vomiting
Genitourinary: Crystalluria, glycosuria, hematuria, polyuria, renal failure
Hematologic: Agranulocytosis, aplastic anemia, leukopenia, thrombocytopenia, thrombocytopenic purpura
Hepatic: Cholestatic jaundice, fulminant hepatic necrosis, hepatic insufficiency, liver function tests abnormal
Local: Pain at injection site
Neuromuscular & skeletal: Flaccid paralysis, paresthesia
Ocular: Myopia
Otic: Hearing disturbance, tinnitus
Miscellaneous: Anaphylaxis
CONTRAINDICATIONS — Hypersensitivity to acetazolamide, sulfonamides, or any component of the formulation; hepatic disease or insufficiency; decreased sodium and/or potassium levels; adrenocortical insufficiency, cirrhosis; hyperchloremic acidosis, severe renal disease or dysfunction; severe pulmonary obstruction; long-term use in noncongestive angle-closure glaucoma
WARNINGS / PRECAUTIONS Concerns related to adverse effects: CNS effects: Impairment of mental alertness and/or physical coordination may occur. Sulfa allergy: Chemical similarities are present among sulfonamides, sulfonylureas, carbonic anhydrase inhibitors, thiazides, and loop diuretics (except ethacrynic acid). Use in patients with sulfonylurea allergy is specifically contraindicated in product labeling, however, a risk of cross-reaction exists in patients with allergy to any of these compounds; avoid use when previous reaction has been severe. Discontinue if signs of hypersensitivity are noted.
Disease-related concerns: Diabetes: Use with caution in patients with prediabetes or diabetes mellitus; may see a change in glucose control. Hepatic impairment: Use with caution in patients with hepatic dysfunction; in cirrhosis, avoid electrolyte and acid/base imbalances that might lead to hepatic encephalopathy. Respiratory acidosis: Use with caution in patients with respiratory acidosis.
Special populations: Elderly: Use with caution in the elderly; may be more sensitive to side effects.
Other warnings/precautions: I.M. administration: Painful because of the alkaline pH of the drug; use by this route is not recommended.
DRUG INTERACTIONS — Inhibits CYP3A4 (weak)
Amphetamines: Urinary excretion of amphetamine may be decreased; magnitude and duration of effects may be enhanced.
Carbamazepine: May increase serum concentrations of carbamazepine.
Cyclosporine trough concentrations may be increased resulting in possible nephrotoxicity and neurotoxicity.
Flecainide: May decrease excretion of flecainide.
Lithium: Serum concentrations may be decreased by acetazolamide; monitor.
Memantine: May decrease excretion of memantine.
Methenamine: Urinary antiseptic effect may be prevented by acetazolamide.
Phenytoin: Serum concentrations of phenytoin may be increased; incidence of osteomalacia may be enhanced or increased in patients on chronic phenytoin therapy.
Primidone serum concentrations may be decreased; carbonic anhydrase inhibitors may enhance the adverse/toxic effects of primidone.
Quinidine: Urinary excretion of quinidine may be decreased and effects may be enhanced.
Salicylate use (high dose) may result in carbonic anhydrase inhibitor accumulation and toxicity including CNS depression and metabolic acidosis. Salicylate toxicity might also be enhanced.
PREGNANCY RISK FACTOR — C (show table)
PREGNANCY IMPLICATIONS — Teratogenic in animal studies, however, there are no adequate and well-controlled studies in pregnant women.
LACTATION — Enters breast milk/not recommended (AAP rates "compatible")
DIETARY CONSIDERATIONS — May be taken with food to decrease GI upset. May have additive effects with other folic acid antagonists. Sodium content of 500 mg injection: 47.2 mg (2.05 mEq).
PRICING — (data from drugstore.com)Capsule, 12-hour (Diamox Sequels) 500 mg (60): $169.03
Tablets (AcetaZOLAMIDE) 125 mg (60): $8.98 250 mg (60): $18.99
MONITORING PARAMETERS — Intraocular pressure, potassium, serum bicarbonate; serum electrolytes, periodic CBC with differential; monitor growth in pediatric patients
TOXICOLOGY / OVERDOSE COMPREHENSIVE — Symptoms include low blood sugar, tingling of lips and tongue, nausea, yawning, confusion, agitation, tachycardia, sweating, convulsions, stupor, and coma. Hypoglycemia should be managed with 50 mL I.V. dextrose 50% followed immediately with a continuous infusion of 10% dextrose in water (administer at a rate sufficient enough to approach a serum glucose level of 100 mg/dL). The use of corticosteroids to treat the hypoglycemia is controversial, however, the addition of 100 mg of hydrocortisone to the dextrose infusion may prove helpful. In certain instances, hemodialysis may be helpful.
CANADIAN BRAND NAMES — Apo-Acetazolamide®; Diamox®
INTERNATIONAL BRAND NAMES — Acetadiazol (MX); Albox (JP); Apo-Acetazolamide (CA, MY); Azol (TW); Carbinib (PT); Cetamid (PH); Defiltran (DE); Dehydratin (BG); Diamox (AE, AR, AT, AU, BE, BH, BR, CA, CH, CN, CO, CY, DK, EC, EG, ES, FI, FR, GB, HR, ID, IE, IN, IQ, IR, IT, JO, JP, KW, LB, LY, MX, MY, NL, NO, NZ, OM, PH, PY, QA, RU, SA, SE, SG, SY, TH, VE, YE, ZA); Diamox Sustets (CO); Diluran (CZ); Diural (UY); Diuramid (DE, PL); Edemox (ES); Evamox (PK); Genephamide (PE); Glaucomed (CO); Glaupax (CH, DK, HR, IE, JP, NO, TH); Huma-Zolamide (HU); Ledamox (JP); Lediamox (PT); Renamid (HR); Stazol (PY); Uramox (IL)
MECHANISM OF ACTION — Reversible inhibition of the enzyme carbonic anhydrase resulting in reduction of hydrogen ion secretion at renal tubule and an increased renal excretion of sodium, potassium, bicarbonate, and water to decrease production of aqueous humor; also inhibits carbonic anhydrase in central nervous system to retard abnormal and excessive discharge from CNS neurons
PHARMACODYNAMICS / KINETICS Onset of action: Capsule, extended release: 2 hours; I.V.: 2 minutes Peak effect: Capsule, extended release: 8-12 hours; I.V.: 15 minutes; Tablet: 2-4 hours
Duration: Inhibition of aqueous humor secretion: Capsule, extended release: 18-24 hours; I.V.: 4-5 hours; Tablet: 8-12 hours
Distribution: Erythrocytes, kidneys; blood-brain barrier and placenta; distributes into milk (~30% of plasma concentrations)
Excretion: Urine (70% to 100% as unchanged drug)
PATIENT INFORMATION — Report numbness or tingling of extremities. Do not crush, chew, or swallow contents of long-acting capsule; may be opened and sprinkled on soft food. Ability to perform tasks requiring mental alertness and/or physical coordination may be impaired. Take with food; drug may cause substantial increase in blood glucose in some diabetic patients.
(For additional information see "Acetazolamide: Patient drug information")