Drug Information

Acetazolamide

Acetazolamide
Copyright 1978-2011 Lexicomp, Inc. All rights reserved.

(For additional information see “Acetazolamide: Patient drug information” and see “Acetazolamide: Pediatric drug information”)

Brand Names: U.S.

  • Diamox® Sequels®
Brand Names: Canada

  • Apo-Acetazolamide®;
  • Diamox®
Pharmacologic Category

  • Anticonvulsant, Miscellaneous;
  • Carbonic Anhydrase Inhibitor;
  • Diuretic, Carbonic Anhydrase Inhibitor;
  • Ophthalmic Agent, Antiglaucoma
Dosing: AdultNote: 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: Manufacturer’s labeling: 500-1000 mg daily, in divided doses every 8-12 hours (immediate release tablets) or divided every 12-24 hours (extended release capsules ). Alternative recommendations suggest use of lower doses to reduce side effects: 125-250 mg twice daily for prevention or treatment of mild sickness, and 250 mg twice daily for treatment of moderate sickness (Hackett, 2001). 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 (manufacturer’s labeling).

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(For additional information see “Acetazolamide: Pediatric drug information”)Note: I.M. administration is not recommended.

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: GeriatricOral: Initial: 250 mg once or twice daily; use lowest effective dose possible.
Dosing: Renal ImpairmentClcr 10-50 mL/minute: Administer every 12 hours.Clcr <10 mL/minute: Avoid use (ineffective).

Moderately dialyzable (20% to 50%)

Dosage Forms: U.S.Excipient information presented when available (limited, particularly for generics); consult specific product labeling.Capsule, extended release, oral: 500 mg

Capsule, sustained release, oral:

Diamox® Sequels®: 500 mg

Injection, powder for reconstitution: 500 mg

Tablet, oral: 125 mg, 250 mg

Generic Equivalent Available: U.S.Yes
AdministrationOral: May be administered with food. 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.

I.V.: No specific guidance given by manufacturer, but I.V. push at a rate of up to 500 mg over 3 minutes has been reported in a clinical trial (Mazur, 1999); a study to assess cerebrovascular reserve has used rapid I.V. push of up to 1 g over ≤1 minute (Piepgras, 1990)

CompatibilityStable in D5LR, D5NS, D51/2NS, D51/4NS, D5R, D5W, D10W, LR, NS, 1/2NS, R, SL.Y-site administration: Compatible: Pantoprazole. Incompatible: TrophAmine®. Variable (consult detailed reference): Diltiazem, TPN.

Compatibility in syringe: Compatible: Pantoprazole

UseTreatment 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/InvestigationalMetabolic alkalosis; respiratory stimulant in COPD; urine alkalinization
Medication Safety Issues

International issues:

Diamox [Canada and multiple international markets] may be confused with Diabinese brand name for chlorpropamide [Multiple international markets]; Dobutrex brand name for dobutamine [Multiple international markets]; Trimox brand name for amoxicillin [Brazil]; Zimox brand name for amoxicillin [Italy] and carbidopa/levodopa [Greece]

Adverse Reactions SignificantFrequency not defined.Cardiovascular: Flushing

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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

ContraindicationsHypersensitivity 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.

Metabolism/Transport EffectsInhibits CYP3A4 (weak)
Drug Interactions

(For additional information: Launch Lexi-Interact™ Drug Interactions Program )

Alcohol (Ethyl): CNS Depressants may enhance the CNS depressant effect of Alcohol (Ethyl). Risk C: Monitor therapy

Alfuzosin: May enhance the hypotensive effect of Antihypertensives. Risk C: Monitor therapy

Alpha-/Beta-Agonists: Carbonic Anhydrase Inhibitors may decrease the excretion of Alpha-/Beta-Agonists. Exceptions: Dipivefrin. Risk C: Monitor therapy

Amifostine: Antihypertensives may enhance the hypotensive effect of Amifostine. Management: When amifostine is used at chemotherapy doses, antihypertensive medications should be withheld for 24 hours prior to amifostine administration. If antihypertensive therapy can not be withheld, amifostine should not be administered. Risk D: Consider therapy modification

Amphetamines: Carbonic Anhydrase Inhibitors may decrease the excretion of Amphetamines. Risk C: Monitor therapy

Anticonvulsants (Barbiturate): Carbonic Anhydrase Inhibitors may enhance the adverse/toxic effect of Anticonvulsants (Barbiturate). Specifically, osteomalacia and rickets. Risk C: Monitor therapy

Anticonvulsants (Hydantoin): Carbonic Anhydrase Inhibitors may enhance the adverse/toxic effect of Anticonvulsants (Hydantoin). Specifically, osteomalacia and rickets. Risk C: Monitor therapy

Antihypertensives: May enhance the hypotensive effect of other Antihypertensives. Risk C: Monitor therapy

CarBAMazepine: Carbonic Anhydrase Inhibitors may increase the serum concentration of CarBAMazepine. Risk C: Monitor therapy

Carbonic Anhydrase Inhibitors: May enhance the adverse/toxic effect of other Carbonic Anhydrase Inhibitors. The development of acid-base disorders with concurrent use of ophthalmic and oral carbonic anhydrase inhibitors has been reported. Management: Avoid concurrent use of different carbonic anhydrase inhibitors if possible. Monitor patients closely for the occurrence of kidney stones and with regards to severity of metabolic acidosis. Risk X: Avoid combination

CNS Depressants: May enhance the adverse/toxic effect of other CNS Depressants. Exceptions: Levocabastine (Nasal). Risk C: Monitor therapy

Diazoxide: May enhance the hypotensive effect of Antihypertensives. Risk C: Monitor therapy

Droperidol: May enhance the CNS depressant effect of CNS Depressants. Management: Consider dose reductions of droperidol or of other CNS agents (e.g., opioids, barbiturates) with concomitant use. Risk D: Consider therapy modification

Flecainide: Carbonic Anhydrase Inhibitors may decrease the excretion of Flecainide. Risk C: Monitor therapy

Herbs (Hypertensive Properties): May diminish the antihypertensive effect of Antihypertensives. Risk C: Monitor therapy

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Herbs (Hypotensive Properties): May enhance the hypotensive effect of Antihypertensives. Risk C: Monitor therapy

HydrOXYzine: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Hypotensive Agents: May enhance the adverse/toxic effect of other Hypotensive Agents. Risk C: Monitor therapy

Ketorolac: May diminish the therapeutic effect of Anticonvulsants. Risk C: Monitor therapy

Ketorolac (Nasal): May diminish the therapeutic effect of Anticonvulsants. Risk C: Monitor therapy

Ketorolac (Systemic): May diminish the therapeutic effect of Anticonvulsants. Risk C: Monitor therapy

Lithium: Carbonic Anhydrase Inhibitors may decrease the serum concentration of Lithium. Risk C: Monitor therapy

MAO Inhibitors: May enhance the orthostatic hypotensive effect of Orthostatic Hypotension Producing Agents. Risk C: Monitor therapy

Mefloquine: May diminish the therapeutic effect of Anticonvulsants. Mefloquine may decrease the serum concentration of Anticonvulsants. Management: Mefloquine is contraindicated for malaria prophylaxis in persons with a history of convulsions. Monitor anticonvulsant concentrations and treatment response closely with concurrent use. Risk D: Consider therapy modification

Memantine: Carbonic Anhydrase Inhibitors may decrease the excretion of Memantine. Risk C: Monitor therapy

Methenamine: Carbonic Anhydrase Inhibitors may diminish the therapeutic effect of Methenamine. Management: Consider avoiding this combination. Monitor for decreased therapeutic effects of methenamine if used concomitant with a carbonic anhydrase inhibitor. Risk D: Consider therapy modification

Methotrimeprazine: CNS Depressants may enhance the CNS depressant effect of Methotrimeprazine. Methotrimeprazine may enhance the CNS depressant effect of CNS Depressants. Management: Reduce adult dose of CNS depressant agents by 50% with initiation of concomitant methotrimeprazine therapy. Further CNS depressant dosage adjustments should be initiated only after clinically effective methotrimeprazine dose is established. Risk D: Consider therapy modification

Methylphenidate: May diminish the antihypertensive effect of Antihypertensives. Risk C: Monitor therapy

Pentoxifylline: May enhance the hypotensive effect of Antihypertensives. Risk C: Monitor therapy

Phosphodiesterase 5 Inhibitors: May enhance the antihypertensive effect of Antihypertensives. Risk C: Monitor therapy

Primidone: Carbonic Anhydrase Inhibitors may enhance the adverse/toxic effect of Primidone. Specifically, osteomalacia and rickets. Carbonic Anhydrase Inhibitors may decrease the serum concentration of Primidone. Risk C: Monitor therapy

Prostacyclin Analogues: May enhance the hypotensive effect of Antihypertensives. Risk C: Monitor therapy

QuiNIDine: Carbonic Anhydrase Inhibitors may decrease the excretion of QuiNIDine. Risk C: Monitor therapy

RiTUXimab: Antihypertensives may enhance the hypotensive effect of RiTUXimab. Risk D: Consider therapy modification

Salicylates: May enhance the adverse/toxic effect of Carbonic Anhydrase Inhibitors. Salicylate toxicity might be enhanced by this same combination. Risk D: Consider therapy modification

Selective Serotonin Reuptake Inhibitors: CNS Depressants may enhance the adverse/toxic effect of Selective Serotonin Reuptake Inhibitors. Specifically, the risk of psychomotor impairment may be enhanced. Risk C: Monitor therapy

Sodium Phosphates: Diuretics may enhance the nephrotoxic effect of Sodium Phosphates. Specifically, the risk of acute phosphate nephropathy may be enhanced. Management: Consider avoiding this combination by temporarily suspending treatment with diuretics, or seeking alternatives to oral sodium phosphate bowel preparation. If the combination cannot be avoided, hydrate adequately and monitor fluid and renal status. Risk D: Consider therapy modification

Trientine: Carbonic Anhydrase Inhibitor Diuretics may decrease the serum concentration of Trientine. Risk C: Monitor therapy

Yohimbine: May diminish the antihypertensive effect of Antihypertensives. Risk C: Monitor therapy

Pregnancy Risk FactorC (show table)
Pregnancy ImplicationsTeratogenic effects have been observed in animal reproduction studies.
LactationEnters breast milk/not recommended (AAP rates “compatible”; AAP 2001 update pending)
Breast-Feeding ConsiderationsIn a case report, low concentrations of acetazolamide were detected in the breast milk and the infant serum following a maternal dose of acetazolamide 500 mg twice daily. Acetazolamide concentrations in the breast milk were 1.3-2.1 mcg/mL, 1-9 hours after the dose. Acetazolamide concentrations in the infant serum were 0.2-0.6 mcg/mL, 2-12 hours after nursing. Maternal plasma concentrations were 5.2-6.4 mcg/mL, 1-7 hours after the dose. All levels were obtained on days 4-5 of therapy, 10 days after delivery. Due to the potential for adverse events in a nursing infant, breast-feeding is not recommended by the manufacturer.
Dietary ConsiderationsMay be taken with food to decrease GI upset. May have additive effects with other folic acid antagonists. Some products may contain sodium.
Monitoring ParametersIntraocular pressure; potassium, serum bicarbonate, serum electrolytes, periodic CBC with differential; monitor growth in pediatric patients
International Brand Names

  • Acetadiazol (MX);
  • Acetak (PE);
  • Albox (JP);
  • Apo-Acetazolamide (MY);
  • Azol (TW);
  • Carbinib (PT);
  • Cetamid (PH);
  • Diacarb (RU);
  • Diamox (AE, AR, AT, AU, BD, BE, BG, BH, BR, CH, CL, CY, DK, EE, EG, ES, FI, FR, GB, GR, HK, HR, ID, IE, IN, IQ, IR, IT, JO, JP, KP, KW, LB, LU, LY, MT, MY, NL, NO, NZ, OM, QA, RU, SA, SE, SG, SK, SY, TH, VE, YE, ZA);
  • Diamox Sustets (CO);
  • Diazomid (TR);
  • Diluran (CZ);
  • Diural (UY);
  • Diuramid (PL);
  • Evamox (PK);
  • Fonurit (HU);
  • Glaupax (CH, DE, HR, JP, TH);
  • Huma-Zolamide (HN, HU);
  • Ledamox (JP);
  • Medene (TH);
  • Oculten (DO, SV);
  • Odemin (FI);
  • Renamid (HR);
  • Stazol (PY);
  • Synomax (IN);
  • Uramox (IL);
  • Zolmide (PH)
Mechanism of ActionReversible 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/KineticsOnset of action: Capsule, extended release: 2 hours; I.V.: 2 minutesPeak 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

Excretion: Urine (70% to 100% as unchanged drug)

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REFERENCES

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