Drug class: Carbonic Anhydrase Inhibitors
ATC class: S01EC01
VA class: CV703
CAS number: 59-66-5

Medically reviewed by Drugs.com on May 15, 2023. Written by ASHP.

Introduction

Carbonic anhydrase inhibitor; nonbacteriostatic sulfonamide derivative.^{100 101 102 a b}

Uses for Acetazolamide

Glaucoma

Adjunctive treatment of open-angle glaucoma.^{100 101 102} Used principally in situations involving acute IOP elevation or chronically elevated IOP that is refractory to maximal topical ocular hypotensive therapy prior to a more definitive procedure to reduce IOP.¹³⁶ Long-term use limited by systemic adverse effects.^{134 136}

Adjunctive treatment of secondary glaucoma.^{100 101 102}

Short-term use in acute angle-closure glaucoma to lower IOP before appropriate laser or incisional surgery.^{100 101 102 135 136 137 a b} Should not be used for long-term treatment of angle-closure glaucoma.^{100 101 102 b} (See Contraindications under Cautions.)

Acute Mountain Sickness

Prevention or amelioration of symptoms (e.g., headache, lassitude, insomnia, nausea, shortness of breath, dizziness) associated with acute mountain sickness.^{100 101 103 a b}

Shortens the time of acclimatization.¹⁰³ If acute mountain sickness develops, shortens duration; does notobviate need to stop ascent or to descend.¹⁰³

Also used in the treatment and prevention of high-altitude sleep disorders.^{100 101 103} Decreases periodic breathing and apnea and improves oxygenation.¹⁰³

Seizure Disorders

Management (in combination with other anticonvulsants) of centrencephalic epilepsies (e.g., petit mal, unlocalized seizures);^{100 102} may be ineffective for prolonged therapy.^{a b} Has not been evaluated in controlled clinical studies in specific seizure types.^{a b}

Edema

Adjunctive treatment of edema due to CHF or drug therapy.^{100 102 b} Less potent diuretic than thiazide diuretics; metabolic acidosis resulting in loss of diuretic effect occurs after 2–4 days of continuous therapy.^b

Periodic Paralysis

Has been used in the treatment of hyperkalemic and hypokalemic forms of periodic paralysis^{† [off-label]}.^{404 405 407 409 412 413}

Acetazolamide Dosage and Administration

Administration

Administer orally or by direct IV injection.^{100 101 102}

Do not administer IM; injection is painful.^{102 b}

Oral Administration

When an oral liquid preparation is needed, crush the appropriate number of tablets and suspend in a highly flavored carbohydrate syrup.^a Can suspend up to 500 mg of acetazolamide in 5 mL of syrup; suspensions containing 250 mg per 5 mL are more palatable.^a Alternatively, soften a tablet in 2 teaspoonsful of hot water and add 2 teaspoonsful of honey or syrup; swallow immediately.^a

When the extended-release capsules are used for glaucoma, if adequate response is not achieved with twice-daily administration of this preparation, consider using other acetazolamide preparations that are administered more frequently (i.e., tablet, parenteral preparation) to achieve IOP control.¹⁰¹

IV Administration

For solution and drug compatibility information, see Compatibility under Stability.

Administer IV when rapid lowering of IOP is necessary or if patient is unable to take oral medication.^{102 a}

Reconstitution

Reconstitute vial containing 500 mg of acetazolamide with 5 mL of sterile water for injection to provide a solution containing 100 mg/mL.^{102 a}

Dosage

Available as acetazolamide (oral preparations) and acetazolamide sodium; dosage expressed in terms of acetazolamide.^{100 101 102}

Adjust dosage based on patient response and requirements.^a

Pediatric Patients

Glaucoma

Oral

8–30 mg/kg or 300–900 mg/m² daily in 3 divided doses has been used.^a

Open-angle or Secondary Glaucoma

Oral

Extended-release capsules in children ≥12 years of age: 500 mg twice daily.¹⁰¹

Acute Angle-closure Glaucoma

Oral

Extended-release capsules in children ≥12 years of age: 500 mg twice daily.¹⁰¹

IV

5–10 mg/kg every 6 hours has been used.^a

Acute Mountain Sickness

Oral

Extended-release capsules in children ≥12 years of age: 500 mg once or twice daily.¹⁰¹ Initiate 24–48 hours before ascent; continue for 48 hours while at high altitude or longer if needed to control symptoms.¹⁰¹

Seizure Disorders† [off-label]

Oral

8–30 mg/kg daily in divided doses has been used.^{100 a}

Edema† [off-label]

Oral or IV

5 mg/kg or 150 mg/m² once daily in the morning has been used.^a

Adults

Glaucoma

Open-angle Glaucoma

Oral

Conventional tablets: 250 mg to 1 g daily.¹⁰⁰ For daily dosages >250 mg, administer in divided doses.¹⁰⁰

Extended-release capsules: 500 mg twice daily.¹⁰¹

IV

250 mg to 1 g daily.¹⁰² For daily dosages >250 mg, administer in divided doses.¹⁰²

Secondary Glaucoma

Oral

Conventional tablets: 250 mg every 4 hours.¹⁰⁰ Some patients respond to short-term therapy with 250 mg twice daily.¹⁰⁰

Extended-release capsules: 500 mg twice daily.¹⁰¹

IV

250 mg every 4 hours.¹⁰² Some patients respond to short-term therapy with 250 mg twice daily.¹⁰²

Acute Angle-closure Glaucoma

Oral

Conventional tablets: 250 mg every 4 hours.^{100 a} Alternatively, 250 mg twice daily or an initial dose of 500 mg followed by 125–250 mg every 4 hours.^{100 a}

Extended-release capsules: 500 mg twice daily.¹⁰¹

IV

250 mg every 4 hours.¹⁰² Alternatively, 250 mg twice daily or an initial dose of 500 mg followed by 125–250 mg every 4 hours.¹⁰²

Acute Mountain Sickness

Oral

Conventional tablets and extended-release capsules: 500 mg to 1 g daily in divided doses.^{100 101} Initiate 24–48 hours before ascent; continue for 48 hours while at high altitude or longer if needed to control symptoms.^{100 101}

125–250 mg twice daily starting 24 hours before ascent has been effective for prevention of acute mountain sickness; 500 mg (as extended-release capsules) every 24 hours also has been effective.¹⁰³ 750 mg daily may be more effective than 500 mg daily.¹⁰³

125 mg at bedtime has been used for the management of high-altitude sleep disorders.¹⁰³

For treatment of acute mountain sickness, some experts recommend 250 mg given within 24 hours of onset of symptoms and a second 250-mg dose 8 hours later.¹⁰³

Seizure Disorders

Oral

Conventional tablets: 8–30 mg/kg daily in divided doses.¹⁰⁰

Usual dosage range: 375 mg to 1 g daily.¹⁰⁰

When used in conjunction with other anticonvulsants, initiate at 250 mg once daily and increase dosage as needed.¹⁰⁰

IV

8–30 mg/kg daily in divided doses; usual dosage range is 375 mg to 1 g daily.¹⁰²

When given in conjunction with other anticonvulsants, initiate at 250 mg once daily and increase dosage as needed.¹⁰²

Edema

CHF

Oral

Conventional tablets: Initially, 250–375 mg (5 mg/kg) once daily in the morning.¹⁰⁰

If patient fails to lose edema fluid after initial response, hold drug for 1 day.¹⁰⁰ To avoid loss of diuretic effect, administer intermittently (on alternate days or for 2 days followed by a drug-free day).¹⁰⁰

IV

Initially, 250–375 mg (5 mg/kg) once daily in the morning.¹⁰²

If patient fails to lose edema fluid after initial response, hold drug for 1 day.¹⁰² To avoid loss of diuretic effect, administer intermittently (on alternate days or for 2 days followed by a drug-free day).¹⁰²

Drug-induced Edema

Oral

Conventional tablets: 250–375 mg once daily for 1 or 2 days, alternating with a drug-free day.¹⁰⁰

IV

250–375 mg once daily for 1 or 2 days, alternating with a drug-free day.¹⁰²

Periodic Paralysis† [off-label]

Oral

250 mg 2 to 3 times daily has been used.^a

Prescribing Limits

When used in glaucoma or seizure disorders, dosage >1 g daily is not associated with additional clinical benefit.^{100 101 102}

When used for diuresis, increasing dosage does not produce greater response and may result in decreased response.^{100 101 102}

Special Populations

Geriatric Patients

Select dosage with caution because of age-related decreases in hepatic, renal, and/or cardiac function and concomitant disease and drug therapy.¹⁰¹

Cautions for Acetazolamide

Contraindications

• Marked impairment of hepatic function.^{100 101 102} Cirrhosis.^{100 101 102} (See Hepatic Impairment under Cautions.)

• Depressed serum concentrations of sodium and/or potassium.^{100 101 102}

• Adrenocortical insufficiency.^{100 101 102}

• Hyperchloremic acidosis.^{100 101 102}

• Marked impairment of renal function.^{100 101 102}

• Long-term treatment of angle-closure glaucoma; further closure of the angle may occur while worsening of glaucoma is masked by lower IOP.^{100 101 102 b}

• Hypersensitivity to acetazolamide or any ingredients in the formulation.^{101 102}

Warnings/Precautions

Sensitivity Reactions

Sulfonamide Sensitivity Reactions

Serious adverse events (e.g., Stevens-Johnson syndrome, toxic epidermal necrolysis, fulminant hepatic necrosis, agranulocytosis, aplastic anemia, other blood dyscrasias) associated with sulfonamide therapy possible.^{100 101 102 b}

Discontinue if signs of hypersensitivity, blood dyscrasias, or other serious reactions occur.^{100 102 b}

General Precautions

CNS Effects

Drowsiness and/or paresthesia reported with high dosages.^{100 101 102 b}

Respiratory Effects

Caution in patients with pulmonary obstruction, emphysema, or advanced pulmonary disease where alveolar ventilation may be impaired.^{100 101 102 b} Acetazolamide may precipitate or aggravate acidosis in these patients.^{100 101 102}

Laboratory Monitoring

Monitor for hematologic reactions associated with sulfonamides; obtain a CBC and platelet count before therapy and periodically during therapy.^{100 101 102} Discontinue the drug if clinically important changes occur.^{100 101 102}

Monitor serum electrolytes periodically for electrolyte imbalances (i.e., hyponatremia, hypokalemia, metabolic acidosis).^{100 101 102}

Glucose Concentrations

Increased or decreased blood glucose concentrations reported.¹⁰¹ Caution in patients with impaired glucose tolerance or diabetes mellitus.^b

Specific Populations

Pregnancy

Category C.^{100 101 102}

Lactation

Discontinue nursing or the drug.^{100 101 102}

Pediatric Use

Conventional tablets and parenteral preparation: Manufacturers state that safety and efficacy not established.^{100 102}

Extended-release capsules: Safety and efficacy not established in pediatric patients <12 years of age.¹⁰¹

Growth retardation has been reported in children receiving long-term therapy with extended-release capsules.¹⁰¹

Geriatric Use

Risk of metabolic acidosis (may be severe) in geriatric patients with reduced renal function.¹⁰¹

Hepatic Impairment

Avoid use in patients with marked hepatic impairment, including those with cirrhosis, because of the risk of developing hepatic encephalopathy.^{100 101 102} (See Contraindications.)

Renal Impairment

Avoid use in patients with marked renal impairment.^{100 101 102} (See Contraindications.)

Common Adverse Effects

Paresthesias, hearing dysfunction or tinnitus, anorexia, altered taste, nausea, vomiting, diarrhea, polyuria, drowsiness, confusion.^{100 102}

Drug Interactions

Specific Drugs and Laboratory Tests

Acetazolamide Pharmacokinetics

Absorption

Bioavailability

Well absorbed from GI tract.^{a b} Peak plasma concentrations attained within 1–4 or 3–6 hours following administration of conventional tablets or extended-release capsules, respectively.¹⁰¹

Onset

Following IV administration, reduction in IOP occurs in 2 minutes.^b

Following administration of conventional tablets or extended-release capsules, reduction in IOP occurs in 1 or 2 hours, respectively.^b

Duration

Following IV administration, reduction in IOP persists for 4–5 hours.^b

Following administration of conventional tablets or extended-release capsules, reduction in IOP persists for 8–12 or 18–24 hours, respectively.^{101 b}

Food

Extended-release capsules: Food does not affect absorption.¹⁰¹

Distribution

Extent

Distributed into erythrocytes, renal cortex, and aqueous humor of eye.^{101 a}

Crosses the placenta.^{a b}

Distributed into milk in dogs; not known whether distributed into human milk.^a

Elimination

Elimination Route

Excreted principally in the urine as unchanged drug.^a

Stability

Storage

Oral

Tablets

Tight, light-resistant container at 20–25°C (may be exposed to 15–30°C).¹⁰⁰

Capsules

Extended-release: tight container at 20–25°C.¹⁰¹

Parenteral

Powder for Injection

20–25°C.¹⁰²

Reconstituted solutions prepared using sterile water for injection are stable for 3 days at 2–8°C or 12 hours at 20–25°C.¹⁰²

Store reconstituted solutions at 2–8°C and use within 12 hours to minimize the risk of microbial contamination.¹⁰²

Compatibility

Parenteral

Solution CompatibilityHID

Drug CompatibilityHID

Actions

• Noncompetitive reversible inhibitor of the carbonic anhydrase enzyme.^{100 101 102 b}

• Reduces the formation of hydrogen and bicarbonate ions from carbon dioxide and water, thereby reducing availability of these ions for active transport into secretions.^b

• Decreases aqueous humor secretion and IOP.^{100 101 b}

• Increases urinary excretion of bicarbonate, sodium, and potassium due to decrease in hydrogen ions in the renal tubules.^b Decreases reabsorption of water, increases urine volume, urine becomes alkaline.^b

• When used as a diuretic, plasma bicarbonate concentration is decreased and chloride concentration may be increased, resulting in metabolic acidosis.^b In the presence of acidosis, diuretic effect ceases.^b

• In acute mountain sickness, the effect of acetazolamide on acid-base balance (i.e., increased renal excretion of bicarbonate that leads to metabolic acidosis) results in compensatory hyperventilation and improved oxygenation.¹⁰³

• Exact mechanism of anticonvulsant activity unclear; may be due to metabolic acidosis, inhibition of carbonic anhydrase in the CNS, or other mechanisms.^b

Advice to Patients

• Risk of adverse effects, including sensitivity reactions; discontinue therapy and consult clinician if signs of sensitivity occur.^{100 101 102}

• When used to prevent acute mountain sickness, importance of gradual ascent.^{100 103} Use of acetazolamide does not obviate need to stop ascent if acute mountain sickness develops or descend if severe forms of altitude sickness (e.g., high attitude pulmonary or cerebral edema) occur.^{100 103}

• Potential for the drug to impair mental alertness or impair vision (myopia); use caution when driving a vehicle or operating machinery until effects on individual are known.¹⁰¹

• Advise patients with pulmonary obstruction or emphysema that the drug may precipitate or aggravate acidosis.^{100 101}

• Advise patients with diabetes or impaired glucose tolerance that increases and decreases in blood glucose have occurred in acetazolamide-treated patients.¹⁰¹

• Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs (e.g., high-dose aspirin), as well as concomitant diseases.^{100 101 102}

• Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.^{100 101 102}

• Importance of informing patients of other precautionary information.^{100 101 102} (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

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