Acetazolamide

Name: Acetazolamide

What should I do if I forget a dose?

Take the missed dose as soon as you remember it. However, if it is almost time for the next dose, skip the missed dose and continue your regular dosing schedule. Do not take a double dose to make up for the missed one.

What is the most important information I should know about acetazolamide?

You should not use this medicine if you have cirrhosis, severe liver or kidney disease, an electrolyte imbalance, adrenal gland failure, or an allergy to acetazolamide or sulfa drugs.

Advice to Patients

  • Risk of adverse effects, including sensitivity reactions; discontinue therapy and consult clinician if signs of sensitivity occur.c d e

  • When used to prevent acute mountain sickness, importance of gradual ascent.c f Use of acetazolamide does notobviate 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.c f

  • 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.d

  • Advise patients with pulmonary obstruction or emphysema that the drug may precipitate or aggravate acidosis.c d

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

  • 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.c d e

  • Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.c d e

  • Importance of informing patients of other precautionary information.c d e (See Cautions.)

Contraindications

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 noncongestive angle-closure glaucoma since it may permit organic closure of the angle to occur while the worsening glaucoma is masked by lowered intraocular pressure.

Warnings

Fatalities have occurred, although rarely, due to severe reactions to sulfonamides including Stevens-Johnson syndrome, toxic epidermal necrolysis, fulminant hepatic necrosis, agranulocytosis, aplastic anemia, and other blood dyscrasias. Sensitizations may recur when a sulfonamide is readministered irrespective of the route of administration. If signs of hypersensitivity or other serious reactions occur, discontinue use of this drug.

Caution is advised for patients receiving concomitant high-dose aspirin and Acetazolamide, as anorexia, tachypnea, lethargy, coma and death have been reported.

Precautions

GENERAL

Increasing the dose does not increase the diuresis and may increase the incidence of drowsiness and/or paresthesia. Increasing the dose often results in a decrease in diuresis. Under certain circumstances, however, very large doses have been given in conjunction with other diuretics in order to secure diuresis in complete refractory failure.

Information for Patients

Adverse reactions common to all sulfonamide derivatives may occur: anaphylaxis, fever, rash (including erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis), crystalluria, renal calculus, bone marrow depression, thrombocytopenic purpura, hemolytic anemia, leukopenia, pancytopenia and agranulocytosis. Precaution is advised for early detection of such reactions and the drug should be discontinued and appropriate therapy instituted.

In patients with pulmonary obstruction or emphysema where alveolar ventilation may be impaired, Acetazolamide which may precipitate or aggravate acidosis should be used with caution.

Caution is advised for patients receiving concomitant high-dose aspirin and Acetazolamide, as anorexia, tachypnea, lethargy, coma and death have been reported (see WARNINGS).

Laboratory Tests

To monitor for hematologic reactions common to all sulfonamides, it is recommended that a baseline CBC and platelet count be obtained on patients prior to initiating Acetazolamide therapy and at regular intervals during therapy. If significant changes occur, early discontinuance and institution of appropriate therapy are important. Periodic monitoring of serum electrolytes is recommended.

Carcinogenesis, Mutagenesis, Impairment of Fertility

Long-term studies in animals to evaluate the carcinogenic potential of Acetazolamide have 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.

Pregnancy

Teratogenic Effects

Pregnancy Category C: 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 reaction 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.

Pediatric Use

The safety and effectiveness of Acetazolamide in children have not been established.

Dosing Adult

Note: IM administration is not recommended because of pain secondary to the alkaline pH.

Altitude illness: Oral: Manufacturer's labeling: 500 to 1,000 mg/day in divided doses every 8 to 12 hours (immediate release tablets) or divided every 12 to 24 hours (extended release capsules). These doses are associated with more frequent and/or increased side effects. Alternative dosing has been recommended:

Prevention: 125 mg twice daily; beginning either the day before (preferred) or on the day of ascent; may be discontinued after staying at the same elevation for 2 to 3 days or if descent initiated (Basnyat, 2006; Luks, 2010). Note: In situations of rapid ascent (such as rescue or military operations), 1,000 mg/day is recommended by the manufacturer. The Wilderness Medical Society recommends consideration of using dexamethasone in addition to acetazolamide in these situations (Luks, 2010).

Treatment: 250 mg twice daily. Note: With high altitude cerebral edema, dexamethasone is the primary treatment; however, acetazolamide may be used adjunctively with the same treatment dose (Luks, 2010).

Edema: Oral, IV: 250 to 375 mg once daily

Epilepsy: Oral: 8 to 30 mg/kg/day in divided doses. A lower dosing range of 4 to 16 mg/kg/day in 1 to 4 divided doses has also been recommended; maximum dose: 30 mg/kg/day or 1 g/day (Oles, 1989; Reiss, 1996). Note: Minimal additional benefit with doses >16 mg/kg/day. Extended release capsule is not recommended for treatment of epilepsy.

Familial periodic paralysis (off-label use): Oral: 125 mg 3 times daily (Links 1988) or 250 mg once daily (Venance 2004) or 250 mg every 6 hours (Hoskins 1974). Additional data may be necessary to further define the role of acetazolamide in the treatment of this condition.

Glaucoma: Oral, IV:

Chronic simple (open-angle): 250 mg 1 to 4 times/day or 500 mg extended release capsule twice daily

Secondary or acute (closed-angle): Initial: 250 to 500 mg; maintenance: 125 to 250 mg every 4 hours (250 mg every 12 hours has been effective in short-term treatment of some patients).

Metabolic alkalosis (off-label use): IV: 500 mg as a single dose; reassess need based upon acid-base status (Marik, 1991; Mazur, 1999)

Prevention of cystine renal calculi (adjunctive therapy) (off-label use): Oral: 500 mg daily at bedtime in combination with potassium citrate and captopril (Sterrett 2008)

Respiratory stimulant in stable hypercapnic COPD (off-label use): Oral: 250 mg twice daily (Wagenaar, 2003)

Dietary Considerations

May be taken with food to decrease GI upset. May have additive effects with other folic acid antagonists. Some products may contain sodium.

Adverse Reactions

Frequency not defined.

Cardiovascular: Flushing

Central nervous system: Ataxia, confusion, convulsions, depression, dizziness, drowsiness, excitement, fatigue, flaccid paralysis, headache, malaise, paresthesia

Dermatologic: Allergic skin reaction, skin photosensitivity, Stevens-Johnson syndrome, toxic epidermal necrolysis, urticaria

Endocrine & metabolic: Electrolyte imbalance, growth retardation (children), hyperglycemia, hypoglycemia, hypokalemia, hyponatremia, metabolic acidosis

Gastrointestinal: Decreased appetite, diarrhea, dysgeusia, glycosuria, melena, nausea, vomiting

Genitourinary: Crystalluria, hematuria

Hematologic and oncologic: Agranulocytosis, aplastic anemia, leukopenia, thrombocytopenia, thrombocytopenic purpura

Hepatic: Abnormal hepatic function tests, cholestatic jaundice, fulminant hepatic necrosis, hepatic insufficiency

Hypersensitivity: Anaphylaxis

Local: Pain at injection site

Ophthalmic: Myopia

Otic: Auditory disturbance, tinnitus

Renal: Polyuria, renal failure

Miscellaneous: Fever

Acetazolamide and Pregnancy

Tell your doctor if you are pregnant or plan to become pregnant.

The FDA categorizes medications based on safety for use during pregnancy. Five categories - A, B, C, D, and X, are used to classify the possible risks to an unborn baby when a medication is taken during pregnancy.

Acetazolamide fall into category C. There are no well-controlled studies that have been done in pregnant women. Acetazolamide  should be used during pregnancy only if the possible benefit outweighs the possible risk to the unborn baby.

Dosing & Uses

Dosage Forms & Strengths

tablet

  • 125mg
  • 250mg

powder for injection

  • 500mg

capsule, extended-release

  • 500mg

Glaucoma

Closed-angle (acute congestive) glaucoma

  • 500 mg PO/IV, followed by 125-250 mg PO q4hr
  • Sustained-release: 500 mg PO q12hr

Open-angle (chronic simple) glaucoma

  • 250 mg-1 g PO/IV qDay or divided q6-12hr
  • Sustained-release: 500 mg PO q12hr

Secondary glaucoma

  • 500 mg PO/IV, followed by 125-250 mg PO q4hr
  • Sustained-release: 500 mg PO q12hr

Acute Altitude Sickness

Immediate release: 500-1000 mg/day PO divided q8-12hr

Extended release: 500-1000 mg PO q12-24hr

Dosing considerations

  • Start 24-48 hours before ascent and continue for 48 hours at high altitude or longer, to control symptoms if necessary

Congestive Heart Failure

CHF-associated edema

250-375 mg (5 mg/kg) PO qAM 

Seizure

8-30 mg/kg/day PO qDay or divided q12hr  

Drug-induced Edema

250-375 mg PO/IV qDay

Dosing considerations

  • Do not increase dose if edema fails to decrease following an initial response; allow instead kidney recovery by skipping medication for a day; best results obtained when given on alternate days or for 2 days followed by a day of rest

Epilepsy

Tablet: 8-30 mg/kg/day PO qDay, OR divided q6-12 hr; not to exceed 30 mg/kg/day or 1 g/day 

Extended-release capsule: Not recommended

Dosing Modifications

Renal impairment

  • CrCl 10-50 mL/min: Administer no more frequently than q12hr
  • CrCl <10 mL/min: Ineffective (avoid use)
  • Hemodialysis: 20-50% dialyzable
  • Peritoneal dialysis: Dose adjustment not necessary

Dosage Forms & Strengths

tablet

  • 125mg
  • 250mg

powder for injection

  • 500mg

capsule, extended-release

  • 500mg

Epilepsy

<12 years

  • Safety and efficacy not established

>12 years

  • Tablet: 8-30 mg/kg/day PO qDay or divided q6-12 hr; not to exceed 30 mg/kg/day or 1 g/day 
  • Extended-release capsule: Not recommended

Acute Altitude Sickness

<12 years

  • Safety and efficacy not established

>12 years

  • Immediate release: 500-1000 mg/day PO divided q8-12hr
  • Extended release: 500-1000 mg PO q12-24hr

Dosing considerations

  • Start 24-48 hr before ascent and continue for 48 hr at high altitude to control symptoms, if necessary

250 mg PO qDay or q12hr; use lowest effective dose possible

Warnings

Contraindications

Hypokalemia

Hyponatremia

Hyperchloremic acidosis

Hypersensitivity to acetazolamide or sulfa

Liver disease

Severe renal disease or dysfunction

Long term use in noncongestive angle-closure glaucoma

Cirrhosis

Long-term administration in patients with chronic, noncongestive angle-closure glaucoma

Cautions

Use caution in COPD, emphysema, and concomitant high-dose aspirin

Use caution in diabetes, respiratory acidosis, and hepatic impairment

Adverse drug reactions common to sulfonamide derivatives; Stevens-Johnson syndrome and toxic epidermal necrolysis (TEN) may occur

May impair alertness and/or physical coordination

FDA-approved product labeling for many medications have included a broad contraindication in patients with a prior allregic reaction to sulfonamides; however, recent studies have suggested that crossreactivity between antibiotic sulfonamides and nonantibiotic sulfonamides is unlikely to occur

May impair alertness and/or physical coordination

Severe adverse effects including tachypnea, anorexia, coma, lethargy, and death reported with high-dose aspirin; use caution or avoid administration

Increasing dose does not increase diuresis; may instead increase the incidence of paresthesia and/or drowsiness

IM administration not recommended due to alkaline pH, which may cause pain

Administration

IV Incompatibilities

Additive: Multivitamins

Y-site: Diltiazem(?), multivitamins

IV Compatibilities

Solution: Compatible with most common solvents

Additive: Cimetidine, ranitidine

IV Preparation

Standard diluent: 500 mg/50 mL D5W

Minimum volume: 50 mL D5W

IV Administration

IV push: 100-500 mg/min

Infusion: 4-8 hr

Storage

Store intact vials at room temperature

May store reconstituted solution in refrigerator for 3 days or at room temperature for 12 hr

Renal Dose Adjustments

Contraindicated in marked renal disease or impairment (specific CrCl level not provided, however, less than 10 mL/min has been provided by some authorities)

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