Acetazolamide

Name: Acetazolamide

What is acetazolamide?

Acetazolamide reduces the activity of a protein in your body called carbonic anhydrase. Blocking this protein can help reduce the build-up of certain fluids in the body.

Acetazolamide is used in people with certain types of glaucoma to reduce the amount of fluid in the eye, which decreases pressure inside the eye.

Acetazolamide is also used as a diuretic ("water pill") in people with congestive heart failure, to reduce the build-up of fluid in the body. This build-up is called edema.

Acetazolamide is also used to treat certain types of seizures, and to treat or prevent altitude sickness.

Acetazolamide may also be used for purposes not listed in this medication guide.

Introduction

Carbonic anhydrase inhibitor; nonbacteriostatic sulfonamide derivative.a b c d e

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.d

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.b d

Food

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

Distribution

Extent

Distributed into erythrocytes, renal cortex, and aqueous humor of eye.a d

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

Actions

  • Noncompetitive reversible inhibitor of the carbonic anhydrase enzyme.b d c e

  • 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.b c d

  • 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.f

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

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

acetaZOLAMIDE

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Capsules, extended-release*

500 mg*

Diamox

Duramed

Tablets

125 mg*

Acetazolamide Tablets

250 mg*

Acetazolamide Tablets

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

acetaZOLAMIDE Sodium

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Parenteral

For injection, for IV use

500 mg (of acetazolamide)*

Acetazolamide Sodium for Injection

How is Acetazolamide Supplied

Acetazolamide for Injection USP is a white powder.

Intravenous Acetazolamide for Injection USP (lyophilized) powder.

Supplied as single vial of 500 mg in a carton (NDC 23155-313-31)

Store at 20° to 25°C (68° to 77°F) excursions permitted between 15° to 30°C (59° to 86°F) [see USP Controlled Room Temperature]. Reconstituted solution should be stored in refrigerator at 2° to 8°C (36° to 46°F). Use within 12 hours of reconstitution. Contains no preservative. Discard unused portion.

Manufactured by:

Emcure Pharmaceuticals Ltd.,

Hinjwadi, Pune, India.

Manufactured for:

Heritage Pharmaceuticals Inc.

Eatontown, NJ 07724

1.866.901.DRUG (3784)

Rev. 11/14

Package label.principal display panel

Acetazolamide for Injection USP

500 mg

FOR IV USE

NDC 23155-313-31

Rx only

Each vial contains: Acetazolamide Sodium equivalent to 500 mg Acetazolamide USP and pH adjusted to approximately 9.6 with Sodium Hydroxide NF and, if necessary, Hydrochloric Acid NF.

Store at 20° to 25°C (68° to 77°F); excursions permitted between 15° to 30°C (59° to 86°F) [see USP Controlled Room Temperature].

Store reconstituted solution in refrigerator at 2° to 8°C (36° to 46°F).

Use within 12 hours of reconstitution.

Must be reconstituted. See insert.

Discard unused portion.

Manufactured by:

Emcure Pharmaceuticals Ltd.,

Hinjwadi, Pune, India.

Manufactured for:

Heritage Pharmaceuticals Inc.

Eatontown, NJ 07724

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Capsule Extended Release 12 Hour, Oral:

Diamox Sequels: 500 mg

Generic: 500 mg

Solution Reconstituted, Injection [preservative free]:

Generic: 500 mg (1 ea)

Tablet, Oral:

Generic: 125 mg, 250 mg

Brand Names U.S.

  • Diamox Sequels

Dosing Renal Impairment

Note: Use is contraindicated in marked renal impairment; creatinine clearance cutoff not specified in manufacturer’s labeling.

CrCl 10-50 mL/minute: Administer every 12 hours.

CrCl <10 mL/minute: Avoid use.

Hemodialysis: Moderately dialyzable (20% to 50%).

Peritoneal dialysis: Supplemental dose is not necessary (Schwenk, 1994).

Warnings/Precautions

Concerns related to adverse effects:

• CNS effects: Impairment of mental alertness and/or physical coordination may occur.

• Sulfonamide (“sulfa”) allergy: The FDA-approved product labeling for many medications containing a sulfonamide chemical group includes a broad contraindication in patients with a prior allergic reaction to sulfonamides. There is a potential for cross-reactivity between members of a specific class (eg, two antibiotic sulfonamides). However, concerns for cross-reactivity have previously extended to all compounds containing the sulfonamide structure (SO2NH2). An expanded understanding of allergic mechanisms indicates cross-reactivity between antibiotic sulfonamides and nonantibiotic sulfonamides may not occur or at the very least this potential is extremely low (Brackett 2004; Johnson 2005; Slatore 2004; Tornero 2004). In particular, mechanisms of cross-reaction due to antibody production (anaphylaxis) are unlikely to occur with nonantibiotic sulfonamides. T-cell-mediated (type IV) reactions (eg, maculopapular rash) are less well understood and it is not possible to completely exclude this potential based on current insights. In cases where prior reactions were severe (Stevens-Johnson syndrome/TEN), some clinicians choose to avoid exposure to these classes.

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; may worsen acidosis.

Concurrent drug therapy issues:

• Aspirin (high dose): Use with caution or avoid in patients taking high-dose aspirin concurrently; may lead to severe adverse effects including tachypnea, anorexia, lethargy, coma, and death.

Special populations:

• Elderly: Use with caution in the elderly; may be more sensitive to side effects.

Other warnings/precautions:

• Appropriate use: Increasing the dose does not increase diuresis and may increase the incidence of drowsiness and/or paresthesia; often results in a reduction of diuresis.

• IM administration: Painful because of the alkaline pH of the drug; use by this route is not recommended.

Pregnancy Risk Factor C Pregnancy Considerations

Adverse events have been observed in animal reproduction studies. Limited data is available following the use of acetazolamide in pregnant women for the treatment of idiopathic intracranial hypertension (Falardeau, 2013; Kesler, 2013).

Pregnant women exposed to acetazolamide during pregnancy for the treatment of seizure disorders are encouraged to enroll themselves into the AED Pregnancy Registry by calling 1-888-233-2334. Additional information is available at aedpregnancyregistry.org

Acetazolamide Food Interactions

Medications can interact with certain foods. In some cases, this may be harmful and your doctor may advise you to avoid certain foods. In the case of acetazolamide, there are no specific foods that you must exclude from your diet when receiving this medication.

Inform MD

Before taking acetazolamide, tell your doctor about all of your medical conditions. Especially tell your doctor if you:

  • are allergic to acetazolamide or to any ingredient in acetazolamide
  • have a sulfonamide allergy
  • have liver problems
  • have kidney problems
  • have lung problems
  • have adrenal gland problems
  • have chronic non-congestive angle-closure glaucoma
  • are pregnant or breastfeeding

Tell your doctor about all the medicines you take including prescription and non-prescription medicines, vitamins, and herbal supplements.

Acetazolamide Usage

Take acetazolamide exactly as prescribed.

This medication comes in a tablet form and can be given up to four times a day.

This medication comes in an extended release capsule form and is taken up to two times a day, with or without food.

  • Do not chew, divide, or break acetazolamide capsules. Swallow capsules whole.

Acetazolamide also available in an injectable form to be given directly into a vein (IV) by a healthcare professional.

If you miss a dose, take the missed dose as soon as you remember. If it is almost time for the next dose, skip the missed dose and take your next dose at the regular time. Do not take two doses of acetazolamide at the same time.

Acetazolamide FDA Warning

Warning:

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.

Usual Pediatric Dose for Acute Mountain Sickness

12 years or older:
Extended-release capsules: 500 mg orally once or twice a day

Guideline dose (immediate-release): 2.5 mg/kg orally every 12 hours
Maximum: 125 mg per dose

Comments:
-Therapy should be initiated 24 to 48 hours before ascent and continued for 48 hours while at high altitude, or longer as necessary to control symptoms.
-Guideline dose is from the Wilderness Medical Society Consensus Guidelines; according to Wilderness Medical Society Consensus Guidelines, higher doses are effective but they are associated with more frequent and/or increased side effects.

Use: For the prevention or amelioration of symptoms associated with acute mountain sickness despite gradual ascent.

Other Comments

Administration advice:
-For oral or IV administration; IM administration is not recommended

Reconstitution/preparation techniques:
-Reconstitute with sterile water for injection (5 mL for 500 mg vial)
-Reconstituted solutions maintain chemical and physical properties for 3 days under refrigeration (2C to 8C [36F to 46F]) or 12 hours at room temperature (20C to 25C [68F to 77F])
-Manufacturer recommendation: Refrigerate reconstituted solutions, use within 12 hours of reconstitution

General:
-The dose used to treat congestive heart failure and drug induced edema differs considerably from that used to treat glaucoma and epilepsy as dependence on carbonic anhydrase inhibition in the kidney requires intermittent dosing to allow recovery from inhibitory effect.
-Adverse effects common to sulfonamide derivatives may occur with this drug.

Monitoring:
-CBC and platelet count: Obtain at baseline and check periodically during therapy
-Electrolytes: Periodically check, especially with long term use.

Patient advice:
-Patients should be instructed that this drug may cause drowsiness, fatigue, and myopia and that they should avoid activities such as driving or operating machinery until they know how this drug affects them.
-Patients should be instructed to report skin reactions or any symptoms of blood dyscrasias such as fatigue, shortness of breath, and bruising to their health care provider.
-Patients with diabetes or impaired glucose tolerance should be advised that this drug may affect their blood d glucose; reports of both high and low blood sugars have been received.

Acetazolamide Levels and Effects while Breastfeeding

Summary of Use during Lactation

Limited information indicates that maternal doses of acetazolamide up to 1000 mg daily produce low levels in milk and would not be expected to cause any adverse effects in breastfed infants.

Drug Levels

Maternal Levels. A woman who was 6 days postpartum was given a sustained-release acetazolamide (Diamox Sequels) 500 mg twice daily by mouth for increased intraocular pressure. Milk acetazolamide levels ranged from 1.3 to 2.1 mg/L from 1 to 9 hours after the dose. The authors estimated that the infant received a daily dose of 0.6 mg, which was less than 0.7% of the maternal weight-adjusted dosage.[1]

Infant Levels.A 10-day old breastfed (extent not stated) infant whose mother was taking sustained-release acetazolamide (Diamox Sequels) 500 mg twice daily from day 6 postpartum. The infant's acetazolamide plasma levels were 0.2, 0.6 and 0.2 mg/L at 2, 3.5 and 12 hours after the maternal dose. These levels averaged 1.5% of 3 maternal plasma levels taken on the same day.[1]

Effects in Breastfed Infants

A breastfed (extent not stated) infant whose mother was taking sustained-release acetazolamide (Diamox Sequels) 500 mg twice daily exhibited no apparent adverse effects related to acetazolamide from day 6 to day 10 postpartum.[1]

A mother who was taking acetazolamide 250 mg orally twice daily as well as using 2 drops of timolol 0.5% eye drops daily and pilocarpine eye drops twice daily delivered a preterm infant at 36 weeks of gestation. The infant began 5 months of exclusive breastfeeding at 6 hours after birth. On day 2, the infant developed electrolyte abnormalities consisting of hypocalcemia, hypomagnesemia, and metabolic acidosis. The infant was treated with oral calcium gluconate and a single dose of intramuscular magnesium sulfate. Despite continued breastfeeding and maternal drug therapy, the infant's mild metabolic acidosis disappeared on day 4 of life and the infant was gaining weight normally at 1, 3 and 8 months, but had mild hypotonicity. The authors considered the metabolic effects to be caused by transplacental passage of acetazolamide that resolved despite the infant being breastfed. The infant gained weight adequately during breastfeeding, but had some mild, residual hypertonicity of the lower limbs requiring physical therapy.[2]

References

1. Soderman P, Hartvig P, Fagerlund C. Acetazolamide excretion into human breast milk. Br J Clin Pharmacol. 1984;17:599-600. Letter. PMID: 6733009

2. Merlob P, Litwin A, Mor N. Possible association between acetazolamide administration during pregnancy and metabolic disorders in the newborn. Eur J Obstet Gynecol Reprod Biol. 1990;35:85-8. PMID: 2311821

3. Bedrosian L, Erzurumlu K, Levine LS. Acetazolamide (Diamox) in the inhibition of postpartum breast engorgement. N Y State J Med. 1957;57:3997-8. PMID: 13493780

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