Acetazolamide

Name: Acetazolamide

Acetazolamide Interactions

Discuss all your medications with your doctor and pharmacist before taking acetazolamide.

This includes prescription and over-the-counter drugs, vitamins and other dietary supplements (nutritional shakes, protein powders, herbal remedies, etc.), and any illegal or recreational drugs.

You shouldn't take acetazolamide if you're taking the following drugs:

  • Drugs that contain topiramate, like Topamax, Trokendi XR, Qsymia, or Qudexy XR
  • Eye drops that contain brinzolamide, like Azopt or Simbrina
  • Salicylates like aspirin, Doan's Pills (magnesium salicylate), or Pepto-Bismol (bismuth subsalicylate)
  • Stimulants like amphetamine, dextroamphetamine, or Vyvanse (lisdexamfetamine)

Other drugs that may have serious interactions with acetazolamide include:

  • Antibiotics like Avelox (moxifloxacin), Biaxin (clarithromycin), Ketek (telithromycin), or Z-pak or Zithromax (azithyromycin)
  • Antidepressants like doxepin, Elavil (amitriptyline), Effexor (venlafaxine), or Pristiq (desvenlafaxine)
  • Cancer drugs like Leupron or Eligard (leuprolide), Paraplatin (carboplatin), Sprycel (dasatinib), or Tykerb (lapatinib)
  • Diabetes drugs like Jardiance (empagliflozin) or Tanzeum (albiflutide)
  • Diuretics (water pills) like Bumex (bumetanide), Microzide (hydrochlorothiazide), or Thalitone (chlorthalidone)
  • Heartburn drugs like Aciphex (rabeprazole), Dexilant (dexlansoprazole), or Prilosec (omeprazole)
  • Lanoxin (digoxin)
  • Mood-disorder drugs like Geodon (ziprasidone), Lithobid (lithium), or Seroquel (quetiapine)
  • Steroids like cortisone, hydrocortisone, budesonide, or methylprednisolone

Acetazolamide and Alcohol

You should avoid or limit alcohol consumption while taking acetazolamide.

Acetazolamide and Grapefruit Juice

You should avoid eating grapefruit or drinking grapefruit juice while taking acetazolamide.

Grapefruit slows down the body's breakdown of acetazolamide, which may cause blood levels of the drug to become dangerously high.

Acetazolamide Dosage

Acetazolamide comes in extended-release capsules that contain 500 milligrams (mg) of the drug, and regular-release tablets of 125 mg, 250 mg, and 500 mg.

The drug is also available in liquid form for injection, but this form is used mainly in hospital settings, with the dose depending on the weight of the patient.

You shouldn't take more than 1 gram (1,000 mg) of acetazolamide per day without your doctor's permission.

Acetazolamide Overdose

If you suspect an overdose of acetazolamide, call 911 or contact your local poison control center at 800-222-1222 right away.

Missed Dose of Acetazolamide

If you miss a dose of acetazolamide, take it as soon as you remember.

But if it's almost time for your next dose, skip the missed dose and continue on your regular medication schedule.

Don't double up on doses to make up for a missed one.

How should I take acetazolamide?

Follow all directions on your prescription label. Your doctor may occasionally change your dose to make sure you get the best results. Do not use this medicine in larger or smaller amounts or for longer than recommended.

Your dose of this medicine will depend on the condition you are treating. If you take acetazolamide for congestive heart failure, your doctor may tell you to skip your medication for a day. Follow your doctor's dosing instructions very carefully.

Take this medicine with a full glass of water.

While using acetazolamide, you may need frequent blood tests.

Acetazolamide may be only part of a complete treatment program that may also include other medications. Follow your doctor's instructions very closely.

Store at room temperature away from moisture and heat. Keep the bottle tightly closed when not in use.

What should I avoid while taking acetazolamide?

This medicine may impair your thinking or reactions. Be careful if you drive or do anything that requires you to be alert.

Avoid exposure to sunlight or tanning beds. Acetazolamide can make you sunburn more easily. Wear protective clothing and use sunscreen (SPF 30 or higher) when you are outdoors.

What other drugs will affect acetazolamide?

Other drugs may interact with acetazolamide, including prescription and over-the-counter medicines, vitamins, and herbal products. Tell each of your health care providers about all medicines you use now and any medicine you start or stop using.

Cautions for Acetazolamide

Contraindications

  • Marked impairment of hepatic function.c d e Cirrhosis.c d e (See Hepatic Impairment under Cautions.)

  • Depressed serum concentrations of sodium and/or potassium.c d e

  • Adrenocortical insufficiency.c d e

  • Hyperchloremic acidosis.c d e

  • Marked impairment of renal function.c d e

  • Long-term treatment of angle-closure glaucoma; further closure of the angle may occur while worsening of glaucoma is masked by lower IOP.b c d e

  • Hypersensitivity to acetazolamide or any ingredients in the formulation.c d e

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.b c d e

Discontinue if signs of hypersensitivity, blood dyscrasias, or other serious reactions occur.b c e

General Precautions

CNS Effects

Drowsiness and/or paresthesia reported with high dosages.b c d e

Respiratory Effects

Caution in patients with pulmonary obstruction, emphysema, or advanced pulmonary disease where alveolar ventilation may be impaired.b c d e Acetazolamide may precipitate or aggravate acidosis in these patients.c d e

Laboratory Monitoring

Monitor for hematologic reactions associated with sulfonamides; obtain a CBC and platelet count before therapy and periodically during therapy.c d e Discontinue the drug if clinically important changes occur.c d e

Monitor serum electrolytes periodically for electrolyte imbalances (i.e., hyponatremia, hypokalemia, metabolic acidosis).c d e

Glucose Concentrations

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

Specific Populations

Pregnancy

Category C.c d e

Lactation

Discontinue nursing or the drug.c d e

Pediatric Use

Conventional tablets and parenteral preparation: Manufacturers state that safety and efficacy not established.c e

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

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

Geriatric Use

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

Hepatic Impairment

Avoid use in patients with marked hepatic impairment, including those with cirrhosis, because of the risk of developing hepatic encephalopathy.c d e (See Contraindications.)

Renal Impairment

Avoid use in patients with marked renal impairment.c d e (See Contraindications.)

Common Adverse Effects

Paresthesias, hearing dysfunction or tinnitus, anorexia, altered taste, nausea, vomiting, diarrhea, polyuria, drowsiness, confusion.c e

Acetazolamide - Clinical Pharmacology

Acetazolamide is a potent carbonic anhydrase inhibitor, effective in the control of fluid secretion (e.g., some types of glaucoma), in the treatment of certain convulsive disorders (e.g., epilepsy) and in the promotion of diuresis in instances of abnormal fluid retention (e.g., cardiac edema).

Acetazolamide is not a mercurial diuretic. Rather, it is a nonbacteriostatic sulfonamide possessing a chemical structure and pharmacological activity distinctly different from the bacteriostatic sulfonamides.

Acetazolamide is an enzyme inhibitor that acts specifically on carbonic anhydrase, the enzyme that catalyzes the reversible reaction involving the hydration of carbon dioxide and the dehydration of carbonic acid. In the eye, this inhibitory action of Acetazolamide decreases the secretion of aqueous humor and results in a drop in intraocular pressure, a reaction considered desirable in cases of glaucoma and even in certain nonglaucomatous conditions. Evidence seems to indicate that Acetazolamide has utility as an adjuvant in the treatment of certain dysfunctions of the central nervous system (e.g., epilepsy). Inhibition of carbonic anhydrase in this area appears to retard abnormal, paroxysmal, excessive discharge from central nervous system neurons. The diuretic effect of Acetazolamide is due to its action in the kidney on the reversible reaction involving hydration of carbon dioxide and dehydration of carbonic acid.

The result is renal loss of HCO3 ion, which carries out sodium, water, and potassium. Alkalinization of the urine and promotion of diuresis are thus effected. Alteration in ammonia metabolism occurs due to increased reabsorption of ammonia by the renal tubules as a result of urinary alkalinization.

Off Label Uses

Familial periodic paralysis

Limited data from controlled trials and case reports suggest that acetazolamide may have some benefits in the treatment of hypokalemic and hyperkalemic periodic paralysis. Studies have shown that acetazolamide improves muscle strength in patients with hypokalemic periodic paralysis. In patients with hyperkalemic periodic paralysis, acetazolamide may decrease the steady-state potassium exchange rates and increase potassium uptake by other tissues, resulting in protection from hyperkalemic paralysis. Further controlled studies enrolling more patients are needed to determine the role of acetazolamide in the treatment of familial periodic paralysis.

Metabolic alkalosis

Data from a randomized placebo-controlled, double blinded study in critically-ill medical patients [Mazur 1999] and an open label, uncontrolled, unblinded study [Marik 1991] supports the use of acetazolamide in the treatment of metabolic alkalosis. Additional trials may be necessary to further define the role of acetazolamide in this condition.

Prevention of cystine renal calculi (adjunctive therapy)

Data from a limited number of patients in a retrospective review suggest that acetazolamide may have some benefits as adjunctive therapy for urinary alkalinization in the prevention of cystine renal calculi formation in patients who are recalcitrant to potassium citrate therapy. Additional data may be necessary to further define the role of acetazolamide in this condition.

Respiratory stimulant in stable hypercapnic COPD

Data from a randomized, double-blind, crossover study supports the use of acetazolamide as a respiratory stimulant in the treatment of stable hypercapnic COPD [Wagenaar 2003]. Additional trials may be necessary to further define the role of acetazolamide in this condition.

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; long-term use in noncongestive angle-closure glaucoma

Note: Although the FDA approved product labeling states this medication is contraindicated with other sulfonamide-containing drug classes, the scientific basis of this statement has been challenged. See “Warnings/Precautions” for more detail.

Dosing Pediatric

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

Epilepsy: Oral: Refer to adult dosing.

Altitude illness: Oral:

Prevention: 2.5 mg/kg/dose every 12 hours started either the day before (preferred) or on the day of ascent and may be discontinued after staying at the same elevation for 2-3 days or if descent initiated; maximum dose: 125 mg/dose (Luks, 2010). Note: The International Society for Mountain Medicine does not recommend prophylaxis in children except in the rare circumstance of unavoidable rapid ascent or in children with known previous susceptibility to acute mountain sickness (Pollard, 2001).

Treatment: 2.5 mg/kg/dose every 8-12 hours; maximum dose: 250 mg/dose. Note: With high altitude cerebral edema, dexamethasone is the primary treatment; however, acetazolamide may be used adjunctively with the same treatment dose (Luks, 2010; Pollard, 2001).

Reconstitution

Injection: Reconstitute with at least 5 mL sterile water to provide a solution containing not more than 100 mg/mL.

Extemporaneously Prepared

A 25 mg/mL oral suspension may be made with tablets and either a 1:1 mixture of Ora-Sweet® and Ora-Plus® or a 1:1 mixture of Ora-Sweet® SF and Ora-Plus®. Crush twelve 250 mg tablets in a mortar and reduce to a fine powder. Add small portions of chosen vehicle and mix to a uniform paste; mix while adding the vehicle in incremental proportions to almost 120 mL; transfer to a calibrated bottle, rinse mortar with vehicle, and add quantity of vehicle sufficient to make 120 mL. Label “shake well” and “refrigerate”. Stable for 60 days (Allen, 1996). When diluted in 120 mL solution of cherry syrup concentrate diluted 1:4 with simple syrup, NF, it is stable 60 days refrigerated (preferred) or at room temperature (Nahata, 2004).

Allen LV Jr and Erickson MA 3rd, "Stability of Acetazolamide, Allopurinol, Azathioprine, Clonazepam, and Flucytosine in Extemporaneously Compounded Oral Liquids," Am J Health Syst Pharm, 1996, 53(16):1944-9.8862208Nahata MC, Pai VB, and Hipple TF, Pediatric Drug Formulations, 5th ed, Cincinnati, OH: Harvey Whitney Books Co, 2004.

Administration

Oral: 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.

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

IV: Direct IV injection is the preferred parenteral route of administration. Specific IV push rates are not provided in the manufacturer’s labeling. However, an IV push rate of up to 500 mg over 3 minutes has been reported in a clinical trial (Mazur, 1999). Additionally, a study to assess cerebrovascular reserve used a rapid IV push of up to 1 g over ≤1 minute (Piepgras, 1990).

Monitoring Parameters

Intraocular pressure; serum electrolytes, periodic CBC with differential; monitor growth in pediatric patients

Acetazolamide Brand Names

Acetazolamide may be found in some form under the following brand names:

  • Diamox

Side Effects of Acetazolamide

Serious side effects have been reported with acetazolamide. See the “Drug Precautions” section.

Common side effects of acetazolamide are:

  • rash
  • fever
  • reduced field of vision
  • upset stomach
  • vomiting
  • loss of appetite
  • change in taste

This is not a complete list of acetazolamide side effects. Ask your doctor or pharmacist for more information.

Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

Other Requirements

  • Store acetazolamide capsules and tablets at room temperature between 20° to 25°C (68° to 77°F).
  • Keep this and all medicines out of the reach of children.

For the Consumer

Applies to acetazolamide: oral capsules, oral tablets, parenteral powder for injection

Side effects include:

Paresthesias, hearing dysfunction or tinnitus, anorexia, altered taste, nausea, vomiting, diarrhea, polyuria, drowsiness, confusion.

Usual Adult Dose for Glaucoma

Open-Angle Glaucoma:
-Immediate-release (IR) tablets: 250 to 1000 mg orally per day; amounts over 250 mg should be administered in divided doses
-Extended-release (ER) capsules: 500 mg orally 2 times a day
Maintenance: Adjust doses individually based on symptomatology and ocular tension; for patients inadequately controlled on ER capsules 1 g/day, may supplement with IR tablets
-Doses in excess of 1 g/24 hours generally do not produce increased effects

Preoperatively in Closed-Angle Glaucoma:
-Various regimens have been used including: 250 mg orally every 4 hours; 250 mg orally twice a day; OR 500 mg orally followed by 125 mg or 250 mg orally every 4 hours

Comments:
-In acute cases, IV therapy (at same oral dosage) has been used for rapid relief of ocular tension.
-A complementary effect has been observed when used in conjunction with miotics or mydriatics.

Uses: For the adjunctive treatment of chronic simple (open-angle) glaucoma, secondary glaucoma, and preoperatively in acute angle-closure glaucoma where a delay of surgery is desirable so as to decrease intraocular pressure.

Usual Adult Dose for Glaucoma (Open Angle)

Open-Angle Glaucoma:
-Immediate-release (IR) tablets: 250 to 1000 mg orally per day; amounts over 250 mg should be administered in divided doses
-Extended-release (ER) capsules: 500 mg orally 2 times a day
Maintenance: Adjust doses individually based on symptomatology and ocular tension; for patients inadequately controlled on ER capsules 1 g/day, may supplement with IR tablets
-Doses in excess of 1 g/24 hours generally do not produce increased effects

Preoperatively in Closed-Angle Glaucoma:
-Various regimens have been used including: 250 mg orally every 4 hours; 250 mg orally twice a day; OR 500 mg orally followed by 125 mg or 250 mg orally every 4 hours

Comments:
-In acute cases, IV therapy (at same oral dosage) has been used for rapid relief of ocular tension.
-A complementary effect has been observed when used in conjunction with miotics or mydriatics.

Uses: For the adjunctive treatment of chronic simple (open-angle) glaucoma, secondary glaucoma, and preoperatively in acute angle-closure glaucoma where a delay of surgery is desirable so as to decrease intraocular pressure.

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