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Acetazolamide

Pronunciation

Pronunciation: a-seet-a-ZOLE-a-mide
Class: Anticonvulsant, Carbonic anhydrase inhibitor

Trade Names

Acetazolamide
- Tablets 125 mg
- Tablets 250 mg
- Injection, lyophilized powder for solution 500 mg

Diamox Sequels
- Capsules, ER 500 mg

APO-Acetazolamide (Canada)

Pharmacology

Inhibits carbonic anhydrase enzyme, reducing rate of aqueous humor formation and thus lowering IOP; produces diuretic effect; retards neuronal conduction in brain.

Slideshow: Flashback: FDA Drug Approvals 2013

Pharmacokinetics

Absorption

ER T max is 3 to 6 h. Immediate-release T max is 1 to 4 h.

Duration

ER is 18 to 24 h; immediate-release is 8 to 12 h.

Indications and Usage

Prevention or lessening of symptoms associated with acute mountain sickness (oral only); adjunctive treatment of chronic simple (open-angle) glaucoma and secondary glaucoma; preoperative treatment of acute congestive (closed-angle) glaucoma; adjunctive treatment of centrencephalic epilepsies (eg, petit mal, generalized seizures); edema caused by CHF and drug-induced edema (tablet and IV only).

Unlabeled Uses

Familial periodic paralysis; malignant glaucoma; prevention of migraine.

Contraindications

Hypersensitivity to any ingredients in the formulations; depressed sodium and/or potassium serum levels; marked kidney and liver disease or dysfunction; suprarenal gland failure; hyperchloremic acidosis; cirrhosis; long-term use in chronic noncongestive angle-closure glaucoma.

Dosage and Administration

Acute Mountain Sickness
Adults and Children 12 yr of age and older

PO 500 to 1,000 mg per day in divided doses twice daily. In circumstances of rapid ascent, 1,000 mg is recommended. It is preferable to initiate dosing 24 to 48 h before ascent. Continue for 48 h while at high altitude, or longer as necessary to control symptoms.

Chronic Simple (Open-Angle) Glaucoma
Adults

PO Tablets / IV 250 mg to 1 g per day, usually in divided doses for amounts above 250 mg.

Adults and Children 12 yr of age and older

PO ER capsules 500 mg 2 times daily. It may be necessary to adjust the dose, but it has usually been found that a dose in excess of 1 g does not produce an increased effect.

Diuresis in CHF
Adults

PO Tablets / IV Initially 250 to 375 mg (5 mg/kg) every morning; then give on alternate days or for 2 days alternating with 1 day of rest.

Drug-Induced Edema
Adults

PO Tablets / IV 250 to 375 mg daily for 1 to 2 days, alternating with a day of rest.

Secondary Glaucoma/Acute Congestive Closed-Angle Glaucoma
Adults

PO Tablets / IV 250 mg every 4 h or 250 mg twice daily. In some acute cases, initially administer 500 mg, then 125 to 250 mg every 4 h.

Adults and Children 12 yr of age and younger

ER capsules 500 mg 2 times daily. It may be necessary to adjust the dose, but it has usually been found that a dose in excess of 1 g does not produce an increased effect.

Seizures
Adults

PO Tablets / IV 8 to 30 mg/kg per day in divided doses; optimum range is 375 to 1,000 mg/day. When drug is given in combination with other anticonvulsants, initial dosage is 250 mg daily.

General Advice

  • Direct IV administration is preferred. IM administration is not recommended.
  • Reconstitute following manufacturer's guidelines using at least 5 mL of sterile water for injection.
  • Do not administer if particulate matter, cloudiness, or discoloration is noted.
  • Discard any unused solution.

Storage/Stability

Store ER capsules at 68° to 77°F. Store tablets and powder for injection at 59° to 86°F. Store reconstituted injectable solution at 36° to 46°F for up to 3 days or use within 12 h of reconstitution if stored at 59° to 86°F.

Drug Interactions

Amphetamines

By alkalinizing the urine, the urinary excretion of amphetamines is decreased, enhancing the magnitude and duration of effects. Avoid coadministration, especially in overdose situations.

Beta-blockers

Coadministration may cause severe mixed acidosis in patients with respiratory disorders. Use with caution. If acidosis occurs, discontinue one or both drugs.

Carbonic anhydrase inhibitors (eg, methazolamide)

Because of additive effects, avoid other carbonic anhydrase inhibitors.

Cyclosporine

Cyclosporine concentrations may be elevated, increasing the pharmacologic effect and adverse reactions. Monitor cyclosporine concentrations and adjust the cyclosporine dose as needed.

Folic acid antagonists

The pharmacologic effects of folic acid antagonists may be increased. Use with caution.

Hydantoins (phenytoin)

Phenytoin serum concentrations may be elevated, increasing the pharmacologic effects and risk of toxicity. Use with caution. Monitor phenytoin concentrations and the patient's response. Adjust the phenytoin dose as needed.

Lithium

Lithium serum concentrations may be reduced, decreasing the therapeutic response. Monitor lithium concentrations and the patient's response. If an interaction is suspected, adjust the lithium dose as needed.

Methenamine

Acetazolamide may interfere with the antibacterial effect of methenamine. Avoid coadministration. Consider use of a urinary antimicrobial agent not affected by urinary alkalinization.

Primidone

Plasma concentrations of primidone and its metabolites may be reduced, decreasing the anticonvulsant effect. Use with caution when starting, stopping, or changing the dose of acetazolamide. If an interaction is suspected, consider use of an alternative anticonvulsant agent.

Quinidine

Quinidine serum levels may be increased. Because of urinary alkalinization, urinary excretion of quinidine is decreased, increasing the pharmacologic and toxic effects. Use with caution. Monitor quinidine concentrations and cardiac function when starting or stopping acetazolamide. Adjust the quinidine dose as needed.

Salicylates

May cause acetazolamide accumulation and toxicity, including CNS depression, and metabolic acidosis, coma, and death. Monitor salicylate concentrations, acid-base parameters, and CNS status. Adjust the acetazolamide dose as needed.

Sodium bicarbonate

Coadministration increases the risk of renal calculus formation. Avoid coadministration.

Topiramate

Concomitant use of topiramate with acetazolamide may increase the risk of kidney stone formation. Avoid coadministration.

Laboratory Test Interactions

Acetazolamide may give false positive or decreased values for urinary phenolsulfonphthalein and phenol red elimination values for urinary protein, serum non-protein, and serum uric acid. Acetazolamide may produce an increased level of crystals in the urine. Acetazolamide interferes with the high-performance liquid chromatography method of assay for theophylline. Because interference with the theophylline assay by acetazolamide depends on the solvent used in extraction, acetazolamide may not interfere with other theophylline assay methods.

Adverse Reactions

CNS

Ataxia, confusion, convulsions, depression, dizziness, drowsiness, excitement, headache, malaise, paresthesia.

EENT

Hearing disturbances, tinnitus, transient myopia.

GI

Diarrhea, loss of appetite, melena, nausea, taste alterations, vomiting.

Genitourinary

Crystalluria, glycosuria, hematuria, nephrolithiasis with long-term therapy, polyuria, renal failure.

Hematologic

Agranulocytosis, aplastic anemia, leukopenia, thrombocytopenic purpura.

Hepatic

Abnormal liver function, cholestatic jaundice, fulminant hepatic necrosis, hepatic insufficiency.

Hypersensitivity

Allergic skin reactions, including urticaria, Stevens-Johnson syndrome, TEN, photosensitivity; anaphylaxis.

Metabolic

Metabolic acidosis, electrolyte imbalance (hypokalemia, hyponatremia), hyperglycemia, hypoglycemia.

Miscellaneous

Fever, flaccid paralysis, flushing, growth retardation in children, injection-site pain.

Precautions

Warnings

Fatalities have occurred, although rarely, because of severe reactions to sulfonamides, including agranulocytosis, aplastic anemia, fulminant hepatic necrosis, Stevens-Johnson syndrome, TEN, 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 because anorexia, tachypnea, lethargy, coma, and death have been reported.


Monitor

Obtain a baseline CBC and platelet count 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.


Pregnancy

Category C .

Lactation

Undetermined.

Children

Safety and efficacy not established (tablets/IV); safety and efficacy not established in children younger than 12 yr of age (ER capsules).

Elderly

Metabolic acidosis, which can be severe, may occur in elderly patients with reduced renal function.

Hypersensitivity

Cross-sensitivity between acetazolamide, sulfonamides, and other sulfonamide derivatives is possible.

Renal Function

Use with caution.

Hazardous Tasks

Some adverse reactions, such as drowsiness, fatigue, and myopia, may impair the ability to drive and operate machinery.

Diabetes

Both increases and decreases in blood glucose have occurred.

Dose increases

Increasing dose does not augment diuresis, but may increase drowsiness and paresthesias.

Electrolyte imbalances

Hyponatremia, hypokalemia, and metabolic acidosis may occur.

Pulmonary conditions

Use in pulmonary obstruction and emphysema may aggravate or precipitate acidosis.

Overdosage

Symptoms

Acidosis, CNS effects, electrolyte imbalance.

Patient Information

  • Advise patient with glaucoma to continue to use other glaucoma medications prescribed by health care provider unless advised otherwise.
  • Advise patient with epilepsy to continue to use other antiepileptic drugs prescribed by health care provider unless advised otherwise.
  • Advise patient that urine production may increase following the first few doses of the medication and that this is normal and of no concern. Advise patient to inform health care provider if excessive urine production occurs.
  • Advise patient using medication for preventing symptoms of high altitude sickness that if rapid ascent produces symptoms of high altitude sickness, rapid descent is necessary.
  • Advise patient to discontinue therapy and contact health care provider immediately if any of the following occur: blood in urine, flank or loin pain, hives, itching, pallor, purple spots under the skin, rash, ringing in ears or hearing changes, sore throat, tingling or tremors in hands or feet, unexplained fever, unusual bleeding or bruising.
  • Advise patient to avoid unnecessary exposure to sunlight or tanning lamps and to use sunscreen and wear protective clothing to avoid photosensitivity reactions.
  • Advise patient that drug may cause drowsiness and to use caution while driving or performing other tasks requiring mental alertness until tolerance is determined.
  • Advise patients with diabetes that hyperglycemia or hypoglycemia may occur.

Copyright © 2009 Wolters Kluwer Health.

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