Acetazolamide

CLASSIFICATION: 

Anticonvulsant, Carbonic Anhydrase Inhibitor, Diuretic.

INDICATIONS AND USAGE: Treatment of glaucoma (chronic simple open-angle, secondary glaucoma, preoperatively in acute angle-closure); drug-induced edema or edema due to congestive heart failure (adjunctive therapy; I.V. and immediate release dosage forms); centrencephalic epilepsies (I.V. and immediate release dosage forms); prevention or amelioration of symptoms associated with acute mountain sickness (immediate and extended release dosage forms)

DOSAGE AND ADMINISTRATION: 

Adult:

Oral: Manufacturer's labeling: 500-1000 mg/day in divided doses every 8-12 hours (immediate release tablets) or divided every 12-24 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 2-3 days or if descent initiated.

Edema: Oral, I.V.: 250-375 mg once daily

Epilepsy: Oral: 8-30 mg/kg/day in divided doses. A lower dosing range of 4-16 mg/kg/day in 1-4 divided doses has also been recommended; maximum dose: 30 mg/kg/day or 1 g/day.

Glaucoma: Oral, I.V.:

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

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

Metabolic alkalosis (unlabeled use): I.V.: 500 mg as a single dose; reassess need based upon acid-base status Respiratory stimulant in stable hypercapnic COPD (unlabeled use): Oral: 250 mg twice daily

Geriatric

Oral: Initial doses should begin at the low end of the dosage range.

Renal Impairment

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

Clcr <10 mL/minute: Avoid use.

MECHANISM OF ACTION:

Acetazolamide reversibly inhibits the enzyme carbonic anhydrase, resulting in reduction of hydrogen ion secretion at renal tubule and an increased renal excretion of Na, K, bicarbonate, and water. It decreases the production of aqueous humour and inhibits carbonic anhydrase in CNS to retard abnormal and excessive discharge from CNS neurons

Acetazolamide MOA

SIDE EFFECTS:  

• Cardiovascular: Flushing
• Central nervous system: Ataxia, confusion, convulsions, depression, dizziness, drowsiness, excitement, fatigue, fever, headache, malaise
• Dermatologic: Allergic skin reactions, photosensitivity, Stevens-Johnson syndrome, toxic epidermal necrolysis, urticaria
• Endocrine & metabolic: Electrolyte imbalance, growth retardation (children), hyperglycemia, hypoglycemia, hypokalemia, hyponatremia, metabolic acidosis
• Gastrointestinal: Appetite decreased, diarrhea, melena, nausea, taste alteration, vomiting
• Genitourinary: Crystalluria, glycosuria, hematuria, polyuria, renal failure
• Hematologic: Agranulocytosis, aplastic anemia, leukopenia, thrombocytopenia, thrombocytopenic purpura
• Hepatic: Cholestatic jaundice, fulminant hepatic necrosis, hepatic insufficiency, liver function tests abnormal
• Local: Pain at injection site
• Neuromuscular & skeletal: Flaccid paralysis, paresthesia
• Ocular: Myopia
• Otic: Hearing disturbance, tinnitus
• Miscellaneous: Anaphylaxis

PREGNANCY RISK FACTORS: C

CONTRAINDICATIONS:

• Use contraindicated in patients with cirrhosis or marked liver disease or dysfunction.
• Hyperchloremic acidosis
• Impaired kidney function
• Hypersensitivity to acetazolamide or other sulfonamides.
• Marked liver disease or impairment of liver function, including cirrhosis because of the risk of development of hepatic encephalopathy. Acetazolamide decreases ammonia clearance.
• Adrenal insufficiency
• Hyponatremia (low blood sodium)
• Hypokalemia (low blood potassium)

DRUG INTERACTIONS:

1. Amphitamines: 
due to the fact it increases the pH of the renal tubular urine, hence reducing the clearance of amphetamines.
2. Other carbonic anhydrase inhibitors: 

potential for additive inhibitory effects on carbonic anhydrase and hence potential for toxicity.
3. Ciclosporin: 

may increase plasma levels of ciclosporin.
4. Hypoglycemics:

Acetazolamide can both increase or decrease blood glucose levels.
5. Lithium: 

Increases excretion, hence reducing therapeutic effect.
6. Methenamine compounds: 

Reduces the urinary secretion of methenamines.
7. Phenytoin: 

Reduces phenytoin secretion, hence increasing the potential for toxicity.
8. Primidone: 

Reduces plasma levels of primidone. Hence reducing anticonvulsant effect.
9. Quinidine: 

Reduces urinary secretion of quinidine, hence increasing the potential for toxicity.
10. Salicylates: 

Potential for severe toxicity.
11. Sodium bicarbonates: 

Potential for kidney stone formation.

12. Anticoagulants & 

cardiac glycosides: 

May have their effects potentiated by acetazolamide

BRANDS

• Aceact 
• Acetamide 
• Acetamin
• Acetariv
• Aceta-SR
• Acetazolamide
• ACMox
• Actamid
• Actamide
• Actazid
• Avva
• Avva SR
• Axytex
• Diamox
• Iopar - Sr