Acetazolamide

Acetazolamide is an antihypertensive agent belonging to Carbonic Anhydrase Inhibitor.

Acetazolamide is a carbonic anhydrase inhibitor used to treat edema from heart failure or medications, certain types of epilepsy, and glaucoma.

Acetazolamide is well absorbed. Acetazolamide is highly bound to plasma protein about 98%. Carbonic anhydrase inhibitors such as acetazolamide are avidly bound by carbonic anhydrase; consequently, tissues rich in enzymes, such as kidneys and RBC, will have higher concentrations of carbonic anhydrase inhibitors (acetazolamide). Acetazolamide does not undergo metabolic alteration. Plasma half-Life found to be approximately 6-9 hours. Renal excretion is the primary route of elimination about 90% is excreted by urine.

Acetazolamide shows common side effects like Diarrhoea, Vomiting, Loss of appetite, Numbness, tingling in arms or legs, Increased thirst, Increased urination frequency, Drowsiness, Headache, Fever and cough, yellowing of skin and eyes, Sore throat, unusual bleeding or bruising, altered blood glucose levels, change in taste/ Metallic taste, Decrease in sexual drive, etc.

Acetazolamide is available in the form of Oral Tablets, Oral Capsule and Powder for Injection.

Acetazolamide is available in India, US, UK, Canada, Singapore, China, Japan and Australia.

Acetazolamide belonging to the Carbonic Anhydrase Inhibitor, acts as an antihypertensive agent.

The anticonvulsant activity of Acetazolamide may depend on a direct inhibition of carbonic anhydrase in the CNS, which decreases carbon dioxide tension in the pulmonary alveoli, thus increasing arterial oxygen tension. The diuretic effect depends on the inhibition of carbonic anhydrase, causing a reduction in the availability of hydrogen ions for active transport in the renal tubule lumen. This leads to alkaline urine and an increase in the excretion of bicarbonate, sodium, potassium, and water.

The onset of action of Acetazolamide occurs within 1-1.5 hour (by Tablet), 2 hour (by Capsule), and 5-10min (by Intravenous).

The Duration of Action for Acetazolamide in the body is approximately 8-12 hours (by Tablet), 18-24 hour (by Capsule), and 4-5 hours (by Intravenous).

The Tmax was found within 1-4 hours (by mouth), 8-18 hour (by Capsule), and 15 min (Intravenous) following the administration of Acetazolamide.

Acetazolamide is available in the form of Oral Tablets, Oral Capsule and Powder for Injection.

Acetazolamide Oral Tablet and Oral Capsule taken by mouth. Usually once a day or twice a day.

Acetazolamide Powder for Injection by Intravenous once a day or twice a day.

Acetazolamide is a carbonic anhydrase inhibitor used to treat edema from heart failure or medications, certain types of epilepsy, and glaucoma. This medication can decrease headache, tiredness, nausea, dizziness, and shortness of breath that can occur when you climb quickly to high altitudes. It is particularly useful in situations when you cannot make a slow ascent. In addition, it is used off-label for central sleep apnea, Marfan syndrome, prevention of high-dose methotrexate nephrotoxicity, and prevention of contrast-induced nephropathy.

Acetazolamide is an antihypertensive agent belonging to Carbonic Anhydrase Inhibitor.

This medicine works by blocking the action of an enzyme called carbonic anhydrase in your body. This leads to a decrease in the production of fluid inside your eyes thereby reducing pressure within your eye. It also reduces the fluid buildup in your body, thereby reducing oedema. Acetazolamide is a carbonic anhydrase inhibitor used to treat edema from heart failure or medications, certain types of epilepsy, and glaucoma.

Acetazolamide is approved for use in the following clinical indications

• For adjunctive treatment of edema due to congestive heart failure; drug-induced edema.
• For Treatment of Centrencephalic epilepsies (petit mal, unlocalized seizures).
• Acetazolamide used in treatment of chronic simple (open-angle) glaucoma, secondary glaucoma, and preoperatively in acute angle-closure glaucoma where delay of surgery is desired in order to lower intraocular pressure.
• Acetazolamide is also indicated for the prevention or amelioration of symptoms associated with acute mountain sickness in climbers attempting rapid ascent and in those who are very susceptible to acute mountain sickness despite gradual ascent.

• Edema

Drug-Induced Edema

Initial dose: 250 to 375 mg orally/IV once a day

If after initial response there is a lack of response, hold therapy for a day

Maintenance dose: One dose every other day or once a day for 2 days alternating with a day of rest.

Congestive Heart Failure

For diuresis in congestive heart failure, the starting dose is usually 250 to 375 mg once daily in the morning (5 mg/kg). If after an initial response, the patient fails to continue to lose edema fluid, do not increase the dose but allow for kidney recovery by skipping medication for a day. Acetazolamide yields best diuretic results when given on alternate days, or for two days alternating with a day of rest.

• Acute Mountain Sickness

Adult Dose:

Dosage is 500 mg to 1000 mg daily, in divided doses using tablets or sustained-release capsules as appropriate. In circumstances of rapid ascent, such as in rescue or military operations, the higher dose level of 1000 mg is recommended. It is preferable to initiate dosing 24 to 28 hours before ascent and to continue for 48 hours while at high altitude, or longer as necessary to control symptoms.

Pediatric Dose:

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.

• Glaucoma

Adult Dose:

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.

Pediatric Dose:

12 years or older:

Extended-release (ER) capsules: 500 mg orally 2 times a day.

Comments: Doses in excess of 1 g/24 hours generally do not produce increased effects.

• Epilepsy

Initial dose: 8 to 30 mg/kg orally/IV in divided doses

Range: 375 to 1000 mg per day

Initial dose for patients on other anticonvulsants: 250 mg orally/IV once a day.

Acetazolamide is available in various strengths 125mg, 250mg and 500mg.

Acetazolamide is available in the form of Oral Tablets, Oral Capsule and Powder for Injection.

Drink plenty of liquids to prevent dehydration.

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

• Hypersensitivity reaction

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.

• Electrolyte imbalances

Acetazolamide treatment may cause electrolyte imbalances, including hyponatremia and hypokalemia, as well as metabolic acidosis. Therefore, periodic monitoring of serum electrolytes is recommended. Particular caution is recommended in patients with conditions that are associated with, or predispose a patient to, electrolyte and acid/base imbalances, such as patients with impaired renal, patients with diabetes mellitus, and patients with impaired alveolar ventilation.

• Concomitant Therapy

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

• In Patients with pulmonary obstruction or emphysema

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. Gradual ascent is desirable to try to avoid acute mountain sickness. If rapid ascent is undertaken and Acetazolamide is used, it should be noted that such use does not obviate the need for prompt descent if severe forms of high-altitude sickness occur, i.e., high altitude pulmonary edema (HAPE) or high-altitude cerebral edema.

• In Patients with diabetes mellitus

Both increases and decreases in blood glucose have been described in patients treated with acetazolamide. This should be taken into consideration in patients with impaired glucose tolerance or diabetes mellitus.

Consumption of alcohol is not recommended as drowsiness is caused by Acetazolamide.

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.

The use of Acetazolamide in pregnancy has not been recommended because of teratogenic effects in preclinical studies. But in a study of pregnant patients with idiopathic intracranial hypertension, no conclusive evidence of the adverse effects of acetazolamide during pregnancy was observed. Acetazolamide was a Category C drug under the prior FDA pregnancy categorization system and should only be used in pregnancy if the benefits outweigh the risks to the unborn baby. Consequently, clinicians should prescribe acetazolamide only when indicated.

No information available.

• Common Adverse effects

Anaphylaxis, fever, rash (including erythema multiforme, Steven-Johnson syndrome, toxic epidermal necrolysis), crystalluria, renal calculus, bone marrow depression, thrombocytopenic purpura, hemolytic anemia, leukopenia, pancytopenia, and agranulocytosis.

• Rare Adverse effects

Urticaria, melaena, hematuria, glycosuria, hepatic insufficiency, flaccid paralysis, photosensitivity and convulsions.

• Aspirin

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

• Phenytoin

Acetazolamide modifies phenytoin metabolism with increased serum levels of phenytoin. This may increase or enhance the occurrence of osteomalacia in some patients receiving chronic phenytoin therapy. Caution is advised in patients receiving chronic concomitant therapy.

• Primidone

By decreasing the gastrointestinal absorption of primidone, Acetazolamide may decrease serum concentrations of primidone and its metabolites, with a consequent possible decrease in anticonvulsant effect. Caution is advised when beginning, discontinuing, or changing the dose of Acetazolamide in patients receiving primidone.

• Carbonic anhydrase inhibitors

Because of possible additive effects with other carbonic anhydrase inhibitors, concomitant use is not advisable.

• Folic acid antagonists

Acetazolamide may increase the effects of other folic acid antagonists.

• Amphetamine

Acetazolamide decreases urinary excretion of amphetamine and may enhance the magnitude and duration of their effect.

• Quinidine

Acetazolamide reduces urinary excretion of quinidine and may enhance its effect.

• Methenamine

Acetazolamide may prevent the urinary antiseptic effect of methenamine.

• Lithium

Acetazolamide increases lithium excretion, and the lithium may be decreased.

• Sodium bicarbonate

Acetazolamide and sodium bicarbonate used concurrently increases the risk of renal calculus formation.

The common side of Acetazolamide include the following

• Common
  

Diarrhoea, Vomiting, Loss of appetite, Numbness, tingling in arms or legs, Increased thirst, Increased urination frequency, Drowsiness, Headache, Fever and cough, yellowing of skin and eyes, Sore throat, unusual bleeding or bruising, altered blood glucose levels, change in taste/ Metallic taste, Decrease in sexual drive.

• Rare

Confusion, Blood in urine, Ringing or buzzing in the ears, Abdominal pain, Severe skin rash and hives.

• 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 below the age of 12 years have not been established. Growth retardation has been reported in children receiving long-term therapy, believed secondary to chronic acidosis.

• Geriatric Use

Metabolic acidosis, which can be severe, may occur in the elderly with reduced renal function. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and concomitant disease or other drug therapy.

• No specific antidote is known. Treatment should be symptomatic and supportive.
• Electrolyte imbalance, development of an acidotic state, and central nervous system effects might be expected to occur. Serum electrolyte levels (particularly potassium) and blood pH levels should be monitored.
• Supportive measures are required to restore electrolyte and pH balance. The acidotic state can usually be corrected by the administration of bicarbonate.
• Despite its high intraerythrocytic distribution and plasma protein binding properties, Acetazolamide may be dialyzable. This may be particularly important in the management of Acetazolamide overdosage when complicated by the presence of renal failure.

Pharmacodynamic

Acetazolamide is a potent carbonic anhydrase inhibitor, effective in the control of fluid secretion, in the treatment of certain convulsive disorders and in the promotion of diuresis in instances of abnormal fluid retention. Acetazolamide is not a mercurial diuretic. Rather, it is a non-bacteriostatic sulfonamide possessing a chemical structure and pharmacological activity distinctly different from the bacteriostatic sulfonamides.

Pharmacokinetics

• Absorption

Well absorbed

• Distribution
  

Acetazolamide is highly bound to plasma protein about 98%. Carbonic anhydrase inhibitors such as acetazolamide are avidly bound by carbonic anhydrase; consequently, tissues rich in enzymes, such as kidneys and RBC, will have higher concentrations of carbonic anhydrase inhibitors (acetazolamide).

• Metabolism and Excretion
  

Acetazolamide does not undergo metabolic alteration. Plasma half-Life found to be approximately 6-9 hours. Renal excretion is the primary route of elimination about 90% is excreted by urine.

• https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/205358Orig1s000lbl.pdf
• https://www.accessdata.fda.gov/drugsatfda_docs/label/2005/12945s037,038lbl.pdf
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• https://www.rxlist.com/acetazolamide-drug.htm#dosage
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