Acetazolamide

Description

AcetaZOLAMIDE is an inhibitor of the enzyme carbonic anhydrase, presented as a white to faintly yellowish white crystalline, odorless powder. It is characterized as weakly acidic, very slightly soluble in water, and slightly soluble in alcohol. The chemical name for acetaZOLAMIDE is N-(5-Sulfamoyl-1,3,4-thiadiazol-2-yl)-acetamide, with a specific structural formula. Each tablet intended for oral administration contains 250 mg of acetaZOLAMIDE. The formulation also includes inactive ingredients such as lactose monohydrate, sodium starch glycolate, corn starch, and calcium stearate.

Uses and Indications

This drug is indicated for the adjunctive treatment of various conditions, including edema due to congestive heart failure, drug-induced edema, and centrencephalic epilepsies, specifically petit mal and unlocalized seizures. It is also indicated for the management of chronic simple (open-angle) glaucoma and secondary glaucoma. Additionally, this drug may be used preoperatively in cases of acute angle-closure glaucoma when a delay in surgery is desired to lower intraocular pressure.

Furthermore, this drug is indicated for the prevention or amelioration of symptoms associated with acute mountain sickness in climbers who are attempting rapid ascent, as well as in individuals who are particularly susceptible to acute mountain sickness, even with gradual ascent.

No teratogenic or nonteratogenic effects have been reported.

Dosage and Administration

For the management of glaucoma, the recommended dosage of acetaZOLAMIDE ranges from 250 mg to 1 g per 24 hours, typically administered in divided doses for amounts exceeding 250 mg. The preferred dosage for secondary glaucoma and preoperative treatment of acute congestive glaucoma is 250 mg every four hours. In acute cases, an initial dose of 500 mg may be administered, followed by subsequent doses of 125 mg or 250 mg every four hours. Intravenous therapy may be utilized for rapid relief of ocular tension in acute situations.

In the treatment of epilepsy, the suggested total daily dose is between 8 to 30 mg per kg, divided into multiple doses. The optimum dosage range appears to be from 375 mg to 1000 mg daily. When acetaZOLAMIDE is prescribed in conjunction with other anticonvulsants, a starting dose of 250 mg once daily is recommended.

For patients with congestive heart failure, the starting dose is generally 250 to 375 mg once daily in the morning, which corresponds to approximately 5 mg/kg. For optimal diuretic effects, it is advised to administer the medication on alternate days or for two consecutive days followed by a day of rest.

In cases of drug-induced edema, the recommended dosage is 250 to 375 mg of acetaZOLAMIDE once daily for one or two days, alternating with a day of rest.

For the prevention and treatment of acute mountain sickness, the dosage is typically between 500 mg to 1000 mg daily, divided into multiple doses. A higher dosage of 1000 mg is recommended for individuals ascending rapidly. It is preferable to initiate dosing 24 to 28 hours prior to ascent and to continue for 48 hours while at high altitude, or longer as necessary to manage symptoms effectively.

Contraindications

AcetaZOLAMIDE therapy is contraindicated in the following conditions:

• Patients with depressed sodium and/or potassium blood serum levels due to the potential for exacerbating electrolyte imbalances.

• Individuals with marked kidney and liver disease or dysfunction, as the drug may further compromise renal and hepatic function.

• Patients experiencing suprarenal gland failure, which may lead to adrenal insufficiency.

• Individuals with hyperchloremic acidosis, as the drug may worsen acid-base balance.

• Patients with cirrhosis, due to the risk of developing hepatic encephalopathy.

• Long-term administration is contraindicated in patients with chronic non-congestive angle-closure glaucoma, as it may allow for organic closure of the angle while masking the progression of glaucoma through lowered intraocular pressure.

Warnings and Precautions

Fatalities, although rare, have been reported due to severe reactions associated with sulfonamides, including but not limited to Stevens-Johnson syndrome, toxic epidermal necrolysis, fulminant hepatic necrosis, agranulocytosis, aplastic anemia, and other blood dyscrasias. It is crucial to recognize that sensitizations may recur upon readministration of a sulfonamide, regardless of the route of administration. In the event of any signs of hypersensitivity or other serious reactions, the use of this drug must be discontinued immediately.

Caution is particularly advised for patients who are concurrently receiving high doses of aspirin and acetaZOLAMIDE. Reports have indicated that such combinations may lead to severe adverse effects, including anorexia, tachypnea, lethargy, coma, and even death.

In terms of general precautions, it is important to note that increasing the dose of acetaZOLAMIDE does not enhance diuresis and may, in fact, lead to an increased incidence of drowsiness and/or paresthesia. Additionally, higher doses often result in a decrease in diuresis. However, in specific circumstances, very large doses may be administered alongside other diuretics to achieve diuresis in cases of complete refractory failure.

To ensure patient safety, it is recommended that a baseline complete blood count (CBC) and platelet count be obtained prior to initiating acetaZOLAMIDE therapy. Regular monitoring of these parameters should continue throughout the treatment course to detect any hematologic reactions common to sulfonamides. Should significant changes in laboratory results occur, early discontinuation of the drug and the initiation of appropriate therapy are imperative. Furthermore, periodic monitoring of serum electrolytes is advised to maintain patient safety during treatment.

Side Effects

Adverse reactions associated with the use of this medication include a range of serious and common effects. Serious adverse reactions, although rare, can include fatalities due to severe reactions to sulfonamides such as Stevens-Johnson syndrome, toxic epidermal necrolysis, fulminant hepatic necrosis, agranulocytosis, aplastic anemia, and other blood dyscrasias. Patients should be monitored for signs of hypersensitivity or other serious reactions, and the medication should be discontinued immediately if such signs occur.

Common adverse reactions reported in clinical trials and postmarketing experiences include paresthesias, particularly a tingling sensation in the extremities, hearing dysfunction or tinnitus, loss of appetite, and taste alteration. Gastrointestinal disturbances such as nausea, vomiting, and diarrhea are also frequently observed. Other common reactions include polyuria, occasional drowsiness, and confusion.

Transient myopia has been noted, which invariably subsides upon reduction or discontinuation of the medication. Additionally, metabolic acidosis and electrolyte imbalances have been reported. Other occasional adverse reactions may include urticaria, melena, hematuria, glycosuria, hepatic insufficiency, flaccid paralysis, photosensitivity, and convulsions.

Patients receiving concomitant high-dose aspirin and acetaZOLAMIDE should be approached with caution, as there have been reports of anorexia, tachypnea, lethargy, coma, and death in this population. It is essential for healthcare providers to remain vigilant for the early detection of adverse reactions, and appropriate therapy should be instituted as necessary.

Drug Interactions

Caution is advised for patients receiving concomitant high-dose aspirin and acetazolamide due to the potential for serious adverse effects, including anorexia, tachypnea, lethargy, coma, and death.

For patients initiating acetazolamide therapy, it is recommended to obtain a baseline complete blood count (CBC) and platelet count prior to treatment. Regular monitoring of these parameters should continue throughout the course of therapy to detect any hematologic reactions that may arise, which are common to all sulfonamides.

Additionally, periodic monitoring of serum electrolytes is advised to ensure patient safety and to manage any potential imbalances that may occur during treatment with acetazolamide.

Packaging & NDC

The table below lists all NDC Code configurations of Acetazolamide, the U.S. brand-name prescription product. Columns show Packaging, Formulation Type, and Active Ingredient Strength.

Pediatric Use

The safety and effectiveness of acetaZOLAMIDE in pediatric patients have not been established. Therefore, caution is advised when considering its use in children. Further studies are necessary to determine appropriate dosing and potential outcomes in this population.

Geriatric Use

Elderly patients may not require specific dosage adjustments when using acetaZOLAMIDE, as there are no recommendations provided for this population. However, caution is advised for geriatric patients with pre-existing pulmonary conditions, such as pulmonary obstruction or emphysema, as the use of acetaZOLAMIDE may precipitate or exacerbate acidosis in these individuals.

Healthcare providers should monitor elderly patients closely for any adverse effects, particularly those with respiratory issues, to ensure safe and effective use of the medication.

Pregnancy

AcetaZOLAMIDE is classified as a Pregnancy Category C medication. Animal studies have demonstrated teratogenic effects, including limb defects, in mice, rats, hamsters, and rabbits. However, there are no adequate and well-controlled studies in pregnant women to fully assess the risks associated with its use during pregnancy.

Given the potential for fetal harm, AcetaZOLAMIDE should be administered to pregnant patients only if the potential benefits outweigh the risks to the fetus. Healthcare professionals are advised to carefully evaluate the necessity of this medication in pregnant patients and consider alternative treatments when appropriate.

Lactation

Because of the potential for serious adverse reactions 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.

Renal Impairment

Patients with renal impairment have not been specifically addressed in the available data regarding dosage adjustments, special monitoring, or safety considerations. Therefore, healthcare professionals should exercise caution when prescribing this medication to patients with reduced kidney function, as the lack of information necessitates careful clinical judgment and monitoring.

Hepatic Impairment

Patients with hepatic impairment should be treated with caution due to the potential for severe reactions, including fulminant hepatic necrosis, which has been reported in association with sulfonamide use. Fatalities have occurred in patients with compromised liver function as a result of these severe hepatic complications.

It is recommended that healthcare providers closely monitor liver function in patients with existing liver problems. Adjustments to dosage may be necessary based on the severity of hepatic impairment, and ongoing assessment of liver function is advised to mitigate risks associated with treatment.

Overdosage

In the event of an acetaZOLAMIDE overdosage, it is important to note that there are currently no reported cases of acute poisoning in humans, and available data from animal studies indicate that acetaZOLAMIDE is remarkably nontoxic. As such, no specific antidote exists for this medication. Management of an overdose should focus on symptomatic and supportive care.

Potential Symptoms and Monitoring Healthcare professionals should be vigilant for potential symptoms associated with overdosage, which may include electrolyte imbalances, the development of an acidotic state, and central nervous system effects. It is essential to monitor serum electrolyte levels, particularly potassium, as well as blood pH levels to assess the patient's condition accurately.

Management Procedures Supportive measures are critical in restoring electrolyte and pH balance. The acidotic state that may arise from an overdose can typically be corrected through the administration of bicarbonate. Additionally, despite acetaZOLAMIDE's high intraerythrocytic distribution and plasma protein binding properties, it may be dialyzable. This characteristic is particularly relevant in cases of overdosage complicated by renal failure, where dialysis may aid in the removal of the drug from the system.

In summary, while acetaZOLAMIDE overdose is not commonly reported and is considered nontoxic, appropriate monitoring and supportive treatment are essential to manage any potential complications effectively.

Nonclinical Toxicology

Long-term studies in animals to evaluate the carcinogenic potential of acetaZOLAMIDE have not been conducted. In a bacterial mutagenicity assay, acetaZOLAMIDE was not found to be mutagenic when evaluated with and without metabolic activation.

The drug demonstrated no effect on fertility when administered in the diet to male and female rats at a daily intake of up to four times the recommended human dose of 1000 mg in a 50 kg individual.

Postmarketing Experience

Fatalities have been reported, albeit infrequently, due to severe reactions associated with sulfonamides, including Stevens-Johnson syndrome, toxic epidermal necrolysis, fulminant hepatic necrosis, agranulocytosis, aplastic anemia, and other blood dyscrasias. Sensitization may recur upon re-administration of a sulfonamide, regardless of the route of administration. In cases where signs of hypersensitivity or other serious reactions manifest, discontinuation of the drug is recommended.

Caution is advised for patients concurrently receiving high-dose aspirin and acetazolamide, as reports indicate occurrences of anorexia, tachypnea, lethargy, coma, and death. Adverse reactions are most commonly observed early in therapy and include paresthesias, particularly a tingling sensation in the extremities, hearing dysfunction or tinnitus, loss of appetite, taste alterations, and gastrointestinal disturbances such as nausea, vomiting, diarrhea, and polyuria. Occasional instances of drowsiness and confusion have also been noted.

Metabolic acidosis and electrolyte imbalances may arise during treatment. Transient myopia has been documented, typically resolving with a reduction or cessation of the medication. Other less frequent adverse reactions include urticaria, melena, hematuria, glycosuria, hepatic insufficiency, flaccid paralysis, photosensitivity, and convulsions.

Patient Counseling

Healthcare providers should advise patients that the use of acetaZOLAMIDE may lead to adverse reactions common to all sulfonamide derivatives. These reactions include, but are not limited to, anaphylaxis, fever, rash (such as erythema multiforme, Stevens-Johnson syndrome, and toxic epidermal necrolysis), crystalluria, renal calculus, bone marrow depression, thrombocytopenic purpura, hemolytic anemia, leukopenia, pancytopenia, and agranulocytosis. Patients should be informed of the importance of early detection of these reactions, and that the drug should be discontinued immediately if any significant adverse effects occur, with appropriate therapy instituted.

For patients with pulmonary obstruction or emphysema, healthcare providers should emphasize the need for caution when using acetaZOLAMIDE, as it may precipitate or worsen acidosis in individuals with impaired alveolar ventilation.

Patients should be counseled on the importance of gradual ascent to avoid acute mountain sickness. If rapid ascent is necessary and acetaZOLAMIDE is used, it should be clearly communicated that this does not eliminate the need for immediate descent in the event of severe high altitude sickness, such as high altitude pulmonary edema (HAPE) or high-altitude cerebral edema.

Healthcare providers should also caution patients receiving high-dose aspirin concurrently with acetaZOLAMIDE, as this combination has been associated with serious adverse effects, including anorexia, tachypnea, lethargy, coma, and even death.

To monitor for hematologic reactions associated with sulfonamides, it is recommended that a baseline complete blood count (CBC) and platelet count be obtained prior to initiating acetaZOLAMIDE therapy, with regular monitoring throughout treatment. If significant changes in blood counts are observed, early discontinuation of the drug and appropriate therapeutic measures should be taken. Additionally, periodic monitoring of serum electrolytes is advised.

Healthcare providers should inform patients that acetaZOLAMIDE has been shown to be teratogenic in animal studies, leading to limb defects. Due to the lack of adequate and well-controlled studies in pregnant women, acetaZOLAMIDE should only be used during pregnancy if the potential benefits outweigh the risks to the fetus.

For nursing mothers, it is crucial to discuss the potential for serious adverse reactions in nursing infants due to acetaZOLAMIDE. A decision should be made regarding whether to discontinue nursing or to discontinue the medication, considering the importance of the drug to the mother.

Finally, healthcare providers should communicate that the safety and effectiveness of acetaZOLAMIDE in pediatric patients have not been established, and caution should be exercised when considering its use in children.

Storage and Handling

The product is supplied in a well-closed container, as defined by the United States Pharmacopeia (USP). It should be stored at a controlled room temperature ranging from 15° to 30° C (59° to 86° F) to ensure optimal stability and efficacy.

Additional Clinical Information

To ensure patient safety during acetaZOLAMIDE therapy, clinicians are advised to obtain a baseline complete blood count (CBC) and platelet count prior to treatment initiation. Regular monitoring of these parameters should continue throughout the therapy to detect any hematologic reactions commonly associated with sulfonamides. In the event of significant changes in blood counts, early discontinuation of the medication and initiation of appropriate therapeutic measures are crucial. Additionally, periodic monitoring of serum electrolytes is recommended to manage potential imbalances.

FDA Insert (PDF)

This document is the official FDA-approved prescribing information for Acetazolamide as submitted by Marlex Pharmaceuticals Inc. It includes detailed information about indications, dosage, contraindications, warnings, and clinical pharmacology.

View full prescribing information (PDF)