Acetazolamide

Description

Acetazolamide, an inhibitor of the enzyme carbonic anhydrase, is presented as a white to faintly yellowish white crystalline, odorless powder. It exhibits very slight solubility in water, sparing solubility in practically boiling water, and slight solubility in alcohol. The chemical name for acetazolamide is N-(5-Sulfamoyl-1,3,4-thiadiazol-2-yl)-acetamide, with a molecular weight of 222.25 and a molecular formula of C₄H₆N₄O₃S₂.

Acetazolamide is available in oral tablet form, containing 125 mg and 250 mg of acetazolamide, respectively. The tablets include the following inactive ingredients: corn starch, gelatin, glycerin, lactose monohydrate, magnesium stearate, purified water, sodium starch glycolate (potato), and talc.

Uses and Indications

This drug is indicated for the adjunctive treatment of edema due to congestive heart failure, drug-induced edema, and centrencephalic epilepsies, including 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 despite 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; however, some patients may respond adequately to 250 mg twice daily for short-term therapy. 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 as needed.

In the treatment of epilepsy, the suggested total daily dose is between 8 to 30 mg per kg, divided into multiple doses, with an optimal range of 375 to 1000 mg daily. When acetazolamide is used in conjunction with other anticonvulsants, the starting dose should be 250 mg once daily, with the possibility of increasing the dosage based on clinical response.

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. To achieve optimal diuretic effects, acetazolamide tablets are best administered 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 advised in situations involving rapid ascent. It is preferable to initiate dosing 24 to 48 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 patients with depressed sodium and/or potassium blood serum levels due to the risk of exacerbating electrolyte imbalances. It is also contraindicated in individuals with marked kidney and liver disease or dysfunction, as these conditions may impair drug metabolism and excretion. Additionally, the use of acetazolamide is contraindicated in cases of suprarenal gland failure and hyperchloremic acidosis, which may lead to further metabolic disturbances.

Patients with cirrhosis should not use acetazolamide due to the potential risk of developing hepatic encephalopathy. Furthermore, long-term administration of acetazolamide is contraindicated in patients with chronic non-congestive angle-closure glaucoma, as it may allow for organic closure of the angle while masking the worsening 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 critical to recognize that sensitization may recur upon re-administration of a sulfonamide, regardless of the route of administration. In the event of any signs of hypersensitivity or other serious adverse reactions, the use of this drug must be discontinued immediately.

Caution is particularly warranted for patients who are concurrently receiving high-dose aspirin alongside acetazolamide. Serious adverse effects such as anorexia, tachypnea, lethargy, coma, and even death have been documented in these cases.

To ensure patient safety and monitor for hematologic reactions that are common to all sulfonamides, it is recommended that a baseline complete blood count (CBC) and platelet count be obtained prior to the initiation of acetazolamide tablet therapy. Regular monitoring of these parameters should continue throughout the course of treatment. Should significant changes in hematologic status be observed, it is imperative to discontinue the medication promptly and initiate appropriate therapeutic measures. Additionally, periodic monitoring of serum electrolytes is advised to further safeguard patient health during therapy.

Side Effects

Patients may experience a range of adverse reactions while using this medication. Common adverse reactions include paresthesias, particularly a "tingling" sensation in the extremities, hearing dysfunction or tinnitus, loss of appetite, taste alteration, gastrointestinal disturbances such as nausea, vomiting, and diarrhea, polyuria, and occasional instances of drowsiness and confusion.

In addition to these common reactions, other occasional adverse reactions have been reported. These include urticaria, melena, hematuria, glycosuria, hepatic insufficiency, flaccid paralysis, photosensitivity, and convulsions.

Serious adverse reactions, although rare, have been associated with the use of sulfonamides. Fatalities have occurred due to severe reactions such as Stevens-Johnson syndrome, toxic epidermal necrolysis, fulminant hepatic necrosis, agranulocytosis, aplastic anemia, and other blood dyscrasias. It is important to note that sensitizations may recur upon readministration of a sulfonamide, regardless of the route of administration. If any signs of hypersensitivity or other serious reactions occur, the use of this drug should be discontinued immediately.

Caution is advised for patients receiving concomitant high-dose aspirin and acetazolamide, as reports have indicated that such combinations may lead to anorexia, tachypnea, lethargy, coma, and even death.

Drug Interactions

Caution is advised when acetazolamide is administered concomitantly with high-dose aspirin. The combination may lead to severe adverse effects, including anorexia, tachypnea, lethargy, coma, and potentially fatal outcomes.

For patients receiving acetazolamide, it is recommended to obtain a baseline complete blood count (CBC) and platelet count prior to the initiation of therapy. Regular monitoring of these parameters should continue throughout treatment to detect any hematologic reactions associated with sulfonamides. In the event of significant changes in blood counts, early discontinuation of acetazolamide and the implementation of appropriate therapeutic measures are essential.

Additionally, periodic monitoring of serum electrolytes is advised to ensure patient safety and to manage any potential imbalances that may arise 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 has not been established. Therefore, caution is advised when considering its use in this population. Further studies are needed to determine appropriate dosing and outcomes in children, infants, and adolescents.

Geriatric Use

Elderly patients may exhibit increased sensitivity to the side effects of acetazolamide. Therefore, caution is advised when prescribing this medication to geriatric patients, especially those with comorbidities or those taking concurrent medications that could impact renal function or electrolyte balance.

Dosage adjustments may be necessary for elderly patients due to the potential for reduced kidney function. It is important for healthcare providers to monitor renal function and electrolyte levels closely in this population to ensure safe and effective use of acetazolamide.

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 following oral or parenteral administration. 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 prescribed to pregnant patients only if the potential benefits outweigh the risks to the fetus. Healthcare professionals are advised to carefully evaluate the necessity of acetazolamide 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. Regular monitoring of renal function may be advisable in these patients to ensure safety and efficacy.

Hepatic Impairment

Patients with hepatic impairment may experience an increased risk of severe reactions to sulfonamides, including fulminant hepatic necrosis, which can lead to fatalities, albeit rarely. Due to the potential for serious adverse effects in this population, careful consideration should be given to the use of this medication in patients with compromised liver function.

Monitoring of liver function is recommended for patients with hepatic impairment who are prescribed this medication. Regular assessment of liver enzymes and overall liver health should be conducted to detect any signs of hepatic toxicity early.

Dosage adjustments may be necessary based on the severity of hepatic impairment, and it is advised that clinicians exercise caution when prescribing this medication to affected individuals.

Overdosage

In the event of acetazolamide overdosage, it is important to note that there are no reported cases of acute poisoning in humans, and thus, no specific data are available. Animal studies indicate that acetazolamide exhibits a remarkably low toxicity profile. Currently, there is no known antidote for acetazolamide overdosage; therefore, treatment 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 overdosage can typically be corrected through the administration of bicarbonate. Additionally, despite acetazolamide's high intraerythrocytic distribution and significant plasma protein binding, it may be dialyzable. This characteristic could be particularly relevant in cases of overdosage complicated by renal failure, where dialysis may aid in the management of the condition.

In summary, while acetazolamide is considered to have a low toxicity risk, appropriate monitoring and supportive care are essential in the event of overdosage to mitigate potential complications.

Nonclinical Toxicology

Acetazolamide has demonstrated teratogenic effects in animal studies, with oral or parenteral administration resulting in limb defects in mice, rats, hamsters, and rabbits. There are no adequate and well-controlled studies available in pregnant women; therefore, acetazolamide should be used during pregnancy only if the potential benefits outweigh the potential risks to the fetus.

In terms of non-teratogenic effects, acetazolamide did not affect 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 for a 50 kg individual.

Long-term studies to assess the carcinogenic potential of acetazolamide have not been conducted in animals. Additionally, acetazolamide was evaluated in a bacterial mutagenicity assay and was found to be non-mutagenic, both with and without metabolic activation. No further specific statements regarding animal pharmacology and toxicology were provided beyond the aforementioned mutagenicity and fertility effects.

Postmarketing Experience

Fatalities have been reported, albeit rarely, in association with severe reactions to sulfonamides, including but not limited to Stevens-Johnson syndrome, toxic epidermal necrolysis, fulminant hepatic necrosis, agranulocytosis, aplastic anemia, and other blood dyscrasias. It is noted that sensitizations 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 advised.

Common adverse reactions associated with sulfonamide derivatives include anaphylaxis, fever, rash (which may encompass erythema multiforme, Stevens-Johnson syndrome, and toxic epidermal necrolysis), crystalluria, renal calculus, bone marrow depression, thrombocytopenic purpura, hemolytic anemia, leukopenia, pancytopenia, and agranulocytosis. Early detection of these reactions is crucial, and the drug should be discontinued with appropriate therapy initiated as necessary.

Occasional adverse reactions reported include urticaria, melena, hematuria, glycosuria, hepatic insufficiency, flaccid paralysis, photosensitivity, and convulsions. The occurrence of fatalities, although rare, has been linked to severe reactions to sulfonamides, including those previously mentioned.

For the reporting of suspected adverse reactions, individuals are encouraged to contact AvKARE at 1-855-361-3993, via email at drugsafety@avkare.com, or the FDA at 1-800-FDA-1088 or through the website www.fda.gov/medwatch.

Patient Counseling

Healthcare providers should advise patients that adverse reactions common to all sulfonamide derivatives may occur, including but 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 such reactions, and that the drug should be discontinued immediately if any adverse effects are observed, with appropriate therapy instituted.

For patients with pulmonary obstruction or emphysema, healthcare providers should exercise caution when prescribing acetazolamide, as it may precipitate or aggravate acidosis in individuals where alveolar ventilation may be impaired.

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

Caution should also be communicated to patients receiving concomitant high-dose aspirin and acetazolamide, as serious adverse effects including anorexia, tachypnea, lethargy, coma, and death have been reported in such cases.

Healthcare providers are encouraged to recommend 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 hematologic parameters occur, early discontinuation of the drug and appropriate therapy are crucial. Periodic monitoring of serum electrolytes is also advised.

It is important to inform patients that acetazolamide has been shown to be teratogenic in animal studies, with potential limb defects observed in mice, rats, hamsters, and rabbits. Due to the lack of adequate and well-controlled studies in pregnant women, acetazolamide should only be used during pregnancy if the potential benefits justify the risks to the fetus.

For nursing mothers, healthcare providers should 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 drug, considering the importance of the medication 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 this population.

Storage and Handling

The product is supplied in accordance with the National Drug Code (NDC) specifications. It should be stored at a controlled room temperature of 20° to 25°C (68° to 77°F), as defined by the United States Pharmacopeia (USP) guidelines. Proper storage conditions are essential to maintain the integrity and efficacy of the product.

Additional Clinical Information

To ensure patient safety during acetazolamide tablet 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 implementation of appropriate therapeutic measures are crucial. Additionally, periodic assessment of serum electrolytes is recommended to monitor for potential imbalances.

FDA Insert (PDF)

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

View full prescribing information (PDF)