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 is 250 mg every four hours; however, some patients may respond adequately to 250 mg twice daily. In acute cases, an initial dose of 500 mg may be given, followed by 125 mg or 250 mg every four hours as needed. Intravenous therapy may be employed for rapid relief of ocular tension in acute situations.

In the treatment of epilepsy, the suggested total daily dose of acetaZOLAMIDE is between 8 to 30 mg per kg, administered in divided doses. The optimum dosage range appears to be from 375 mg to 1000 mg daily, with doses exceeding 1 g generally not yielding improved outcomes. When used in conjunction with other anticonvulsants, a starting dose of 250 mg once daily is recommended, which can be adjusted based on clinical response.

For patients with congestive heart failure, the starting dose is 250 to 375 mg once daily in the morning, equivalent to approximately 5 mg/kg. If the patient does not continue to lose edema fluid, it is advisable to skip the medication for one day rather than increasing the dose. Optimal diuretic effects are achieved when the medication is 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 500 mg to 1000 mg daily, divided into multiple doses using tablets or sustained-release capsules. A higher dose of 1000 mg is recommended for patients 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 if necessary.

Contraindications

AcetaZOLAMIDE therapy is contraindicated in the following conditions:

Use is contraindicated in patients with depressed sodium and/or potassium blood serum levels due to the potential for 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.

Patients with suprarenal gland failure should not use this medication, given the risk of adrenal insufficiency.

AcetaZOLAMIDE is contraindicated in cases of hyperchloremic acidosis, as it may worsen acid-base imbalances.

In patients with cirrhosis, the use of this medication is contraindicated 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 worsening of glaucoma symptoms through lowered intraocular pressure.

Warnings and Precautions

Fatalities, although rare, have been reported due to severe reactions associated with sulfonamides, including Stevens-Johnson syndrome, toxic epidermal necrolysis, fulminant hepatic necrosis, agranulocytosis, aplastic anemia, and other blood dyscrasias. It is crucial to recognize that sensitization may recur upon re-administration of a sulfonamide, regardless of the route of administration. In the event of hypersensitivity signs or other serious reactions, the use of this drug must be discontinued immediately. Caution is particularly advised for patients concurrently receiving high-dose aspirin and acetaZOLAMIDE, as there have been reports of severe adverse effects such as anorexia, tachypnea, lethargy, coma, and even death.

Increasing the dosage of acetaZOLAMIDE does not enhance diuresis and may lead to an increased incidence of drowsiness and/or paresthesia. In fact, higher doses can 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 initiation of appropriate therapy are essential. Additionally, periodic monitoring of serum electrolytes is advised to maintain patient safety during treatment.

Side Effects

Patients may experience a range of adverse reactions while using this medication, which can be categorized by frequency and seriousness.

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

Less common adverse reactions reported include transient myopia, which typically resolves upon reduction or discontinuation of the medication, as well as urticaria, melena, hematuria, glycosuria, hepatic insufficiency, flaccid paralysis, photosensitivity, and convulsions.

Serious adverse reactions, although rare, can be life-threatening and include fatalities due to severe reactions to sulfonamides. These serious reactions encompass 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 there have been reports of anorexia, tachypnea, lethargy, coma, and death in such cases.

Additional adverse reactions common to all sulfonamide derivatives may also occur, including anaphylaxis, fever, rash (which may include erythema multiforme, Stevens-Johnson syndrome, and toxic epidermal necrolysis), crystalluria, renal calculus, bone marrow depression, thrombocytopenic purpura, hemolytic anemia, leukopenia, pancytopenia, and agranulocytosis.

It is noteworthy that increasing the dose of the medication does not enhance diuresis and may actually increase the incidence of drowsiness and/or paresthesia, often resulting in a decrease in diuresis.

Drug Interactions

Caution is advised when acetaZOLAMIDE is administered concurrently with high-dose aspirin. This combination has been associated with severe adverse effects, including anorexia, tachypnea, lethargy, coma, and in some cases, death.

To ensure patient safety, it is recommended that a baseline complete blood count (CBC) and platelet count be obtained prior to the initiation of acetaZOLAMIDE therapy. Regular monitoring of these parameters should continue throughout the course of treatment to detect any hematologic reactions that may arise, which are common to all sulfonamides.

Additionally, periodic monitoring of serum electrolytes is advised to manage potential imbalances that may occur during therapy 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

Caution is advised when administering acetaZOLAMIDE to elderly patients, as they may experience reduced kidney function, which could necessitate dosage adjustments. This population may also exhibit increased sensitivity to side effects, including drowsiness and confusion, warranting careful monitoring.

It is recommended that healthcare providers closely monitor serum electrolytes and renal function in geriatric patients receiving acetaZOLAMIDE. Dosage adjustments should be made with careful individual attention to symptomatology and response, particularly in this age group, to ensure safety and efficacy.

Pregnancy

AcetaZOLAMIDE is classified as Pregnancy Category C. Animal studies have demonstrated that AcetaZOLAMIDE, when administered orally or parenterally, is teratogenic, resulting in limb defects in mice, rats, hamsters, and rabbits. However, there are no adequate and well-controlled studies available in pregnant women to fully assess the drug's safety profile during pregnancy.

Given the potential risks identified in animal studies, AcetaZOLAMIDE should be used in pregnant patients only if the potential benefits outweigh the risks to the fetus. Healthcare professionals are advised to carefully consider the necessity of AcetaZOLAMIDE therapy in this population and to discuss the potential risks with women of childbearing potential.

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

There is no specific information available regarding dosage adjustments, special monitoring, or safety considerations for patients with renal impairment. Healthcare professionals should exercise caution when prescribing to patients with reduced kidney function, as the absence of detailed guidance necessitates careful clinical judgment. Regular monitoring of renal function may be advisable in this patient population.

Hepatic Impairment

Patients with hepatic impairment should be treated with caution due to the potential for severe reactions associated with sulfonamides, including the rare occurrence of fulminant hepatic necrosis, which can be fatal.

It is advisable to closely monitor liver function in these patients, particularly when they are receiving concomitant high-dose aspirin and acetazolamide. Reports have indicated that such combinations may lead to serious adverse effects, including anorexia, tachypnea, lethargy, coma, and even death.

Due to the risks involved, healthcare providers should consider the severity of hepatic impairment when determining the appropriateness of treatment and may need to adjust dosages accordingly. Regular assessment of liver function tests is recommended to ensure patient safety and to mitigate the risk of severe hepatic reactions.

Overdosage

In the event of an acetaZOLAMIDE overdosage, it is important to note that no data are available regarding overdose in humans, as no cases of acute poisoning with this medication have been reported. Animal studies indicate that acetaZOLAMIDE exhibits a remarkably low toxicity profile. Currently, there is no specific antidote for acetaZOLAMIDE overdose; 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 an overdose 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 is particularly relevant in cases of acetaZOLAMIDE overdosage complicated by renal failure, where dialysis may aid in the management of the overdose.

In summary, while acetaZOLAMIDE is considered to have a low toxicity risk, appropriate monitoring and supportive care are essential in the event of an overdose.

Nonclinical Toxicology

AcetaZOLAMIDE is classified as a Pregnancy Category C drug, indicating that it may pose risks during pregnancy. Teratogenic effects have been observed in animal studies, where oral or parenteral administration resulted in limb defects in mice, rats, hamsters, and rabbits. There are no adequate and well-controlled studies in pregnant women, and therefore, AcetaZOLAMIDE should only be used during pregnancy if the potential benefits outweigh the risks to the fetus.

In terms of non-teratogenic effects, AcetaZOLAMIDE did not affect fertility in male and female rats when administered in the diet at doses 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, results from a bacterial mutagenicity assay indicate that AcetaZOLAMIDE is not mutagenic, both with and without metabolic activation.

No further specific details regarding animal pharmacology and toxicology are available beyond the information provided in the non-teratogenic effects and nonclinical toxicology sections.

Postmarketing Experience

Fatalities have been reported, albeit infrequently, due to severe reactions associated with sulfonamides. These reactions include 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 in such scenarios.

Common adverse reactions associated with all sulfonamide derivatives may include anaphylaxis, fever, rash (which encompasses erythema multiforme, Stevens-Johnson syndrome, and toxic epidermal necrolysis), crystalluria, renal calculus, bone marrow depression, thrombocytopenic purpura, hemolytic anemia, leukopenia, pancytopenia, and agranulocytosis.

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 they should be instructed to discontinue the medication and seek appropriate therapy if any adverse effects occur.

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

Patients planning to ascend to high altitudes should be counseled on the benefits of gradual ascent to minimize the risk of acute mountain sickness. If rapid ascent is necessary and acetaZOLAMIDE is used, it is crucial to communicate 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 outcomes, including anorexia, tachypnea, lethargy, coma, and 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. Patients should be informed that significant changes in these parameters may necessitate early discontinuation of the drug and the initiation of appropriate therapy. Additionally, periodic monitoring of serum electrolytes is advised.

In the context of pregnancy, healthcare providers should discuss the use of acetaZOLAMIDE only if the potential benefits outweigh the risks to the fetus. For nursing mothers, it is important to evaluate whether to discontinue breastfeeding or to stop the medication, considering the significance of the drug for the mother’s health.

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, early discontinuation of the medication and implementation of appropriate therapeutic measures are crucial. Additionally, periodic assessment of serum electrolytes is recommended to further safeguard patient health.

FDA Insert (PDF)

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

View full prescribing information (PDF)