Acetazolamide

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, or alternatively, 250 mg twice daily for short-term therapy. 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 is between 8 to 30 mg per kg, divided into multiple doses, with an optimum range of 375 to 1000 mg daily. When administered alongside other anticonvulsants, the starting dose is typically 250 mg once daily, which may be increased based on clinical response.

For patients with congestive heart failure, the starting dose is generally 250 to 375 mg once daily in the morning, equivalent to approximately 5 mg/kg. To achieve optimal diuretic effects, it is recommended 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 500 mg to 1000 mg daily, administered in divided doses using tablets or sustained-release capsules. A higher dose 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

Use of acetazolamide is contraindicated in the following situations:

Patients with hypersensitivity to acetazolamide or any excipients in the formulation, as cross-sensitivity with sulfonamides and other sulfonamide derivatives may occur.

Acetazolamide therapy is contraindicated in patients with depressed sodium and/or potassium serum levels, marked kidney and liver disease or dysfunction, suprarenal gland failure, and hyperchloremic acidosis. It is also contraindicated in patients with cirrhosis due to the risk of developing hepatic encephalopathy.

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

Warnings and Precautions

Fatalities have been reported, albeit infrequently, as a result of severe reactions to sulfonamides. These reactions include, but are not limited to, Stevens-Johnson syndrome, toxic epidermal necrolysis, fulminant hepatic necrosis, agranulocytosis, aplastic anemia, and other blood dyscrasias, as well as anaphylaxis. It is important to note that sensitization may recur upon re-administration of a sulfonamide, regardless of the route of administration. Should any signs of hypersensitivity or other serious adverse reactions manifest, the use of this drug must be discontinued immediately.

Healthcare professionals should exercise caution when prescribing this medication to patients who are concurrently receiving high doses of aspirin and acetazolamide. There have been reports of serious adverse effects in such cases, including anorexia, tachypnea, lethargy, metabolic acidosis, coma, and even death. Continuous monitoring of the patient's clinical status is recommended to mitigate these risks.

Side Effects

Patients may experience a range of adverse reactions associated with the use of this medication. Serious adverse reactions, although rare, can include fatalities due to severe hypersensitivity reactions such as anaphylaxis, Stevens-Johnson syndrome, toxic epidermal necrolysis, fulminant hepatic necrosis, agranulocytosis, and aplastic anemia. It is important to note that sensitization may recur upon re-administration of the drug, regardless of the route of administration. If any signs of hypersensitivity or other serious reactions occur, the use of this medication should be discontinued immediately.

Common adverse reactions reported in clinical trials and postmarketing experiences include:

Body as a Whole: Patients may report headache, malaise, fatigue, fever, pain at the injection site, flushing, and in children, growth retardation. Additionally, flaccid paralysis has been noted.

Digestive System: Gastrointestinal disturbances such as nausea, vomiting, and diarrhea are frequently observed.

Hematological/Lymphatic System: Blood dyscrasias, including aplastic anemia, agranulocytosis, leukopenia, thrombocytopenia, thrombocytopenic purpura, and melena, have been documented.

Hepato-biliary Disorders: Abnormal liver function tests, cholestatic jaundice, hepatic insufficiency, and fulminant hepatic necrosis are serious concerns that may arise.

Metabolic/Nutritional Effects: Patients may experience metabolic acidosis, electrolyte imbalances (including hypokalemia and hyponatremia), osteomalacia with long-term phenytoin therapy, loss of appetite, taste alterations, and hyperglycemia or hypoglycemia.

Nervous System: Adverse reactions affecting the nervous system include drowsiness, paraesthesia (numbness and tingling of extremities and face), depression, excitement, ataxia, confusion, dizziness, and convulsions.

Skin Reactions: Allergic skin reactions such as urticaria, photosensitivity, Stevens-Johnson syndrome, and toxic epidermal necrolysis have been reported.

Otologic Effects: Hearing disturbances and tinnitus are noted in some patients.

Eye Disorders: Choroidal effusion, choroidal detachment, and transient myopia, which results from the forward movement of the ciliary body leading to a narrowing of the angle, have been observed.

Urogenital Effects: Patients may experience crystalluria, an increased risk of nephrolithiasis with long-term therapy, hematuria, glycosuria, renal failure, and polyuria.

Caution is advised for patients receiving concomitant high-dose aspirin and acetazolamide, as serious reactions such as anorexia, tachypnea, lethargy, metabolic acidosis, coma, and death have been reported in these cases.

Drug Interactions

Caution is advised when administering high-dose aspirin concomitantly with acetazolamide. This combination has been associated with serious adverse effects, including anorexia, tachypnea, lethargy, metabolic acidosis, coma, and in some cases, death. Close monitoring of patients receiving this combination is recommended.

In the context of laboratory assessments, the use of sulfonamides may lead to false negative or decreased values in urinary phenolsulfonphthalein and phenol red elimination tests, as well as in serum non-protein and serum uric acid measurements. Clinicians should consider these potential interferences when interpreting laboratory results.

Acetazolamide has been noted to increase the level of crystals in urine, which may necessitate monitoring of urinary parameters in patients receiving this medication.

Additionally, acetazolamide can interfere with the high-performance liquid chromatography (HPLC) assay for theophylline. The extent of this interference is dependent on the solvent used during the extraction process. It is important to consider alternative assay methods for theophylline if acetazolamide is being administered concurrently.

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

Acetazolamide may cause growth retardation in pediatric patients. For the management of epilepsy, the suggested total daily dose for children is 8 to 30 mg per kg, administered in divided doses, with an optimum range of 375 to 1000 mg daily. When transitioning from other medications to acetazolamide, this change should be gradual and in accordance with standard practices in epilepsy therapy. Additionally, when acetazolamide tablets are prescribed in combination with other anticonvulsants, a recommended starting dose is 250 mg once daily, in addition to the existing medications.

Geriatric Use

Elderly patients may exhibit increased sensitivity to side effects, necessitating caution when prescribing this medication. Continuous supervision by a physician is advisable for all cases, particularly for geriatric patients.

Dosage adjustments should be made with careful individual attention to both symptomatology and ocular tension. This is especially important for elderly patients who may have reduced kidney function or other age-related health concerns. Additionally, caution is advised for patients receiving concomitant high-dose aspirin and acetazolamide, as serious adverse effects such as anorexia, tachypnea, lethargy, metabolic acidosis, coma, and death have been reported in this population.

Pregnancy

Acetazolamide is contraindicated in pregnancy due to the associated risks to the fetus. The use of acetazolamide during this period may lead to adverse fetal outcomes. Healthcare professionals should advise pregnant patients to avoid this medication and consider alternative treatments that are safer for use during pregnancy. Women of childbearing potential should be informed of these risks and the importance of effective contraception while on acetazolamide.

Lactation

Caution should be exercised when administering acetazolamide to lactating mothers. There is a potential for excretion of acetazolamide in breast milk; however, the effects on the nursing infant are not known.

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, although rare, can lead to fatalities. It is essential to monitor liver function closely in these patients.

No specific dosage adjustments are recommended for patients with mild to moderate hepatic impairment; however, the prescribing physician should consider the overall clinical status of the patient and the potential for increased risk of adverse reactions. Regular assessment of liver function tests is advised to ensure patient safety and to detect any deterioration in liver status promptly.

In patients with severe hepatic impairment, the use of this medication is not recommended due to the heightened risk of serious adverse effects.

Overdosage

In the event of an overdosage, no specific antidote is available. Management should focus on symptomatic and supportive care tailored to the patient's clinical presentation.

Potential Symptoms and Monitoring Patients may exhibit symptoms related to electrolyte imbalances, the development of an acidotic state, and central nervous system effects. It is essential to monitor serum electrolyte levels, with particular attention to potassium, as well as blood pH levels to assess the patient's metabolic status.

Management Procedures Supportive measures are critical in restoring electrolyte and pH balance. The acidotic state can typically be corrected through the administration of bicarbonate, which helps to neutralize excess acidity in the blood.

Dialysis Considerations Despite acetazolamide's high distribution within erythrocytes and its significant plasma protein binding, it is important to note that the drug is dialyzable. This characteristic may be particularly relevant in cases of acetazolamide overdosage, especially when complicated by renal failure, as dialysis can aid in the removal of the drug from the system.

Nonclinical Toxicology

In animal studies, acetazolamide has been associated with various toxic effects, including metabolic acidosis and electrolyte imbalances. Adverse developmental outcomes have been observed, although no teratogenic effects were noted. Additionally, studies have demonstrated that acetazolamide can lead to growth retardation and other developmental issues. The compound has also been shown to affect renal function and electrolyte balance in animal models.

Postmarketing Experience

Fatalities have been reported, albeit rarely, due to severe reactions associated with sulfonamides, including Stevens-Johnson syndrome, toxic epidermal necrolysis, fulminant hepatic necrosis, agranulocytosis, aplastic anemia, and other blood dyscrasias, as well as anaphylaxis. It is noted that sensitizations may recur upon re-administration of a sulfonamide, regardless of the route of administration. In cases of hypersensitivity or other serious reactions, discontinuation of the drug is advised.

Caution is recommended for patients receiving concomitant high-dose aspirin and acetazolamide, as adverse events such as anorexia, tachypnea, lethargy, metabolic acidosis, coma, and death have been documented.

Additional adverse events reported include headache, malaise, fatigue, fever, pain at the injection site, flushing, growth retardation in children, flaccid paralysis, and anaphylaxis. Gastrointestinal disturbances such as nausea, vomiting, and diarrhea have also been observed.

Blood dyscrasias, including aplastic anemia, agranulocytosis, leukopenia, thrombocytopenia, thrombocytopenic purpura, and melena, have been reported. Abnormal liver function, cholestatic jaundice, hepatic insufficiency, and fulminant hepatic necrosis are also noted.

Metabolic acidosis and electrolyte imbalances, including hypokalemia and hyponatremia, have been associated with long-term phenytoin therapy. Other reported effects include loss of appetite, taste alteration, and hyper/hypoglycemia. Neurological effects such as drowsiness, paraesthesia (including numbness and tingling of extremities and face), depression, excitement, ataxia, confusion, convulsions, and dizziness have been documented.

Allergic skin reactions, including urticaria, photosensitivity, Stevens-Johnson syndrome, and toxic epidermal necrolysis, have been reported. Hearing disturbances, including tinnitus, have also been noted.

Ocular effects such as choroidal effusion, choroidal detachment, and transient myopia have been observed, with transient myopia resulting from the forward movement of the ciliary body leading to a narrowing of the angle. Renal effects, including crystalluria, increased risk of nephrolithiasis with long-term therapy, hematuria, glycosuria, renal failure, and polyuria, have been documented.

For reporting suspected adverse reactions, individuals are encouraged to contact Strides Pharma Inc. at 1-877-244-9825 or visit www.strides.com, or to reach out to the FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

Patient Counseling

Healthcare providers should inform patients that the medication is available by prescription only. Patients should be advised to report any suspected adverse reactions they experience while using the medication. They can do this by contacting Strides Pharma Inc. at 1-877-244-9825 or visiting the company’s website at www.strides.com. Additionally, patients should be made aware that they can report adverse reactions to the FDA by calling 1-800-FDA-1088 or visiting www.fda.gov/medwatch. It is important for healthcare providers to encourage open communication regarding any side effects or concerns patients may have during their treatment.

Storage and Handling

The product is supplied in accordance with the National Drug Code (NDC) specifications. It should be stored at a temperature range of 20° to 25°C (68° to 77°F), in compliance with USP Controlled Room Temperature guidelines. Proper storage conditions are essential to maintain the integrity and efficacy of the product.

Additional Clinical Information

Sulfonamides may lead to false negative or decreased values in laboratory tests for urinary phenolsulfonphthalein and phenol red elimination, as well as for urinary protein, serum non-protein, and serum uric acid. Additionally, acetazolamide can result in an increased level of crystals in the urine and may interfere with the high-performance liquid chromatography (HPLC) method for theophylline assay, with the extent of interference depending on the solvent used in the extraction. However, acetazolamide is not expected to interfere with other assay methods for theophylline.

FDA Insert (PDF)

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

View full prescribing information (PDF)