Methazolamide

Methazolamide
Adult Indications & Dosage
Pediatric Indications & Dosage
Contraindications
Warnings & Precautions
Adverse Reactions
Drug Interactions
Use in Specific Populations
Administration & Monitoring
Overdosage
Pharmacology
Clinical Studies
How Supplied
Images
Patient Counseling Information
Precautions with Alcohol
Brand Names
Look-Alike Names

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Gerald Chi

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Overview

Methazolamide is a carbonic anhydrase inhibitor that is FDA approved for the {{{indicationType}}} of ocular conditions where lowering intraocular pressure is likely to be of therapeutic benefit, such as chronic open-angle glaucoma, secondary glaucoma, and preoperatively in acute angle-closure glaucoma where lowering the intraocular pressure is desired before surgery. Common adverse reactions include diarrhea, taste alterations, loss of appetite, nausea, vomiting, confusion, paresthesia, somnolence, polyuria, fatigue, and malaise.

Adult Indications and Dosage

FDA-Labeled Indications and Dosage (Adult)

Glaucoma

• Dosing Information

• 50–100 mg two or three times daily

Off-Label Use and Dosage (Adult)

Guideline-Supported Use

There is limited information regarding Off-Label Guideline-Supported Use of Methazolamide in adult patients.

Non–Guideline-Supported Use

There is limited information regarding Off-Label Non–Guideline-Supported Use of Methazolamide in adult patients.

Pediatric Indications and Dosage

FDA-Labeled Indications and Dosage (Pediatric)

• The safety and effectiveness of methazolamide in children have not been established.

Off-Label Use and Dosage (Pediatric)

Guideline-Supported Use

There is limited information regarding Off-Label Guideline-Supported Use of Methazolamide in pediatric patients.

Non–Guideline-Supported Use

There is limited information regarding Off-Label Non–Guideline-Supported Use of Methazolamide in pediatric patients.

Contraindications

• Methazolamide therapy is contraindicated in situations in which sodium and/or potassium serum levels are depressed, in cases of marked kidney or liver disease or dysfunction, in adrenal gland failure, and in hyperchloremic acidosis.
• In patients with cirrhosis, use may precipitate the development of hepatic encephalopathy.
• Long-term administration of methazolamide is contraindicated in patients with angle-closure glaucoma, since organic closure of the angle may occur in spite of lowered intraocular pressure.

Warnings

• 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. Hypersensitivity reactions may recur when a sulfonamide is readministered, irrespective of the route of administration.
• If hypersensitivity or other serious reactions occur, the use of this drug should be discontinued.
• Caution is advised for patients receiving high-dose aspirin and methazolamide concomitantly, as anorexia, tachypnea, lethargy, coma, and death have been reported with concomitant use of high-dose aspirin and carbonic anhydrase inhibitors.

Precautions

• Potassium excretion is increased initially upon administration of methazolamide and in patients with cirrhosis or hepatic insufficiency could precipitate a hepatic coma.
• In patients with pulmonary obstruction or emphysema, where alveolar ventilation may be impaired, methazolamide should be used with caution because it may precipitate or aggravate acidosis.

Laboratory Tests

• To monitor for hematologic reactions common to all sulfonamides, it is recommended that a baseline CBC and platelet count be obtained on patients prior to initiating methazolamide therapy and at regular intervals during therapy. If significant changes occur, early discontinuance and institution of appropriate therapy are important. Periodic monitoring of serum electrolytes is also recommended.

Adverse Reactions

Clinical Trials Experience

There is limited information regarding Clinical Trial Experience of Methazolamide in the drug label.

Postmarketing Experience

• Adverse reactions, occurring most often early in therapy, include paresthesias, particularly a “tingling” feeling in the extremities; hearing dysfunction or tinnitus; fatigue; malaise; loss of appetite; taste alteration; gastrointestinal disturbances such as nausea, vomiting, and diarrhea; polyuria; and occasional instances of drowsiness and confusion.
• Metabolic acidosis and electrolyte imbalance may occur.
• Transient myopia has been reported. This condition invariably subsides upon diminution or discontinuance of the medication.
• Other occasional adverse reactions include urticaria, melena, hematuria, glycosuria, hepatic insufficiency, flaccid paralysis, photosensitivity, convulsions, and, rarely, crystalluria and renal calculi.
• 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.

Drug Interactions

• Steroids

• Methazolamide should be used with caution in patients on steroid therapy because of the potential for developing hypokalemia.

• Aspirin

• Caution is advised for patients receiving high-dose aspirin and methazolamide concomitantly, as anorexia, tachypnea, lethargy, coma and death have been reported with concomitant use of high-dose aspirin and carbonic anhydrase inhibitors.

Use in Specific Populations

Pregnancy

Pregnancy Category (FDA):

• Pregnancy Category C

• Methazolamide has been shown to be teratogenic (skeletal anomalies) in rats when given in doses approximately 40 times the human dose. There are no adequate and well controlled studies in pregnant women. Methazolamide should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Pregnancy Category (AUS):

• Australian Drug Evaluation Committee (ADEC) Pregnancy Category

There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Methazolamide in women who are pregnant.

Labor and Delivery

There is no FDA guidance on use of Methazolamide during labor and delivery.

Nursing Mothers

• It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing infants from methazolamide, 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 methazolamide in children have not been established.

Geriatic Use

There is no FDA guidance on the use of Methazolamide with respect to geriatric patients.

Gender

There is no FDA guidance on the use of Methazolamide with respect to specific gender populations.

Race

There is no FDA guidance on the use of Methazolamide with respect to specific racial populations.

Renal Impairment

There is no FDA guidance on the use of Methazolamide in patients with renal impairment.

Hepatic Impairment

There is no FDA guidance on the use of Methazolamide in patients with hepatic impairment.

Females of Reproductive Potential and Males

There is no FDA guidance on the use of Methazolamide in women of reproductive potentials and males.

Immunocompromised Patients

There is no FDA guidance one the use of Methazolamide in patients who are immunocompromised.

Administration and Monitoring

Administration

• Oral

Monitoring

• It is recommended that a baseline CBC and platelet count be obtained on patients prior to initiating methazolamide therapy and at regular intervals during therapy. If significant changes occur, early discontinuance and institution of appropriate therapy are important. Periodic monitoring of serum electrolytes is also recommended.

IV Compatibility

There is limited information regarding IV Compatibility of Methazolamide in the drug label.

Overdosage

Acute Overdose

Signs and Symptoms

• No data are available regarding methazolamide overdosage in humans as no cases of acute poisoning with this drug have been reported. Animal data suggest that even a high dose of methazolamide is nontoxic.
• 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.

Management

• No specific antidote is known. Treatment should be symptomatic and supportive.

Chronic Overdose

There is limited information regarding Chronic Overdose of Methazolamide in the drug label.

Pharmacology

Mechanism of Action

• Methazolamide is a potent inhibitor of carbonic anhydrase.

Structure

• Methazolamide, a sulfonamide derivative, is a white crystalline powder, weakly acidic, slightly soluble in water, alcohol and acetone. The chemical name for methazolamide is: N-[5-(aminosulfonyl)-3-methyl-1,3,4-thiadiazo1-2(3H)-ylidene]-acetamide and it has the following structural formula:

This image is provided by the National Library of Medicine.

• Each tablet, for oral administration, contains 25 mg or 50 mg methazolamide. In addition, each tablet contains the following inactive ingredients: colloidal silicon dioxide, croscarmellose sodium, dibasic calcium phosphate dihydrate, magnesium stearate (powder), and microcrystalline cellulose.

Pharmacodynamics

• Methazolamide is well absorbed from the gastrointestinal tract. Peak plasma concentrations are observed 1 to 2 hours after dosing. In a multiple-dose, pharmacokinetic study, administration of methazolamide 25 mg bid, 50 mg bid, and 100 mg bid demonstrated a linear relationship between plasma methazolamide levels and methazolamide dose. Peak plasma concentrations (Cmax) for the 25 mg, 50 mg and 100 mg bid regimens were 2.5 mcg/mL, 5.1 mcg/mL, and 10.7 mcg/mL, respectively. The area under the plasma concentration-time curves (AUC) was 1130 mcg.min/mL, 2571 mcg.min/mL, and 5418 mcg.min/mL for the 25 mg, 50 mg, and 100 mg dosage regimens, respectively.

• Methazolamide is distributed throughout the body including the plasma, cerebrospinal fluid, aqueous humor of the eye, red blood cells, bile and extra-cellular fluid. The mean apparent volume of distribution (Varea/F) ranges from 17 L to 23 L. Approximately 55% is bound to plasma proteins. The steady-state methazolamide red blood cell:plasma ratio varies with dose and was found to be 27:1, 16:1, and 10:1 following the administration of methazolamide 25 mg bid, 50 mg bid, and 100 mg bid, respectively.

• The mean steady-state plasma elimination half-life for methazolamide is approximately 14 hours. At steady-state, approximately 25% of the dose is recovered unchanged in the urine over the dosing interval. Renal clearance accounts for 20% to 25% of the total clearance of drug. After repeated bid-tid dosing, methazolamide accumulates to steady-state concentrations in 7 days.

• Methazolamide's inhibitory action on carbonic anhydrase decreases the secretion of aqueous humor and results in a decrease in intraocular pressure. The onset of the decrease in intraocular pressure generally occurs within 2 to 4 hours, has a peak effect in 6 to 8 hours and a total duration of 10 to 18 hours.

• Methazolamide is a sulfonamide derivative; however, it does not have any clinically significant antimicrobial properties. Although methazolamide achieves a high concentration in the cerebrospinal fluid, it is not considered an effective anticonvulsant

Pharmacokinetics

• Methazolamide has a weak and transient diuretic effect; therefore, use results in an increase in urinary volume, with excretion of sodium, potassium, and chloride. The drug should not be used as a diuretic. Inhibition of renal bicarbonate reabsorption produces an alkaline urine. Plasma bicarbonate decreases, and a relative, transient metabolic acidosis may occur due to a disequilibrium in carbon dioxide transport in the red blood cell. Urinary citrate excretion is decreased by approximately 40% after doses of 100 mg every 8 hours. Uric acid output has been shown to decrease 36% in the first 24 hour period.

Nonclinical Toxicology

• Carcinogenesis, Mutagenesis, Impairment of Fertility

• Long-term studies in animals to evaluate the carcinogenic potential of methazolamide and its effect on fertility have not been conducted. Methazolamide was not mutagenic in the Ames bacterial test.

Clinical Studies

There is limited information regarding Clinical Studies of Methazolamide in the drug label.

How Supplied

• Methazolamide Tablets USP, 25 mg, are round, white tablets, debossed “EFF” on one side and “21” on the other side and are supplied in bottles of 100, NDC 55806-021-03.
• Methazolamide Tablets USP, 50 mg, are round, white, scored tablets debossed “EFF” on one side and “20” on the other side and are supplied in bottles of 100, NDC 55806-020-03.
• Store at 20° to 25°C (68° to 77°F).
• Dispense in a tight container as defined in the USP, with a child-resistant closure (as required).

Storage

There is limited information regarding Methazolamide Storage in the drug label.

Images

Drug Images

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Package and Label Display Panel

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Patient Counseling Information

There is limited information regarding Patient Counseling Information of Methazolamide in the drug label.

Precautions with Alcohol

• Alcohol-Methazolamide interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.

Brand Names

• Neptazane®
• Glauctabs®

Look-Alike Drug Names

• N/A

Drug Shortage Status

Price

References

The contents of this FDA label are provided by the National Library of Medicine.

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