Methazolamide (Monograph)

Drug class: Carbonic Anhydrase Inhibitors
ATC class: S01EC05
VA class: CV703
CAS number: 554-57-4

Medically reviewed by Drugs.com on May 14, 2024. Written by ASHP.

Introduction

Carbonic anhydrase inhibitor; nonbacteriostatic sulfonamide derivative.^{150 a b}

Uses for Methazolamide

Glaucoma

Adjunctive treatment of open-angle glaucoma.^{150 a} Used principally in situations involving acute IOP elevation or chronically elevated IOP that is refractory to maximal topical ocular hypotensive therapy prior to a more definitive procedure to reduce IOP.¹³⁶ Long-term use limited by systemic adverse effects.^{134 136}

Adjunctive treatment of secondary glaucoma.^{150 a}

Short-term use in acute angle-closure glaucoma to lower IOP before appropriate laser or incisional surgery.^{135 136 137 150} Should not be used for long-term treatment of angle-closure glaucoma.¹⁵⁰ (See Contraindications under Cautions.)

Methazolamide Dosage and Administration

Administration

Administer orally.¹⁵⁰

Dosage

Adults

Glaucoma

Open-angle or Secondary Glaucoma, Acute Angle-closure Glaucoma

Oral

50–100 mg 2 or 3 times daily.¹⁵⁰ Adjust dosage based on patient response and requirements.^a

Related/similar drugs

acetazolamide, pilocarpine ophthalmic, Diamox, Combigan, carbachol ophthalmic, mitomycin ophthalmic

Cautions for Methazolamide

Contraindications

• Marked impairment of hepatic function.¹⁵⁰ Cirrhosis.¹⁵⁰ (See Hepatic Impairment under Cautions.)

• Depressed serum concentrations of sodium and/or potassium.¹⁵⁰

• Adrenocortical insufficiency.¹⁵⁰

• Hyperchloremic acidosis.¹⁵⁰

• Marked impairment of renal function.¹⁵⁰

• Long-term treatment of angle-closure glaucoma; further closure of the angle may occur while worsening of glaucoma is masked by lower IOP.^{150 b}

• Hypersensitivity to methazolamide or any ingredients in the formulation.¹⁵⁰

Warnings/Precautions

Sensitivity Reactions

Sulfonamide Sensitivity Reactions

Serious adverse events (e.g., Stevens-Johnson syndrome, toxic epidermal necrolysis, fulminant hepatic necrosis, agranulocytosis, aplastic anemia, other blood dyscrasias) associated with sulfonamide therapy possible.^{150 b}

Discontinue if signs of hypersensitivity, blood dyscrasias, or other serious reactions occur.^{150 b}

General Precautions

Respiratory Effects

Caution in patients with pulmonary obstruction, emphysema, or advanced pulmonary disease where alveolar ventilation may be impaired.^{150 b} Methazolamide may precipitate or aggravate acidosis in these patients.¹⁵⁰

Laboratory Monitoring

Monitor for hematologic reactions associated with sulfonamides; obtain a CBC and platelet count before therapy and periodically during therapy.¹⁵⁰ Discontinue the drug if clinically important changes occur.¹⁵⁰

Monitor serum electrolytes periodically.¹⁵⁰

Specific Populations

Pregnancy

Category C.¹⁵⁰

Lactation

Not known whether methazolamide is distributed into human milk.^{150 a} Discontinue nursing or drug.¹⁵⁰

Pediatric Use

Safety and efficacy not established.¹⁵⁰

Hepatic Impairment

Avoid use in patients with marked hepatic impairment, including those with cirrhosis, because of the risk of developing hepatic encephalopathy.¹⁵⁰ (See Contraindications.)

Renal Impairment

Avoid use in patients with marked renal impairment.¹⁵⁰ (See Contraindications.)

Common Adverse Effects

Paresthesia, hearing dysfunction or tinnitus, fatigue, malaise, anorexia, altered taste, nausea, vomiting, diarrhea, polyuria, drowsiness, confusion.¹⁵⁰

Drug Interactions

Specific Drugs and Laboratory Tests

Methazolamide Pharmacokinetics

Absorption

Bioavailability

Well absorbed from the GI tract, with peak plasma concentrations usually attained within 1–2 hours.¹⁵⁰

Onset

Reduction in IOP occurs in 2–4 hours; peak effect occurs in 6–8 hours.^{150 b}

Duration

Reduction in IOP persists for 10–18 hours.^{150 b}

Distribution

Extent

Distributed into erythrocytes, extracellular fluid, bile, the aqueous humor of the eye, and CSF.¹⁵⁰

Crosses placenta in unknown quantities.^a

Not known whether methazolamide is distributed into human milk.¹⁵⁰

Plasma Protein Binding

55%.¹⁵⁰

Elimination

Metabolism

Partially metabolized in liver.^a

Elimination Route

About 20–30% of a dose is excreted in urine as active metabolites.^a Fate of the remainder of the dose not determined.^a

Half-life

14 hours.¹⁵⁰

Stability

Storage

Oral

Tablets

Tight container at 20–25°C.¹⁵⁰

Actions

• Noncompetitive reversible inhibitor of the carbonic anhydrase enzyme.^b

• Reduces the formation of hydrogen and bicarbonate ions from carbon dioxide and water, thereby reducing availability of these ions for active transport into secretions.^b

• Decreases aqueous humor secretion and IOP.^{150 b}

• Increases urinary excretion of bicarbonate, sodium, and potassium due to decrease in hydrogen ions in the renal tubules.^b Decreases reabsorption of water, increases urine volume, urine becomes alkaline.^b Plasma bicarbonate concentration is decreased and chloride concentration is increased, resulting in metabolic acidosis.^b The manufacturer states that methazolamide should not be used as a diuretic.¹⁵⁰

• Systemically administered carbonic anhydrase inhibitors have anticonvulsant activity in animals.^b The manufacturer states that methazolamide is not considered an effective anticonvulsant.¹⁵⁰

Advice to Patients

• Risk of adverse effects, including sensitivity reactions; discontinue therapy and consult clinician if signs of sensitivity occur.¹⁵⁰

• Advise patients with pulmonary obstruction or emphysema that the drug may precipitate or aggravate acidosis.¹⁵⁰

• Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs (e.g., high-dose aspirin), as well as concomitant diseases.¹⁵⁰

• Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.¹⁵⁰

• Importance of informing patients of other precautionary information.¹⁵⁰ (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

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