Methazolamide

Class: Carbonic Anhydrase Inhibitors
ATC Class: S01EC05
VA Class: CV703
CAS Number: 554-57-4

Introduction

Carbonic anhydrase inhibitor; nonbacteriostatic sulfonamide derivative.a b c

Uses for Methazolamide

Glaucoma

Adjunctive treatment of open-angle or secondary glaucoma.a c

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Short-term use in acute angle-closure glaucoma to lower intraocular pressure (IOP) before surgery.c Should notbe used for long-term treatment of angle-closure glaucoma.c (See Contraindications.)

Methazolamide Dosage and Administration

Administration

Administer orally.c

Dosage

Adjust dosage based on patient response and requirements. a

Adults

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

50–100 mg 2 or 3 times daily. c

Cautions for Methazolamide

Contraindications

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

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

  • Adrenocortical insufficiency.c

  • Hyperchloremic acidosis.c

  • Marked impairment of renal function.c

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

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

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.b c

Discontinue if signs of hypersensitivity, blood dyscrasias, or other serious reactions occur.b c

General Precautions

Respiratory Effects

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

Laboratory Monitoring

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

Monitor serum electrolytes periodically.c

Specific Populations

Pregnancy

Category C.c

Lactation

Not known whether methazolamide is distributed into human milk.a c Discontinue nursing or drug.c

Pediatric Use

Safety and efficacy not established.c

Hepatic Impairment

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

Renal Impairment

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

Common Adverse Effects

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

Interactions for Methazolamide

Specific Drugs and Laboratory Tests

Drug or Test

Interaction

Comments

Amphetamine

Decreased urinary excretion of amphetamines; potentiates the effects of amphetaminesb

Amphotericin B

Possible enhanced potassium depletionb

Antidiabetic agents (oral agents, insulin)

May interfere with the hypoglycemic responseb

Aspirin

Increased risk of toxicityc

Avoid concomitant use in patients receiving high-dose aspirinc

Carbonic anhydrase inhibitors, topical

Additive systemic effectsd

Concomitant use not recommendedd

Corticosteroids

Possible enhanced potassium depletionc

Digitalis glycosides

Methazolamide-induced hypokalemia may potentiate toxicity of digitalisb

Lithium

Increased renal excretion of lithiumb

Monitor patientb

Methenamine

May interfere with urinary antiseptic effect of methenamineb

Quinidine

Decreased urinary excretion of quinidineb

Tests for urinary protein

False-positive results with tests that use bromophenol blue reagent (Albustix) or sulfosalicylic acidb

Methazolamide Pharmacokinetics

Absorption

Bioavailability

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

Onset

Reduction in IOP occurs in 2–4 hours; peak effect occurs in 6–8 hours.b c

Duration

Reduction in IOP persists for 10–18 hours.b c

Distribution

Extent

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

Crosses placenta in unknown quantities.a

Not known whether methazolamide is distributed into human milk.c

Plasma Protein Binding

55%.c

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.c

Stability

Storage

Oral

Tablets

Well-closed containers at 15–30°C.c

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.b c

  • 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.c

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

Advice to Patients

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

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

  • 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.c

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

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

Preparations

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

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

Methazolamide

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Tablets

25 mg*

Methazolamide Tablets

Sandoz, Teva

50 mg*

Methazolamide Tablets

Sandoz, Teva

AHFS DI Essentials. © Copyright, 2004-2014, Selected Revisions September 1, 2007. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

References

a. AHFS drug information 2007. McEvoy GK, ed. Methazolamide. Bethesda, MD: American Society of Health-System Pharmacists; 2007: 2885-6.

b. AHFS drug information 2007. McEvoy GK, ed. Carbonic Anhydrase Inhibitors General Statement. Bethesda, MD: American Society of Health-System Pharmacists; 2007: 2877-80.

c. Effcon Laboratories. Methazolamide tablet prescribing information. Marietta, GA; 1993 Oct.

d. Alcon. Azopt (brinzolamide) ophthalmic suspension 1% prescribing information. Fort Worth, TX; 2003 Dec.

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