Methazolamide

Mechanism of Action

Carbonic anhydrase inhibitor, decr rate of aqueous humor formation and decreased IOP

Pharmacokinetics

Half-life: 14 d

Onset: 2-4 hr

Max Effect: 6-8 hr

Duration: 10-18 hr

Bioavailability: absorbed more slowly than acetazolamide

Excretion: urine 15%

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

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.

Supportive measures may be required to restore electrolyte and pH balance.

Adverse reactions common to all sulfonamide derivatives may occur: anaphylaxis, fever, rash (including erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis), crystalluria, renal calculus, bone marrow depression, thrombocytopenic purpura, hemolytic anemia, leukopenia, pancytopenia and agranulocytosis. Precaution is advised for early detection of such reactions and the drug should be discontinued and appropriate therapy instituted.

Caution is advised for patients receiving high-dose aspirin and methazolamide concomitantly.

Methazolamide is used in the treatment of:

• Glaucoma, Angle-Closure
• Glaucoma, Open-Angle

This medication may be prescribed for other uses. Ask your doctor or pharmacist for more information.

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. Also see PRECAUTIONS: Information for Patients for possible reactions common to sulfonamide derivatives. 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 (see WARNINGS).

Read the entire FDA prescribing information for Methazolamide (Methazolamide)

• Diuretics
• Glaucoma

© Methazolamide Patient Information is supplied by Cerner Multum, Inc. and Methazolamide Consumer information is supplied by First Databank, Inc., used under license and subject to their respective copyrights.

Take the missed dose as soon as you remember. Skip the missed dose if it is almost time for your next scheduled dose. Do not take extra medicine to make up the missed dose.

Usual Adult Dose for Glaucoma:

50 to 100 mg orally 2 or 3 times a day

Comments: May be used concomitantly with miotic and osmotic agents.

Use: Treatment 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.

• 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

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

• Tell all of your health care providers that you take this medicine. This includes your doctors, nurses, pharmacists, and dentists.
• Avoid driving and doing other tasks or actions that call for you to be alert until you see how methazolamide affects you.
• Have your eye pressure and eyesight checked as you have been told by the doctor.
• Have blood work checked as you have been told by the doctor. Talk with the doctor.
• This medicine may affect certain lab tests. Tell all of your health care providers and lab workers that you take this medicine.
• This medicine may make you sunburn more easily. Use care if you will be in the sun. Tell your doctor if you sunburn easily while taking this drug.
• If you are also taking aspirin, talk with your doctor. Loss of hunger, fast breathing, sluggishness, coma, and death have happened in people taking high doses of aspirin with methazolamide.
• If you are 65 or older, use this medicine with care. You could have more side effects.
• Tell your doctor if you are pregnant or plan on getting pregnant. You will need to talk about the benefits and risks of using methazolamide while you are pregnant.

WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:

• Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.
• Signs of electrolyte problems like mood changes, confusion, muscle pain or weakness, a heartbeat that does not feel normal, seizures, not hungry, or very bad upset stomach or throwing up.
• Signs of too much acid in the blood (acidosis) like confusion; fast breathing; fast heartbeat; a heartbeat the does not feel normal; very bad stomach pain, upset stomach, or throwing up; feeling very sleepy; shortness of breath; or feeling very tired or weak.
• Change in eyesight.
• Change in hearing.
• Ringing in ears.
• A burning, numbness, or tingling feeling that is not normal.
• Passing urine more often.
• Very bad and rarely deadly effects have happened with sulfa (sulfonamide) drugs like this one. These effects have included liver problems, blood problems, and very bad skin reactions (Stevens-Johnson syndrome/toxic epidermal necrolysis). Call your doctor right away if you have a rash; red, swollen, blistered, or peeling skin; red or irritated eyes; sores in your mouth, throat, nose, or eyes; fever, chills, or sore throat; cough that is new or worse; feeling very tired or weak; any bruising or bleeding; or signs of liver problems like dark urine, feeling tired, not hungry, upset stomach or stomach pain, light-colored stools, throwing up, or yellow skin or eyes.

Methazolamide is a potent inhibitor of carbonic anhydrase.

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.

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.

Methazolamide Tablets USP, 25 mg
NDC 62559-240-01
Rx Only
100 Tablets

(meth a ZOE la mide)

Alpha-/Beta-Agonists (Indirect-Acting): Carbonic Anhydrase Inhibitors may increase the serum concentration of Alpha-/Beta-Agonists (Indirect-Acting). Monitor therapy

Amantadine: Carbonic Anhydrase Inhibitors may increase the serum concentration of Amantadine. Monitor therapy

Amphetamines: Carbonic Anhydrase Inhibitors may decrease the excretion of Amphetamines. Monitor therapy

Analgesics (Opioid): May enhance the adverse/toxic effect of Diuretics. Analgesics (Opioid) may diminish the therapeutic effect of Diuretics. Monitor therapy

CarBAMazepine: Carbonic Anhydrase Inhibitors may increase the serum concentration of CarBAMazepine. Monitor therapy

Carbonic Anhydrase Inhibitors: May enhance the adverse/toxic effect of other Carbonic Anhydrase Inhibitors. The development of acid-base disorders with concurrent use of ophthalmic and oral carbonic anhydrase inhibitors has been reported. Management: Avoid concurrent use of different carbonic anhydrase inhibitors if possible. Monitor patients closely for the occurrence of kidney stones and with regards to severity of metabolic acidosis. Avoid combination

Diacerein: May enhance the therapeutic effect of Diuretics. Specifically, the risk for dehydration or hypokalemia may be increased. Monitor therapy

Flecainide: Carbonic Anhydrase Inhibitors may increase the serum concentration of Flecainide. Monitor therapy

Fosphenytoin-Phenytoin: Carbonic Anhydrase Inhibitors may enhance the adverse/toxic effect of Fosphenytoin-Phenytoin. Specifically, the risk for osteomalacia or rickets may be increased. Monitor therapy

Lithium: Carbonic Anhydrase Inhibitors may decrease the serum concentration of Lithium. Monitor therapy

Memantine: Carbonic Anhydrase Inhibitors may increase the serum concentration of Memantine. Monitor therapy

MetFORMIN: Carbonic Anhydrase Inhibitors may enhance the adverse/toxic effect of MetFORMIN. Specifically, the risk of developing lactic acidosis may be increased. Monitor therapy

Methenamine: Carbonic Anhydrase Inhibitors may diminish the therapeutic effect of Methenamine. Management: Consider avoiding this combination. Monitor for decreased therapeutic effects of methenamine if used concomitant with a carbonic anhydrase inhibitor. Consider therapy modification

Primidone: Carbonic Anhydrase Inhibitors may enhance the adverse/toxic effect of Primidone. Specifically, osteomalacia and rickets. Carbonic Anhydrase Inhibitors may decrease the serum concentration of Primidone. Monitor therapy

QuiNIDine: Carbonic Anhydrase Inhibitors may decrease the excretion of QuiNIDine. Monitor therapy

Salicylates: May enhance the adverse/toxic effect of Carbonic Anhydrase Inhibitors. Salicylate toxicity might be enhanced by this same combination. Management: Avoid these combinations when possible.Dichlorphenamide use with high-dose aspirin as contraindicated. If another combination is used, monitor patients closely for adverse effects. Tachypnea, anorexia, lethargy, and coma have been reported. Consider therapy modification

Sodium Phosphates: Diuretics may enhance the nephrotoxic effect of Sodium Phosphates. Specifically, the risk of acute phosphate nephropathy may be enhanced. Management: Consider avoiding this combination by temporarily suspending treatment with diuretics, or seeking alternatives to oral sodium phosphate bowel preparation. If the combination cannot be avoided, hydrate adequately and monitor fluid and renal status. Consider therapy modification

Trientine: Carbonic Anhydrase Inhibitor Diuretics may decrease the serum concentration of Trientine. Monitor therapy

LactMed Record Number

777

Last Revision Date

20150310

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