Methazolamide Information
Methazolamide () Description
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-thiadiazol-2(3H)-ylidene]-acetamide, and it has the following structural formula:
Molecular formula: CHNOS
Molecular weight: 236.26
Methazolamide () is available for oral administration as 25 mg and 50 mg tablets containing the following inactive ingredients: Dicalcium Phosphate Dihydrate, Glyceryl Tribehenate, Povidone, Pregelatinized Starch and Sodium Starch Glycolate.
Methazolamide () Clinical Pharmacology
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 (C) 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) were 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 (V/F) ranges from 17 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 20-25% of the total clearance of drug. After repeated BID-TID dosing, Methazolamide () accumulates to steady state concentrations in seven 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 two to four hours, has a peak effect in six to eight hours, and a total duration of ten to eighteen 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 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 () Indications And Usage
Methazolamide () is indicated in the 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 where lowering the intraocular pressure is desired before surgery.
Methazolamide () 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.
Methazolamide () 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.
Methazolamide () 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.
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 () should be used with caution in patients on steroid therapy because of the potential for developing hypokalemia.
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 (see ).
Methazolamide () Adverse Reactions
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 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 ).
Methazolamide () Overdosage
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.
Methazolamide () Dosage And Administration
The effective therapeutic dose administered varies from 50 mg to 100 mg two to three times daily. The drug may be used concomitantly with miotic and osmotic agents.
Methazolamide () How Supplied
Methazolamide () Tablets, 25 mg, are square, white, unscored tablets debossed “93” on one side and debossed “9411” on the other side, supplied in bottles of 100.
Methazolamide () Tablets, 50 mg, are round, white tablets, scored and plain on one side and debossed “93” - “9424” on the other side, supplied in bottles of 100.
Store at controlled room temperature, between 20° and 25°C (68° and 77°F) (see USP).
Manufactured By:
Jerusalem, 91010, Israel
Manufactured For:
Sellersville, PA 18960
Rev. B 5/2003
Methazolamide () Principal Display Panel
Methazolamide ()
Tablets USP
25 mg
Each tablet contains:
Methazolamide () , USP 25 mg
Rx only
100 TABLETS
TEVA
Methazolamide () Principal Display Panel
Methazolamide ()
Tablets USP
50 mg
Each tablet contains:
Methazolamide () , USP 50 mg
Rx only
100 TABLETS
TEVA
