METHAZOLAMIDE- methazolamide tablet
Sandoz Inc
DESCRIPTION
Methazolamide, a sulfonamide derivative, is a white crystalline powder, weakly acidic, and slightly soluble in water, alcohol and acetone. It is available as 25 mg and 50 mg tablets. The chemical name for methazolamide is N -[5-(aminosulfonyl)-3-methyl-1,3,4-thiadiazol-2(3H)-ylidene]-acetamide. Methazolamide tablets, USP contain 25 mg or 50 mg of methazolamide. Inactive ingredients: croscarmellose sodium, hydroxypropyl methylcellulose, lactose (monohydrate), magnesium stearate, microcrystalline cellulose, and sodium lauryl sulfate.
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 b.i.d., 50 mg b.i.d. and 100 mg b.i.d. demonstrated a linear relationship between plasma methazolamide levels and methazolamide dose. Peak plasma concentrations (Cmax ) for the 25 mg, 50 mg and 100 mg b.i.d. 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 extracellular fluid. The mean apparent volume of distribution (Varea /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 b.i.d., 50 mg b.i.d. and 100 mg b.i.d., 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 b.i.d.-t.i.d. 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.
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.
