ZAROXOLYN- metolazone tablet
DO NOT INTERCHANGE ZAROXOLYN TABLETS AND OTHER FORMULATIONS OF METOLAZONE THAT SHARE ITS SLOW AND INCOMPLETE BIOAVAILABILITY AND ARE THERAPEUTICALLY EQUIVALENT AT THE SAME DOSES TO MYKROX� TABLETS, A MORE RAPIDLY AVAILABLE AND COMPLETELY BIOAVAILABLE METOLAZONE PRODUCT. FORMULATIONS BIOEQUIVALENT TO ZAROXOLYN AND FORMULATIONS BIOEQUIVALENT TO MYKROX SHOULD BE INTERCHANGED FOR ONE ANOTHER.DO NOT INTERCHANGE:
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DESCRIPTION
ZAROXOLYN Tablets (metolazone tablets, USP) for oral administration contain 2� or 5 mg of metolazone, USP, a diuretic/saluretic/antihypertensive drug of the quinazoline class.
Metolazone has the molecular formula C H ClN S, the chemical name 7-chloro-1, 2, 3, 4-tetrahydro-2-methyl-3-(2-methylphenyl)-4-oxo-6-quinazolinesulfonamide, and a molecular weight of 365.83.
Metolazone is only sparingly soluble in water, but more soluble in plasma, blood, alkali, and organic solvents.
Inactive Ingredients: Magnesium stearate, microcrystalline cellulose and dye: 2� mg-D&C Red No. 33; 5 mg-FD&C Blue No. 2.
CLINICAL PHARMACOLOGY
ZAROXOLYN (metolazone) is a quinazoline diuretic, with properties generally similar to the thiazide diuretics. The actions of ZAROXOLYN result from interference with the renal tubular mechanism of electrolyte reabsorption. ZAROXOLYN acts primarily to inhibit sodium reabsorption at the cortical diluting site and to a lesser extent in the proximal convoluted tubule. Sodium and chloride ions are excreted in approximately equivalent amounts. The increased delivery of sodium to the distal tubular exchange site results in increased potassium excretion. ZAROXOLYN does not inhibit carbonic anhydrase. A proximal action of metolazone has been shown in humans by increased excretion of phosphate and magnesium ions and by a markedly increased fractional excretion of sodium in patients with severely compromised glomerular filtration. This action has been demonstrated in animals by micropuncture studies.
When ZAROXOLYN Tablets are given, diuresis and saluresis usually begin within one hour and may persist for 24 hours or more. For most patients, the duration of effect can be varied by adjusting the daily dose. High doses may prolong the effect. A single daily dose is recommended. When a desired therapeutic effect has been obtained, it may be possible to reduce dosage to a lower maintenance level.
The diuretic potency of ZAROXOLYN at maximum therapeutic dosage is approximately equal to thiazide diuretics. However, unlike thiazides, ZAROXOLYN may produce diuresis in patients with glomerular filtration rates below 20 mL/min.
ZAROXOLYN and furosemide administered concurrently have produced marked diuresis in some patients where edema or ascites was refractory to treatment with maximum recommended doses of these or other diuretics administered alone. The mechanism of this interaction is unknown (see and ).WARNINGSPRECAUTIONS, Drug Interactions
Maximum blood levels of metolazone are found approximately eight hours after dosing. A small fraction of metolazone is metabolized. Most of the drug is excreted in the unconverted form in the urine.
Zaroxolyn Indications and Usage
ZAROXOLYN is indicated for the treatment of salt and water retention including:
edema accompanying congestive heart failure;
edema accompanying renal diseases, including the nephrotic syndrome and states of diminished renal function.
ZAROXOLYN is also indicated for the treatment of hypertension, alone or in combination with other antihypertensive drugs of a different class. MYKROX Tablets, a more rapidly available form of metolazone, are intended for the treatment of new patients with mild to moderate hypertension. A dose titration is necessary if MYKROX Tablets are to be substituted for ZAROXOLYN in the treatment of hypertension. See package circular for MYKROX Tablet
DOSAGE AND ADMINISTRATION
Effective dosage of ZAROXOLYN should be individualized according to indication and patient response. A single daily dose is recommended. Therapy with ZAROXOLYN should be titrated to gain an initial therapeutic response and to determine the minimal dose possible to maintain the desired therapeutic response.
Usual Single Daily Dosage Schedules
Suitable initial dosages will usually fall in the ranges given.
Edema of cardiac failure: ZAROXOLYN 5 to 20 mg once daily.
Edema of renal disease: ZAROXOLYN 5 to 20 mg once daily.
Mild to moderate essential hypertension: ZAROXOLYN 2� to 5 mg once daily.
New patients � MYKROX Tablets (metolazone tablets, USP) (see MYKROX package circular). If considered desirable to switch patients currently on ZAROXOLYN to MYKROX, the dose should be determined by titration starting at one tablet (1/2 mg) once daily and increasing to two tablets (1 mg) once daily if needed.
