Zaroxolyn Information
Zaroxolyn () Description
Zaroxolyn () Tablets (metolazone tablets, USP) for oral administration contain 2½, 5, or 10 mg of metolazone, USP, a diuretic/saluretic/antihypertensive drug of the quinazoline class.
Metolazone has the molecular formula CHClNS, 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. The structural formula is:
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: 2½ mg-D&C Red No. 33; 5 mg-FD&C Blue No. 2; 10 mg-D&C Yellow No. 10 and FD&C Yellow No. 6.
Zaroxolyn () 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 ).
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:
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 Tablets (UCB).
Zaroxolyn () Contraindications
Anuria, hepatic coma or precoma, known allergy or hypersensitivity to metolazone.
Zaroxolyn () Adverse Reactions
Zaroxolyn () is usually well tolerated, and most reported adverse reactions have been mild and transient. Many Zaroxolyn () related adverse reactions represent extensions of its expected pharmacologic activity and can be attributed to either its antihypertensive action or its renal/metabolic actions. The following adverse reactions have been reported. Several are single or comparably rare occurrences. Adverse reactions are listed in decreasing order of severity within body systems.
Transient blurred vision, chills, dry mouth.
In addition, adverse reactions reported with similar antihypertensive-diuretics, but which have not been reported to date for Zaroxolyn () include: bitter taste, sialadenitis, xanthopsia, respiratory distress (including pneumonitis), and anaphylactic reactions. These reactions should be considered as possible occurrences with clinical usage of Zaroxolyn () .
Whenever adverse reactions are moderate or severe, Zaroxolyn () dosage should be reduced or therapy withdrawn.
Zaroxolyn () Overdosage
Intentional overdosage has been reported rarely with metolazone and similar diuretic drugs.
Zaroxolyn () 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.
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 () 2½ 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.
Zaroxolyn () How Supplied
Zaroxolyn () Tablets (metolazone tablets, USP) are shallow biconvex, round tablets, and are available in three strengths:
2½ mg, pink, debossed “Zaroxolyn () ” on one side, and “2½” on reverse side.
NDC 53014-975-71 Bottle of 100’s
5 mg, blue, debossed “Zaroxolyn () ” on one side, and “5” on reverse side.
NDC 53014-850-71 Bottle of 100’s
10 mg, yellow, debossed “Zaroxolyn () ” on one side, and “10” on reverse side.
NDC 53014-835-71 Bottle of 100’s
Zaroxolyn () For Medical Information
Contact: Medical Affairs Department Phone: (866) 822-0068 Fax: (770) 970-8859
UCB, Inc. Smyrna, GA 30080
Zaroxolyn () is a registered trademark of UCB Manufacturing, Inc., Rochester, NY 14623© 2007, UCB, Inc., Smyrna, GA 30080 All rights reserved.
Rev. 1E 06/2007 4000671
