Zaroxolyn (Metolazone) - Description and Clinical Pharmacology

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 WARNINGS and PRECAUTIONS, 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.