Rapid Onset Hyponatremia and/or Hypokalemia
Rarely, the rapid onset of severe hyponatremia and/or hypokalemia has been reported following initial doses of thiazide and non-thiazide diuretics. When symptoms consistent with severe electrolyte imbalance appear rapidly, drug should be discontinued and supportive measures should be initiated immediately. Parenteral electrolytes may be required. Appropriateness of therapy with this class of drugs should be carefully reevaluated.
Hypokalemia
Hypokalemia may occur with consequent weakness, cramps, and cardiac dysrhythmias. Serum potassium should be determined at regular and appropriate intervals, and dose reduction, potassium supplementation or addition of a potassium-sparing diuretic instituted whenever indicated. Hypokalemia is a particular hazard in patients who are digitalized or who have or have had a ventricular arrhythmia; dangerous or fatal arrhythmias may be precipitated. Hypokalemia is dose related.
Concomitant Therapy
Lithium
In general, diuretics should not be given concomitantly with lithium because they reduce its renal clearance and add a high risk of lithium toxicity. Read prescribing information for lithium preparations before use of such concomitant therapy.
Furosemide
Unusually large or prolonged losses of fluids and electrolytes may result when metolazone is administered concomitantly to patients receiving furosemide (see PRECAUTIONS, Drug Interactions).
Other Antihypertensive Drugs
When metolazone is used with other antihypertensive drugs, particular care must be taken to avoid excessive reduction of blood pressure, especially during initial therapy.
Cross-Allergy
Cross-allergy may occur when metolazone is given to patients known to be allergic to sulfonamide-derived drugs, thiazides, or quinethazone.
Sensitivity Reactions
Sensitivity reactions (e.g., angioedema, bronchospasm) may occur with or without a history of allergy or bronchial asthma and may occur with the first dose of metolazone.
There is currently no manufacturer warning information available for this drug.
Metolazone tablets USP are 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.
Metolazone tablets USP are 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® tablets and other formulations of metolazone that share its slow and incomplete bioavailability, in the treatment of hypertension.
Usage In Pregnancy
The routine use of diuretics in an otherwise healthy woman is inappropriate and exposes mother and fetus to unnecessary hazard. Diuretics do not prevent development of toxemia of pregnancy, and there is no evidence that they are useful in the treatment of developed toxemia.
Edema during pregnancy may arise from pathologic causes or from the physiologic and mechanical consequence of pregnancy. Metolazone tablets USP are indicated in pregnancy when edema is due to pathologic causes, just as it is in the absence of pregnancy (see PRECAUTIONS). Dependent edema in pregnancy resulting from restriction of venous return by the expanded uterus is properly treated through elevation of the lower extremities and use of support hose; use of diuretics to lower intravascular volume in this case is illogical and unnecessary. There is hypervolemia during normal pregnancy which is harmful to neither the fetus nor the mother (in the absence of cardiovascular disease), but which is associated with edema, including generalized edema, in the majority of pregnant women. If this edema produces discomfort, increased recumbency will often provide relief. In rare instances, this edema may cause extreme discomfort which is not relieved by rest. In these cases, a short course of diuretics may be appropriate.
Metolazone Tablets USP for oral administration contain 2.5 mg, 5 mg or 10 mg of metolazone USP, a diuretic/saluretic/antihypertensive drug of the quinazoline class.
Metolazone has the molecular formula C16H16ClN3O3S, the chemical name 7-chloro-1,2,3,4-tetrahydro-2-methyl-4-oxo-3-o-tolyl-6-quinazolinesulfonamide, and a molecular weight of 365.84. The structural formula is:
Metolazone is only sparingly soluble in water, but more soluble in plasma, blood, alkali, and organic solvents.
Inactive Ingredients: colloidal silicon dioxide, magnesium stearate, microcrystalline cellulose and dye: 2.5 mg – D&C red No. 30 and FD&C blue No. 2; 5 mg – FD&C blue No. 2; 10 mg – D&C yellow No. 10 and FD&C yellow No. 6.
