Metolazone

What it is used for

Metolazone tablets 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 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 metolazone tablets in the treatment of hypertension. See package circular for MYKROX Tablets.

How to take it

Effective dosage of metolazone tablets should be individualized according to indication and patient response. A single daily dose is recommended. Therapy with metolazone tablets should be titrated to gain an initial therapeutic response and to determine the minimal dose possible to maintain the desired therapeutic response.

Side effects, and when to stop

Metolazone tablets are usually well tolerated, and most reported adverse reactions have been mild and transient. Many of metolazone tablets 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.

Who should not take it

Anuria, hepatic coma or precoma, known allergy or hypersensitivity to metolazone.

Warnings

DO NOT INTERCHANGE

DO NOT INTERCHANGE METOLAZONE TABLETS ZAROXOLYN TABLETS, AND OTHER FORMULATIONS OF METOLAZONE THAT SHARE THEIR SLOW AND INCOMPLETE BIOAVAILABILITY AND ARE NOT 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 NOT BE INTERCHANGED FOR ONE ANOTHER.

Other medicines and interactions

Diuretics

Furosemide and probably other loop diuretics given concomitantly with metolazone can cause unusually large or prolonged losses of fluid and electrolytes (see WARNINGS ).

Other Antihypertensives

When metolazone tablets are used with other antihypertensive drugs, care must be taken, especially during initial therapy. Dosage adjustments of other antihypertensives may be necessary.

Alcohol, Barbiturates, And Narcotics

The hypotensive effects of these drugs may be potentiated by the volume contraction that may be associated with metolazone therapy.

Digitalis Glycosides

Diuretic-induced hypokalemia can increase the sensitivity of the myocardium to digitalis. Serious arrhythmias can result.

Corticosteroids Or ACTH

May increase the risk of hypokalemia and increase salt and water retention.

Lithium

Serum lithium levels may increase (see WARNINGS ).

Curariform Drugs

Diuretic-induced hypokalemia may enhance neuromuscular blocking effects of curariform drugs (such as tubocurarine) – the most serious effect would be respiratory depression which could proceed to apnea. Accordingly, it may be advisable to discontinue metolazone tablets three days before elective surgery.

Salicylates And Other Non-Steroidal Anti-Inflammatory Drugs

May decrease the antihypertensive effects of metolazone tablets.

Sympathomimetics

Metolazone may decrease arterial responsiveness to norepinephrine, but this diminution is not sufficient to preclude effectiveness of the pressor agent for therapeutic use.

Insulin And Oral Antidiabetic Agents

See Glucose Tolerance under PRECAUTIONS, General.

Methenamine

Efficacy may be decreased due to urinary alkalizing effect of metolazone.

Anticoagulants

Metolazone, as well as other thiazide-like diuretics, may affect the hypoprothrombinemic response to anticoagulants; dosage adjustments may be necessary.

General

Fluid And Electrolytes

All patients receiving therapy with metolazone tablets should have serum electrolyte measurements done at appropriate intervals and be observed for clinical signs of fluid and/or electrolyte imbalance: namely, hyponatremia, hypochloremic alkalosis, and hypokalemia. In patients with severe edema accompanying cardiac failure or renal disease, a low-salt syndrome may be produced, especially with hot weather and a low-salt diet. Serum and urine electrolyte determinations are particularly important when the patient has protracted vomiting, severe diarrhea, or is receiving parenteral fluids. Warning signs of imbalance are: dryness of mouth, thirst, weakness, lethargy, drowsiness, restlessness, muscle pains or cramps, muscle fatigue, hypotension, oliguria, tachycardia, and gastrointestinal disturbances such as nausea and vomiting. Hyponatremia may occur at any time during long term therapy and, on rare occasions, may be life threatening.

The risk of hypokalemia is increased when larger doses are used, when diuresis is rapid, when severe liver disease is present, when corticosteroids are given concomitantly, when oral intake is inadequate or when excess potassium is being lost extrarenally, such as with vomiting or diarrhea.

Thiazide-like diuretics have been shown to increase the urinary excretion of magnesium; this may result in hypomagnesemia.

Glucose Tolerance

Metolazone may raise blood glucose concentrations possibly causing hyperglycemia and glycosuria in patients with diabetes or latent diabetes.

Hyperuricemia

Metolazone tablets regularly cause an increase in serum uric acid and can occasionally precipitate gouty attacks even in patients without a prior history of them.

Azotemia

Azotemia, presumably prerenal azotemia, may be precipitated during the administration of metolazone tablets. If azotemia and oliguria worsen during treatment of patients with severe renal disease, metolazone tablets should be discontinued.

Renal Impairment

Use caution when administering metolazone tablets to patients with severely impaired renal function. As most of the drug is excreted by the renal route, accumulation may occur.

Orthostatic Hypotension

Orthostatic hypotension may occur; this may be potentiated by alcohol, barbiturates, narcotics, or concurrent therapy with other antihypertensive drugs.

Hypercalcemia

Hypercalcemia may infrequently occur with metolazone, especially in patients taking high doses of vitamin D or with high bone turnover states, and may signify hidden hyperparathyroidism. Metolazone should be discontinued before tests for parathyroid function are performed.

Systemic Lupus Erythematosus

Thiazide diuretics have exacerbated or activated systemic lupus erythematosus and this possibility should be considered with metolazone tablets.