Metolazone

Metolazone 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. Metolazone 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. …

• 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
• Usual Single Daily Dosage Schedules Suitable initial dosages will usually fall in the ranges given
• Edema of cardiac failure: Metolazone tablets, 5 mg to 20 mg once daily
• Edema of renal disease: Metolazone tablets, 5 mg to 20 mg once daily
• Mild to moderate essential hypertension: Metolazone tablets, 2.5 mg to 5 mg once daily
• New patients - If considered desirable to switch patients currently on Zaroxolyn ® tablets and other formulations of metolazone that share its slow and incomplete bioavailability to Mykrox ® , the dose should be determined by titration starting at one tablet (0.5 mg) once daily and increasing to two tablets (1 mg) once daily if needed
• Treatment of Edematous States The time interval required for the initial dosage to produce an effect may vary
• Diuresis and saluresis usually begin within one hour and persist for 24 hours or longer
• When a desired therapeutic effect has been obtained, it may be advisable to reduce the dose if possible
• The daily dose depends on the severity of the patient's condition, sodium intake, and responsiveness
• A decision to change the daily dose should be based on the results of thorough clinical and laboratory evaluations. …

• Safety and effectiveness
• In pediatric patients have not been established in controlled clinical trials
• There is limited experience with the use of metolazone
• In pediatric patients with congestive heart failure, hypertension, bronchopulmonary dysplasia, nephrotic syndrome and nephrogenic diabetes insipidus
• Doses used generally ranged from 0.05 mg/kg to 0.1 mg/kg administered once daily and usually resulted in a 1 kg to 2.8 kg weight loss and 150 cc to 300 cc increase in urine output
• Not all patients responded and some gained weight. …

Clinical studies of metolazone did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. …

Patients should be informed of possible adverse effects, advised to take the medication as directed and promptly report any possible adverse reactions to the treating physician.

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

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. …

Metolazone is usually well tolerated and most reported adverse reactions have been mild and transient. Many metolazone 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. Cardiovascular Chest pain/discomfort, orthostatic hypotension, excessive volume depletion, hemoconcentration, venous thrombosis, palpitations. …

Pregnancy Teratogenic Effects Reproduction studies performed in mice, rabbits and rats treated during the appropriate period of gestation at doses up to 50 mg/kg/day have revealed no evidence of harm to the fetus due to metolazone. There are, however, no adequate and well-controlled studies in pregnant women. …

Intentional overdosage has been reported rarely with metolazone and similar diuretic drugs. Signs and Symptoms Orthostatic hypotension, dizziness, drowsiness, syncope, electrolyte abnormalities, hemoconcentration and hemodynamic changes due to plasma volume depletion may occur. In some instances depressed respiration may be observed. At high doses, lethargy of varying degree may progress to coma within a few hours. The mechanism of CNS depression with thiazide overdosage is unknown. …

Take it when you remember, unless it is nearly time for the next dose. Then skip the missed one. Never take two doses at once to make up for it. Check your leaflet, as some medicines are different.