METOLAZONE (Page 3 of 4)

Pediatric Use

Safety and effectiveness in pediatric patients have not been established in controlled clinical trials. There is limited experience with the use of metolazone tablets, USP, in pediatric patients with congestive heart failure, hypertension, bronchopulmonary dysplasia, nephrotic syndrome and nephrogenic diabetes insipidus. Doses used generally ranged from 0.05 to 0.1 mg/kg administered once daily and usually resulted in a 1 to 2.8 kg weight loss and 150 to 300 cc increase in urine output. Not all patients responded and some gained weight. Those patients who did respond did so in the first few days of treatment. Prolonged use (beyond a few days) was generally associated with no further beneficial effect or a return to baseline status and is not recommended.

There is limited experience with the combination of metolazone tablets, USP, and furosemide in pediatric patients with furosemide-resistant edema. Some benefited while others did not or had an exaggerated response with hypovolemia, tachycardia, and orthostatic hypotension requiring fluid replacement. Severe hypokalemia was reported and there was a tendency for diuresis to persist for up to 24 hours after metolazone tablets, USP, were discontinued. Hyperbilirubinemia has been reported in 1 neonate. Close clinical and laboratory monitoring of all children treated with diuretics is indicated. See CONTRAINDICATIONS, WARNINGS, PRECAUTIONS.

Geriatric Use

Clinical studies of metolazone tablets, USP, 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. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.

This drug is known to be substantially excreted by the kidney, and the risk of toxic reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function.

ADVERSE REACTIONS

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

Central And Peripheral Nervous System

Syncope, neuropathy, vertigo, paresthesias, psychotic depression, impotence, dizziness/lightheadedness, drowsiness, fatigue, weakness, restlessness (sometimes resulting in insomnia), headache.

Dermatologic/Hypersensitivity

Toxic epidermal necrolysis (TEN), Stevens-Johnson Syndrome, necrotizing angiitis (cutaneous vasculitis), skin necrosis, purpura, petechiae, dermatitis (photosensitivity), urticaria, pruritus, skin rashes.

Gastrointestinal

Hepatitis, intrahepatic cholestatic jaundice, pancreatitis, vomiting, nausea, epigastric distress, diarrhea, constipation, anorexia, abdominal bloating, abdominal pain.

Hematologic

Aplastic/hypoplastic anemia, agranulocytosis, leukopenia, thrombocytopenia.

Metabolic

Hypokalemia, hyponatremia, hyperuricemia, hypochloremia, hypochloremic alkalosis, hyperglycemia, glycosuria, increase in serum urea nitrogen (BUN) or creatinine, hypophosphatemia, hypomagnesemia, hypercalcemia.

Musculoskeletal

Joint pain, acute gouty attacks, muscle cramps or spasm.

Other

Transient blurred vision, chills, dry mouth.

In addition, adverse reactions reported with similar antihypertensive-diuretics, but which have not been reported to date for metolazone tablets, USP, include: bitter taste, sialadenitis, xanthopsia, respiratory distress (including pneumonitis), and anaphylactic reactions. These reactions should be considered as possible occurrences with clinical usage of metolazone tablets, USP.

Whenever adverse reactions are moderate or severe, metolazone tablets, USP, dosage should be reduced or therapy withdrawn.

OVERDOSAGE

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. Also, GI irritation and hypermotility may occur. Temporary elevation of BUN has been reported, especially in patients with impairment of renal function. Serum electrolyte changes and cardiovascular and renal function should be closely monitored.

Treatment

There is no specific antidote available but immediate evacuation of stomach contents is advised. Dialysis is not likely to be effective. Care should be taken when evacuating the gastric contents to prevent aspiration, especially in the stuporous or comatose patient. Supportive measures should be initiated as required to maintain hydration, electrolyte balance, respiration, and cardiovascular and renal function.

DOSAGE AND ADMINISTRATION

Effective dosage of metolazone tablets, USP, should be individualized according to indication and patient response. A single daily dose is recommended. Therapy with metolazone tablets, USP, 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, USP, 5 to 20 mg once daily.
  • Edema of renal disease:
    Metolazone tablets, USP, 5 to 20 mg once daily.
  • Mild to moderate essential hypertension:
    Metolazone tablets, USP, 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 metolazone tablets, USP, to MYKROX, the dose should be determined by titration starting at one tablet (½ 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. If antihypertensive drugs or diuretics are given concurrently with metolazone tablets, USP, more careful dosage adjustment may be necessary. For patients who tend to experience paroxysmal nocturnal dyspnea, it may be advisable to employ a larger dose to ensure prolongation of diuresis and saluresis for a full 24-hour period.

Treatment Of Hypertension

The time interval required for the initial dosage regimen to show effect may vary from three or four days to three to six weeks in the treatment of elevated blood pressure. Doses should be adjusted at appropriate intervals to achieve maximum therapeutic effect.

HOW SUPPLIED

Metolazone tablets, USP, are round tablets, and are available in three strengths:

2½ mg, White to off-white, debossed with “17” on one side and “Λ” on the other side.

NDC 72888-052-01 Bottle of 100’s

5 mg, White to off-white, debossed with “25” on one side and “Λ” on the other side.

NDC 72888-053-01 Bottle of 100’s

10 mg, Pale yellow to yellow colored, debossed with “27” on one side and “Λ” on the other side.

NDC 72888-054-01 Bottle of 100’s

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