Metolazone: Package Insert and Label Information (Page 2 of 2)

Pregnancy Category B

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. Because animal reproduction studies are not always predictive of human response, metolazone tablets, USP, should be used during pregnancy only if clearly needed. Metolazone crosses the placental barrier and appears in cord blood.

Non-Teratogenic Effects

The use of metolazone tablets, USP, in pregnant women requires that the anticipated benefit be weighed against possible hazards to the fetus. These hazards include fetal or neonatal jaundice, thrombocytopenia, and possibly other adverse reactions which have occurred in the adult. It is not known what effect the use of the drug during pregnancy has on the later growth, development, and functional maturation of the child. No such effects have been reported with metolazone.

Labor And Delivery

Based on clinical studies in which women received metolazone in late pregnancy until the time of delivery, there is no evidence that the drug has any adverse effects on the normal course of labor or delivery.

Nursing Mothers

Metolazone appears in breast milk. Because of the potential for serious adverse reactions in nursing infants from metolazone, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.

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 shallow biconvex, round tablets, and are available in three strengths:

2½ mg, pink, debossed “643” on one side, and “2½” on reverse side.

NDC 0527-2215-37 Bottle of 100’s

5 mg, blue, debossed “644” on one side, and “5” on reverse side.

NDC 0527-2216-37 Bottle of 100’s

10 mg, yellow, debossed “645” on one side, and “10” on reverse side.

NDC 0527-2217-37 Bottle of 100’s

Storage

Store at 25°C (77°F); excursions permitted to 15°-30°C (59°-86°F) [See USP Controlled Room Temperature].

Protect from light. Keep out of the reach of children.

For more information about Metolazone Tablets, USP call 1-844-834-0530.

Distributed by:
Lannett Company, Inc.
Philadelphia, PA 19136

All brand names are the trademarks of their respective owners.


L6789B

Rev. 10/18

PRINCIPAL DISPLAY PANEL — 2½ mg Bottle Label

DC 0527-2215 -37

Metolazone Tablets, USP

2½ mg

Rx Only
100 Tablets

Lannett

label
(click image for full-size original)

PRINCIPAL DISPLAY PANEL — 5 mg Bottle Label

NDC 0527-2216 -37

Metolazone Tablets, USP

5 mg

Rx Only
100 Tablets

Lannett

label
(click image for full-size original)

PRINCIPAL DISPLAY PANEL — 10 mg Bottle Label

NDC 0527-2217 -37

Metolazone Tablets, USP

10 mg

Rx Only
100 Tablets

Lannett

label
(click image for full-size original)


METOLAZONE
metolazone tablet
Product Information
Product Type HUMAN PRESCRIPTION DRUG Item Code (Source) NDC:0527-2215
Route of Administration ORAL DEA Schedule
Active Ingredient/Active Moiety
Ingredient Name Basis of Strength Strength
METOLAZONE (METOLAZONE) METOLAZONE 2.5 mg
Inactive Ingredients
Ingredient Name Strength
MAGNESIUM STEARATE
CELLULOSE, MICROCRYSTALLINE
FD&C RED NO. 40
FD&C BLUE NO. 1
D&C RED NO. 27
Product Characteristics
Color PINK Score no score
Shape ROUND Size 6mm
Flavor Imprint Code 643;2;5
Contains
Packaging
# Item Code Package Description Multilevel Packaging
1 NDC:0527-2215-37 100 TABLET in 1 BOTTLE, PLASTIC None
Marketing Information
Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date
NDA AUTHORIZED GENERIC NDA017386 11/27/1973
METOLAZONE
metolazone tablet
Product Information
Product Type HUMAN PRESCRIPTION DRUG Item Code (Source) NDC:0527-2216
Route of Administration ORAL DEA Schedule
Active Ingredient/Active Moiety
Ingredient Name Basis of Strength Strength
METOLAZONE (METOLAZONE) METOLAZONE 5 mg
Inactive Ingredients
Ingredient Name Strength
MAGNESIUM STEARATE
CELLULOSE, MICROCRYSTALLINE
FD&C BLUE NO. 2
Product Characteristics
Color BLUE Score no score
Shape ROUND Size 6mm
Flavor Imprint Code 644;5
Contains
Packaging
# Item Code Package Description Multilevel Packaging
1 NDC:0527-2216-37 100 TABLET in 1 BOTTLE, PLASTIC None
Marketing Information
Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date
NDA AUTHORIZED GENERIC NDA017386 11/27/1973
METOLAZONE
metolazone tablet
Product Information
Product Type HUMAN PRESCRIPTION DRUG Item Code (Source) NDC:0527-2217
Route of Administration ORAL DEA Schedule
Active Ingredient/Active Moiety
Ingredient Name Basis of Strength Strength
METOLAZONE (METOLAZONE) METOLAZONE 10 mg
Inactive Ingredients
Ingredient Name Strength
MAGNESIUM STEARATE
CELLULOSE, MICROCRYSTALLINE
FD&C YELLOW NO. 6
D&C YELLOW NO. 10
Product Characteristics
Color YELLOW Score no score
Shape ROUND Size 6mm
Flavor Imprint Code 645;10
Contains
Packaging
# Item Code Package Description Multilevel Packaging
1 NDC:0527-2217-37 100 TABLET in 1 BOTTLE, PLASTIC None
Marketing Information
Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date
NDA AUTHORIZED GENERIC NDA017386 11/27/1973
Labeler — Lannett Company, Inc. (002277481)

Revised: 06/2019 Lannett Company, Inc.

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