ZAROXOLYN

1 Dosing Considerations Effective dosage of ZAROXOLYN should be individualized according to indications and patient response. A single daily dose is recommended. Therapy with ZAROXOLYN should be titrated to gain an initial therapeutic response and to determine the minimal dose possible to maintain the desired therapeutic response.

2 Recommended Dose and Dosage Adjustment Edema The recommended dose of ZAROXOLYN for treatment of edema of cardiac failure is 5-10 mg once daily and 20 mg once daily for treatment of edema of renal disease. The time interval for the initial dosage to show effect may vary; diuresis and saluresis usually begin within one hour and persist for 12 to 24 hours, depending on dosage.

When a desired therapeutic ZAROXOLYN® (metolazone) Page 5 of 23 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 upon the results of thorough clinical and laboratory determinations. If other antihypertensive drugs or diuretics are given concurrently with ZAROXOLYN, more careful dosage adjustment may be necessary.

For patients with congestive cardiac failure who tend to experience paroxysmal nocturnal dyspnea, it is usually advisable to employ a dosage near the upper end of the range to ensure prolongation of diuresis and saluresis for a full 24-hour period.

5 to 5 mg, once daily. The time interval required for the initial dosage regimen of ZAROXOLYN to show effect may vary from three to 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.

Drug discontinuation When symptoms consistent with severe electrolyte imbalance appear rapidly, the drug should be discontinued, and supportive measures should be initiated immediately. If azotemia and oliguria worsen during treatment of patients with severe renal disease, metolazone should be discontinued.

5 Administration Take ZAROXOLYN as prescribed by your healthcare professional. 6 Missed Dose Patients should be instructed to take ZAROXOLYN at the next scheduled dose and not take two doses at the same time if they miss a dose.

). 1 Pregnant Women Since metolazone crosses the placenta and appears in cord blood, its administration to women of childbearing age requires that the potential benefits of the drug be weighed against its possible hazards to the fetus.

The potential effects on the fetus include fetal or neonatal jaundice, thrombocytopenia, and possibly other adverse reactions which have occurred in the adult. However, teratogenic studies in mice, rats and rabbits, have not shown teratologic effects in these animals.

2 Breast-feeding Metolazone appears in breast milk. Thus, it is possible that the effects of metolazone may occur in the newborn under these circumstances. If the use of metolazone is deemed essential for a nursing mother, the patient should stop nursing.

3 Pediatrics Based on the data submitted and reviewed by Health Canada, the safety and effectiveness in children have not been established; therefore, metolazone is not recommended for use in the pediatric age group. 4 Geriatrics Due to the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy, elderly patients should be treated with caution, usually starting at the low end of the dosing range.

1 Adverse Reaction Overview 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. 2 Clinical Trial Adverse Reactions Clinical trials are conducted under very specific conditions.

The adverse reaction rates observed in the clinical trials; therefore, may not reflect the rates observed in practice and should not be compared to the rates in the clinical trials of another drug. Adverse reaction information from clinical trials may be useful in identifying and approximating rates of adverse drug reactions in real-world use.

12/2022 TABLE OF CONTENTS Sections or subsections that are not applicable at the time of authorization are not listed . RECENT MAJOR LABEL CHANGES............................................................................................

2 TABLE OF CONTENTS .............................................................................................................. 2 PART I: HEALTH PROFESSIONAL INFORMATION .....................................................................

4 1 INDICATIONS .............................................................................................................. 1 Pediatrics ..........................................................................................................

2 Geriatrics........................................................................................................... 4 2 CONTRAINDICATIONS .................................................................................................

4 4 DOSAGE AND ADMINISTRATION................................................................................. 1 Dosing Considerations ....................................................................................... 2 Recommended Dose and Dosage Adjustment.....................................................

5 Administration................................................................................................... 6 Missed Dose ......................................................................................................

5 5 OVERDOSAGE ............................................................................................................. 5 6 DOSAGE FORMS, STRENGTHS, COMPOSITION AND PACKAGING ................................. 6 7 WARNINGS AND PRECAUTIONS ..................................................................................

ZAROXOLYN is contraindicated in patients:  with anuria  with hepatic coma or pre-coma  who are hypersensitive to this drug or to any ingredient in the formulation, including any non- medical ingredient, or component of the container.

For a complete listing, see 6 DOSAGE FORMS, STRENGTHS, COMPOSITION AND PACKAGING.