PRO-DOMPERIDONE

4 Drug-Drug Interactions). Patients at a higher risk of QT interval prolongation and/or cardiac arrhythmia should be considered for cardiac assessment including ECG (electrocardiogram) before initiation of domperidone therapy and during the treatment.

1 Dosing Considerations Important considerations: • The expected benefit of an increased dose should outweigh the potential risks. • Recent post-market epidemiological studies and review of post-market safety data have shown that the risk of serious ventricular arrhythmias or sudden cardiac death may be higher in patients older than 60 years of age or in patients taking a daily dose of more than Pr PRO-DOMPERIDONE (domperidone maleate) Page 6 of 37 30 mg.

4 Drug-Drug Interactions). • PRO-DOMPERIDONE should be used at the lowest possible dose for the shortest duration necessary. 2 Recommended Dose and Dosage Adjustment One 10 mg tablet three times per day with a maximum dose of 30 mg per day is recommended for all indications as the risk of serious cardiac events may be increased in association with daily doses> 30 mg (see 2 CONTRAINDICATIONS and 3 SERIOUS WARNINGS AND PRECAUTIONS BOX).

Patients with renal impairment Since very little unchanged drug is excreted via the kidneys, it is unlikely that a single administration needs to be adjusted in patients with renal insufficiency. However, on repeated administration, the dosing frequency should be reduced to once or twice daily, depending on the severity of the impairment, and the dose may need to be reduced.

Generally, patients on prolonged therapy should be reviewed regularly (see 7 WARNINGS AND PRECAUTIONS, Renal). Patients with hepatic impairment PRO-DOMPERIDONE (domperidone maleate) is contraindicated in patients with moderate or severe hepatic impairment (see 2 CONTRAINDICATIONS).

Pediatrics (<18 years of age) Health Canada has not authorized an indication for pediatric use. 4 Administration PRO-DOMPERIDONE Tablets are for oral administration and should be taken 15 to 30 minutes before the meals. 5 Missed Dose If the patient misses a dose, instruct the patient to take the dose as soon as they remember.

If it is almost time for the next dose, inform the patient to skip the missed dose and continue the regular dosing schedule. Do not take a double dose to make up for the forgotten dose.

1 Adverse Reaction Overview In clinical studies with oral domperidone the overall incidence of side effects was <7%. Some of these side effects are an extension of the dopamine antagonist properties of domperidone. Most side effects resolve spontaneously during continued therapy or are easily tolerated.

The more serious or troublesome side effects (galactorrhea, gynecomastia, menstrual irregularities) are dose-related and gradually resolve after lowering the dose or discontinuing therapy. 2 Clinical Trial Adverse Reactions Clinical trials are conducted under very specific conditions.

Therefore, the adverse reaction rates observed in the clinical trials 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.

The safety of domperidone was evaluated in clinical trials included in the safety database. Adverse Reactions (ARs) - of patients treated with domperidone in these clinical trials are shown in Table 2. 3 Less Common Clinical Trial Adverse Reactions This information is not available for this drug product.

4 Abnormal Laboratory Findings: Hematologic, Clinical Chemistry and Other Quantitative Data Laboratory parameters: elevated serum prolactin, elevation of SGOT, SGPT and cholesterol (all <1%). Extrapyramidal phenomena are rare in adults; they reverse spontaneously as soon as treatment is stopped.

When the blood-brain barrier is immature (as in infants) or impaired, the possible occurrence of neurological side effects cannot be excluded. 5 Post-Market Adverse Reactions Cardiovascular: torsade de pointes, serious ventricular arrhythmia (frequency unknown), sudden cardiac death (frequency unknown).

2 Breast-feeding TABLE OF CONTENTS Certain sections or subsections that are not applicable at the time of the preparation of the most recent authorized product monograph 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 3 SERIOUS WARNINGS AND PRECAUTIONS BOX................................................................. 5 4 DOSAGE AND ADMINISTRATION ..................................................................................... 1 Dosing Considerations...................................................................................................

2 Recommended Dose and Dosage Adjustment.............................................................. 4 Administration ............................................................................................................... 5 Missed Dose ..................................................................................................................

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

Domperidone Maleate Tablets are contraindicated in: • Patients who are hypersensitive to this drug or to any ingredient in the formulation, including any non-medicinal ingredient, or component of the container. For a complete listing, see 6 DOSAGE FORMS, STRENGTHS, COMPOSITION AND PACKAGING.

• Patients with known existing prolongation of cardiac conduction intervals, particularly QT; • Patients who have significant electrolyte disturbances; • Patients with underlying cardiac diseases, such as congestive heart failure; • Patients with moderate or severe liver impairment.

• The co-administration of domperidone with QT-prolonging drugs. 4 Drug-Drug Interactions). , gastrointestinal hemorrhage, mechanical obstruction or perforation. • Patients with a prolactin-releasing pituitary tumour (prolactinoma). Pr PRO-DOMPERIDONE (domperidone maleate) Page 5 of 37