TEVA-DOMPERIDONE

1 Dosing Considerations Important considerations: • The expected benefit of an increased dose should outweigh the potential risks. 5 Post-Market Adverse Reactions). The risk may be higher in patients older than 60 years or in patients taking a daily dose of more than 30 mg.

4 Drug-Drug Interactions). Domperidone should be used at the lowest possible dose for the shortest duration necessary. 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 dose > 30 mg.

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

TEVA-DOMPERIDONE Page 6 of 37 • 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 30 mg.

4 Drug-Drug Interactions). • 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 dose > 30 mg.

(see 2 CONTRAINDICATIONS and 3 SERIOUS WARNINGS AND PRECAUTIONS BOX) Patient 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 adminstration, 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 Domperidone maleate is contraindicated in patients with moderate to severe hepatic impairment (see 2 CONTRAINDICATIONS). Pediatrics (<18 years of age) Health Canada has not authorized an indication for pediatric use.

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 TEVA-DOMPERIDONE Page 11 of 37 more serious or troublesome side effects (galactorrhea, gynecomastia, menstrual irregularities) are dose-related and gradually resolve after lowering the dose or discontinuing of therapy. 2 Clinical Trial Adverse Reactions Clinical trials are conducted under very specific conditions.

Therefore, 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.

2%), insomnia, nervousness, dizziness, thirst, lethargy, irritability (all <1%). 4%; abdominal cramps, diarrhea, regurgitation, nausea, changes in appetite, heartburn, constipation (all <1%). 3%; hot flushes, mastalgia, galactorrhea, gynecomastia, menstrual irregularities.

1%; rash, pruritus, urticaria, stomatitis, conjunctivitis. 8%; urinary frequency, dysuria. 5%; edema, palpitations. 1%; leg cramps, asthenia. 1%; drug intolerance. 0%). 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 points, serious ventricular arrhythmias (frequency unknown), sudden cardiac death (frequency unknown).

2 Breast-feeding 09/2024 TABLE OF CONTENTS Sections or subsections that are not applicable at the time of authorization are not listed. 1 Pediatrics..............................................................................................................................

2 Geriatrics .............................................................................................................................. 1 Dosing Considerations ..........................................................................................................

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

5 Missed Dose ......................................................................................................................... 1 Special Populations ............................................................................................................

1 Pregnant Women ............................................................................................................ 2 Breast-feeding .................................................................................................................

3 Pediatrics ......................................................................................................................... 4 Geriatrics .........................................................................................................................

10 8 ADVERSE REACTIONS ........................................................................................................... 1 Adverse Reaction Overview ...............................................................................................

Domperidone Maleate Tablets are contraindicated in • patients who are hypersensitive to this drug or any ingredient in the formulation. 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. TEVA-DOMPERIDONE Page 5 of 37 • patients with a prolactin-releasing pituitory tumour (prolactinoma).