PERINDOPRIL ERBUMINE/ INDAPAMIDE HD

). The safety and efficacy of PERINDOPRIL ERBUMINE / INDAPAMIDE and PERINDOPRIL ERBUMINE / INDAPAMIDE HD in renovascular hypertension and in congestive heart failure have not been established and therefore, their use in this condition is not recommended.

1 Pediatrics (<18 years of age) The safety and effectiveness of PERINDOPRIL ERBUMINE / INDAPAMIDE and PERINDOPRIL ERBUMINE / INDAPAMIDE HD in children have not been established. Its use in this age group, therefore, is not recommended.

2 Geriatrics (> 65 years of age) Although the blood pressure response and safety profile of PERINDOPRIL ERBUMINE / INDAPAMIDE and PERINDOPRIL ERBUMINE / INDAPAMIDE HD in patients >65 years old were comparable to those of the younger adult patients, greater sensitivity of some elderly patients cannot be ruled out.

73m2). PERINDOPRIL ERBUMINE / INDAPAMIDE, PERINDOPRIL ERBUMINE / INDAPAMIDE HD (perindopril erbumine / indapamide) are contraindicated in: • Patients who are hypersensitive to this drug or to any ingredient in the formulation. For a complete listing, see the

). Treatment of progressive angioedema should be aggressive. Failing a rapid response to medical therapy, mechanical methods to secure an airway should be undertaken before massive oedema complicates oral or nasal intubation. Patients who respond to medical treatment should be observed carefully for a possible rebound phenomenon.

The onset of angioedema associated with the use of ACE inhibitors may be delayed for weeks or months.

Product Monograph:

PERINDOPRIL ERBUMINE / INDAPAMIDE and PERINDOPRIL ERBUMINE / INDAPAMIDE HD Page 9 of 64 Patients may have multiple episodes of angioedema with long symptom-free intervals. Angioedema may occur with or without urticaria. The incidence of angioedema during ACE inhibitor therapy has been reported to be higher in black than in non-black patients.

There are reports that switching a patient to another ACE inhibitor could be followed by a recurrence of angioedema. Because of the potential severity of this rare event, another ACE inhibitor should not be used in patients with a history of angioedema (see 2 CONTRAINDICATIONS).

Patients with a history of angioedema unrelated to ACE inhibitor therapy may be at increased risk of angioedema while receiving an ACE inhibitor (see 2 CONTRAINDICATIONS). g. g. g. swelling of the airways or tongue, with or without respiratory impairment).

Caution should be used when initiating ACE inhibitor therapy in patients already taking a mTOR, DPP-IV or NEP inhibitor or vice versa (see

, General). • Women who are pregnant, intend to become pregnant, or of childbearing potential who are not using adequate contraception (see 7 WARNINGS AND PRECAUTIONS, Special Populations, Pregnant Women). • Nursing women (see 7 WARNINGS AND PRECAUTIONS, Special Populations, Breast-feeding).

73m2). • Patients with hypokalemia. • Patients with severe hepatic impairment. • Patients with hepatic encephalopathy. • Combination with anti-arrhythmic agents causing torsade de pointes (see 9 DRUG INTERACTIONS – Drug-Drug Interactions).

• Patients with hereditary problems of galactose intolerance, glucose-galactose malabsorption, or the total lactase deficiency as PERINDOPRIL ERBUMINE / INDAPAMIDE, PERINDOPRIL ERBUMINE / INDAPAMIDE HD contain lactose (see 7 WARNINGS AND PRECAUTIONS, Sensitivity/Resistance).

• Combination with sacubitril/valsartan due to an increased risk of angioedema. 73m2) (see 7 WARNINGS AND PRECAUTIONS, Dual Blockade of the Renin-Angiotensin-System (RAS) and Renal, and 9 DRUG INTERACTIONS, Drug-Drug Interactions, Dual Blockade of the Renin-Angiotensin-System (RAS) with ACE inhibitors, ARBs or aliskiren-containing drugs).

• Patients with extracorporeal treatments leading to contact of blood with negatively charged surfaces (see 9 DRUG INTERACTIONS), • Patients with bilateral renal artery stenosis or renal artery stenosis in a single functioning kidney (see 7 WARNINGS AND PRECAUTIONS, Renal).

3 SERIOUS WARNINGS AND PRECAUTIONS BOX Serious Warnings and Precautions • When used in pregnancy, angiotensin converting enzyme (ACE) inhibitors can cause injury or even death of the developing fetus. • When pregnancy is detected, PERINDOPRIL ERBUMINE / INDAPAMIDE, PERINDOPRIL ERBUMINE / INDAPAMIDE HD should be discontinued as soon as possible.

1 Dosing Considerations Dosage of PERINDOPRIL ERBUMINE / INDAPAMIDE, PERINDOPRIL ERBUMINE / INDAPAMIDE HD (perindopril erbumine / indapamide) must be individualized and adjustment is required in the elderly, and in case of renal impairment.

08/2023 7 WARNING AND PRECAUTIONS 08/2023 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 (< 18 years of age) ...................................................................................

2 Geriatrics (> 65 years of age) ................................................................................... 4 2 CONTRAINDICATIONS ................................................................................................

4