The SmPC is updated to implement the outcome of the PSUSA procedure on cilazapril and cilazapril/hydrochlorothiazide, applicable to the whole class of medicinal products containing ACE inhibitors. 

Main changes to the SmPC safety sections:

4.3-Contraindications: Concomitant use with sacubitril/valsartan therapy. Zofenil must not be initiated earlier than 36 hours after the last dose of sacubitril/valsartan (see also sections 4.4 and 4.5).

4.4-Special warnings and precautions for use: Concomitant use of ACE inhibitors with sacubitril/valsartan is contraindicated due to the increased risk of angioedema. Treatment with sacubitril/valsartan must not be initiated earlier than 36 hours after the last dose of Zofenil. Treatment with Zofenil must not be initiated earlier than 36 hours after the last dose of sacubitril/valsartan (see sections 4.3 and 4.5).

Concomitant use of ACE inhibitors with racecadotril, mTOR inhibitors (e.g. sirolimus, everolimus, temsirolimus) and vildagliptin: caution should be used when starting racecadotril, mTOR inhibitors (e.g. sirolimus, everolimus, temsirolimus) and vildagliptin in a patient already taking any ACE inhibitor. This may lead to an increased risk for angioedema.  Warning on serum potassium updated.

4.5-Interactions: Medicines increasing the risk of angioedema have been added.  Co-administration with other agents that increase serum potassium. Cyclosporin interaction updated. Heparin has been added

The SmPC was updated to implement the outcome of PSUSA on Captopril / Hydrochlorothiazide, applicable to the whole class of medicinal products containing ACE inhibitors.

 The following amendments were made:

-          update in line with the latest QRD template;

-          addition of the standard statement on sodium content in the PL in accordance with the Annex to the EC guideline on excipients;

-          addition of ‘Endocrine effects’ in section 4.8 of the SmPC as  text alignment of a known class effect.

Administrative amendments (to align to the current QRD template)

Sections 2, 3, 4.2, 4.4, 4.6, 4.8, 5.2, 6.6.

Section 4.3 Contraindications

New contra-indication added on the concomitant use with aliskiren-containing products in patients with diabetes mellitus or renal impairment.

Section 4.4 Special warnings and precautions

New warning added regarding the dual blockade of RAAS through the combined use of ACE-inhibitors, angiotensin II receptor blockers or aliskiren is not recommended,

Section 4.5 Interactions with other medicinal products and other forms of interaction

New interaction added under ‘Concomitant use not recommended’:

ACE-inhibitors, angiotensin II receptor blockers or aliskiren:

Section 4.8 Undesirable effects

Reporting of side-effects details added.

Section 5.1 Pharmacodynamic properties

Details of two studies added with details about the use of combination of an ACE-inhibitor with an angiotensin II receptor blocker.

Information added on a further study to test the benefit of adding aliskiren to a standard therapy of an ACE-inhibitor or an angiotensin II receptor blocker in patients with type 2 diabetes mellitus and chronic kidney disease, cardiovascular disease, or both.

Section 10 Date of revision of the text

Updated to November 2014

Main changes:

• Section 2 Qualitative and Quantative composition: reference added on excipients including lactose.
• Section 3 Pharmaceutical form: Zofenil 15 mg tablets – the tablet can be divided into equal halves.
• Section 4.3 Contraindications: Specify second and third trimester of pregnancy.  Remove lactation period.
• Section 4.4 Special warnings and precautions for use: Further information added on hypotension and heart failure, anaphylactic reactions during desensitisation or after insect bites, angioedema, cough, hyperkalaemia, surgery/anaesthesia, aortic and mitral valve stenosis/hypertrophic cardiomyopathy,  neutropenia/agranulocytosis, proteinuria. New information included on hepatic failure, diabetic patients, lithium, race, pregnancy and lactose.
• Section 4.5 Interactions:  Further information added on potassium sparing diuretics or potassium supplements, diuretics (thiazide or loop diuretics),other antihypertensive agents,  lithium, NSAIDs, sympathomimetics. New information added on gold, tricyclic antidepressants, barbiturates, procainamide, cytostatic or immunosuppressive agents, antidiabetics.
• Section 4.6 Pregnancy and lactation: Information updated.  Use in first trimester of pregnancy not recommended, contraindicated during the second and third trimester.  Not recommended during breastfeeding.
• Section 4.8 Undesirable effects: Section rewritten to add adverse reactions associated with ACE inhibitors therapy.
• Section 9 Date of first authorisation/renewal – updated.
• Section 10 Date of the revision of the text – updated.