ZANERIL

Patients whose blood pressure is not adequately controlled by treatment with enalapril 20 mg alone could either be titrated up to the higher dose of enalapril monotherapy or switched to Zaneril 20mg/10mg. Individual dose titration with the components can be recommended.

When clinically appropriate, direct switch from monotherapy to the fixed combination may be considered. Posology The recommended dose is one tablet once a day at least 15 minutes before meals.

Elderly:

The dose should depend on the patient's renal function (see "Use in renal impairment"). 4). Particular caution is needed when initiating treatment in patients with mild to moderate renal dysfunction.

Hepatic impairment:

Zaneril is contraindicated in severe hepatic dysfunction. Particular caution is needed when initiating treatment in patients with mild to moderate hepatic dysfunction. Paediatric population There is no relevant use of Zaneril in the paediatric population for the indication of hypertension.

Method of administration Precautions to be taken before handling or administering the medicinal product: - Treatment should be preferably administered in the morning at least 15 minutes before breakfast. 5).

Summary of the safety profile The safety of Zaneril has been evaluated in five double-blind controlled clinical studies and in two long term open-label extension phases. In total, 1,141 patients have received Zaneril at a dose of 10 mg/10 mg, 20 mg/10 mg and 20 mg/20 mg.

The undesirable effects observed with combination therapy have been similar to those already observed with one or the other of the constituents given alone. 67%). Tabulated summary of adverse reactions In the table below, adverse reactions reported in clinical studies with Zaneril 10 mg/10 mg, 20 mg/10 mg and 20 mg/20 mg and for which a reasonable causal relationship exists are listed by MedDRA system organ class and frequency: very common (> 1/10), common (≥1/100 to <1/10), uncommon (≥1/1,000 to <1/100), rare (≥ 1/10,000 to < 1/1,000), very rare (<1/10,000) not known (cannot be estimated from the available data).

Blood and lymphatic system disorders Uncommon:

Thrombocytopenia Rare: Haemoglobin decreased Immune System Disorders Rare: Hypersensitivity Metabolism and nutrition disorders Uncommon: Hyperkalaemia Psychiatric disorders Uncommon: Anxiety Nervous system disorders Common: Dizziness, headache Uncommon: Dizziness postural Ear and labyrinth disorders Uncommon: Vertigo Rare: Tinnitus Cardiac Disorders Uncommon: Tachycardia, palpitations Vascular disorders Uncommon: Flushing, hypotension Rare: Circulatory collapse Respiratory, thoracic and mediastinal disorders Common: Cough Rare: Dry throat, oropharingeal pain Gastrointestinal disorders Uncommon: Abdominal pain, constipation, nausea Rare: Dyspepsia, lip oedema, tongue disorder, diarrhoea, dry mouth, gingivitis Hepatobiliary Disorders Uncommon: ALT increased, AST increased Skin and sub-cutaneous tissue disorders Uncommon: Erythema Rare: Angioedema, swelling face, dermatitis, rash, urticaria Musculoskeletal, connective tissue disorders Uncommon: Arthralgia Renal and urinary disorders Uncommon: Pollakiuria Rare: Nocturia, polyuria Reproductive System and Breast Disorders Rare: Erectile dysfunction General disorders and administration site conditions Uncommon: Asthenia, fatigue, feeling hot, oedema peripheral Undesirable effects occurring in one patient only are reported under the frequency rare.

Symptomatic hypotension Symptomatic hypotension is rarely seen in uncomplicated hypertensive patients. g. 5). In patients with heart failure, with or without associated renal insufficiency, symptomatic hypotension has been observed. This is most likely to occur in those patients with more severe degrees of heart failure, as reflected by the use of high doses of loop diuretics, hyponatremia or functional renal impairment.

In these patients, therapy should be started under medical supervision and the patients should be followed closely whenever the dose of enalapril and/or diuretic is adjusted. Similar considerations may apply to patients with ischemic heart or cerebrovascular disease in whom an excessive fall in blood pressure could result in a myocardial infarction or cerebrovascular accident.

If hypotension occurs, the patient should be placed in the supine position and, if necessary, should receive an intravenous infusion of normal saline. A transient hypotensive response is not a contraindication to further doses, which can be given usually without difficulty once the blood pressure has increased after volume expansion.

In some patients with heart failure who have normal or low blood pressure, additional lowering of systematic blood pressure may occur with enalapril. This effect is anticipated and usually is not a reason to discontinue treatment. If hypotension becomes symptomatic, a reduction of dose and/or discontinuation of the diuretic and/or enalapril may be necessary.

Sick-sinus syndrome Lercanidipine should be administered with caution in patients with sick-sinus syndrome (without a pacemaker). Left ventricular dysfunction Although haemodynamic controlled studies revealed no impairment of ventricular function, care is required in patients with left ventricular dysfunction.

Ischaemic heart disease It has been suggested that some short-acting dihydropyridines may be associated with increased cardiovascular risk in patients with ischaemic heart disease. Although lercanidipine is long-acting, caution is required in such patients.

1. • History of angioedema associated with ACE-inhibitor therapy. • Hereditary or idiopathic angioedema. 6). • Left ventricular outflow tract obstruction. • Untreated congestive cardiac failure. • Unstable angina pectoris or recent (within 1 month) myocardial infarction.

• Severe hepatic impairment. • Severe renal impairment (GFR < 30 ml/min), including patients undergoing dialysis. 5) • Concomitant use with sacubitril/valsartan therapy. 5). 1).