SACUBITRIL/VALSARTAN

Posology General considerations Sacubitril/Valsartan should not be co-administered with an angiotensin-converting enzyme (ACE) inhibitor or an angiotensin II receptor blocker (ARB). 5). 2). If a dose is missed, the patient should take the next dose at the scheduled time.

Adult heart failure The recommended starting dose of Sacubitril/Valsartan is one tablet of 49 mg/51 mg twice daily, except in the situations described below. 1). 4). 1). There is limited experience in patients not currently taking an ACE inhibitor or an ARB or taking low doses of these medicinal products.

Sacubitril/Valsartan should not be used for up-titration of the dose in these patients. Sacubitril/Valsartan is intended for use in these patients only after they have successfully completed titration and have reached their tolerated dose.

4). A starting dose of 24 mg/26 mg twice daily should be considered for patients with SBP ≥100 to 110 mmHg. Sacubitril/Valsartan should not be used for up-titration of the dose in these patients. Sacubitril/Valsartan is intended for use in these patients only after they have successfully completed titration and have reached their tolerated dose.

Special populations Elderly The dose should be in line with the renal function of the elderly patient. 73 m2) renal impairment. 73 m2). 1), Sacubitril/Valsartan should be used with caution and half of the starting dose is recommended.

After initiation, the dose should be increased following the recommended dose titration every 2-4 weeks. Sacubitril/Valsartan should not be used for up-titration of the dose in these patients. Sacubitril/Valsartan is intended for use in these patients only after they have successfully completed titration and have reached their tolerated dose.

There is no experience in patients with end-stage renal disease and use of Sacubitril/Valsartan is not recommended. Hepatic impairment No dose adjustment is required when administering Sacubitril/Valsartan to patients with mild hepatic impairment (Child-Pugh A classification).

There is limited clinical experience in patients with moderate hepatic impairment (Child-Pugh B classification) or with aspartate transaminase (AST)/alanine transaminase (ALT) values more than twice the upper limit of the normal range.

2). After initiation, the dose should be increased following the recommended dose titration every 2-4 weeks. Sacubitril/Valsartan should not be used for up-titration of the dose in these patients. Sacubitril/Valsartan is intended for use in these patients only after they have successfully completed titration and have reached their tolerated dose.

4). 5%) (see description of selected adverse reactions). Tabulated list of adverse reactions Adverse reactions are ranked by System organ class and then by frequency with the most frequent first, using the following convention: 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 (frequency cannot be estimated from the available data).

Within each frequency grouping, adverse reactions are ranked in order of decreasing seriousness. Table 1 List of adverse reactions System organ class Preferred term Frequency categoryBlood and lymphatic system disorders Anaemia Common Immune system disorders Hypersensitivity Uncommon Hyperkalaemia* Very common Hypokalaemia Common Hypoglycaemia Common Metabolism and nutrition disorders Hyponatraemia Uncommon Hallucinations** Rare Sleep disorders RarePsychiatric disorders Paranoia Very rare Dizziness Common Headache Common Syncope Common Dizziness postural Uncommon Nervous system disorders Myoclonus Not known Ear and labyrinth disorders Vertigo Common Hypotension* Very commonVascular disorders Orthostatic hypotension Common Respiratory, thoracic and mediastinal disorders Cough Common Diarrhoea CommonGastrointestinal disorders Nausea Common Gastritis Common Intestinal angioedema Very rare Pruritus Uncommon Rash Uncommon Skin and subcutaneous tissue disorders Angioedema* Uncommon Renal impairment* Very common Renal and urinary disorders Renal failure (renal failure, acute renal failure) Common Fatigue CommonGeneral disorders and administration site conditions Asthenia Common *See description of selected adverse reactions.

**Including auditory and visual hallucinations Description of selected adverse reactions Angioedema Angioedema has been reported in patients treated with sacubitril/valsartan. 2% of patients treated with enalapril. 4). 1% of enalapril-treated patients, respectively.

67% of enalapril-treated patients, respectively. 5% of enalapril-treated patients. Reporting of suspected adverse reactions Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product.

3). Sacubitril/valsartan must not be initiated until 36 hours after taking the last dose of ACE inhibitor therapy. 5). 5). 5). 5). Hypotension Treatment should not be initiated unless SBP is ≥100 mmHg for adult patients. 1). 8), especially in patients ≥65 years old, patients with renal disease and patients with low SBP (<112 mmHg).

When initiating therapy or during dose titration with sacubitril/valsartan, blood pressure should be monitored routinely. 2). g. hypovolaemia) should be considered. g. by diuretic therapy, dietary salt restriction, diarrhoea or vomiting.

Sodium and/or volume depletion should be corrected before starting treatment with sacubitril/valsartan, however, such corrective action must be carefully weighed against the risk of volume overload. Renal impairment Evaluation of patients with heart failure should always include assessment of renal function.

2). 2). There is no experience in patients with end-stage renal disease and use of sacubitril/valsartan is not recommended. Worsening renal function Use of sacubitril/valsartan may be associated with decreased renal function. 5). Down-titration should be considered in patients who develop a clinically significant decrease in renal function.

4 mmol/l in adult patients. 8). 2). If patients experience clinically significant hyperkalaemia adjustment of concomitant medicinal products, or temporary down–titration or discontinuation is recommended. 4 mmol/l discontinuation should be considered.

Angioedema Angioedema has been reported in patients treated with sacubitril/valsartan. If angioedema occurs, sacubitril/valsartan should be immediately discontinued and appropriate therapy and monitoring should be provided until complete and sustained resolution of signs and symptoms has occurred.

It must not be re-administered. In cases of confirmed angioedema where swelling has been confined to the face and lips, the condition has generally resolved without treatment, although antihistamines have been useful in relieving symptoms.

1. 5). Sacubitril/Valsartan must not be administered until 36 hours after discontinuing ACE inhibitor therapy. 4). 4). 5). 2). 6).