Neparvis

Posology General considerations Neparvis 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 Neparvis is one tablet of 49 mg/51 mg twice daily, except in the situations described below. 1). 4). 1). 1). 4). A starting dose of 24 mg/26 mg twice daily should be considered for patients with SBP ≥100 to 110 mmHg.

Paediatric heart failure Table 1 shows the recommended dose for paediatric patients. The recommended dose should be taken orally twice daily. The dose should be increased every 2-4 weeks to the target dose, as tolerated by the patient.

Neparvis film-coated tablets are not suitable for children weighing less than 40 kg. Neparvis granules are available for these patients. 73 m2) and patients who have moderate hepatic impairment (see special populations). 1 mg/kg refer to the combined amount of sacubitril and valsartan and are to be given using granules.

In patients not currently taking an ACE inhibitor or an ARB or taking low doses of these medicinal products, half of the starting dose is recommended. 8 mg/kg twice daily (given as granules) is recommended. After initiation, the dose should be increased to the standard starting dose following the recommended dose titration in Table 1 and adjusted every 3-4 weeks.

8 mg/kg) twice daily, given as granules. After rounding to the closest number of full capsules, this corresponds to 2 capsules of 6 mg/6 mg sacubitril/valsartan twice daily. 3 mmol/l or with SBP <5th percentile for the age of the patient.

4). Special populations Elderly The dose should be in line with the renal function of the elderly patient. 73 m2) renal impairment. 73 m2). 1), Neparvis should be used with caution and half of the starting dose is recommended. 8 mg/kg twice daily (given as granules) is recommended.

After initiation, the dose should be increased following the recommended dose titration every 2-4 weeks. There is no experience in patients with end-stage renal disease and use of Neparvis is not recommended. Hepatic impairment No dose adjustment is required when administering Neparvis to patients with mild hepatic impairment (Child-Pugh A classification).

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. 11 Table 2 List of adverse reactions System organ class Preferred term Frequency category Blood and lymphatic system disorders Anaemia Common Immune system disorders Hypersensitivity Uncommon Metabolism and nutrition disorders Hyperkalaemia* Very common Hypokalaemia Common Hypoglycaemia Common Hyponatraemia Uncommon Psychiatric disorders Hallucinations** Rare Sleep disorders Rare Paranoia Very rare Nervous system disorders Dizziness Common Headache Common Syncope Common Dizziness postural Uncommon Myoclonus Not known Ear and labyrinth disorders Vertigo Common Vascular disorders Hypotension* Very common Orthostatic hypotension Common Respiratory, thoracic and mediastinal disorders Cough Common Gastrointestinal disorders Diarrhoea Common Nausea Common Gastritis Common Intestinal angioedema Very rare Skin and subcutaneous tissue disorders Pruritus Uncommon Rash Uncommon Angioedema* Uncommon Renal and urinary disorders Renal impairment* Very common Renal failure (renal failure, acute renal failure) Common General disorders and administration site conditions Fatigue Common 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.

3). Sacubitril/valsartan must not be initiated until 36 hours after taking the last dose of ACE inhibitor therapy. 5). 5). 5). 5). 6 Hypotension Treatment should not be initiated unless SBP is ≥100 mmHg for adult patients or ≥5th percentile SBP for the age of the paediatric patient.

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. 3 mmol/l in paediatric 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.

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