Posology : מינונים

4.2    Posology and method of administration

Posology
The recommended starting dose of Entresto is one tablet of 100 mg twice daily, except in the situations described below. The dose should be doubled after 2-4 weeks to the target maintenance dose of one tablet of 200 mg twice daily, as tolerated by the patient (see section 5.1).


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If patients experience tolerability issues (systolic blood pressure [SBP] ≤95 mmHg, symptomatic hypotension, hyperkalaemia, renal dysfunction), adjustment of concomitant medicinal products, temporary down–titration or discontinuation of Entresto is recommended (see section 4.4).

In PARADIGM-HF study, Entresto was administered in conjunction with other heart failure therapies, in place of an ACE inhibitor or other angiotensin II receptor blocker (ARB) (see section 5.1). There is limited experience in patients not currently taking an ACE inhibitor or an ARB or taking low doses of these medicinal products, therefore a starting dose of 50mg twice daily and slow dose titration (doubling every 3-4 weeks) are recommended in these patients (see “Titration” in section 5.1).

Treatment should not be initiated in patients with serum potassium level >5.4 mmol/l or with SBP <100 mmHg (see section 4.4). A starting dose of 50 mg twice daily should be considered for patients with SBP ≥100 to 110 mmHg.

Entresto should not be co-administered with an ACE inhibitor or an ARB. Due to the potential risk of angioedema when used concomitantly with an ACE inhibitor, it must not be started for at least 36 hours after discontinuing ACE inhibitor therapy (see sections 4.3, 4.4 and 4.5).

The valsartan contained within Entresto is more bioavailable than the valsartan in other marketed tablet formulations (see section 5.2).

If a dose is missed, the patient should take the next dose at the scheduled time. Splitting or crushing of the tablets is not recommended.


Special populations
Elderly population
The dose should be in line with the renal function of the elderly patient. In patients ≥75 years old, a starting dose of 50 mg Entresto twice daily should be considered.

Renal impairment
No dose adjustment is required in patients with mild (Estimated Glomerular Filtration Rate [eGFR] 60-90 ml/min/1.73 m2) renal impairment. A starting dose of 50 mg twice daily should be considered in patients with moderate renal impairment (eGFR 30-60 ml/min/1.73 m2). As there is very limited clinical experience in patients with severe renal impairment (eGFR <30 ml/min/1.73 m2) (see section 5.1) Entresto should be used with caution and a starting dose of 50 mg twice daily is recommended. There is no experience in patients with end-stage renal disease and use of Entresto is not recommended.

Hepatic impairment
No dose adjustment is required when administering Entresto 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 AST/ALT values more than twice the upper limit of the normal range. Entresto should be used with caution in these patients and the recommended starting dose is 50 mg twice daily (see sections 4.4 and 5.2). Entresto is contraindicated in patients with severe hepatic impairment, biliary cirrhosis or cholestasis (Child-Pugh C classification) (see section 4.3).

Paediatric population
The safety and efficacy of Entresto in children and adolescents aged below 18 years have not been established. No data are available.

Method of administration

Oral use.
Entresto may be administered with or without food (see section 5.2). The tablets must be swallowed 
ENT API JUL21 V2                                                                  EU SmPC 05.2021 with a glass of water.