Entresto Dosage/Direction for Use

Posology: Heart failure: The recommended starting dose of Entresto is one tablet of 100 mg twice daily, except in the situations described as follows. The dose should be doubled at 2-4 weeks to the target dose of one tablet of 200 mg twice daily, as tolerated by the patient (see Pharmacology: Pharmacodynamics under Actions).
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 Precautions).
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 Pharmacology: Pharmacodynamics under Actions). 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 50 mg twice daily and slow dose titration (doubling every 3-4 weeks) are recommended in these patients (see Pharmacology: Pharmacodynamics: Titration under Actions).
Treatment should not be initiated in patients with serum potassium level >5.4 mmol/l or with SBP <100 mmHg (see Precautions). 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 Contraindications, Precautions and Interactions).
The valsartan contained within Entresto is more bioavailable than the valsartan in other marketed tablet formulations (see Pharmacology: Pharmacokinetics under Actions).
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.
Hypertension: The recommended starting dose of Entresto is 200 mg once daily. In patients whose blood pressure could not be adequately controlled with Entresto 200 mg once daily, the dose can be increased to 400 mg once daily. In hypertensive patients with heart failure, the heart failure dosing is recommended. Entresto may be used alone or in combination with other antihypertensive agents except angiotensin-converting enzyme (ACE) inhibitors (see Contraindications) and angiotensin II receptor blockers (ARBs) (see Precautions).
Special patient populations: Elderly population: The dose should be in line with the renal function of the elderly patient.
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 heart failure patients with moderate renal impairment (eGFR 30-60 ml/min/1.73 m²). As there is very limited clinical experience in heart failure patients with severe renal impairment (eGFR <30 ml/min/1.73 m²) (see Pharmacology: Pharmacodynamics under Actions) Entresto should be used with caution and a starting dose of 50 mg twice daily is recommended.
Safety and efficacy of Entresto in patients with essential hypertension and with severe renal impairment (eGFR <30 mL/min/1.73 m²) have not been established (see Pharmacology: Pharmacokinetics under Actions).
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 heart failure patients and the recommended starting dose is 50 mg twice daily (see Precautions and Pharmacology: Pharmacokinetics under Actions). A starting dose of 100 mg once daily is recommended for essential hypertensive patients with moderate hepatic impairment (Child-Pugh B classification). Entresto is contraindicated in patients with severe hepatic impairment, biliary cirrhosis or cholestasis (Child-Pugh C classification) (see Contraindications).
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 Pharmacology: Pharmacokinetics under Actions). The tablets must be swallowed with a glass of water.