Entresto Dosage/Direction for Use

Dosage regimen: The recommended starting dose is 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 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, hyperkalemia, renal dysfunction), adjustment of concomitant medicinal products, temporary down-titration or discontinuation of treatment is recommended (see PRECAUTIONS).
In PARADIGM-HF study, sacubitril-valsartan (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. A starting dose of 50 mg twice daily should be considered for patients with SBP ≥100 to 110 mmHg.
Sacubitril-valsartan (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 sacubitril-valsartan (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.
Special populations: Geriatric patients (older than 65 years): 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 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 PHARMACOLOGY: PHARMACODYNAMICS under ACTIONS) sacubitril-valsartan (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 treatment is not recommended.
Hepatic impairment: No dose adjustment is required when administering 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. Sacubitril-valsartan (Entresto) should be used with caution in these patients and the recommended starting dose is 50 mg twice daily (see PRECAUTIONS and PHARMACOLOGY: PHARMACOKINETICS under ACTIONS). It is contraindicated in patients with severe hepatic impairment, biliary cirrhosis or cholestasis (Child-Pugh C classification) (see CONTRAINDICATIONS).
Pediatric patients: The safety and efficacy in children and adolescents aged below 18 years have not been established. No data are available.
Method of administration: Oral use.
May be administered with or without food (see PHARMACOLOGY: PHARMACOKINETICS under ACTIONS). The tablets must be swallowed with a glass of water.