Sacubitril/Valsartan

eMC SPC for Entresto 24 mg/26 mg film-coated tablets. Must not be co-administered with an ACE inhibitor or an ARB; because of the risk of angioedema it must not be started for at least 36 hours after discontinuing ACE inhibitor therapy. A starting dose of 24 mg/26 mg twice daily with slow titration (doubling every 3-4 weeks) is recommended in patients not currently taking an ACE inhibitor or an ARB or taking low doses of these medicinal products; a starting dose of 24 mg/26 mg twice daily should also be considered for patients with SBP 100 to 110 mmHg. Treatment should not be initiated in patients with serum potassium > 5.4 mmol/l or with SBP < 100 mmHg. If tolerability issues occur (SBP <= 95 mmHg, symptomatic hypotension, hyperkalaemia, renal dysfunction), adjust concomitant medicines and consider temporary down-titration or discontinuation. If a dose is missed, the patient should take the next dose at the scheduled time. The valsartan in Entresto is more bioavailable than valsartan in other marketed tablet formulations. Elderly: the dose should be in line with the patient's renal function. Hepatic impairment: no adjustment in mild impairment (Child-Pugh A); use with caution and half the starting dose in moderate impairment (Child-Pugh B) or with AST/ALT more than twice the upper limit of normal; contraindicated in severe hepatic impairment, biliary cirrhosis or cholestasis (Child-Pugh C).

Paediatric heart failure, from the SPC Table 1 dose-titration table. mg/kg figures refer to the combined amount of sacubitril and valsartan and are to be given using granules. Paediatric patients less than 40 kg: half the starting dose 0.8 mg/kg, starting dose 1.6 mg/kg, intermediate dose 2.3 mg/kg, target dose 3.1 mg/kg — all twice daily. Paediatric patients at least 40 kg and less than 50 kg: half the starting dose 0.8 mg/kg, then 24 mg/26 mg, 49 mg/51 mg, target 72 mg/78 mg twice daily. Paediatric patients at least 50 kg: 24 mg/26 mg, 49 mg/51 mg, 72 mg/78 mg, target 97 mg/103 mg twice daily. Half the starting dose is recommended in patients not previously taking an ACE inhibitor or ARB or taking low doses, in renal impairment (eGFR < 60 ml/min/1.73 m2), and in moderate hepatic impairment; in these patients the dose is then increased to the standard starting dose and adjusted every 3-4 weeks. Treatment should not be initiated in paediatric patients with serum potassium > 5.3 mmol/l or SBP below the 5th percentile for age. Safety and efficacy in children aged below 1 year have not been established and no posology recommendation can be made. Clinician to verify against a children's formulary.