Sacubitril-Valsartan

Indication per SPC: adult heart failure. 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; a starting dose of 24 mg/26 mg twice daily should also be considered for patients with SBP 100 to 110 mmHg. Must not be co-administered with an ACE inhibitor or an ARB, and must not be started for at least 36 hours after discontinuing ACE inhibitor therapy (angioedema risk). Do not initiate if serum potassium is greater than 5.4 mmol/l or SBP is less than 100 mmHg. If tolerability issues occur (SBP 95 mmHg or below, symptomatic hypotension, hyperkalaemia, renal dysfunction), adjust concomitant medicinal products and consider temporary down-titration or discontinuation. The valsartan contained in this product is more bioavailable than the valsartan in other marketed tablet formulations - doses are not interchangeable. If a dose is missed, take the next dose at the scheduled time. Elderly: the dose should be in line with the renal function of the patient. Hepatic impairment: no adjustment in mild (Child-Pugh A); use with caution and half the starting dose in moderate (Child-Pugh B) or where AST/ALT are more than twice the upper limit of normal; contraindicated in severe hepatic impairment, biliary cirrhosis or cholestasis (Child-Pugh C). Source: Entresto 24 mg/26 mg film-coated tablets SPC (eMC product 7751), section 4.2. In this bundle several comparator symbols were lost in capture; the threshold directions above were read from a parallel capture of the SAME SPC (eMC product 7751, stored as sacubitril-with-valsartan) in which the symbols were intact - clinician to confirm against the live SPC. Section 4.5 was not included in the fetched bundle - the interaction entries below are drawn from the section 4.2/4.3/4.4 text only.

Paediatric heart failure, eMC section 4.2 Table 1. All doses are given twice daily; the mg/kg figures refer to the COMBINED amount of sacubitril and valsartan and are to be given using granules. Less than 40 kg: half starting dose 0.8 mg/kg, starting dose 1.6 mg/kg, intermediate 2.3 mg/kg, target 3.1 mg/kg. At least 40 kg and less than 50 kg: half starting dose 0.8 mg/kg (granules), starting dose 24 mg/26 mg, intermediate 49 mg/51 mg, target 72 mg/78 mg. At least 50 kg: half starting dose 24 mg/26 mg, starting dose 49 mg/51 mg, intermediate 72 mg/78 mg, target 97 mg/103 mg. Half the starting dose is recommended in patients not previously taking an ACE inhibitor or an ARB or taking low doses of these, in renal impairment (eGFR less than 60 ml/min/1.73 m2) and in moderate hepatic impairment; where half the starting dose is used, adjust every 3-4 weeks. SPC worked example: a 25 kg patient not previously on an ACE inhibitor starts at half the standard starting dose = 20 mg (25 kg x 0.8 mg/kg) twice daily as granules, which after rounding to the closest number of full capsules corresponds to 2 capsules of 6 mg/6 mg twice daily. Do not initiate if serum potassium is greater than 5.3 mmol/l or if SBP is below the 5th percentile for the age of the patient. If tolerability issues occur (SBP below the 5th percentile for age, symptomatic hypotension, hyperkalaemia, renal dysfunction), adjust concomitant medicinal products and consider temporary down-titration or discontinuation. Safety and efficacy in children aged below 1 year have not been established and no recommendation on a posology can be made. Verify all paediatric doses against a children's formulary and local policy before prescribing.