Sacubitril/Valsartan (Elderly HFrEF)

Source: UK SPC (eMC) for Entresto 24 mg/26 mg film-coated tablets, §4.2 (https://www.medicines.org.uk/emc/product/7751/smpc). ELDERLY (the focus of this page): §4.2 states only 'The dose should be in line with the renal function of the elderly patient' — there is no separate numeric elderly regimen, so the starting dose is driven by renal function (see renalAdjustment) and by systolic blood pressure. §4.4 notes that symptomatic hypotension was reported especially in patients ≥65 years old, patients with renal disease and patients with low SBP (<112 mmHg), and that blood pressure should be monitored routinely when initiating therapy or during dose titration. LOWER STARTING DOSE OF 24 mg/26 mg TWICE DAILY, with slow titration (doubling every 3–4 weeks), is recommended for: patients not currently taking an ACE inhibitor or an ARB, or taking low doses of these medicines (limited experience); and should be considered for patients with SBP ≥100 to 110 mmHg. INITIATION LIMITS: treatment should NOT be initiated in patients with a serum potassium level >5.4 mmol/l or with SBP <100 mmHg. GENERAL: 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 (and, per §4.4, ACE inhibitor therapy must not be started until 36 hours after the last sacubitril/valsartan dose). The valsartan in this product is more bioavailable than the valsartan in other marketed tablet formulations. MISSED DOSE: take the next dose at the scheduled time. TOLERABILITY PROBLEMS (SBP ≤95 mmHg, symptomatic hypotension, hyperkalaemia, renal dysfunction): adjust concomitant medicines, and temporarily down-titrate or discontinue sacubitril/valsartan. Correct sodium and/or volume depletion before starting, weighed against the risk of volume overload. 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). METHOD: oral use, with or without food; swallow the tablets with a glass of water; splitting or crushing is not recommended. NOTE ON SOURCES: §4.5 was not retrieved in this bundle — the interaction entries below come from UK §4.3/§4.4 plus §7 of the US label (Novartis ENTRESTO, https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=27616611-6b9c-4e50-b93b-ed29c24f9857). §4.4 and §4.8 were truncated at the fetch limit.

SPC §4.2 Table 1 (paediatric heart failure), for patients weighing less than 40 kg: half the starting dose 0.8 mg/kg, starting dose 1.6 mg/kg (the value given here), intermediate dose 2.3 mg/kg, target dose 3.1 mg/kg — all twice daily and all referring to the COMBINED amount of sacubitril and valsartan, to be given using granules. Half the starting dose (0.8 mg/kg twice daily) is recommended for patients who have not been taking an ACE inhibitor or an ARB or have been taking low doses, patients with renal impairment (eGFR <60 ml/min/1.73 m2), and patients with moderate hepatic impairment. For patients weighing at least 40 kg but less than 50 kg the titration is 24 mg/26 mg, then 49 mg/51 mg, then 72 mg/78 mg twice daily (half starting dose 0.8 mg/kg twice daily as granules); for patients at least 50 kg it is 24 mg/26 mg, 49 mg/51 mg, 72 mg/78 mg, then 97 mg/103 mg twice daily. Worked example from the SPC: a 25 kg child not previously on an ACE inhibitor starts at half the standard starting dose, i.e. 20 mg (25 kg x 0.8 mg/kg) twice daily as granules, rounded to 2 capsules of 6 mg/6 mg twice daily. Do not initiate if serum potassium is >5.3 mmol/l or SBP is below the 5th percentile for age. Safety and efficacy below 1 year of age have not been established and no posology recommendation can be made. This is a geriatric-focused page — verify any under-18 use against a children's formulary before it is acted on.