Drug Action
Sacubitril (a prodrug) inhibits the breakdown of natriuretic peptides resulting in varied effects including increased diuresis, natriuresis, and vasodilation.
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Drug reference
Sacubitril (a prodrug) inhibits the breakdown of natriuretic peptides resulting in varied effects including increased diuresis, natriuresis, and vasodilation.
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Symptomatic chronic heart failure with reduced ejection fraction (in patients not currently taking an ACE inhibitor or angiotensin II receptor antagonist, or stabilised on low doses of either of these agents) ▶BY MOUTH ▶Adult: Initially 24/26 mg twice daily for 3–4 weeks, increased if tolerated to 49/51 mg twice daily for 3–4 weeks, then increased if tolerated to 97/103 mg twice daily Symptomatic chronic heart failure with reduced ejection fraction (in patients currently stabilised on an ACE inhibitor or angiotensin II receptor antagonist) ▶BY MOUTH ▶Adult: Initially 49/51 mg twice daily for 2–4 weeks, increased if tolerated to 97/103 mg twice daily, consider a starting dose of 24/26 mg if systolic blood pressure less than 110 mmHg DOSE EQUIVALENCE AND CONVERSION ▶Entresto ® tablets contain sacubitril and valsartan; the proportions are expressed in the form x/y where x and y are the strength in milligrams of sacubitril and valsartan respectively. Valsartan, in this formulation, is more bioavailable than other tablet formulations— 26 mg, 51 mg, and 103 mg valsartan is equivalent to 40 mg, 80 mg and 160 mg, respectively. Furthermore, note that the 24/26 mg, 49/51 mg and 97/103 mg strengths are sometimes referred to as a total of both drug strengths, that is, 50 mg, 100 mg and 200 mg, respectively.
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Concomitant use with an ACE inhibitor (do not initiate until at least 36 hours after discontinuing ACE inhibitor—risk of angioedema). concomitant use with an angiotensin II receptor antagonist. systolic blood pressure less than 100 mmHg
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NICE decisions ▶Sacubitril valsartan for treating symptomatic chronic heart failure with reduced ejection fraction (April 2016) NICE TA388 Sacubitril valsartan (Entresto ®) is recommended as an option for treating symptomatic chronic heart failure with reduced ejection fraction, only in adults: . with New York Heart Association class II to IV symptoms, and . a left ventricular ejection fraction of 35% or less, and . who are already taking a stable dose of an ACE inhibitor or angiotensin II receptor antagonist. Patients whose treatment was started within the NHS before this guidance was published should have the option to continue treatment, without change to their funding arrangements, until they and their NHS clinician consider it appropriate to stop. www.nice.org.uk/guidance/ta388
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→Appendix 1: angiotensin-II receptor antagonists. sacubitril
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▶Common or very common Anaemia. asthenia. cough. diarrhoea. dizziness. electrolyte imbalance. gastritis. headache. hypoglycaemia. hypotension. nausea. renal impairment. syncope. vertigo ▶Uncommon Angioedema. skin reactions
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Manufacturer advises avoid—toxicity with sacubitril in animal studies.
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Manufacturer advises avoid—present in milk in animal studies.
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Manufacturer advises caution in moderate impairment or if hepatic transaminases exceed 2 times the upper limit of normal (limited information available); avoid in severe impairment, biliary cirrhosis or cholestasis (no information available). Dose adjustments Manufacturer advises initial dose reduction to 24/26 mg twice daily in moderate impairment or if hepatic transaminases exceed 2 times the upper limit of normal.
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Dose adjustments Manufacturer recommends a starting dose of 24/26 mg twice daily if eGFR less than 30 mL/minute/1.73m2. Also consider this starting dose if Cardiovascular system eGFR 30 to 60 mL/minute/1.73m2.
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There can be variation in the licensing of different medicines containing the same drug. Tablet ▶Entresto (Novartis Pharmaceuticals UK Ltd) A Sacubitril 24 mg,Valsartan 26 mg Entresto 24mg/26mg tablets | 28 tablet P £45.78 DT = £45.78 Sacubitril 49 mg,Valsartan 51 mg Entresto 49mg/51mg tablets | 28 tablet P £45.78 | 56 tablet P £91.56 DT = £91.56 Sacubitril 97 mg,Valsartan 103 mg Entresto 97mg/103mg tablets | 56 tablet P £91.56 DT = £91.56 PHOSPHODIESTERASE TYPE-3 INHIBITORS
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Initially 24/26 mg twice daily for 3–4 weeks,
First-line fragment. Read the complete Indications and Dose section above.
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Initially 49/51 mg twice daily for 2–4 weeks,
First-line fragment. Read the complete Indications and Dose section above.
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