Sacubitril + Valsartan

Thông tin thuốc gốc
Chỉ định và Liều dùng
Chronic heart failure
Adult: Available preparations:
Sacubitril 24 mg and Valsartan 26 mg
Sacubitril 49 mg and Valsartan 51 mg
Sacubitril 97 mg and Valsartan 103 mg

In patient with reduced ejection fraction: Initially, 49 mg/51 mg bid. Dosage is individualised and may be increased after 2-4 weeks as tolerated to target maintenance dose of 97 mg/103 mg bid.
Nhóm bệnh nhân đặc biệt
Patient with systolic blood pressure 100-110 mmHg: Initially, 24 mg/26 mg tab bid.

Patient not currently or previously taking low doses of ACE inhibitors or ARB: 24 mg/26 mg bid, double the dose as tolerated every 2-4 weeks. Maintenance: 97 mg/103 mg bid.

Patient previously taking moderate to high dose of ACE inhibitors or ARB: 49 mg/51 mg bid, double the dose as tolerated every 2-4 weeks. Maintenance: 97 mg/103 mg bid.
Suy thận
Moderate (eGFR 30-60 mL/min/1.73 m2) and severe (eGFR <30 mL/min/1.73 m2): Initially, 24 mg/26 mg bid.
Suy gan
Moderate (Child-Pugh class B): Initially, 24 mg/26 mg bid. Severe (Child-Pugh class C): Contraindicated.
Cách dùng
May be taken with or without food.
Chống chỉ định
Hypersensitivity or history of angioedema, biliary cirrhosis, cholestasis. Concomitant use or use within 36 hours of ACE inhibitors or Angiotensin II Receptor Blockers (ARBs). Concomitant use with aliskiren-containing products in patients with diabetes mellitus. Severe hepatic impairment (Child-Pugh class C). Pregnancy.
Thận trọng
Patient with risk factors for hypotension (e.g. salt- or volume depletion, MI); aortic/mitral stenosis, risk factors for renal failure (e.g. diabetes mellitus, hypoaldosteronism). Moderate to severe renal and moderate hepatic impairment (Child-Pugh class B). Lactation.
Tác dụng không mong muốn
Significant: Hypotension, hyperkalaemia, decreased renal function.
Blood and lymphatic system disorders: Anaemia.
Gastrointestinal disorders: Diarrhoea, nausea, gastritis.
General disorders and administration site conditions: Fatigue, asthenia.
Investigations: Increased serum creatinine.
Metabolism and nutrition disorders: Hypokalaemia, hypoglycaemia.
Nervous system disorders: Dizziness, headache, vertigo.
Renal and urinary disorders: Renal failure.
Respiratory, thoracic and mediastinal disorders: Cough.
Vascular disorders: Orthostatic hypotension, syncope.
Potentially Fatal: Angioedema.
Thông tin tư vấn bệnh nhân
This drug may cause dizziness or fatigue, if affected, do not drive or operate machinery.
Chỉ số theo dõi
Monitor K levels at baseline and periodically thereafter, blood pressure, LFT, renal function (e.g. serum creatinine, BUN). Correct hyperkalaemia, volume and Na depletion prior to initiation of treatment.
Tương tác
Additive hypotensive effect with sildenafil and other PDE5 inhibitors. Increased risk of acute renal failure with NSAID(s). Increased serum concentration with rifampicin, ciclosporin, ritonavir. May reduce serum concentration of metformin.
Sacubitril: May increase serum concentration of OATP1B1, OATP1B3 substrates (e.g. atorvastatin). Increased concentration of statins.
Valsartan: May increase serum lithium concentration and toxicity. Increased risk of hyperkalaemia with potassium-sparing diuretics (e.g. triamterene), mineralocorticoid antagonists (e.g. spironolactone), K supplements, or other K-containing salt substitutes (e.g. heparin).
Potentially Fatal: Increased risk of angioedema with ACE inhibitors/ARBs. Increased risk of hypotension, hyperkalaemia, and acute renal failure with aliskiren in patients with diabetes mellitus.
Tác dụng
Mechanism of Action: Sacubitril is a prodrug of sacubitrilat (LBQ-657) which inhibits neprilysin, a neutral endopeptidase (NEP), leading to increased levels of endogenous vasoactive peptides including natriuretic peptides, bradykinin and adrenomedullin.
Valsartan is an angiotensin II type 1 (AT1) receptor blocker. It antagonizes AT1-induced vasoconstriction, aldosterone, catecholamine and arginine vasopressin release, water intake, and hypertrophic response.
Absorption: Sacubitril: Absolute bioavailability: >60%. Time to peak plasma concentration: Approx 0.5-1 hour (sacubitril); 2 hours (LBQ657).
Valsartan: Rapidly absorbed from the gastrointestinal tract. Bioavailability: Approx 23% (tab); approx 39% (solution). Time to peak plasma concentration: 1.5 hours.
Distribution: Sacubitril: LBQ657 crosses the blood brain barrier to limited extent (0.28%). Volume of distribution: 103 L. Plasma protein binding: 94-97%.
Valsartan: Volume of distribution: 75 L. Plasma protein binding: 94-97%.
Metabolism: Sacubitril: Metabolised by esterases to active metabolite, LBQ657.
Valsartan: Minimally metabolised (approx 20%; <10% as hydroxyl metabolite).
Excretion: Sacubitril: Via urine (approx 52-68%, primarily as LBQ657); faeces (37-48%, primarily as LBQ657). Elimination half-life: 1.4 hours (sacubitril); 11.5 hours (LBQ657).
Valsartan: Mainly via faeces (86%); urine (approx 13%). Elimination half-life: Approx 9.9 hours.
Đặc tính

Chemical Structure Image

Source: National Center for Biotechnology Information. PubChem Database. Sacubitril, CID=9811834, (accessed on Jan. 23, 2020)

Chemical Structure Image

Source: National Center for Biotechnology Information. PubChem Compound Summary for CID 60846, Valsartan. Accessed Oct. 25, 2023.

Bảo quản
Store at 25°C. Protect from moisture.
Phân loại MIMS
Thuốc đối kháng thụ thể angiotensin II / Các loại thuốc tim mạch khác
Phân loại ATC
C09DX04 - valsartan and sacubitril ; Belongs to the class of angiotensin II receptor blockers (ARBs), other combinations. Used in the treatment of cardiovascular disease.
Tài liệu tham khảo
Anon. Sacubitril and Valsartan. Lexicomp Online. Hudson, Ohio. Wolters Kluwer Clinical Drug Information, Inc. Accessed 05/02/2018.

Buckingham R (ed). Sacubitril. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. . Accessed 05/02/2018.

Buckingham R (ed). Valsartan. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. Accessed 05/02/2018.

Entresto Film Coated Tablet (Novartis Pharmaceuticals Corporation). DailyMed. Source: U.S. National Library of Medicine. Accessed 05/02/2018.

Joint Formulary Committee. Valsartan with Sacubitril. British National Formulary [online]. London. BMJ Group and Pharmaceutical Press. Accessed 05/02/2018.

Thông báo miễn trừ trách nhiệm: Thông tin này được MIMS biên soạn một cách độc lập dựa trên thông tin của Sacubitril + Valsartan từ nhiều nguồn tài liệu tham khảo và được cung cấp chỉ cho mục đích tham khảo. Việc sử dụng điều trị và thông tin kê toa có thể khác nhau giữa các quốc gia. Vui lòng tham khảo thông tin sản phẩm trong MIMS để biết thông tin kê toa cụ thể đã qua phê duyệt ở quốc gia đó. Mặc dù đã rất nỗ lực để đảm bảo nội dung được chính xác nhưng MIMS sẽ không chịu trách nhiệm hoặc nghĩa vụ pháp lý cho bất kỳ yêu cầu bồi thường hay thiệt hại nào phát sinh do việc sử dụng hoặc sử dụng sai các thông tin ở đây, về nội dung thông tin hoặc về sự thiếu sót thông tin, hoặc về thông tin khác. © 2023 MIMS. Bản quyền thuộc về MIMS. Phát triển bởi
Register or sign in to continue
Asia's one-stop resource for medical news, clinical reference and education
Already a member? Sign in
Register or sign in to continue
Asia's one-stop resource for medical news, clinical reference and education
Already a member? Sign in