LCZ696

Gefahreninformationscode (GHS)

• Bildanzeige (GHS)

  

• Alarmwort

  Warnung

LCZ696 Chemische Eigenschaften,Einsatz,Produktion Methoden

• Beschreibung

  LCZ696 is a dual angiotensin II receptor antagonist and neprilysin inhibitor that is a combination of the nonpeptide angiotensin II receptor antagonist valsartan and AHU377 , a prodrug of LBQ657 , which is an inhibitor of the zinc metallopeptidase neprilysin., LCZ696 (2-60 mg/kg) induces a dose-dependent decrease in mean arterial pressure in rats expressing human renin and angiotensinogen, a double-transgenic model for angiotensin II-dependent hypertension. Formulations containing LCZ696 are under clinical investigation for the treatment of mild to moderate hypertension and chronic heart failure.

• Handelsname

  Entresto

• Mechanism of action

  LCZ696 is a molecule that combines the moieties of valsartan and sacubitril (the neprilysin inhibitor) in a single substance. By inhibiting neprilysin, the degradation of natriuretic peptides, bradykinin, and other peptides is slowed. Hence, high circulating levels of natriuretic peptides enhance diuresis , natriuresis, myocardial relaxation, and anti-remodelling, on top of the ARB effects of valsartan.

• Clinical Use

  LCZ696 (Novartis Pharmaceuticals), a first-in-class inhibitor of dualacting angiotensin-2 type-I receptor and neprilysin inhibitors, was developed as a molecule composed of molecular moieties of valsartan and neprilysin inhibitor prodrug AHU377 in a 1:1 ratio. Several phase 2 randomised clinical trials have been done or are underway in patients with hypertension. In a proof-of-concept randomised trial, LCZ696 was compared with valsartan in 1328 patients with mild-to-moderate hypertension, and provided fully additive reduction of blood pressure. No cases of angio-oedema were reported in the 8 week treatment period. This tolerance should be confirmed, particularly in black patients, for whom omapatrilat resulted in a higher occurrence of angio-oedema than in white patients. Indeed, in the proof-of-concept trial only about 8% of patients were black.

• Nebenwirkungen

  LCZ696 (Sacubitril/valsartan), now known as Entresto, is an FDA-approved drug for the treatment of heart failure with reduced ejection fraction. Entresto is often used in combination with other heart failure therapies as an alternative to ACE inhibitors or other angiotensin receptor blockers to reduce the risk of cardiovascular death and hospitalization for heart failure. The most common side effects of Entresto are low blood pressure, high potassium levels, cough, and dizziness. Serious side effects include: angioedema, low blood pressure (hypotension), kidney damage, high potassium levels, and severe allergic reactions.

• Einzelnachweise

  1. McMurray, John J. V. et al. “Angiotensin-neprilysin inhibition versus enalapril in heart failure.” The New England journal of medicine 371 11 (2014):  993-1004. DOI: 10.1056/NEJMoa1409077
  2. Gu, Jessie et al. “Pharmacokinetics and Pharmacodynamics of LCZ696, a Novel Dual‐Acting Angiotensin Receptor—Neprilysin Inhibitor (ARNi).” The Journal of Clinical Pharmacology 50 (2010): n. pag. DOI: 10.1177/0091270009343932
  3. Langenickel, T.H., & Dole, W.P. (2012). Angiotensin receptor-neprilysin inhibition with LCZ696: a novel approach for the treatment of heart failure. Drug Discovery Today: Therapeutic Strategies, 9. DOI: 10.1016/J.DDSTR.2013.11.002
  4. Suematsu, Yasunori et al. “LCZ696, an angiotensin receptor–neprilysin inhibitor, improves cardiac function with the attenuation of fibrosis in heart failure with reduced ejection fraction in streptozotocin‐induced diabetic mice.” European Journal of Heart Failure 18 (2016): n. pag. DOI: 10.1002/ejhf.474

LCZ696 Anbieter Lieferant Produzent Hersteller Vertrieb Händler.

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