ACE-inhibitors Market been Challenged by Novartis’ new heart failure medicine Entresto™ recommended by CHMP for EU approval
Reporters: Aviva Lev-Ari, PhD, RN and Gerard Loiseau, ESQ
Congestive Heart Failure Explained
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Basel, September 25, 2015 – Novartis announced today that the Committee for Medicinal Products for Human Use (CHMP) has adopted a positive opinion for Entresto™ (sacubitril/valsartan), marking an important milestone towards becoming available in the EU. Pending final approval by the European Commission (EC) Entresto, previously known as LCZ696, will be available for the treatment of adult patients with symptomatic chronic heart failure and reduced ejection fraction (HFrEF).
“The striking results in the PARADIGM-HF trial led me to believe that once approved LCZ696 could quickly replace what has been the bedrock treatment for more than 20 years, ACE-inhibitors” said Professor John McMurray of the University of Glasgow and one of two Principal Investigators. “Thousands of lives could be extended and hospital admissions prevented with LCZ696’s unique ability to boost natriuretic peptides, heart-helpful hormones, while simultaneously inhibiting the RAAS system.”
SOURCE
ENTRESTOTM is indicated to reduce the risk of cardiovascular death and hospitalization for heart failure in patients with chronic heart failure (NYHA Class II–IV) and reduced ejection fraction.
ENTRESTO is usually administered in conjunction with other heart failure therapies, in place of an ACE inhibitor or other ARB.
Entresto exhibits the mechanism of action of an Angiotensin Receptor Neprilysin Inhibitor that reduces the strain on the failing heart. A twice-a-day tablet, it acts to enhance the protective neurohormonal systems of the heart (NP system) while simultaneously suppressing the harmful system (the RAAS)4.
- ENTRESTO 24/26 mg (sacubitril 24 mg and valsartan 26 mg)
- ENTRESTO 49/51 mg (sacubitril 49 mg and valsartan 51 mg)
- ENTRESTO 97/103 mg (sacubitril 97 mg and valsartan 103 mg)
ENTRESTO is contraindicated with concomitant use of an angiotensin-converting enzyme (ACE) inhibitor. If switching from an ACE inhibitor to ENTRESTO, allow a washout period of 36 hours between administration of the two drugs.The recommended starting dose of ENTRESTO is 49/51 mg twice-daily.
Double the dose of ENTRESTO after 2 to 4 weeks to the target maintenance dose of 97/103 mg twice daily, as tolerated by the patient.
DOSE ADJUSTMENT FOR PATIENTS NOT TAKING AN ACE INHIBITOR OR ARB OR PREVIOUSLY TAKING LOW DOSES OF THESE AGENTS1
DOSE ADJUSTMENT FOR SEVERE RENAL IMPAIRMENT1
A starting dose of 24/26 mg twice daily is recommended for patients with severe renal impairment (eGFR <30 mL/min/1.73 m2). Double the dose of ENTRESTO every 2 to 4 weeks to the target maintenance dose of 97/103 mg twice daily, as tolerated by the patient.No starting dose adjustment is needed for mild or moderate renal impairment.
DOSE ADJUSTMENT FOR HEPATIC IMPAIRMENT1
A starting dose of 24/26 mg twice daily is recommended for patients with moderate hepatic impairment (Child-Pugh B classification). Double the dose of ENTRESTO every 2 to 4 weeks to the target maintenance dose of 97/103 mg twice daily, as tolerated by the patient.No starting dose adjustment is needed for mild hepatic impairment.
Use in patients with severe hepatic impairment is not recommended.
SOURCE
HIGHLIGHTS OF PRESCRIBING INFORMATION
These highlights do not include all the information needed to use ENTRESTO safely and effectively. See full prescribing information for ENTRESTO. ENTRESTO™ (sacubitril and valsartan) tablets, for oral use Initial U.S. Approval: 2015 WARNING: FETAL TOXICITY See full prescribing information for complete boxed warning.
When pregnancy is detected, discontinue ENTRESTO as soon as possible. (5.1) Drugs that act directly on the renin-angiotensin system can cause injury and death to the developing fetus. (5.1)
INDICATIONS AND USAGE
ENTRESTO is a combination of sacubitril, a neprilysin inhibitor, and valsartan, an angiotensin II receptor blocker, indicated to reduce the risk of cardiovascular death and hospitalization for heart failure in patients with chronic heart failure (NYHA Class II-IV) and reduced ejection fraction. (1.1) ENTRESTO is usually administered in conjunction with other heart failure therapies, in place of an ACE inhibitor or other ARB. (1.1)
DOSAGE AND ADMINISTRATION
The recommended starting dose of ENTRESTO is 49/51 mg (sacubitril/valsartan) twice-daily. Double the dose of ENTRESTO after 2 to 4 weeks to the target maintenance dose of 97/103 mg (sacubitril/valsartan) twice-daily, as tolerated by the patient. (2.1)
Reduce the starting dose to 24/26 mg (sacubitril/valsartan) twice-daily for: – patients not currently taking an angiotensin-converting enzyme inhibitor (ACEi) or an angiotensin II receptor blocker (ARB) or previously taking a low dose of these agents (2.2) – patients with severe renal impairment (2.3) – patients with moderate hepatic impairment (2.4) Double the dose of ENTRESTO every 2 to 4 weeks to the target maintenance dose of 97/103 mg (sacubitril/valsartan) twice-daily, as tolerated by the patient. (2.2, 2.3, 2.4)
SOURCE
http://www.pharma.us.novartis.com/product/pi/pdf/entresto.pdf
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