Drug Interaction:
Dual blockade of the renin-angiotensin system: Do not use with an ACEi,
do not use with aliskiren in patients with diabetes, and avoid use with an ARB.
Potassium-sparing diuretics: May lead to increased serum potassium.
NSAIDs: May lead to increased risk of renal impairment.
Lithium: Increased risk of lithium toxicity.
Indication:
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.
Drugs that act directly on the renin-angiotensin system can cause injury
and death to the developing fetus.
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.
ENTRESTO is usually administered in conjunction with other heart failure
therapies, in place of an ACE inhibitor or other ARB.
NEW MOLECULAR ENTITY AND NEW THERAPEUTIC BIOLOGICAL
PRODUCTS APPROVED FOR 2015
Certain drugs are classified as New molecular Emtities- NME- for FDA review
Many of these products contain active moieties that have not been approved
by FDA previously, either as a single ingredient or as part of a combination
products; these products frequently provide important new therapies for the
patients.
Some drugs are characterized as NMEs for administrative purposes ,but
nonetheless contain certain active moieties in products that have been
previously approved by FDA. For example, CDER classifies biological
products submitted in an application under section 351(a) of the Public
Service Act as NME for purposes of FDA review, regardless of whether
the agency previously approved a related active moiety in a different
product.
FDAs classification of a drug as an -NME- for review purposes is distinct
from FDAs determination of whether a drug is a - New Chemical Entity or - NCE-
within the meaning of the Federal Food,Drug, and Cosmetic Act
No.16
Drug Name - Sacubitril/Valsartan
Active Ingredient- Entresto
Date of approval - 7/07/2015
FDA-approved use - To treat heart failure
Approved by US FDA on 7/07/2015- (Ref- FDA approved List- 2015)
LIST OF NEW DRUG APPROVED FROM 01-01-2016 To TILL DATE
BY NEW DRUG DIVISION - DRUG CONTROLLER GENERAL- INDIA
Sr.No Name of Drug Indication Date of Issue
11. Sacubutril + valsatran Film 14-07-2016
Coated tablets
50mg/100mg/200mg
To reduce the risk of cardiovascular death and hospitalisation
for heart failure in patients with chronic heart failure
(NYHA Class II- IV) and reduced ejection fraction
Approved by DCG INDIA (Ref- DCGI approved List- 14-078-2016 To Till Date
Adverse Reaction:
Adverse reactions occurring .5% are hypotension, hyperkalemia, cough,
dizziness, and renal failure.
Contra-Indications:
CONTRAINDICATIONS
Hypersensitivity to any component.
History of angioedema related to previous ACE inhibitor or ARB therapy.
Concomitant use with ACE inhibitors.
Concomitant use with aliskiren in patients with diabetes.
WARNINGS AND PRECAUTIONS
Observe for signs and symptoms of angioedema and hypotension.
Monitor renal function and potassium in susceptible patients.
Dosages/ Overdosage Etc:
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.
ENTRESTO is usually administered in conjunction with other heart failure
therapies, in place of an ACE inhibitor or other ARB.
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.
Reduce the starting dose to 24/26 mg (sacubitril/valsartan) twice-daily for:
1.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.patients with severe renal impairment
3.patients with moderate hepatic impairment
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.
DOSAGE FORMS AND STRENGTHS
Film-coated tablets (sacubitril/valsartan): 24/26 mg; 49/51 mg; 97/103 mg
Patient Information:
PATIENT COUNSELING INFORMATION
Advise patients to read the FDA-approved patient labeling (Patient Information).
Pregnancy:
Advise female patients of childbearing age about the consequences
of exposure to ENTRESTO during pregnancy. Discuss treatment options with women
planning to become pregnant.
Ask patients to report pregnancies to their physicians as soon as possible
Angioedema:
Advise patients to discontinue use of their previous ACE inhibitor or ARB.
Advise patients to allow a 36 hour wash-out period if switching from or to an ACE inhibitor.
Patient Information ENTRESTO (en-TRESS-toh) (sacubitril/valsartan) tablets
What is the most important information I should know about ENTRESTO?
ENTRESTO can harm or cause death to your unborn baby.
Talk to your doctor about other ways to treat heart failure if you plan to become pregnant.
If you get pregnant while taking ENTRESTO, tell your doctor right away.
Distributed by:
Novartis Pharmaceuticals Corporation
East Hanover, New Jersey 07936 © Novartis
Pharmacology/ Pharmacokinetics:
CLINICAL PHARMACOLOGY
1. Mechanism of Action
ENTRESTO contains a neprilysin inhibitor, sacubitril, and an angiotensin receptor bl ocker,
valsartan. ENTRESTO inhibits neprilysin (neutral endopeptidase; NEP) via LBQ657,
the active metabolite of the prodrug sacubitril, and blocks the angiotensin II type-1 (AT1)
receptor via valsartan. The cardiovascular and renal effects of ENTRESTO in heart
failure patients are attributed to the increased levels of peptides that are degraded
by neprilysin, such as natriuretic peptides, by LBQ657, and the simultaneous inhibition
of the effects of angiotensin II by valsartan. Valsartan inhibits the effects of angiotensin II
by selectively blocking the AT1 receptor, and also inhibits angiotensin II-dependent
aldosterone release.
2. Pharmacokinetics
Absorption
Following oral administration, ENTRESTO dissociates into sacubitril and valsartan.
Sacubitril is further metabolized to LBQ657. The peak plasma concentrations of sacubitril,
LBQ657, and valsartan are reached in 0.5 hours, 2 hours, and 1.5 hours, respectively.
The oral absolute bioavailability of sacubitril is estimated to be . 60%.
The valsartan in ENTRESTO is more bioavailable than the valsartan in other marketed
tablet formulations; 26 mg, 51 mg, and 103 mg of valsartan in ENTRESTO is equivalent
to 40 mg, 80 mg, and 160 mg of valsartan in other marketed tablet formulations, respectively
Pregnancy and lactation:
USE IN SPECIFIC POPULATIONS
.1 Pregnancy
Risk Summary
ENTRESTO can cause fetal harm when administered to a pregnant woman. Use of drugs
that act on the renin-angiotensin system during the second and third trimesters of
pregnancy reduces fetal renal function and increases fetal and neonatal morbidity
and death.
When pregnancy is detected, consider alternative drug treatment and discontinue
ENTRESTO. However, if there is no appropriate alternative to therapy with drugs
affecting the reninangiotensin system, and if the drug is considered lifesaving
for the mother, advise a pregnant woman of the potential risk to the fetus.
2 Lactation
Risk Summary
There is no information regarding the presence of sacubitril/valsartan in human milk,
Because of the potential for serious adverse reactions in breastfed infants from
exposure to sacubitril/valsartan, advise a nursing woman that breastfeeding is
not recommended during treatment with ENTRESTO.
3.Pediatric use-
Safety and effectiveness in pediatric patients have not been established.
4.Geriatric Use
No relevant pharmacokinetic differences have been observed in elderly (.65 years)
or very elderly (.75 years) patients compared to the overall population .
Manufacturer Details