Cardiovascular Journal of Africa: Vol 28 No 6 (November/December 2017)

HOSPITALISATION PRESENTS AN IDEAL OPPORTUNITY

TO REASSESS CHRONIC HF THERAPY

RESET CHRONIC HF THERAPY IN THE HOSPITAL WITH ENTRESTO

®1,2

In the largest trial ever conducted in Heart Failure, where ~ 60% of patients had a previous hospitalisation,

3,4

ENTRESTO

demonstrated...

Results were consistent across patients with or without previous hospitalisations

reduced risk of CV death or HF

hospitalisation vs enalapril (p<0.001),

with comparable safety and tolerability

lower rate of 30-day readmission for

HF vs enalapril (p=0.006)

References: 1.

Krim SR, Campbell PT, Desai S, et al. Management of patients admitted with acute decompensated heart failure. Oschner J. 2015;15:284-289.

Entresto

package insert. Novartis, South Africa; September 2017.

McMurray JJV, Packer M, Desai

AS, et al; for PARADIGM-HF Committees Investigators. Baseline characteristics and treatment of patients in prospective comparison of ARNI with ACEI to determine impact on global mortality and morbidity in heart failure trial (PARADIGM-HF). Eur J Heart Fail.

2014;16(7):817-825.

McMurray JJV, Packer M, Desai AS, et al. Angiotensin-neprilysin inhibition versus enalapril in heart failure. N Engl J Med. 2014;371(11):993-1004.

Desai AS, Claggett BL, Packer M, et al. Influence of sacubitril/valsartan (LCZ696) on 30-day

readmission after heart failure hospitalization. J Am Coll Cardiol. 2016;68(3):241-248.

CV=cardiovascular; HF=heart failure

SCHEDULING STATUS:

S3 ENTRESTO

50 mg film-coated tablets Reg. No. 50/7.6/1016; ENTRESTO

100 mg film-coated tablets Reg. No. 50/7.6/1017; ENTRESTO

200 mg film-coated tablets Reg. No. 50/7.6/1018

COMPOSITION:

ENTRESTO

50 mg film-

coated tablets contain 24 mg sacubitril and 26 mg valsartan. ENTRESTO

100 mg film-coated tablets contain 49 mg sacubitril and 51 mg valsartan. ENTRESTO

200 mg film-coated tablets contain 97 mg sacubitril and 103 mg valsartan.

PHARMACOLOGICAL

CLASSIFICATION:

A7.6 Vascular medicines Others

INDICATIONS:

ENTRESTO

is indicated as a second-line therapy, replacing ACE inhibitors or ARB for treatment of symptomatic heart failure (NYHA class II-IV) in patients with systolic dysfunction. ENTRESTO

administered in combination with other heart failure therapies as appropriate.

DOSAGE AND DIRECTIONS FOR USE: Adults:

• The target dose of Entresto

is 200 mg twice daily. • The recommended starting dose of Entresto

is 100 mg twice daily. • A starting dose

of 50 mg twice daily is recommended for patients taking low doses of an angiotensin-converting enzyme (ACE) inhibitor or an angiotensin II receptor blocker (ARB). • Dose up titration by resembling the dose every 3 – 4 weeks is recommended until a dose of 200 mg

twice daily is achieved of tolerance.

Geriatric patients:

Patients over the age of 65 years may have impaired renal function, therefore a lower starting dose is recommended.

Pediatric patients:

The safety and efficacy in paediatric patients aged below 18 years has

not been established.

Renal impairment:

contraindicated in patients with severe impaired renal function.

Hepatic impairment:

No dose adjustment is required in patients with mild to moderate hepatic impairment. In patients with severe hepatic impairment use of

Entresto

is not recommended.

METHOD OF ADMINISTRATION:

for oral use. May be administered with or without food.

CONTRAINDICATIONS:

• Hypersensitivity to the active substance, sacubitril, valsartan, or to any of the excipients. • Concomitant use with ACE

inhibitors. Entresto

must not be administered until 36 hours after discontinuing ACE inhibitor therapy. • Known history of angioedema related to previous ACE inhibitor or ARB therapy. • Hereditary or idiopathic angioedema. • Hypertrophic obstructive cardiomyopathy.

• Bilateral renal artery stenosis. • Renal artery stenosis in patients with a single kidney. • Aortic valve stenosis. • Concomitant therapy with potassium sparing diuretics such as spironolactone, triamerene, amiloride • Porphyria • Lithium therapy • Concomitant use

with renin antagonists • Pregnancy and lactation • Severe renal impairment • Concomitant use with aliskiren-containing products

WARNINGS AND SPECIAL PRECAUTIONS: Dual blockade of the Renin-Angiotensin-Aldosterone System (RAAS):

Entresto

must

not be administered with an ACE inhibitor or another ARB due to the risk of angioedema. Entresto

must not be initiated until 36 hours after taking the last dose of ACE inhibitor or ARB therapy. If treatment with Entresto

is stopped, ACE inhibitor or ARB therapy must

not be initiated until 36 hours after the last dose of Entresto

. • Entresto

must not be used concomitantly with aliskiren.

Hypotension:

If hypotension occurs, dose adjustment of diuretics, concomitant antihypertensive medicines, and treatment of other causes of

hypotension (e.g. hypovolemia) should be considered. If hypotension persists despite such measures, the dosage of Entresto

should be reduced or the product should be temporarily discontinued. Sodium and/or volume depletion should be corrected before starting

treatment with Entresto

Impaired renal function:

Down titration of Entresto should be considered in patients who develop a clinically significant decrease in renal function.

Hyperkalemia:

Medications known to raise potassium levels (e.g. potassium-sparing

diuretics, potassium supplements) should not be used with ENTRESTO

. If clinically significant hyperkalemia occurs, measures such as reducing dietary potassium, or adjusting the dose of concomitant medications should be considered. Monitoring of serum potassium

is recommended especially in patients with risk factors such as diabetes mellitus, hypoaldosteronism or receiving a high potassium diet.

Angioedema:

If angioedema occurs, Entresto

should be immediately discontinued and appropriate therapy and monitoring should

be provided until complete and sustained resolution of signs and symptoms has occurred. Entresto

must not be re-administered. Patients with a prior history of angioedema were not studied. Black patients may have increased susceptibility to develop angioedema.

Patients with renal artery stenosis: is contraindicated.

Interactions with statins:

Caution should be exercised upon co-administration with statins

Pregnancy and lactation:

Entresto should not be used during pregnancy or lactation.

INTERACTIONS:

◊

Concomitant

use contraindicated:

Aliskiren, Use with ACE inhibitors. Entresto

must not be started until 36 hours after taking the last dose of ACE inhibitor or ARB therapy. ACE inhibitor therapy must not be started until 36 hours after the last dose of Entresto

. ◊ Caution when

used concomitantly with statins, sildenafil, lithium, potassium-sparing diuretics including mineral corticoid antagonists (e.g. spironolactone, triamterene, amiloride), potassium supplements, or salt substitutes containing potassium, non-steroidal anti-inflammatory

agents (NSAIDs) including selective cyclooxygenase-2 inhibitors (COX-2 Inhibitors), inhibitors of OATP1B1, OATP1B3, OAT3 (e.g. rifampin, cyclosporin) or MPR2 (e.g. ritonavir).

Side effects:

Very common

(≥10%): Hyperkalaemia, hypotension, renal impairment.

Common

(1 to 10%): Anaemia, Cough, dizziness, renal failure, diarrhoea, hypokalaemia, fatigue, headache, syncope, nausea, asthenia, orthostatic hypotension, vertigo, hypoglycaemia, gastritis

Uncommon

(0.1 to 1%): Angioedema, postural dizziness, pruritis, rash

Packs:

14, 28 or 56 tablets packed in PVC/PVDC blister packs.

Note:

Before prescribing consult full prescribing information

Novartis South Africa (Pty) Ltd.

Magwa Crescent West, Waterfall City, Jukskei View, 2090. Tel +27 11 3476000. Company Reg No: 1946/020671/07 For any product related enquiries, please contact the Novartis Customer Contact Centre on 0861 929 929

ZA1802773289 Exp 06/02/2019

NEW

For any Entresto

product related enquiries, please contact the Novartis Customer Contact Centre on 0861 929 929