Download 119 - Coastal West Sussex Formulary

Sacubitril Valsartan (Entresto®) – Pathway for Treating Symptomatic
Chronic Heart Failure with Reduced Ejection Fraction
NICE TA 388 April 2016
(https://www.nice.org.uk/guidance/ta388)
NICE recommendations
Sacubitril valsartan is a combined neprilysin inhibitor +angiotensin II receptor inhibitor.
It is recommended as an option for treating symptomatic chronic heart failure with reduced ejection
fraction, only in people:



with New York Heart Association (NYHA) class II to IV symptoms and
with a left ventricular ejection fraction of 35% or less and
who are already taking a stable dose of angiotensin-converting enzyme (ACE)
inhibitors or angiotensin II receptor-blockers (ARBs).
Treatment should be started by a heart failure specialist with access to a multidisciplinary heart
failure team.
Dose titration and monitoring should be performed by the most appropriate team member.
Preparations



Sacubitril 24mg + valsartan 26mg
Sacubitril 49mg + valsartan 51mg
Sacubitril 97mg + valsartan 103mg
The valsartan in Entresto® is more bioavailable than in other formulations of valsartan: 26mg, 51mg
and 103mg of valsartan in Entresto® is equivalent to 40mg, 80mg and 160mg of valsartan in other
marketed formulations.
Prescribing
Monitoring of renal function, potassium and blood pressure will be undertaken by the team that
initiated treatment until the patient is on the maximum tolerated dose and titration is complete.
Adverse reactions
The most common adverse reactions reported are low blood pressure, hyperkalaemia, and renal
impairment, consistent with those associated with agents acting on the
renin/aldosterone/angiotensin system. For full details of adverse effects see the SPC for Entresto®.
Switching from current ACE or ARB
Discontinue any ACE inhibitor for 2 days prior to initiating sacubitril valsartan (risk of angioedema
if co-prescribed)
Discontinue any ARB the day before starting sacubitril valsartan
1
Sacubitril Valsartan (Entresto®) Care pathway adapted for Western Hospitals NHS Foundation Trust
Ratified: November 2016 APC
Review date: November 2018
Dosing: sacubitril valsartan is given twice a day
Sacubitril 24mg +
valsartan 26mg
Starting dose if on low dose
ACE/ARB prior to initiation
Sacubitril 49mg +
valsartan 51mg
Starting dose if on high dose
ACE/ARB prior to initiation
Sacubitril 97mg +
valsartan 103mg
Target dose
Also consider this dose if any
concerns about low blood
pressure*, renal function* * or
hyperkalaemia***
*Treatment should not be initiated if SBP < 100 mmHg
**There is limited experience in patients with severe renal dysfunction (eGFR < 30ml/minute). Use is
not recommended in end stage renal disease
***Treatment should not be initiated if potassium is > 5.4 mmol/l
Dose titrations can be made at 2-4 week intervals (longer interval if starting on lowest dose)
In the absence of contra-indications beta-blockers and mineralocorticoid receptor
antagonists (MRAs) should be continued.
Anticipated numbers of patients to be prescribed sacubitril/valsartan and anticipated cost
Currently the population in Coastal West Sussex CCG is approx. 480,185 and there are 959 HF
patients eligible for treatment derived from QOF, HES, and NHFA (Quality Outcomes Framework,
Hospital Episode Statistics, National Heart Failure Audit).
The NICE TAG suggests 12% of eligible patients should be initiated on Entresto® per annum.(This info
from Novartis).
Monthly cost of Entresto® = £91.60 (all tablet strengths).
Therefore 115 patients per annum initiated on Entresto® – total drug cost = 115 x £91.60 x12
= £126,408 for first year. This figure would approximately double for the second year as a further
12% of eligible patients were initiated on Entresto®.
Anticipated involvement of specialist nurses: Identify stable patients with heart failure not
decompensating, but who have had a spell of breathlessness recently which resolved with diuretics.
These patients would be on top tolerated dose of ACE inhibitor/ARB. Once identified, the heart
failure nurses would stop the ACE inhibitor/ARB for at least 36 hours. Entresto® should not be coadministered with an ACE inhibitor due to the potential risk of angioedema.
FULL PRESCRIBING INFORMATION AT
http://www.medicines.org.uk/emc/medicine/31244
Adapted by C.Cornford from local implementation document prepared by A.Warren BSUH
2
Sacubitril Valsartan (Entresto®) Care pathway adapted for Western Hospitals NHS Foundation Trust
Ratified: November 2016 APC
Review date: November 2018
Care pathway map for Entresto®
Adult with chronic heart failure due to
left ventricular dysfunction
First line treatment
Optimised ACE/ARB and beta-blocker
unless c/i
NYHA class II to IV symptoms and a left
ventricular ejection fraction of 35% or
less
Second line treatment
Refer for specialist advice for options
which include:
 aldosterone antagonist
 combination ACE/ARB
 hydralazine in combination
with nitrate
 sacubitril valsartan
As per NICE guidelines.
Do not initiate sacubitril
valsartan if serum K >5.4
or SBP < 100mmHg
If SBP ≥ 100 -110 mmHg,
consider starting dose of
24/26 mg bd
Patient initiated on sacubitril valsartan
by specialists (starting dose 49/51mg
bd). Dose increased to 97/103 bd after
2 weeks subject to patient tolerance
(BP and renal function).
Stop ACE /ARB 36 hrs before
starting sacubitril valsartan and
ensure removed from repeat
medication list
Once patient stabilised on treatment
prescribing can be transferred to
primary care.
Sacubitril is a black triangle drug and should be monitored for any side effects and these
reported through the yellow card reporting system www.mhra.gov.uk/yellowcard
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Sacubitril Valsartan (Entresto®) Care pathway adapted for Western Hospitals NHS Foundation Trust
Ratified: November 2016 APC
Review date: November 2018