Download framework - shared care

In Partnership with:
North East Hampshire and Farnham CCG,
Windsor, Ascot and Maidenhead CCG
Bracknell and Ascot CCG
Chiltern CCG
Slough CCG
Shared Care Prescribing Guideline
Sacubitril/valsartan for the treatment of LVSD
Frimley Health Area Prescribing Committee classification: Amber Shared Care
NOTES to the GP
Amber Shared Care drugs: Prescribing to be initiated by a hospital specialist (or if appropriate by a GP with specialist
interest) but with the potential to transfer to primary care when.
. an individual GP has agreed to accept clinical responsibility for an individual patient.
. agreed shared care arrangements have been established and the GP is willing to take over shared care.
. the patient’s condition and/or treatment has been stabilised.
. In one off situations, a specific GP can agree to enter into a ‘shared care arrangement’ without a formal shared
care guideline providing a letter is sent to the GP giving appropriate advice and guidance.
. The request is accompanied by a written proposal to request that the GP accepts ongoing prescribing and
monitoring.
The expectation is that these guidelines should provide sufficient information to enable GPs to be confident to take
clinical and legal responsibility for prescribing these drugs.
The questions below will help you confirm this:
 Is the patient’s condition predictable?
 Do you have the relevant knowledge, skills and access to equipment to allow you to monitor treatment as
indicated in this shared care prescribing guideline?
 Have you been provided with relevant clinical details including monitoring data?
If you can answer YES to all these questions (after reading this shared care guideline), then it is appropriate for you to
accept prescribing responsibility. Sign and return a copy of page 4 to the requesting consultant at the Acute Trust.
Until the requesting consultant at the Acute Trust has received a signed copy of page 4 indicating that shared care
has been agreed all care (including prescribing) remains with the consultant at the Acute Trust.
If the answer is NO to any of these questions, you should not accept prescribing responsibility. You should write to
the consultant outlining your reasons for NOT prescribing. If you do not have the confidence to prescribe, we
suggest you discuss this with your local Trust/specialist service, who will be willing to provide training and support. If
you still lack the confidence to accept clinical responsibility, you still have the right to decline. Your CCG pharmacist
will assist you in making decisions about shared care.
Prescribing unlicensed medicines or medicines outside the recommendations of their marketing authorisation alters
(and probably increases) the prescriber’s professional responsibility and potential liability. The prescriber should be
able to justify and feel competent in using such medicines.
The patient’s best interests are always paramount
The GP has the right to refuse to agree to shared care, in such an event the total clinical responsibility will remain with the consultant
Prepared by :
Sarah Crotty & Ann Parker
Valid from: December 2016
Review date: December 2017
Version: 1
Supersedes version:
Approved by: Frimley Interface
Prescribing Committee, December 2016
This guideline provides prescribing and monitoring guidance for sacubitril valsartan therapy. It
should be read in conjunction with the Summary of Product Characteristics (SPC) available on
www.medicines.org.uk/emc and the BNF.
1.
BACKGROUND FOR USE
Sacubitril valsartan is a neprilysin inhibitor (sacubitril) with an angiotensin II receptor blocker (ARB;
valsartan). It is licensed for treatment of symptomatic chronic heart failure with reduced ejection
fraction in adults.
NICE TA 388 recommends sacubitril valsartan as an option for chronic heart failure patients who
remain symptomatic despite optimal medical treatment. It is offered only in people:
 With New York Heart Association (NYHA) class II to IV symptoms AND
 With a left ventricular ejection fraction (LVEF) of 35% or less AND
 Who are already taking an optimised and stable dose of angiotensin-converting enzyme
inhibitor (ACEI) or angiotensin II receptor-blocker (ARB).
NICE TA 388 states that sacubitril valsartan must be initiated by a heart failure specialist with access
to a multidisciplinary heart failure team. An example checklist to support implementation of the
drug
can
be
found
using
the
following
link:
https://www.nice.org.uk/guidance/ta388/resources/example-checklist-2551344448
The Frimley Health APC has approved the use of sacubitril/valsartan in patients who have LVEF <35%
and who are tolerating optimal medical therapy (OMT) to include ACEI or ARB, Beta blocker and
either spironolactone or eplerenone who:
1. Have had a recent unplanned heart failure admission without an obvious
precipitating cause despite OMT
2. Are at risk of unplanned hospital admission or who have worsening symptoms
despite OMT, but who have a predicted good/ stable prognosis.
3. Patients who remain heavily symptomatic and at risk from unplanned admission
despite OMT i.e. NYHA III.
Under a shared care arrangement, treatment must be initiated by a consultant Cardiologist. Dose
titration, monitoring and prescribing for the first three months must be by the Heart Failure team.
After the dose is stabilised the patient will be transferred to the GP.
Evidence from PARADIGM-HF TRIAL (2014) demonstrated that patients with heart failure with
reduced ejection fraction (LVEF<35%) and NYHA class II-IV treated with sacubitril/valsartan versus
standard of care (ACEI- enalapril) had reduced mortality risk and reduced risk of heart failure
hospitalisation.
Contemporary BNP/ NT-BNP testing and echo are also recommended before initiation to ensure
patient symptoms are consistent with left ventricular systolic dysfunction.
Patients who have severe heart failure, but who remain NYHA IV despite OMT should have access to
quality palliative care support recognising that there is limited clinical experience with
sacubitril/valsartan in this group within the PARADIGM trial and therefore specialist referral is highly
recommended before initiation.
2
SUPPORTING INFORMATION
2.
Contraindications
Contra-indications
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Cautions
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Bilateral renal artery stenosis, refer
patients for advice
Aortic or mitral valve stenosis or
obstructive cardiomyopathy, refer
patients for advice
Known hypersensitivity to ARB,
sacubitril or excipients
History of angioedema of any cause
Pregnancy
Baseline potassium > 5.4 mmol/l
Concomitant use with ACEI or ARB
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sacubitril valsartan must NOT be started
for at least 36 hours after discontinuing
ACEI. (This does not apply when stopping
an ARB and starting sacubitril valsartan.)
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3.
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Known history of angioedema to ACEI
or ARB therapy
Concomitant use with aliskiren
containing products in patients with
diabetes mellitus or in patients with
eGFR<60ml/min
Systolic BP<100mmHg
Serum K+ > 5.4 mmol/l



Patients with a documented
intolerance of ACEI due to
symptomatic hypotension - consider
re-challenging with a longer acting
ACEI (such as perindopril).
Patients on high dose diuretics (i.e.
furosemide > 80mg daily) – increased
risk of hypotension and renal
dysfunction
Breast feeding- suggest avoid
Dose reduction suggested for
patients with moderate renal
impairment, eGFR 30-60ml/min
Limited clinical experience for
eGFR<30ml/min
Baseline potassium > 5 to 5.3mmol/l
Concomitant aliskiren use not
meeting contra indications
Moderate hepatic impairment (ChildPugh B classification) or with AST/ALT
values more than twice the upper
limit of normal
Concomitant use with aliskiren in
patients with diabetes mellitus.
Severe hepatic impairment, biliary
cirrhosis, cholestasis (Child-Pugh C
classification)
Treatment should not be initiated unless
SBP is ≥100 mmHg.
End stage renal disease
Dosage
Initiation must be by specialist review only.
Check baseline blood chemistry. (e.g. serum creatinine, urea, potassium, sodium and eGFR) and
blood pressure (BP)
3
Discontinue potassium supplements/potassium sparing diuretics (except spironolactone or
eplerenone) and review need for concomitant nephrotoxic drugs e.g. NSAIDs
Review dose of diuretic therapy.
Do not start for at least 36hours after discontinuing ACEI
Dose Titration
The recommended starting dose depends on the BP reserve:
i.
If BP is at the low end of usual for LVF or if on a low dose of an ACEI start on 50 mg
(24mg/26mg) twice daily
ii.
Consider a higher starting dose of 100 mg (49mg/51mg) twice daily for patients
on higher doses of ACEI or ARB (i.e. more than 50% of the maximum dose) or for
patients with systolic BP ≥ 100mmHg
iii.
The dose should be doubled every 2 - 4 weeks to the target of 200 mg
(97mg/103mg) twice daily, as tolerated by the patient. Patients will not be
transferred to GP prescribing until stabilized on the maximum tolerated dose for
them. Reduce dose/stop according to “worsening renal function” and
“symptomatic hypotension” in “problem solving” below.
If a dose is missed, the tablet should be taken at the next scheduled time.
Tablets should be swallowed whole with water and can be taken with or without food.
Dose in renal impairment
Mild (eGFR 60-90 ml/min)
Moderate (eGFR 30 to 60 ml/min)
Severe (eGFR <30 ml/min)
End-stage renal disease
4.
No dose adjustment required.
Consider starting dose of 24 mg/26 mg twice daily
Limited clinical experience. Use with caution. Starting dose of
50mg (24 mg/26 mg) twice daily is recommended.
No experience. Use of sacubitril valsartan is not recommended
TIME TO RESPONSE
7 to 10 days for therapeutic effects, effects on BP happen within hours.
4
5.
RESPONSIBILITIES and ROLES
Specialist responsibilities (May be consultant or specialist LVF nurse or specialist pharmacist)
1. Assess the patient. Establish the diagnosis and assess the patient’s ability to adhere to treatment.
2. Initiate treatment, monitor and titrate to a stable dose (supply the first three months of treatment).
3. Send a letter to the GP requesting shared care for the patient, (there is a template below), including this
shared care protocol
4. The Heart Failure Team will be available for verbal (or written) advice to the GP if the patient’s condition
changes or deteriorates. Following this advice GP’s may refer patients back to the Heart Failure Team for
assessment if this is required.
5. The Heart Failure Team will ensure the patient & carer(s) are given information regarding the treatment
and a contact for the heart failure team if they have any concerns.
General Practitioner responsibilities
1. Monitor patient’s overall health and wellbeing.
2. Prescribe the drug treatment as described
3. Report any adverse events to the hospital specialist, where appropriate
4. Monitor blood results in line with recommendations from 4 months onwards
Patient counselling (conducted by Specialist & reinforced by the GP)
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6.
Explain the expected benefits to the patient –treatment can improve their
symptoms, prevent their heart failure getting worse, increase survival and decrease
hospital admissions.
Symptoms may not improve immediately. It may take a few weeks or months to
have a full effect.
Advise patients to report adverse effects e.g. hypotension or dizziness
Advise patients to take the first dose at night as they may experience a first dose
hypotensive effect
Advise patient that renal function monitoring is needed
Advise patients to avoid OTC NSAIDs, soluble tablets and salt substitutes high in K+
Advise patients that if a dose is missed, the tablet should be taken at the next
scheduled time.
Hospital Pharmacy: Duration of Supply
After initiation, a total of 3 months’ treatment will be provided by secondary care, or until the
patient is on a stable dose if this is longer.
7. MONITORING PRE-TREATMENT ASSESSMENT (by the Specialist)
In general patients will be established on ACEI or sartans prior to switching
 Echo demonstrating LVEF <35% within the last 12 months
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Medication review (including optimisation of heart failure medication.
Blood U&E (serum creatinine, urea, potassium, sodium and eGFR).
ECG and resting heart rate /pulse
BP
Weight
5
ONGOING MONITORING SCHEDULE
The following parameters will be monitored 2 - 4 weeks after initiation and at each dose adjustment.
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Pulse
BP
Blood U&E (serum creatinine, urea, potassium, sodium and eGFR)
The Specialist will undertake this monitoring from month 1 to 3 inclusive; the GP will undertake
monitoring from month 4 onwards, including 6-12 monthly reviews.
8.
SIDE EFFECTS AND ACTIONS TO BE TAKEN
The GP may contact the specialist team for advice at any time if there are concerns.
The most commonly reported adverse reactions during treatment with sacubitril valsartan were
hypotension, hyperkalaemia and renal impairment. For other side effects see SPC
Side-effect
Angioedema
hypersensitivity
Action
& 
If symptoms are severe this is a medical emergency and patients may
require urgent hospital treatment.

Stop sacubitril valsartan and monitor until complete and sustained
resolution of signs and symptoms has occurred.* It must not be readministered. In cases of confirmed angioedema where swelling has
been confined to the face and lips, the condition has generally
resolved without treatment, although antihistamines have been
useful in relieving symptoms.

Stop concomitant medication that can increase serum potassium
(e.g. potassium-sparing diuretics (spironolactone, eplerenone,
triamterene, amiloride), mineralocorticoid antagonists, potassium
supplements).

Consider reducing or stopping sacubitril valsartan.*
Hyperkalaemia
Serum K+ >5.4 mmol/L
Asymptomatic low BP
(Systolic BP <100mmHg)
Does not usually warrant a change in therapy, but BP requires monitoring
and watch for worsening renal function.
Symptomatic

hypotension (including

dizziness,
headache,
syncope)
(e.g. Systolic BP
<100mmHg)
Monitor BP, consider ambulatory monitoring if available
Consider dose adjustment of concomitant diuretics or
antihypertensives (stop nitrates or calcium channel blockers 1st then
consider reducing betablocker)

If dehydrated treat. hypovolaemia. Symptomatic hypotension is more
likely to occur if the patient has been volume-depleted, e.g. by
diuretic therapy, dietary salt restriction, diarrhoea or vomiting. Giving
fluids must be carefully weighed against the risk of volume overload.

Consider temporary down-titration or discontinuation of
sacubitril valsartan.*
6

Renal impairment
Persistant Dry cough
An increase in urea, creatinine and K+ is to be expected after
initiation/titration. If the increase is small and asymptomatic, no action is
necessary
If eGFR <60 ml/min consider:
 Stopping concomitant nephrotoxic medication (e.g. NSAID’s,
diuretics, calcium channel blockers or nitrates). If on a diuretic reduce
the dose to increase fluid & perfusion of the kidneys
 Dose reduction of sacubitril valsartan.
 Stopping sacubitril valsartan* (rarely needed unless GFR<30).
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Anaemia,
hypoglycaemia, vertigo,
fatigue, asthenia,
gastro-intestinal
disorders (diarrhoea,
nausea, gastritis)
If affected this may limit the dose possible or longer intervals
between dose adjustments may be needed.

Review aetiology of cough e.g. due to smoking, worsening heart
failure/pulmonary oedema, respiratory disease
Review cough tolerability versus benefits of sacubitril/valsartan
May require discontinuation of treatment. If discontinuation is
required refer patient back to heart failure team for re-assessment
If severe consider seeking specialist advice
*Allow 48 hour wash out period before restarting an ACE inhibitor
7
9.
NOTABLE DRUG INTERACTIONS (refer to BNF AND SPC also)
The following drugs are contraindicated with sacubitril valsartan:
ACEI
Aliskiren
ARB
NSAIDs The risk of worsening renal function and heart failure is increased with use of NSAIDs and
sacubitril valsartan.
Statins The manufacturers state that caution is needed in patients taking statins as use of
sacubitril/valsartan may increase the systemic exposure to metabolites. No formal
recommendations exist on management of the combination however sensible precautions would
include patients being reminded to report symptoms such as muscle pains and jaundice.
Lithium and sacubitril/valsartan has not been tested and is therefore not recommended. If the
combination proves necessary, careful monitoring of serum lithium levels is recommended. If a
diuretic is also used, the risk of lithium toxicity may be increased further.
Potassium supplements & potassium sparing diuretics may increase the risk of hyperkalaemia and
potassium should be monitored.
Sacubitril/valsartan taken with sildenafil is associated with significantly greater hypotension
compared to administration of sacubitril/valsartan alone. Therefore, caution should be exercised
when sildenafil or another PDE5 inhibitor is initiated in patients treated with sacubitril/valsartan.
Co-administration of sacubitril/valsartan with rifampicin, ciclosporin, tenofovir, cidofovir, ritonavir
may increase sacubitril/valsartan levels.
Metformin Co-administration of sacubitril valsartan with metformin reduces the bioavailability of
metformin by 23%. The clinical relevance of these findings is unknown. Therefore, when initiating
therapy with sacubitril/valsartan in patients receiving metformin, the control of the patient’s
diabetes may need to be re-evaluated.
Furosemide- may reduce effectiveness of furosemide
10.
BACK-UP INFORMATION/ADVICE
BHT:
Contact Details
Wycombe and Amersham
Stoke Mandeville
Bucks Heart Failure Specialist
Team
Medicines Information BHT
01494 426919 (8am – 4pm)
On-call Cardiologist Registrar via switchboard (out-of-hours)
01494 425355
Switchboard BHT
01494 526161 (WH)
8
01296 315000 (SMH)
FRIMLEY HEALTH BACK-UP ADVICE AND SUPPORT
Contact Details
Frimley Park
Community heart failure
nurse
Cardiology Pharmacist
Annabel Sturgess,
01276 526969
Ann Parker
01276 604604 bleep 400
Heart Failure Clinical Nurse
Specialist
Heart Failure Consultant
Medicines Information
11.
1.
2.
3.
Dr Lydia Sturridge
Via switchboard
01276 604604
01276 606744
Wexham Park
Preya Fakira
01753 633000 bleep 2215
Mark Stephens
07785996702
Stephanie Murray
07775404609 or
01753 634791
Dr Sofia Metaxa
Via switchboard
01753 63300
REFERENCES
NICE TA388 ‘Sacubitril valsartan for treating symptomatic chronic heart failure with
reduced ejection fraction’ available at :
https://www.nice.org.uk/guidance/TA388/chapter/1-recommendations accessed
12/8/16
Summary of product characteristics for sacubitril valsartan (Entresto®®) tablets
available at http://www.medicines.org.uk/emc/medicine/31244
<accessed 18/10/16>
Entresto dosing and titration guide. Novartis Pharmaceuticals UK Ltd. Published
11/2015
With thanks to St Thomas Hospital London for sharing their sacubitril/valsartan documentation.
9
Appendix 1
SHARED CARE PRESCRIBING GUIDELINE
Sacubitril valsartan for the treatment of LVSD
Agreement for transfer of prescribing to GP
Patient details / addressograph:
Name……………………………………..
Address…………………………………..
…………………………………..
…………………………………..
DOB……………….
Hospital No……………………………….
NHS No……………………………….
Drug name and dose:
Date initiated:………………………………….
Date care transferred…………………………..
The patients has now been stabilised on a dose of: …………………………………………..
Consultant/Specialist:
Agreement to shared care, to be signed by
GP and Consultant/Specialist.
Address:
Consultant Signature:
Contact Number
………………………………………………..
Date:
GP:
Address:
GP Signature:
Contact Number
…………………………………………………
Date:
10
Appendix 2
Patient name
Hospital number
NHS number
Dear Dr………….
This patient has been initiated on sacubitril valsartan in accordance with Frimley Health guideline for treatment of chronic
heart failure with reduced ejection fraction.
Details of treatment plan
Date initiated
Dose on transfer
Date of next review
Sacubitril Valsartan
(ENTRESTO® )
This patient is on maximum tolerated dose and I am writing to transfer the prescribing responsibility for this patient’s ongoing treatment from ….. /…../……
This transfer of care document should be reviewed in conjunction with the sacubitril valsartan guidelines (appendix 1)
All patients receiving sacubitril valsartan therapy should be reviewed at least six monthly throughout their treatment.
Please refer to the guidelines for more details.
Monitoring
Test
Result
Date of test
Please repeat test in:
Serum Creatinine
………….………..months
Estimated GFR
Potassium
………….………..months
Blood pressure
………….………..months
ALT
Liver Function Tests
12 months
ALP
Other relevant information: ……………………………………………………………………………………………………………
……………………………………………………………………………………………………………………………………………
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I confirm that I have prescribed in accordance with the local heart failure guidelines
I confirm that the patient has been made aware of the benefits and risks of sacubitril valsartan and that they
know how to seek medical help
I confirm the patient has consented to treatment
Signed:……………………………………. Name of Clinician:…………………………… Date: …………….
11