Use of sacubitril valsartan for the treatment of symptomatic chronic heart failure with reduced ejection fraction. Shared Care Protocol

Transcription

1 Oxfrdshire Clinical Cmmissining Grup Use f sacubitril valsartan fr the treatment f symptmatic chrnic heart failure with reduced ejectin fractin. Shared Care Prtcl This prtcl prvides prescribing and mnitring guidance fr sacubitril valsartan Therapy. It shuld be read in cnjunctin with the Summary f Prduct Characteristics (SPC) available n and the BNF. Shared Care Respnsibilities Shared care assumes cmmunicatin and agreement between the specialist, GP and patient. The intentin t share care shuld be explained t the patient and accepted by them. Patients are under regular fllw-up and this prvides an pprtunity t discuss drug therapy. Specialist: OUH heart failure team GP T discuss sacubitril valsartan treatment with the patient and ensure the decisin t start treatment is agreed between the patient and the specialist / HF team. As part f this prcess the patient will be prvided with a patient infrmatin leaflet abut the therapy (prduced by the cmpany) and specific infrmatin abut stpping ACEi / ARB therapy. The specialist shuld be satisfied that the patient understands the infrmatin supplied and the imprtance f adhering t treatment. The patient will als be infrmed f the cmplicatins f therapy and their rle in reprting adverse drug reactins prmptly t either the HF team r the GP. Initiate and mnitr sacubitril valsartan treatment in line with lcal and NICE guidance and cntinue t prescribe until the patient is stabilised n therapy (maximum tlerated dse fr at least 1 mnth). T cntact GP frmally by letter nce the decisin t initiate sacubitril valsartan therapy has been made t frmally request agreement with the GP t shared care. T cmmunicate t the GP if the patient will attend the surgery fr mnitring bld tests during the up-titratin phase (fr lgistical reasns). T liaise with the GP regarding changes in disease management, drug dse and missed clinic appintments. Be available t give advice t GP and patient at any time thrughut treatment (see Back-up Infrmatin and advice n hw t cntact the heart failure team, page 3). T ensure nging prescribing f sacubitril valsartan is in line with lcal and NICE guidance, nce patient has been stabilised n treatment by in-patient HF team. Cntact heart failure team at any time during therapy fr further advice regarding sha T be aware that a patient may cme t the surgery fr bld tests during initial uptitratin phase if patient cannt make frequent juneys t OUH. The GP is nt respnsible fr reviewing any f these results during the up-titratin phase. Prescribe medicatin nce the dse is stable and shared care is agreed T ensure BP, renal functin, serum ptassium are mnitred at least 6 mnthly during therapy. Als mnitr liver functin and a full bld cunt annually accrding t shared care prtcl. Written by Janne Cleman Apprved By Helen Jacksn and Dr Margaret Ludn, January 2017 (Based n Prescribing guidance prduced by Suth East Lndn Area Prescribing Cmmittee) Apprved by APCO January

2 Oxfrdshire Clinical Cmmissining Grup Check and recrd results then advise the HF team f any deteriratins r abnrmal results Ntify the HF team specialist t any changes in patients cnditin, any adverse drug reactins r failure t attend tests T cntact the heart failure team at any time during treatment if needed fr further advice abut sacubitril valsartan. T emphasise the imprtance f adherence t sacubitril valsartan and address any patient cncerns Patient Agree t read thrugh the infrmatin supplied abut therapy and discuss with heart failure team t ensure infrmatin is understd. Agree t treatment and mnitring nly after making an infrmed decisin Agree t being under the shared care f the GP and specialist Agree t attend fr bld tests and mnitring when required Reprt any side effects t the GP r a member f the specialist team Backgrund fr Use Sacubitril valsartan (Entrest ) is a cmbinatin drug, including a neprilysin inhibitr (sacubitril) and an angitensin II receptr blcker (ARB; valsartan). It is licensed and apprved by the Natinal Institute fr Health and Care Excellence (NICE) and is recmmended as an ptin fr the treatment f symptmatic chrnic heart failure (HF) with reduced ejectin fractin. In Oxfrd University Hspitals NHS Fundatin Trust (OUHFT), sacubitril valsartan may be cnsidered fr initiatin by the specialist in-patient heart failure team fr treating chrnic HF in patients meeting all f the fllwing criteria: 1. New Yrk Heart Assciatin (NYHA) class II t III symptms* 2. Left ventricular ejectin fractin f 40% r less 3. Taking a stable dse f angitensin-cnverting enzyme inhibitrs (ACEi) r an ARB *Nte: NICE apprved sacubitril valsartan fr patients with NYHA class II t IV symptms. Hwever the HF team will nt rutinely initiate treatment in patients with class IV symptms as there is a lack f trial evidence in this grup. The in-patient HF team will prvide initial patient screening fr suitability f therapy and cunselling, initiatin and up-titratin f dse, mnitring during up-titratin phase and ensure the patient is stabilised n sacubitril valsartan (maximum tlerated dse fr at least ne mnth, in line with NICE recmmendatins). Supprting Infrmatin Sacubitril valsartan is a dual acting angitensin blcker and neprilysin inhibitr (ARNI), inhibiting the renin angitensin aldsterne system and the breakdwn f vasactive peptides. NICE TA 388 (April 2016) gives recmmendatins fr the use f sacubitril valsartan. The pivtal clinical evidence is prvided by the PARADIGM-HF trial, which shwed that sacubitril valsartan was mre clinically effective than enalapril at imprving bth verall mrtality and cardivascular mrtality, and reducing hspitalisatins. Written by Janne Cleman Apprved By Helen Jacksn and Dr Margaret Ludn, January 2017 (Based n Prescribing guidance prduced by Suth East Lndn Area Prescribing Cmmittee) Apprved by APCO January

3 Oxfrdshire Clinical Cmmissining Grup Cntraindicatins and Precautins Cntraindicatins (fr details see BNF r SPC) Cautins (fr details see BNF r SPC) Hypersensitivity t the active substance / excipients Serum ptassium levels greater than 5mml/L Cncmitant use with ACEi. Sacubitril valsartan must Renal artery stensis nt be administered until 36 hurs after discntinuing Renal impairment. Patients with egfr less ACEi therapy. than 30ml/min/1.73m 2 are at greater risk f Cncmitant use with anther ARB (as the hyptensin cmbinatin drug cntains valsartan) Mderate hepatic impairment (Child-Pugh B) r Cncmitant use with aliskiren cntaining prducts in with alanine transaminase (ALT) / aspartate patients with diabetes mellitus. Als avid cncmitant amintransferase (AST) values mre than use with aliskiren cntaining prducts in patients with twice the upper limit f nrmal renal impairment (egfr less than 60ml/min/1,73m 2 ) Dehydratin due t risk f wrsening renal Knwn histry f angiedema related t previus ACEi functin r ARB therapy NYHA class IV patients will nt rutinely be Hereditary r idipathic angiedema started n treatment Systlic bld pressure (SBP) less than 100mmHg Fr cautins fr use with ther medicines see End stage renal disease Ntable Drug Interactins Bilateral renal artery stensis Serum ptassium greater than 5.4mml/L Severe hepatic impairment, biliary cirrhsis and chlestasis (Child-Pugh C) Pregnancy and breast feeding Fr cntra-indicatins fr use with ther medicines see Ntable Drug Interactins BNF = British Natinal Frmulary; SPC = Summary f Prduct Characteristics Dsage Initiatin and up-titratin dne by in-patient HF team at OUH ACEi r ARB therapy MUST BE DISCONTINUED at least 36 hurs befre starting sacubitril valsartan. Prescribe sacubitril valsartan using generic name t avid cncmitant use f ACEi r ARB therapy The starting dse is ne tablet f 49mg/51mg TWICE daily, t be taken with water, with r withut fd. The dse shuld be dubled at 2 t 4 weeks t the target dse f ne tablet f 97mg/103mg TWICE daily. A reduced starting dse f ne tablet f 24mg/26mg TWICE daily with a slw dse titratin (dubling every 3 t 4 weeks) shuld be cnsidered fr patients with: Systlic bld pressure between 100 t 110mmHg Mderate renal impairment (egfr 30 t 60ml/min/1.73m 2 ). Nte fr patients with severe renal impairment (egfr less than 30ml/min/1.73m 2 ), sacubitril valsartan shuld be used with cautin due t very limited experience and greater risk f hyptensin. Mderate liver impairment (Child-Pugh B classificatin r with AST/ALT greater than twice the upper limit f nrmal range) use with cautin due t limited clinical experience. Nte: The valsartan within sacubitril valsartan is mre biavailable than that in ther frmulatins; 26mg, 51mg and 103mg f valsartan in sacubitril valsartan is equivalent t 40mg, 80mg and 160mg in ther frmulatins, respectively. Written by Janne Cleman Apprved By Helen Jacksn and Dr Margaret Ludn, January 2017 (Based n Prescribing guidance prduced by Suth East Lndn Area Prescribing Cmmittee) Apprved by APCO January

4 Oxfrdshire Clinical Cmmissining Grup Time t Respnse The beneficial effect f sacubitril valsartan was bserved early in the PARADIGM-HF study. Pre-Treatment Assessment and mnitring during up-titratin phase by HF team Prir t initiatin and befre and after each dse titratin the fllwing shuld be mnitred: Bld pressure Electrlytes including serum ptassium Renal functin Liver functin and full bld cunt (initiatin nly) Nte: Due t lgistical reasns it may be necessary fr the patient t visit the GP in rder t have bld taken fr the mnitring during the up-titratin phase. The in-patient HF team will be respnsible fr reviewing the results. Onging Mnitring by GPs Once the patient is stabilised n sacubitril valsartan therapy nging mnitring by the GP shuld include: Bld pressure, renal functin and electrlyte mnitring every 6 mnths Liver functin and full bld cunt mnitring every year Mre frequent mnitring shuld be undertaken if clinically indicated r fllwing advice frm the HF team. Actins t be taken (fr full details f side effects see BNF and SPC) The in-patient HF team may be cntacted fr advice regarding tlerability, side effects r ptential cmplicatins f sacubitril valsartan therapy anytime during treatment. Patients may als be referred back t HF team if necessary. See Back-up infrmatin and advice fr cntact details. Side Effects Hyptensin Hyperkalaemia Renal Impairment Hepatic impairment Angiedema Actins t be taken Review medicatin and cnsider adjusting any ther medicines that are cntributing t lw bld pressure r review the dse f sacubitril valsartan which may need t be reduced. Cnsider discntinuing therapy if SBP is cnsistently belw 100mmHg despite abve measures Cnsider dse reductin where the ptassium level is 5mml/L r greater. Discntinue sacubitril valsartan if ptassium level is 5.4mml/L r greater and cntact HF team fr advice. Mnitr renal functin clsely if egfr trending dwnwards. Cnsider dse reductin if mderate renal impairment (egfr 30 t 60 ml/min/1.73m2). In severe renal impairment (egfr less than 30ml/min/1.73m2) cntact HF team fr advice. Severe hepatic impairment, biliary cirrhsis r chlestasis (Child-Pugh C classificatin) discntinue sacubitril valsartan. Mderate liver impairment; cnsider dse reductin (Child-Pugh B classificatin). Discntinue sacubitril valsartan if angiedema ccurs. Patient shuld be given apprpriate therapy and mnitred fr airway cmprmise. Written by Janne Cleman Apprved By Helen Jacksn and Dr Margaret Ludn, January 2017 (Based n Prescribing guidance prduced by Suth East Lndn Area Prescribing Cmmittee) Apprved by APCO January

5 Oxfrdshire Clinical Cmmissining Grup Other side effects include: anaemia, hypkalaemia, cugh, nausea, diarrhea and gastritis Sacubitril valsartan is a black triangle drug any adverse effect must be reprted t the MHRA using the yellw card system and via the lcal incident reprting system. Ntable Drug Interactins (Refer t BNF and SPC fr full details) Drug / Drug class Recmmendatin fr full details see BNF and SPC Avid cncurrent use and allw a washut perid f at ACEi least 36 hurs when switching between ACEi and sacubitril valsartan due t risk f angiedema Avid prescribing any additinal ARBs as sacubitril ARB already cntains the ARB valsartan. Avid cncurrent use due t increased frequency f Aliskiren adverse effects such as hyptensin, hyperkalaemia and renal impairment Ptassium sparing diuretics, Mnitring f serum ptassium is recmmended due t mineralcrticid antagnists, risk f hyperkalaemia ptassium supplements, salt substitutes r any agent that increases ptassium Sacubitril valsartan increased the plasma cncentratin Statins f atrvastatin and its metablites. Cautin shuld be exercised when c-administering statins Phsphdiesterase type 5 (PDE5) inhibitrs e.g. sildenafil, tadalafil, vardenafil Nitrates Nn-steridal anti-inflammatry drugs (NSAIDs) including cyclxygenase-2 (COX-2) inhibitrs Lithium Metfrmin Metablic interactins Cncmitant use can result in a significant reductin in bld pressure after a single dse. Cautin shuld be exercised if a PDE5 inhibitr is initiated C-administratin may reduce heart rate, in general n dsage adjustment is required Cncmitant use f sacubitril valsartan and an NSAID can wrsen renal functin generally avid cmbinatin. If cncmitant use is necessary clse mnitring f renal functin is required. ACEi and ARBs are knwn t cause reversible increases in lithium levels and txicity, therefre the cncmitant use f sacubitril and valsartan is nt recmmended, if unavidable clse mnitring f lithium levels is necessary Sacubitril valsartan can reduce the plasma cncentratin f metfrmin, mnitr bld sugars and adjust metfrmin dse if necessary Cautin shuld be exercised with the c-administratin f sacubitril valsartan with inhibitrs f OATP1B1, OATP1B3, OAT3 (e.g. rifampicin, ciclsprin), OAT1 (tenfvir, cidfvir) r MRP2 (e.g. ritnavir) as these may increase levels f the sacubitril active metablite r f valsartan Written by Janne Cleman Apprved By Helen Jacksn and Dr Margaret Ludn, January 2017 (Based n Prescribing guidance prduced by Suth East Lndn Area Prescribing Cmmittee) Apprved by APCO January

6 Oxfrdshire Clinical Cmmissining Grup Back-up Infrmatin and Advice Cntact the heart failure team:- Telephne: r heartfailure.nurse@uh.nhs.uk References 1. NICE TA 388 Sacubitril valsartan fr treating symptmatic chrnic heart failure with reduced ejectin fractin. April Accessed 24 th Octber 2016 at: 2. SPC Entrest. Nvartis 5 th Feb Accessed 17 th June PARADIGM-HF study. N Engl J Med 2014; 371: Written by Janne Cleman Apprved By Helen Jacksn and Dr Margaret Ludn, January 2017 (Based n Prescribing guidance prduced by Suth East Lndn Area Prescribing Cmmittee) Apprved by APCO January