SHARED CARE AGREEMENT. November Dronedarone (Multaq ) For the treatment and management of non permanent atrial fibrillation

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1 SHARED CARE AGREEMENT Oxfrdshire Nvember 2011 Drnedarne (Multaq ) Fr the treatment and management f nn permanent atrial fibrillatin INTRODUCTION There shuld be willing cnsent f all parties t enter int a shared care agreement. This includes patients (plus carers if necessary) and prescribers (i.e. general practitiners / primary care prescribers and cnsultants / secndary care prescribers). If a general practitiner is nt cnfident t undertake these rles, then he r she is under n bligatin t d s. In such an event, the ttal clinical respnsibility (including prescribing) fr the patient remains with the secndary care specialist. This shared care agreement utlines hw the respnsibilities fr managing the prescribing f drnedarne fr atrial fibrillatin can be shared between the secndary care specialist and general practitiner (GP) / primary care prescriber. Drnedarne (Multaq ) is indicated in adult clinically stable patients with a histry f, r current nn-permanent atrial fibrillatin (AF) t prevent recurrence f AF. Drnedarne is nt licensed fr permanent AF i.e. AF that fails t terminate using cardiversin, r is terminated but relapses within 24 hurs, r lng-lasting persistent AF (usually lnger than 1 year) in which cardiversin has nt been indicated r attempted The NICE TA 197 fr drnedarne was issued in July 2010 and a subsequent review by the EMA in September 2011 (Appendix) such that the Summary f Prduct Characteristics has been changed: Drnedarne is indicated fr the maintenance f sinus rhythm after successful cardiversin in adult clinically stable patients with parxysmal r persistent atrial fibrillatin (AF). Due t its safety prfile, Drnedarne shuld nly be prescribed after alternative treatment ptins have been cnsidered Drnedarne shuld nt be given t patients with left ventricular systlic dysfunctin r t patients with current r previus episdes f heart failure. Based n this and the previus NICE guidance Drnedarne is nw recmmended as an ptin fr the treatment f nn-permanent atrial fibrillatin nly in peple as utlined abve, after 1

2 cnfirmatin using the checklist in the appendix, and: whse atrial fibrillatin is nt cntrlled by first-line therapy (usually including betablckers), that is, as a secnd-line treatment ptin, and wh have at least ne f the fllwing cardivascular risk factrs: - hypertensin requiring drugs f at least tw different classes - diabetes mellitus - previus transient ischaemic attack, strke r systemic emblism - left atrial diameter f 50 mm r greater - age 70 years r lder The recmmended dse fr drnedarne is 400 mg twice daily in adults. It shuld be taken as ne tablet with the mrning meal and ne tablet with the evening meal. KEY PRINCIPLES FOR THE SHARED CARE PROTOCOL Prescribing respnsibility shuld nly be cnsidered fr transfer t primary care when a patient's clinical management and treatment is demnstrably stable. Initiatin dses f drnedarne shuld be prescribed by Cnsultant Cardilgist ONLY; general practitiners shuld nly prescribe maintenance dses. The prescriber wh prescribes drnedarne legally assumes clinical respnsibility fr the drug and the cnsequences f its use. RESPONSIBILITIES AND ROLES Secndary care Cnsultant Cardilgist T cnfirm absence f: Hypersensitivity t the active substance r t any f the excipients Secnd- r third-degree Atri-Ventricular blck r sick sinus syndrme (except when used in cnjunctin with a functining pacemaker) Bradycardia <50 beats per minute Unstable haemdynamic cnditins including patients with any symptms/signs f heart failure C-administratin with ptent cytchrme P 450 (CYP) 3A4 inhibitrs such as ketcnazle, itracnazle, vricnazle, psacnazle, telithrmycin, clarithrmycin, 2

3 nefazdne and ritnavir C-administratin with medicinal prduct inducing trsades de pintes such as phenthiazines, cisapride, bepridil, tricylcic antidepressants, terfenadine, ral macrlides, Class I and III antiarrhythmics QTc 500 millisecnds Ptassium and magnesium deficiency T establish a baseline f the patient's renal and hepatic functin prir t initiatin f drnedarne t cnfirm absence f severe renal and hepatic failure. T discuss the benefits and pssible cmmn and uncmmn side-effects f treatment with the patient including: advising t immediately reprt any symptms f ptential liver injury (such as sustained new-nset abdminal pain, anrexia, nausea, vmiting, fever, malaise, fatigue, jaundice, dark urine r itching) t their physician. advising the patient f the need t avid ingesting grapefruit juice while taking drnedarne taking drnedarne with fd that drnedarne interacts with a number f medicines and they shuld take advice prir t taking any new medicine including prducts such as St Jhn's Wrt fr wmen f child bearing age that they must use reliable cntraceptive methds whilst taking drnedarne T initiate and prescribe drnedarne (as apprpriate) and where treatment is prving effective, stabilise the patient n a maintenance dse. T ensure that patient's renal and hepatic functin are mnitred during treatment initiatin (7 t 10 days pst initiatin) and ensure renal and hepatic functin are nt cmprmised as a result f treatment with drnedarne. Prescribing respnsibility shuld nly be cnsidered fr transfer t primary care when a patient's clinical management and treatment is demnstrably stable. Due t increases in plasma creatinine bserved with drnedarne 400mg, a patient's baseline creatinine shuld be stable prir t transfer t primary care. Drnedarne is expected t increase serum creatinine by apprximately 10 micrml/l at the time f initiatin. This des nt reflect changes in underlying renal functin and shuld nt necessarily trigger the discntinuatin f ther drugs, especially ACE inhibitrs r Angitensin II Receptr Antagnists (AIIRAs). 3

4 Cnsultant Cardilgist t assess ptential adverse events and reprt these t the CSM. Cnsultant Cardilgist t cmmunicate prmptly with the GP when treatment is changed and t advise n any implicatins f c-prescribing with current medicatins; particular cautin with:- Ptent CYP3A4 inducers such as rifampicin, phenbarbitne, carbamazepine, phenytin r St Jhn's Wrt Digxin, beta-blckers, calcium antagnists, statins, sirlimus, tacrlimus, angitensin-cnverting enzyme inhibitrs including dse adjustment f drnedarne r any f the abve drugs Cnsultant team t undertake regular fllw up f the patient with particular emphasis n identifying transitin t permanent AF when drnedarne shuld be discntinued (suggest 3,6, 9 and 12 mnths pst initiatin f therapy, and then every 6 mnths at least). Cnsultant team t arrange fr plasma creatinine levels (egfr) t be mnitred annually (may be dne in assciatin with GP). Cnsultant team t arrange fr a 6 mnthly assessment f patient stability and symptmatic respnse using a 12 lead ECG (basic dcumented ECG rhythm, ECG intervals and cnductin). Primary care GP t prescribe drnedarne at the dse at which the patient treatment has been stabilised after cmmunicatin with the secndary care specialist. GP t adjust dse f any cncmitant medicatin knwn t interact with drnedarne as advised by the secndary care specialist. GP t refer the patient back t the secndary care specialist if the patient's cnditin deterirates between reviews. Particular attentin shuld be paid t symptms f heart failure - bth in terms f patients develping heart failure and signs f deteriratin in patients with heart failure. In line with the Appendix (Sanfi Infrmatin n severe liver injury assciated with the use f Multaq (drnedarne) January 2011) Liver Functin Tests shuld be perfrmed n a mnthly basis fr 6 mnths, at 9 and 12 mnths and peridically thereafter, and shuld be perfrmed in cnjunctin with the Cnsultant team. GP t reprt adverse events t the specialist and CSM. Due t the ptential fr significant drug-drug interactins, the GP must ensure that the fllwing are nt taken with drnedarne: 4

5 Ketcnazle, itracnazle, vricnazle, psacnazle, clarithrmycin, telithrmycin, larithrmycin, nefazdne, ritnavir, cisapride, bepridil, tricyclic antidepressants, terfenadine, flecainide, stall, amidarne, prpafenne, St. Jhns Wrt, grapefruit juice. (This list f interactins is nt exhaustive. Please refer t the drnedarne SPC.) Patient's rle (r that f carer) Reprt t the specialist r GP if he/she des nt have a clear understanding f the treatment. Share any cncerns in relatin t treatment with drnedarne. Pay particular attentin t any ther medicines being taken whilst receiving drnedarne. Patients shuld be advised t immediately reprt any symptms f ptential liver injury (such as sustained new-nset abdminal pain, anrexia, nausea, vmiting, fever, malaise, fatigue, jaundice, dark urine r itching) t their physician. He/she must nt take St Jhn's Wrt r drink grapefruit juice whilst receiving drnedarne. Present rapidly t the GP r secndary care specialist shuld their cnditin significantly wrsen. If he/she develps symptms suggestive f heart failure, the patient must immediately ntify the GP r secndary care specialist i.e. if he/she develps any f the fllwing: Increasing swelling f the feet r legs Wheezing, chest tightness r cughing up frthy sputum at rest, night time r after minr exertin Using mre pillws t prp themself up at night s they can breathe mre easily Gaining mre than 5 punds r 2-3 kilgrams in weight in a shrt perid f time Ntify the GP r secndary care specialist if physical activity causes shrtness f breath r if he/she has shrtness f breath while at rest r after a small amunt f exercise. Immediately ntify the GP r secndary care specialist if they have severe heart failure r have been hspitalised fr heart failure within the last mnth. The patient must nt take drnedarne if they have heart failure. Reprt any adverse effects t the specialist r GP whilst taking drnedarne. 5

6 BACK UP ADVICE AND SUPPORT Secndary care Telephne N. Bleep Fax cntact details Specialist Dr K Rajappan kim.rajappan@uh.nhs.uk Hspital Pharmacy Other

7 Appendix 1 19 January 2011 Infrmatin n severe liver injury assciated with the use f Multaq (drnedarne). Dear Healthcare Prfessinal Summary Cases f liver injury, including tw cases f liver failure requiring transplantatin have been reprted in patients receiving drnedarne. Sme f these cases have ccurred early after start f treatment. Fr patients prescribed drnedarne, liver functin tests shuld be perfrmed: prir t treatment, n a mnthly basis fr six mnths, at mnths 9 and 12, and peridically thereafter. Patients currently receiving drnedarne shuld be cntacted within the next mnth s that liver functin tests culd be perfrmed and thereafter they shuld be tested as listed abve depending n when treatment was initiated If alanine transaminase (ALT) levels are elevated t 3 upper limit f nrmal (ULN), levels shuld be re-measured within 48 t 72 hurs. If ALT levels are cnfirmed t be 3 ULN after re-measurement, drnedarne treatment shuld be withdrawn. Patients shuld be advised t cntact health care prfessinals immediately in case f signs r symptms f liver injury. The cmmunicatin f this infrmatin has been agreed with the Eurpean Medicines Agency (EMA) and Natinal Cmpetent Authrities. Further infrmatin n the safety cncern Drnedarne is indicated in adult clinically stable patients with a histry f, r current nnpermanent atrial fibrillatin (AF) t prevent recurrence f AF r t lwer ventricular rate. Since drnedarne was licensed in 2009, there have been reprts f liver functin test abnrmalities and hepatcellular liver injury in patients taking drnedarne, including tw case reprts f acute liver failure requiring transplantatin. The tw case reprts f liver transplantatin ccurred at 4.5 and 6 mnths after initiatin f treatment in patients with nrmal baseline liver functin tests. In ne case the liver injury was nt reversible after discntinuatin f drnedarne. Althugh bth patients were taking cncmitant medicatins, a causal relatinship with drnedarne culd nt be excluded. - The Sectin 4.4 Warnings and Precautins fr use f the Summary f Prduct Characteristics (SmPC) will be updated with these new specific recmmendatins: 7

8 Liver functin tests shuld be perfrmed prir t initiatin f treatment with drnedarne and then repeated mnthly fr six mnths, at mnths 9 and 12, and peridically thereafter. If ALT levels are elevated 3 upper limit f nrmal (ULN), ALT levels shuld be remeasured within 48 t 72 hurs. If ALT levels are cnfirmed t be 3 ULN, treatment with drnedarne shuld be withdrawn. Apprpriate investigatin and clse bservatin f patients shuld cntinue until nrmalizatin f ALT. Patients shuld be advised t immediately reprt any symptms f ptential liver injury (such as sustained new-nset abdminal pain, anrexia, nausea, vmiting, fever, malaise, fatigue, jaundice, dark urine r itching) t their physician. - The Sectin 4.8 Undesirable effect f the SmPC will include hepatic adverse drug reactins (i.e., liver functin test abnrmal (frequency cmmn 1/100 t <1/10) and hepatcellular liver injury, including life-threatening acute liver failure (frequency rare 1/10,000 t <1/1,000). Fr patients currently taking drnedarne liver functin tests shuld be perfrmed within the next mnth and thereafter accrding t the recmmendatins in the prescribing infrmatin taking int accunt when treatment with drnedarne was started. Prescribers are reminded that drnedarne is cntraindicated in patients with severe hepatic impairment. Call fr reprting: Healthcare prfessinals shuld reprt any serius adverse events suspected t be assciated with the use f Multaq t the Medicines and Healthcare prducts Regulatry Agency using a Yellw Card available directly frm the MHRA, CHM Freepst, Lndn SW8 5BR, r electrnically via the MHRA website ( In additin, this infrmatin may be reprted t the Sanfi-aventis UK Pharmacvigilance department at: Sanfi-aventis, One Onslw Street, Guildfrd, Surrey, GU1 4YS, UK Tel: Fax: uk-drugsafety@sanfi-aventis.cm. Cmmunicatin infrmatin The prduct infrmatin (SmPC and patient infrmatin leaflet) will be revised t include this infrmatin and will be distributed nce it has been reviewed and apprved by the EMA. Updated educatinal materials will be distributed when available. If yu have any questins r require additinal infrmatin, please call Medical Infrmatin Services at Sanfi-aventis, One Onslw Street, Guildfrd, Surrey, GU1 4YS, UK Tel: Fax: uk-medicalinfrmatin@sanfi-aventis.cm. Yurs sincerely, 8

9 Dr Tny Whitehead Medical Directr Sanfi-aventis 9

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