NHS Kent and Medway Medicines Management Dronedarone (Multaq ) Shared Care Guideline For Prescribing Issue No: 2 Review Date (If Applicable): Accountable Officer: Heather Lucas Contact Details: 01233 618158 Document history: Version Created by Date Main Changes/Comments 2 H Lucas 26.10.2011 3 R Brown 02.11.2011 Clarification of monitoring requirements and 8 week initial supply from hospital specialist. 4 H Lucas 02.11.2011 Amendments to patient responsibilities 5 H Lucas 23.11.2011 Addition of NICE criteria for treatment & specialist responsibility for at least 8 weeks stressed. 6 H Lucas 9.12.11 Amendments to consultant responsibilities 2.2 act on results and GP responsibility 5 breathlessness added Date of Issue: 9.12.2011 Page 1 of 7
Shared Care Guideline Shared Care Guideline for prescribing Dronedarone (Multaq ) DRONEDARONE MUST BE INITIATED AND MANAGED BY THE HOSPITALSPECIALIST TEAM FOR AT LEAST THE FIRST 8 WEEKS OF THERAPY. This includes taking responsibility for issuing prescriptions for dronedarone and ensuring appropriate monitoring is undertaken. INDICATION Dronedarone (Multaq ) Dronedarone is an antiarrhythmic drug belonging to the benzofuran class of agents. It is licensed for the maintenance of sinus rhythm after successful cardioversion in adult clinically stable patients with paroxysmal or persistent atrial fibrillation. Due to its safety profile dronedarone should only be prescribed after alternative treatment options have been considered. Dronedarone should not be given to patients with left ventricular systolic dysfunction or to patients with current or previous episodes of heart failure. In accordance with NICE TA 197 : Dronedarone is an option for the maintenance of sinus rhythm in patients with paroxysmal or permanent AND who have at least one of the following CV risk factors: o age 70 years or older o hypertension requiring drugs of at least two different classes o diabetes mellitus o previous TIA, stroke or systemic embolism o left atrial diameter of 50 mm or greater Please note that left ventricular systolic dysfunction or heart failure are now contraindications to treatment. AREAS OF RESPONSIBILITY FOR SHARED CARE This shared care agreement outlines suggested ways in which the responsibilities for managing the prescribing of dronedarone can be shared between the specialist and general practitioner (GP). Shared care must be agreed prior to the patient commencing treatment on dronedarone. GPs are invited to participate. If the GP is not confident to undertake these roles, then he or she is under no obligation to do so. In such an event, the total clinical responsibility for the patient for the diagnosed condition remains with the specialist. If a specialist asks the GP to prescribe this drug, the GP should reply to this request as soon as practicable. Date of Issue: 9.12.2011 Page 2 of 7
Sharing of care assumes communication between the specialist, GP and patient. The intention to share care is usually explained to the patient by the doctor initiating treatment. It is important that patients are consulted about treatment and are in agreement with it. The doctor who prescribes the medication legally assumes clinical responsibility for the drug and the consequences of its use. REFERRAL AND INITIATION Shared Care is only appropriate if it provides the optimum solution for the patient. Patients will only be referred to the GP once the GP has agreed in each individual case Management of atrial fibrillation should be consistent with NICE guidance. Dronedarone is a black triangle drug. The MHRA therefore asks that all suspected reactions (including those not considered to be serious) are reported through the Yellow Card Scheme. Date of Issue: 9.12.2011 Page 3 of 7
Specialist Responsibilities 1. Assess the patient and establish the diagnosis; determine a management strategy and whether the patient s GP will accept shared care prior to commencing dronedarone. If the GP does not accept shared care the total clinical responsibility for the patient for the diagnosed condition remains with the specialist. Ensure appropriate follow-up in conjunction with the GP. 2. To: 2.1. Initiate and stabilise treatment; 2.2. Perform Liver Function Tests (LFT s) prior to initiation, and one week and one month following initiation, and act on the results prior to transferring prescribing to the GP. 2.3. Measure plasma creatinine values prior to treatment and 7 (and possibly 14) days after initiation. To document and communicate to the GP the new reference baseline. 2.4. Monitor the patient and their therapy at six monthly intervals. 2.5. If the GP has accepted shared care, transfer prescribing to the GP once treatment has been stabilised (usually at 8 weeks) 3. Ensure patient is appropriately anticoagulated. 4. Stop treatment in patients with raised levels of the liver enzyme alanine aminotransferase (more than three times above the upper limit of normal) and closely observe the patients should continue until the enzyme levels return to normal. 5. Follow up ECG (if QTc Bazett interval greater than or equal to 500 milliseconds, dronedarone should be stopped). 6. To provide the GP with appropriate prescribing information and any additional information requested. 7. To be available for advice if the patient s condition changes. 8. To ensure that procedures are in place for the rapid re-referral of the patient by the GP. 9. To ensure the patient has given informed consent to their treatment. 10. To liaise with the GP on any suggested changes in prescribed therapy. 11. Patients should be warned to avoid drinking grapefruit juice beverages. 12. Review concurrent medication for potential interactions. Date of Issue: 9.12.2011 Page 4 of 7
General Practitioner Responsibilities 1. Initially, to refer the patient for specialist advice. 2. Where appropriate, to continue to prescribe dronedarone as part of a shared care arrangement (usually after 8 weeks). 3. Check LFT s monthly for 6 months and at month 9 and 12, and every 6 months thereafter. 4. Perform ECG every 6 months to check that patient has not developed permanent AF and to check ventricular heart rate (notify specialist if ventricular rate falls below 50bpm). Treatment discontinuation should be considered if a patient develops permanent AF. 5. Monitor patient every 6 months for signs or symptoms of heart failure that worsen or develop, such as weight gain, dependant oedema, or increased breathlessness. If heart failure develops or worsens consider suspending or discontinuing dronedarone. 6. Monitor renal function every 6 months. Discontinue treatment if further elevations in creatinine. 7. Monitor patient every 6 months for dyspnoea or non productive cough which may indicate the development of interstitial lung disease. 8. To deal with general health issues of the patient. 9. Monitor concordance with therapy. 10. Review concurrent medication for potential interactions Patient's role (or that of carer) 1. Report to the specialist or GP if he or she does not have a clear understanding of the treatment. 2. Attend appropriate GP and other follow up appointments. 3. Immediately report to their doctor any symptoms that could indicate liver injury (such as sustained new-onset abdominal pain, loss of appetite, nausea, vomiting, fever, fatigue, tiredness, yellowing of the skin or whites of the eyes, dark urine or itching). 4. Immediately report to their doctor any signs or symptoms of heart failure that worsen or develop, such as weight gain, swollen feet or legs, or increased shortness of breath. 5. Immediately report to their doctor any shortness of breath or non productive cough. 6. Share any concerns in relation to treatment with dronedarone. 7. Use written and other information on the medication. Date of Issue: 9.12.2011 Page 5 of 7
8. Seek help urgently if side effects are suspected, or is otherwise unwell. SUPPORTING INFORMATION Dosage and Administration Dronedarone (Multaq ) is available as a 400mg film coated tablet. The recommended dose of dronedarone is 400 mg twice daily in adults. One tablet with the morning meal and one tablet with the evening meal. Monitoring Liver Function tests Before starting treatment liver function tests should be performed. Tests should be repeated at month one and then monthly for six months, at months 9 and 12, and every 6 months thereafter. Treatments should be stopped in patients with raised levels of the liver enzyme alanine aminotransferase (more than three times above the upper limit of normal). Appropriate investigation and close observation of patients should continue until the enzyme levels return to normal. Plasma Creatinine Plasma creatinine values should be checked prior to initiation and 7 days after initiation. Any increase should be rechecked after a further 7 days. If the creatinine has stabilised this value is used as the new baseline. Cardiovascular Follow up ECG every 6 months is recommended during treatment. Treatment discontinuation should be considered if permanent AF develops. Monitor patient for any any signs or symptoms of heart failure that worsen or develop, such as weight gain, dependant oedema, or increased dyspnoea. Pulmonary Monitor patient for dyspnoea or non productive cough that may be related to pulmonary toxicity. Contraindications Hypersensitivity to the active substance or to any of the excipients Second or third degree Atrio-Ventricular block, complete bundle block, distal block,sinus node dysfunction, atrial defects or sick sinus syndrome (except when used in conjunction with a functioning pacemaker) Bradycardia<50 beats per minute Permanent AF with an AF duration > /= 6 months ( or duration unknown) and attempts to restore sinus rhythm no longer considered by the physician Patients in unstable hemodynamic conditions History of, or current heart failure or left ventricular systolic dysfunction Patients with liver and lung toxicity related to the previous use of amiodarone Co-administration with potent cytochrome P450 (CYP) 3A4 inhibitors, such as ketoconazole, itraconazole, voriconazole, posaconazole, telithromycin, clarithromycin, nefazodone and ritonavir Date of Issue: 9.12.2011 Page 6 of 7
Medicinal products inducing torsades de pointes such as phenothiazines, cisapride, bepridil, tricyclic antidepressants, terfenadine and certain oral macrolides, Class I and III antiarrhythmics QTc Bazett interval >/= 500milliseconds Severe hepatic impairment Severe renal impairment (CrCl<30ml/min) Special Warnings See manufacturer s SPC. Side Effects Very common: Congestive heart failure Common: blood creatinine increased; LFT abnormalities QTc Bazett prolonged; bradycardia; diarrhoea; vomiting, nausea, abdominal pains, dyspepsia, rashes (including generalised, macular, maculopapular), pruritus, fatique, asthenia. Drug Interactions Dronedarone is primarily metabolised by CYP3A4. Therefore inhibitors and inducers of CYP3A4 have the potential to interact on dronedarone. The following interactions are some of the more common that can occur: Digoxin; concomitant use will cause an increase in digoxin levels. It is recommended that the digoxin dose is halved. Grapefruit juice; significantly increases dronedarone exposure. Patients should not consume. Statins; concomitant use of statins should be undertaken with caution, lower starting and maintenance doses of statins should be considered. Beta blockers and calcium antagonists with depressant effect on sinus and AV node- concomitant use should be undertaken with caution. Warfarin; significant INR elevations have been observed after 1 week. Monitor INR closely. Dabigatran; dronedarone increases the exposure of dabigatran. Co-administration is not recommended.the manufacturer s summary of product characteristics (SPC) and the most current edition of the British National Formulary should be consulted for full information on contra-indications, warnings, sideeffects and drug interactions. At current prices the cost of one year s treatment with dronedarone 400mg bd is 821.25 (BNF November 2010) References 1. Multaq 400mg tablets. Summary of Product Characteristics, Sanofi Aventis. October 2011. 2. Drug Safety Update. October 2011;vol 5,issue 3: MHRA Date of Issue: 9.12.2011 Page 7 of 7