Download 36 - Coastal West Sussex Formulary

WORKING IN
PARTNERSHIP
WITH
EFFECTIVE SHARED CARE AGREEMENT (ESCA)
DRUG NAME: Dronedarone
INDICATION/S COVERED: the maintenance of sinus rhythm after cardioversion in
clinically stable patients with paroxysmal or persistent atrial fibrillation (AF)
Coastal West Sussex Traffic Light system classification: Amber
N.B. The eligibility criteria included here apply to new patients commencing treatment under this agreement &
not to existing patients whose treatment was initiated under the previous version. However, monitoring and
discontinuation criteria apply to all patients.
NOTES to the primary care prescriber
Amber drugs: Prescribing to be initiated by a consultant / specialist but with the potential to transfer to primary
care. The expectation is that this agreement should provide sufficient information to enable primary care
prescribers 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 effective shared care agreement?
 Have you been provided with relevant clinical details including monitoring data?
If you can answer YES to all these questions (after reading this ESCA), then it is appropriate for you to accept
prescribing responsibility. Sign and return a copy of the final page to the requesting consultant / specialist.
Until the requesting consultant / specialist has received a signed copy of the final page indicating that shared
care has been agreed all care (including prescribing) remains with the consultant / specialist.
If the answer is NO to any of these questions, you should not accept prescribing responsibility. You should
write to the consultant / specialist within 14 days, 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, which
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 Medicines Management 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 primary care prescriber has the right to refuse to agree to shared care, in such an event the total clinical responsibility will remain with
the consultant
Effective from: 25/11/2013
Review date: 25/11/2015
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Dronedarone; Version 3
Information
This page should include general information relevant to the specific drug and indication/s. It should include
information on the dose of the drug for the indication, cautions, contraindications, common side effects and
interactions to look out for. This section should have input from a specialist consultant in the field.
This information sheet does not replace the Summary of Product Characteristics (SPC), which should
be read in conjunction with this guidance. Prescribers should also refer to the appropriate paragraph in
the current edition of the BNF.
1. Link to the relevant SPC website:
http://www.medicines.org.uk/emc/medicine/22894/SPC/Multaq+400mg+tablets/
2. Background to use for the indication/s, including licence status
Dronedarone is indicated for the maintenance of sinus rhythm after successful cardioversion in adult clinically
stable patients with paroxysmal or persistent atrial fibrillation (AF), when alternative treatments are unsuitable.
3. Dose & administration
The recommended dose is 400 mg twice daily in adults. It should be taken as:
• one tablet with the morning meal and
• one tablet with the evening meal
If a dose is missed, patients should take the next dose at the regular scheduled time and should not double the
dose.
4. Cautions (including for pregnancy and breast-feeding, where applicable)
- Careful monitoring during dronedarone administration is recommended by regular assessment of cardiac,
hepatic and pulmonary function.
- If AF reoccurs, discontinuation of dronedarone should be considered. Treatment with dronedarone should
be stopped during the course of treatment, in case the patient develops any of the conditions which would
lead to a contraindication (e.g. co-administered drugs like digoxin and anti-coagulants).
- If patients treated with dronedarone develop permanent AF, treatment with dronedarone should be
discontinued.
- Dronedarone is contraindicated in patients in unstable hemodynamic conditions, with history of, or current
heart failure or left ventricular systolic dysfunction.
- Patients should be carefully evaluated for symptoms of Congestive Heart Failure. There have been
spontaneously reported events of new or worsening heart failure during treatment with dronedarone.
Patients should be advised to consult a physician if they develop or experience signs or symptoms of
heart failure, such as weight gain, dependent oedema, or increased dyspnoea. If heart failure develops,
treatment with dronedarone should be discontinued.
- If left ventricular systolic dysfunction develops, treatment with dronedarone should be discontinued.
- Caution is needed in patients with coronary artery disease.
- Caution is needed in elderly patients ≥75 years with multiple co-morbidities
- Hepatocellular liver injury, including life-threatening acute liver failure, has been reported in patients
treated with dronedarone. Liver function tests should be performed prior to initiation of treatment with
dronedarone, after one week and after one month following initiation of treatment and then repeated
monthly for six months, at months 9 and 12, and periodically thereafter.
- If alanine aminotransferase (ALT) levels are elevated ≥3 × upper limit of normal (ULN), ALT levels should
be re-measured within 48 to 72 hours. If ALT levels are confirmed to be ≥3 × ULN, treatment with
dronedarone should be withdrawn. Appropriate investigation and close observation of patients should
continue until normalization of ALT.
- Patients or their carers should be advised how to recognise signs of liver disorders and should
immediately report any symptoms of potential liver injury (such as sustained new-onset abdominal pain,
anorexia, nausea, vomiting, fever, malaise, fatigue, jaundice, dark urine or itching) to their physician.
- It is recommended to measure plasma creatinine values prior to and 7 days after initiation of dronedarone.
If an increase in creatininemia is observed, serum creatinine should be re-measured after a further 7 days.
If no further increase in creatininemia is observed, this value should be used as the new reference
baseline taking into account that this may be expected with dronedarone. If serum creatinine continues to
rise then consideration should be given to further investigation and discontinuing treatment.
- An increase in creatininemia should not necessarily lead to the discontinuation of treatment with ACE
inhibitors or Angiotensin II Receptors Antagonists (AIIRAs).
- Any potassium or magnesium deficiency should be corrected before initiation and during dronedarone
Effective from: 25/10/2013
Review date: 25/10/2015
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Dronedarone; Version 3
therapy.
- The pharmacological action of dronedarone may induce a moderate QTc Bazett prolongation (about 10
msec), related to prolonged repolarisation. Follow up, including ECG, is recommended during treatment. If
QTc Bazett interval is ≥500 milliseconds, dronedarone should be stopped.
- Pro-arrhythmic effects may occur in particular situations such as concomitant use with medicinal products
favouring arrhythmia and/or electrolytic disorders.
- Onset of dyspnoea or non-productive cough may be related to pulmonary toxicity and patients should be
carefully evaluated clinically. If pulmonary toxicity is confirmed treatment should be discontinued.
- Dronedarone is not recommended during pregnancy and in women of childbearing potential not using
contraception.
- It is unknown whether dronedarone and its metabolites are excreted in human milk. Available
pharmacodynamic/ toxicological data in animals have shown excretion of dronedarone and its metabolites
in milk. A risk to the newborns / infants cannot be excluded. A decision must be made whether to
discontinue breast-feeding or to discontinue / abstain from dronedarone therapy taking into account the
benefit of breast-feeding for the child and the benefit of therapy for the woman.
5. Contraindications
 Second- or third- degree Atrio-Ventricular block, complete bundle branch block, distal block, sinus node
dysfunction, atrial conduction defects, or sick sinus syndrome (except when used in conjunction with a
functioning pacemaker).
 Bradycardia <50 beats per minute (bpm)
 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 P 450 (CYP) 3A4 inhibitors, such as ketoconazole, itraconazole,
voriconazole, posaconazole, telithromycin, clarithromycin, nefazodone and ritonavir
 Medicinal products inducing torsades de pointes such as phenothiazines, cisapride, bepridil, tricyclic
antidepressants, terfenadine and certain oral macrolides (such as erythromycin), Class I and III
antiarrhythmics
 QTc Bazett interval ≥500 milliseconds
 Severe hepatic impairment
 Severe renal impairment (CrCl <30 ml/min)
 Co-administration with dabigatran
 The use of dronedarone in unstable patients with NYHA class III and IV heart failure is contraindicated.
6. Side effects
(for all other adverse reactions, please refer to the product’s SPC and the BNF)
Cardiac disorders
- Congestive heart failure (very common)
- Bradycardia (common)
Gastrointestinal disorders (common)
- Diarrhoea
- Vomiting
- Nausea
- Abdominal pains
- Dyspepsia
Hepatobiliary disorders (common)
- Liver function test abnormalities
Skin and subcutaneous tissue disorders (common)
- Rashes (including generalised, macular, maculopapular)
- Pruritus
General disorders and administration site conditions (common)
- Fatigue
- Asthenia
Investigations (very common)
- Blood creatinine increased (≥10% five days after treatment initiation)
- QTc Bazett prolonged (>450 msec in male >470 msec in female)
Effective from: 25/10/2013
Review date: 25/10/2015
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Dronedarone; Version 3
7. Interactions
- Concomitant use of ketoconazole as well as other potent CYP 3A4 inhibitors such as itraconazole,
voriconazole, pozaconazole, ritonavir, telithromycin, clarithromycin or nefazodone is contraindicated.
- Dronedarone has the potential to interact on medicinal products substrates of P-glycoproteins, CYP 3A4
or CYP 2D6.
- A potential pharmacodynamic interaction can also be expected with beta-blockers, calcium antagonists
and digitalis; beta blockers should be used with caution concomitantly with dronedarone.
- Medicinal products inducing torsades de pointes such as phenothiazines, cisapride, bepridil, tricyclic
antidepressants, certain oral macrolides (such as erythromycin), terfenadine and Class I and III
antiarrhythmics are contraindicated.
- Verapamil and diltiazem have the potential to interact with dronedarone and should be used with caution
when associated with dronedarone
- Co-administration of rifampicin and other potent CYP 3A4 inducers such as phenobarbital,
carbamazepine, phenytoin or St John's Wort is not recommended as they decrease dronedarone
exposure.
- Concomitant use of statins should be undertaken with caution.
- Dronedarone could increase plasma concentrations of immunosupressants (tacrolimus, sirolimus,
everolimus and cyclosporine).
- Co-administration of dabigatran and dronedarone is contraindicated.
- INR should be closely monitored after initiating dronedarone in patients taking vitamin K antagonists as
per their label.
- Patients should be warned to avoid grapefruit juice beverages while taking dronedarone.
8. Criteria for use
Dronedarone is recommended as an option (NICE TA197)for the maintenance of sinus rhythm after successful
cardioversion in people with paroxysmal or persistent atrial fibrillation:
 whose atrial fibrillation is not controlled by first-line therapy (usually including beta-blockers), that is, as a
second-line treatment option and after alternative options have been considered and
 who have at least one of the following cardiovascular risk factors:
o hypertension requiring drugs of at least 2 different classes
o diabetes mellitus
o previous transient ischaemic attack, stroke or systemic embolism
o left atrial diameter of 50 mm or greater or
o age 70 years or older and
 who do not have left ventricular systolic dysfunction and
 who do not have a history of, or current, heart failure
9. Any further information (e.g. supporting therapies)
Not applicable
10. References
1. Sanofi, Dronedarone (Multaq). Summary of Product Characteristics. Last updated 08/05/2013. Available
at http://www.medicines.org.uk/emc/medicine/22894/SPC/Multaq+400mg+tablets/ <accessed
28/05/2013>
2. BMJ Group and Pharmaceutical Press, British National Formulary (BNF65), March 2013. Available at
www.bnf.org <accessed 28/05/2013>
3. National Institute for Health and Care Excellence (NICE), Technological Appraisal 197 (TA197). Available
at http://www.nice.org.uk/ta197 <accessed 28/05/2013>
Effective from: 25/10/2013
Review date: 25/10/2015
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Dronedarone; Version 3
RESPONSIBILITIES and ROLES
Consultant / Specialist responsibilities
1
2
3
4
5
6
7
Confirmation of diagnosis and identification of suitable patients.
Discussion of risks and benefits with patients, outlining possible side-effects and explain their roles.
Initiate dronedarone only in line with NICE TA197 and with due consideration of the summary of product characteristics.
Upon initial review, in those patients who fulfil the NICE TA197 criteria, the consultant will send a copy of the shared care
guideline and request agreement of shared care with the GP. Before prescribing responsibility is transferred the consultant
will be in receipt of the signed agreement to shared care from the GP.
Normally to prescribe initial 28 days supply of medication.
Inform the GP of the reasons for initiating the dronedarone
Ensure that all newly treated patients (and/or their carers) receive appropriate education and advice regarding
their drug therapy and shared care arrangements. This should include written information where appropriate.
8
Ensure that patients understand the nature and possible complications of dronedarone and their role in reporting adverse
effects promptly.
9 Agree to discuss promptly with the GP any questions regarding the treatment with dronedarone and review patients
promptly if requested by the GP
Monitoring requirements and appropriate dose adjustments
- Plasma creatinine (7 days after initiation of dronedarone) – If an increase in creatininemia is observed this value should
be used as the new reference baseline taking into account that this may be expected with dronedarone.
Baseline U&Es – any potassium or magnesium deficiency should be corrected prior to treatment initiation
- Measure plasma creatinine values prior to and 7 days after initiation of dronedarone. If an increase in creatininemia
is observed, serum creatinine should be re-measured after a further 7 days.
- Baseline LFTs at 1 week and 1 month.
- Evaluate for symptoms of congestive heart failure.
- Monitoring of co-administered drugs like digoxin and anti-coagulants is necessary
Primary care prescriber responsibilities
1
Subsequent prescribing of dronedarone (normally after the initial 28 days supply) at the dose recommended once the
patient is stable.
2 The GP should inform the consultant of any changes to the patient’s medical condition and/or prescribed medication where
clinically relevant.
3 Monitor for adverse effects throughout treatment and liaise with consultant as appropriate.
Monitoring requirements and appropriate dose adjustments
- U&Es – any potassium or magnesium deficiency should be corrected during treatment with dronedarone.
- LFTs monthly for 6 months, at months 9 and 12, and periodically thereafter – in patients with raised
alanine aminotransferase (more than three times the upper limit of normal) levels should be re-measured within
48 to 72 hours. If ALT levels are confirmed to be more than three times the upper limit of normal after
re-measurement, dronedarone treatment should be withdrawn. Patients or their carers should be told how to
recognise signs of liver disorder and advised to seek prompt medical attention if symptoms such as abdominal
pain, anorexia, nausea, vomiting, fever, malaise, itching, dark urine, or jaundice develop.
- ECGs at least every 6 months. If patient develops permanent AF or QTc Bazett interval
is ≥500 milliseconds, dronedarone treatment should be stopped. Patients or their carers should be told how to
recognise signs of heart failure and advised to seek prompt medical attention if symptoms such as weight
gain, dependent oedema, or dyspnoea develop or worsen.
- If pulmonary toxicity is confirmed treatment should be discontinued.
- Monitoring of co-administered drugs like digoxin and anti-coagulants is necessary
Patient's / Carer’s role
1
2
3
4
5
6
7
Ask the consultant / specialist or primary care prescriber for information, if he or she does not have a clear understanding
of the treatment.
Share any concerns in relation to treatment with dronedarone
Tell the consultant / specialist or primary care prescriber of any other medication being taken, including over-the-counter
products.
Read the patient information leaflet included with your medication and report any side effects or concerns you have to the
consultant / specialist or primary care prescriber.
Report to their doctor any symptoms that could indicate liver injury (such as sustained new-onset abdominal pain, loss of
appetite, nausea, vomiting, fever, malaise, tiredness, jaundice, dark urine or itching).
Report to their doctor if they develop or experience signs or symptoms of heart failure, such as weight gain, oedema
(swelling from excessive accumulation of fluid), or increased difficulty in breathing.
Report to their doctor if they develop painful/difficult breathing or non-productive cough.
Effective from: 25/10/2013
Review date: 25/10/2015
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Dronedarone; Version 3
BACK-UP ADVICE AND SUPPORT
Name / position
Telephone
Dr
01903 205 111, ext 5631
01243 788 122, ext 3531
Other consultant
cardiologist within WSHT
01903 205 111
01243 788 122
Hospital Pharmacy:
Worthing Hospital
St Richards Hospital
01903 205 111, ext 5698
01243 788 122, ext
[email protected]
Out of hours (e.g.
medical team on
call):
On call Medical team
01903 205 111
N/A
Specialist /
Consultant:
Alternative
specialist (e.g.
departmental
contact):
Email
Version History
Document Name:
Dronedarone for the maintenance of sinus rhythm after cardioversion in clinically stable
patients with paroxysmal or persistent AF
Document Type:
Effective Shared Care Agreement
Relevant to:
All primary care prescribers working within Coastal West Sussex and all relevant
clinicians at Western Sussex Hospitals NHS Trust.
Version No.
Date
Author of original development
or review
Details of document development
1
-
-
Original development
2
9/6/2011
Julie Sadler, Medicines
Management Pharmacist
Full review and re-draft
3
9/6/2013
Coralia Wukovich, Medicines
Management Technician
Full review and re-draft
Approval for organisational use
ESCA
authorised for
use in Coastal
West Sussex by
Specialist/consultant: Dr Nicholas Pegge FRCP, Consultant Cardiologist, Worthing Hospital,
23/11/11
Coastal West Sussex Area Prescribing Committee (APC): 23/11/11
Effective from: 25/10/2013
Review date: 25/10/2015
Page 6 of 7
Dronedarone; Version 3
EFFECTIVE SHARED CARE AGREEMENT (ESCA)
DRUG NAME: Dronedarone
INDICATION: the maintenance of sinus rhythm after cardioversion in clinically
stable patients with paroxysmal or persistent atrial fibrillation (AF)
Agreement for transfer of prescribing to PRIMARY CARE PRESCRIBER
Patient details:
Name:
Address:
DoB:
NHS No:
Hospital No:
Drug name and dose:
The following tests and investigations have been carried out:
Details of Tests:
Date treatment initiated:
At the last patient review the drug appeared to be effectively controlling symptoms / providing benefit:
Yes/No
The patients has now been stabilised on a dose of:
I will arrange to review this patient regularly. Date of next clinic appointment:
Title of specialist:
Name:
Department:
Agreement to shared care, to be
signed by primary care prescriber and
consultant/specialist.
Hospital Address:
Consultant/specialist signature:
Contact Number:
Date:
Primary care prescriber:
Address:
Contact Number:
Main Carer:
Contact Number:
Key worker if appropriate:
Contact Number:
Effective from: 25/10/2013
Primary care prescriber signature:
Date:
If shared care is agreed and the
primary care prescriber has signed
above please return a copy of this
page to the requesting consultant or
alternatively fax to:
Review date: 25/10/2015
Page 7 of 7