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Multaq (dronedarone) – Information on Increase in Heart-Related Events in Patients with Permanent Atrial Fibrillation – For Health Professionals

Starting date:
July 29, 2011
Posting date:
August 4, 2011
Type of communication:
Dear Healthcare Professional Letter
Subcategory:
Drugs
Source of recall:
Health Canada
Issue:
Product Safety
Audience:
Healthcare Professionals
Identification number:
RA-17185

Contact: Marketed Health Products Directorate

The Health Products and Food Branch (HPFB) posts on the Health Canada Web site safety alerts, public health advisories, press releases and other notices as a service to health professionals, consumers, and other interested parties. These advisories may be prepared with Directorates in the HPFB which includes pre-market and post-market areas as well as market authorization holders and other stakeholders. Although the HPFB grants market authorizations or licenses for therapeutic products, we do not endorse either the product or the company. Any questions regarding product information should be discussed with your health professional.
 
This is duplicated text of a letter from Sanofi-aventis Canada Inc.
Contact the company for a copy of any references, attachments or enclosures.
 
Health Canada Endorsed Important Safety Information on MULTAQ (dronedarone)                                                                                               
July 29, 2011
 
Subject: Information on increase in cardiovascular events associated with the use of Multaq® (dronedarone) in patients with permanent atrial fibrillation.
 
Dear Health Care Professional,
 
Sanofi-aventis Canada Inc. in collaboration with Health Canada would like to inform you of important new safety information regarding Multaq® (dronedarone).
 
The information is based on preliminary data arising from the recently discontinued PALLAS trial. The PALLAS trial comparing Multaq (dronedarone) to placebo in patients with permanent atrial fibrillation (AF) and additional risk factors was stopped due to an excess of severe cardiovascular events in the dronedarone arm. In PALLAS trial, patients in permanent AF were defined by the presence of AF/AFL (flutter) for at least 6 months prior to randomization and patient and physician decision to allow AF to continue without further efforts to restore sinus rhythm.
 
  • Multaq must not be prescribed in patients with permanent AF (duration for at least 6 months or duration unknown), and in whom an attempt to restore sinus rhythm is no longer considered.
  • Multaq treatment should be stopped in patients with permanent AF.
  • It is recommended to closely monitor patients taking Multaq. If patients treated with Multaq develop permanent AF, treatment with Multaq should be discontinued.
PALLAS Trial:
 
As part of the ongoing development of Multaq, sanofi-aventis undertook the PALLAS study entitled "A randomized, double blind, placebo controlled, parallel group trial for assessing the clinical benefit of dronedarone 400 mg BID on top of standard therapy in patients with permanent atrial fibrillation (AF) and additional risk factors".
 
In PALLAS, patients in permanent AF were defined by the presence of AF/AFL (flutter) for at least 6 months prior to randomization and patient and physician decision to allow AF to continue without further efforts to restore sinus rhythm. Patients also had to have additional cardiovascular risk factors.
 
The trial had two composite co-primary endpoints: 1. Major cardiovascular events (stroke, systemic arterial embolism, myocardial infarction or cardiovascular death). 2. Cardiovascular hospitalization or death from any cause.
 
On July 5th, 2011 the PALLAS Data Monitoring Committee (DMC) reviewed the unblinded data and concluded that there was a significant excess of events in the dronedarone group for both co-primary endpoints, in particular cardiovascular hospitalizations (hazard ratio: 1.43; 95% CI: 1.07-1.92) and stroke (hazard ratio: 2.44; 95% CI: 1.01-5.87), as well as all heart failure events (hazard ratio: 2.53; 95% CI: 1.68-3.82) [Note: These figures are provided by the manufacturer; these figures have not been verified by Health Canada]. Based on these preliminary data, the DMC recommended the PALLAS study be stopped and patients included in the trial were instructed to immediately discontinue study medication.
 
Multaq (dronedarone) is authorized for the treatment of patients with a history of, or current atrial fibrillation to reduce the risk of cardiovascular hospitalization due to AF.
 
Sanofi-aventis is working with Health Canada for the Multaq Product Monograph to reflect this new safety information:
  • Multaq should be prescribed only in patients with a history of, or current non-permanent AF to reduce the risk of cardiovascular hospitalization due to atrial fibrillation.
  • Multaq must not be prescribed in patients with permanent atrial fibrillation (duration for at least 6 months or duration unknown), and in whom an attempt to restore sinus rhythm is no longer considered.
  • It is recommended to closely monitor patients taking Multaq. If patients treated with Multaq develop permanent AF, treatment with Multaq should be discontinued.
It is also reminded that the contraindications, warnings and precautions in the current Product Monograph should be followed. In relation to cardiovascular risk the following are particularly relevant:
  • MULTAQ is contraindicated in patients with:

               • Severe congestive heart failure (Stage NYHA IV) and other unstable hemodynamic conditions

               •  Bradycardia < 50 bpm

  • MULTAQ should be used with caution in patients with moderate congestive heart failure (Stage NYHA III) and only if the benefits are deemed to outweigh the risks involved.
  • If heart failure develops or worsens, consider the suspension or discontinuation of MULTAQ.
Managing marketed health product-related adverse reactions depends on health care professionals and consumers reporting them. Reporting rates determined on the basis of spontaneously reported post-marketing adverse reactions are generally presumed to underestimate the risks associated with health product treatments. Any case of serious cardiovascular adverse reaction or other serious or unexpected adverse reactions in patients receiving MULTAQ (dronedarone) should be reported to sanofi-aventis Canada Inc. or to Health Canada.
 
Sanofi-aventis Canada Inc.
2150 St-Elzear Blvd. West
LAVAL, Quebec
H7L 4A8
Phone: 1-800-265-7927
 
You can report any suspected adverse reactions associated with the use of health products to the Canada Vigilance Program by one of the following 3 ways:
  • Report online at www.healthcanada.gc.ca/medeffect
  • Call toll-free at 1-866-234-2345
  • Complete a Reporting Form and:
         • Fax toll-free to 1-866-678-6789, or
          • Mail to: Canada Vigilance Program                   
                          Health Canada
                          Postal Locator 0701E
                          Ottawa, Ontario   K1A 0K9
The Reporting Forms, postage paid labels, and Guidelines can be found on the MedEffectTM Canada Web site in the Adverse Reaction Reporting section. The Reporting Form is also in the Canadian Compendium of Pharmaceuticals and Specialties.
 
For other health product inquiries related to this communication, please contact Health Canada at: 
Marketed Health Product Directorate
E-mail: mhpd_dpsc@hc-sc.gc.ca
Telephone: 613-954-6522
Fax: 613-952-7738
 
To change your mailing address or fax number, contact the Market Authorization Holder (Industry).
Sincerely,
 
original signed by
 
Franca Mancino, M.Sc.
Senior Director, Regulatory Affairs, Pharmacovigilance &
Medical Quality and Compliance