Multaq (dronedarone) - Information on Important Revisions to Product Monograph - For Health Professionals

Starting date:

December 5, 2011

Posting date:

December 8, 2011

Type of communication:

Dear Healthcare Professional Letter

Subcategory:

Drugs

Source of recall:

Health Canada

Audience:

Healthcare Professionals

Identification number:

RA-170002479

This is duplicated text of a letter from Sanofi-aventis Canada Inc.
Contact the company for a copy of any references, attachments or enclosures.

Notice about Health Canada advisories

Health Canada Endorsed Important Safety Information on MULTAQ (dronedarone)

December 5, 2011

Dear Healthcare Professional,

Subject: Information on important revisions to Multaq^® (dronedarone) Product Monograph

Sanofi-aventis Canada Inc., in collaboration with Health Canada, would like to inform you of important new safety information regarding Multaq (dronedarone).

Further to the communication dated July 29, 2011 which described the premature termination of the PALLAS study conducted in patients with permanent atrial fibrillation (AF), the Product Monograph has been revised. The revisions reflect updated cardiovascular safety information from the analysis of the PALLAS study, and updated pulmonary safety information following post-market reports of pulmonary injury.

The Multaq Product Monograph has been modified to include a revised indication, new contraindications, new warnings and precautions and new monitoring recommendations.

• Multaq is now indicated for the treatment of patients with paroxysmal or persistent atrial fibrillation who are in sinus rhythm or who are intended to be cardioverted, to reduce the risk of cardiovascular hospitalization due to atrial fibrillation.
• Multaq should only be prescribed after alternative treatment options have been considered.
• The use of Multaq has been further restricted to exclude patients with permanent atrial fibrillation of any duration, patients with a history of, or current heart failure, regardless of New York Heart Association (NYHA) functional class, patients with left ventricular systolic dysfunction (LVSD), patients with certain conduction abnormalities and patients with liver or lung toxicity related to previous use of amiodarone.
• Updated information has been added to the "Warnings and Precautions" section of the Product Monograph regarding anticoagulation therapy as well as the use of Multaq in the elderly, in patients with coronary artery disease and in patients who develop congestive heart failure or LVSD during treatment with Multaq. New cardiovascular and renal monitoring recommendations as well as the need for pulmonary clinical evaluation have also been added to the Product Monograph.

The Multaq Product Monograph has been modified to include the following new information under:

Indications and Clinical Use:

Multaq is indicated for the treatment of patients with paroxysmal or persistent atrial fibrillation who are in sinus rhythm or who are intended to be cardioverted, to reduce the risk of cardiovascular hospitalization due to atrial fibrillation. Multaq should only be prescribed after alternative treatment options have been considered.

Contraindications:

• Patients with permanent atrial fibrillation of any duration in which sinus rhythm cannot be restored and attempts to restore it are no longer considered by the attending physician.
• Patients with a history of, or current heart failure, regardless of New York Heart Association (NYHA) functional class.
• Patients with left ventricular systolic dysfunction.
• Patients with second- or third- degree atrio-ventricular (AV) 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).
• Patients with liver or lung toxicity related to the previous use of amiodarone.

Warnings and Precautions:

• under "Congestive Heart Failure/Patients with new or worsening heart failure during treatment": If heart failure or left ventricular systolic dysfunction develops treatment with Multaq should be discontinued.
• under "Patients with Coronary Artery Disease": Caution is needed in patients with coronary artery disease.
• under "Special Populations/ Geriatrics": Caution is needed in elderly patients ≥ 75 years with multiple co-morbidities.

The Multaq Product Monograph has also been modified to include the following new monitoring recommendations for safe use of Multaq:

Cardiovascular:

• It is recommended to perform an ECG at least every 6 months while patients are receiving Multaq. If patients treated with Multaq develop permanent AF, treatment with Multaq should be discontinued.
• Patients should be advised to consult a physician if they develop signs or symptoms of heart failure. If heart failure develops, treatment with Multaq should be discontinued.
• Patients should be followed for the development of left ventricular systolic dysfunction during treatment. If left ventricular systolic dysfunction develops, treatment with Multaq should be discontinued.
• Patients should be appropriately anti-coagulated. Where applicable, International Normalized Ratio (INR) should be closely monitored after initiating dronedarone in patients taking vitamin K antagonists as per their label.

Renal:

• Larger increases in creatinine after dronedarone initiation have been reported in the post-marketing setting. Some cases also reported increases in blood urea nitrogen. Renal function should be monitored periodically.

Pulmonary:

• Cases of interstitial lung disease including pneumonitis and pulmonary fibrosis have been reported in the post-marketing experience. 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.

There are no new revisions to the Product Monograph concerning hepatic monitoring. For previous information see Multaq Health Professional Communication dated March 10, 2011.

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 or pulmonary 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 MedEffect™ Canada
• 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 MedEffect™ 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 Products 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