Amiodarone - Slow Heart Rate in Patients Taking Amiodarone Together with Harvoni or Sovaldi and a Direct Acting Antiviral

Starting date:
April 2, 2015
Posting date:
April 2, 2015
Type of communication:
Dear Healthcare Professional Letter
Subcategory:
Drugs
Source of recall:
Health Canada
Issue:
Important Safety Information
Audience:
Healthcare Professionals, General Public
Identification number:
RA-52801

Audience

Healthcare professionals working in the following settings: Infectious diseases, Gastroenterology, Hepatology, and Pharmacy.

Key messages

  • Postmarketing cases of symptomatic bradycardia, including two cases that occurred in Canada, have been reported in patients taking amiodarone with either a) Harvoni™ or  b) Sovaldi® in combination with another Direct Acting Antiviral (DAA).
  • Health Canada is working with Gilead Sciences Canada to update the Sovaldi® and Harvoni™ product monographs to reflect this new information.
  • The co-administration of amiodarone with Harvoni™ or Sovaldi® in combination with another DAA is not recommended.

          

Issue

Gilead Sciences Canada, in consultation with Health Canada, would like to inform healthcare professionals, caregivers and patients of important safety information related to the development of serious symptomatic bradycardia (slow heart rate) in patients who are treated with amiodarone concomitantly with a) Harvoni™ or b) Sovaldi® in combination with another Direct Acting Antiviral (DAA).  DAA are drugs that directly target specific steps or encoded proteins vital to the replication of the virus within the Hepatitis C Virus (HCV) life cycle.  Nine cases of symptomatic bradycardia have been reported during postmarketing use in patients receiving amiodarone with either Harvoni™, or Sovaldi® in combination with another DAA.

Products affected

Sovaldi® (sofosbuvir tablets) is indicated for the treatment of chronic hepatitis C infection as a component of a combination antiviral treatment regimen. Harvoni™ (ledipasvir and sofosbuvir fixed-dose combination tablets) is indicated for the treatment of chronic hepatitis C genotype 1 infection in adults.

Background information

Nine cases of symptomatic bradycardia have been reported during postmarketing in patients receiving amiodarone with either Harvoni™, or Sovaldi® in combination with another DAA. Seven patients were also receiving a beta blocker.

Bradycardia was observed within hours to two weeks of starting therapy.

Of the nine cases of bradycardia, one resulted in cardiac arrest with a fatal outcome and three cases required pacemaker intervention.

Three of the 9 cases were in patients receiving amiodarone and Harvoni™, six cases were in patients receiving amiodarone and Sovaldi® in combination with another DAA.

Risk factors for the development of symptomatic bradycardia in patients receiving amiodarone may include co-administration of a beta blocker, or use in those patients with underlying cardiac comorbidities and/or advanced liver disease.

The mechanism of this potential drug interaction is unclear at this time.

Who is affected

Information for consumers

Sovaldi® and Harvoni™ are approved for the treatment of chronic Hepatitis C, a viral infection of the liver. Sovaldi® and Harvoni™ act by preventing the multiplication of hepatitis C virus. 

Amiodarone is approved for treating irregular rapid heartbeat and reoccurring heart rhythm problems.

Patients and caregivers should contact their Healthcare Professionals for further evaluation if they are taking amiodarone with either Sovaldi® or Harvoni™.

Patients who develop the following signs or symptoms of symptomatic bradycardia should seek medical evaluation immediately:

  • Near-fainting or fainting
  • Dizziness or lightheadedness
  • Malaise
  • Weakness
  • Excessive tiredness
  • Shortness of breath
  • Chest pains
  • Confusion or memory problems

Patients should not stop taking their medicines before talking to their healthcare provider.

Information for health care professionals

The co-administration of amiodarone with either Harvoni™ or Sovaldi® in combination with another DAA is not recommended. Healthcare professionals should counsel patients about the risk of serious symptomatic bradycardia when co administering amiodarone with either Harvoni™ or Sovaldi® in combination with another DAA.

In cases where concomitant administration of amiodarone and Harvoni™ or Sovaldi® in combination with another DAA is unavoidable as judged by a medical practitioner, it is recommended that heart monitoring within an in-patient setting be conducted in the first 48 hours followed by daily self-monitoring of the heart rate in the first 2 weeks of treatment.

Due to amiodarone’s long half-life (15 – 142 days, mean 58 days), patients discontinuing amiodarone  less than 3 months before starting Harvoni™ or Sovaldi® in combination with a DAA should also undergo cardiac monitoring as outlined above.

Action taken by Health Canada

Health Canada is working with Gilead Sciences Canada to update the Warnings and Precautions, Post-market Adverse Drug Reactions and Drug Interactions Sections of the Sovaldi® and Harvoni™ product monographs to reflect this new information.

Report health or safety concerns

Managing marketed health product-related side effects depends on healthcare professionals and consumers reporting them. Any case of serious symptomatic bradycardia or other serious or unexpected side effects in patients receiving Harvoni™ or Sovaldi® with another DAA should be reported to Gilead Sciences Canada or Health Canada.

Gilead Sciences Canada Inc.
6711 Mississauga Road, Suite 600
Mississauga ON L5N 2W3
Canada
1-866-565-5409

To correct your mailing address or fax number, contact Gilead Sciences Canada, Inc.

You can report any suspected adverse reactions associated with the use of health products to Health Canada by:

  • Calling toll-free at 1-866-234-2345; or
  • Visiting MedEffect Canada's Web page on Adverse Reaction Reporting for information on how to report online, by mail or by fax

For other health product inquiries related to this communication, contact Health Canada at:
Marketed Health Products Directorate
E-mail: mhpd_dpsc.public@hc-sc.gc.ca
Telephone: 613-954-6522
Fax: 613-652-7738

Contact Gilead Medical Information at 1-866-207-4267 if you have additional questions. This information is being sent in agreement with Health Canada.

Sincerely,

Original signed by

John McHutchison, MD
Executive Vice President, Clinical Research
Gilead Sciences, Inc.

For more information

The update to the product monograph was not a result of a Health Canada safety review. Therefore a Summary Safety Review is not available.