Domperidone Maleate - Association with Serious Abnormal Heart Rhythms and Sudden Death (Cardiac Arrest) - For Health Professionals

Starting date:

March 2, 2012

Posting date:

March 7, 2012

Type of communication:

Dear Healthcare Professional Letter

Subcategory:

Drugs

Source of recall:

Health Canada

Audience:

Healthcare Professionals

Identification number:

RA-15857

This is duplicated text of a letter from Teva Canada Limited and other Canadian manufacturers of domperidone.

Contact the company for a copy of any references, attachments or enclosures.

Notice about Health Canada advisories

Health Canada Endorsed Important Safety Information on domperidone maleate

March 2, 2012

Dear Health Care Professional,

Subject: Association of domperidone maleate with serious ventricular arrhythmias and sudden cardiac death

The manufacturers of domperidone, in collaboration with Health Canada, would like to inform healthcare professionals that the gastrointestinal motility modifier domperidone should be initiated at the lowest possible dose in adults. Recent epidemiological studies have shown that the use of domperidone may be associated with an increased risk of serious ventricular arrhythmias or sudden cardiac death, particularly in patients taking daily doses greater than 30 mg, and in patients older than 60 years of age.

Domperidone is indicated in adults for the symptomatic management of upper gastrointestinal motility disorders associated with chronic and subacute gastritis and diabetic gastroparesis. Domperidone is also indicated to prevent gastrointestinal symptoms associated with the use of dopamine agonist antiparkinsonian agents.

• Domperidone should be initiated at the lowest possible dose, including in patients with Parkinson's disease.
• The risk of serious ventricular arrhythmias or sudden cardiac death may be higher in patients taking daily doses greater than 30 mg, and in patients older than 60 years of age.
• Caution should be exercised when using domperidone concomitantly with drugs that prolong the QT interval, in patients who have existing prolongation of cardiac conduction intervals, particularly QTc, and in patients with significant electrolyte disturbances or underlying cardiac disease such as congestive heart failure.

A population-based case-control study¹ conducted in the Integrated Primary Care Information database in the Netherlands showed that the use of oral domperidone was associated with an increased risk of sudden cardiac death, which was higher in patients using daily doses greater than 30 mg. While the exact odds ratio (OR) for sudden cardiac death was not certain given the wide confidence interval (CI), the lower limit of the confidence interval indicated that the risk of sudden cardiac death was at least doubled for daily doses greater than 30 mg (adjusted OR 11.4; 95% CI 1.99, 65.2).

A nested case-control study² performed in the linked administrative databases of Saskatchewan Health showed that the use of oral domperidone was associated with an increased risk of a composite endpoint of sudden cardiac death and serious ventricular arrhythmia, which was higher in patients older than 60 years of age (adjusted OR 1.64 ; 95% CI 1.31, 2.05). In this study, the composite endpoint of sudden cardiac death and serious ventricular arrhythmia consisted mostly of sudden cardiac death cases.

Domperidone should be initiated at the lowest possible dose, which may be adjusted upward with caution to achieve the desired effect as needed. In addition, the expected benefit of an increased dose should outweigh the potential risks.

Co-administration of domperidone with ketoconazole is contraindicated. Caution should be exercised when using domperidone concomitantly with other CYP3A4 inhibitors, which may increase plasma levels of domperidone.

Patients should be advised to stop taking domperidone and seek immediate medical attention if they experience signs or symptoms of an abnormal heart rate or rhythm while taking domperidone. These include dizziness, palpitations, syncope or seizures.

The manufacturers of all domperidone products are working with Health Canada

to include this new drug dosage and usage recommendations, as well as information about the risk of serious ventricular arrhythmias and sudden cardiac death, in all Canadian Product Monographs for domperidone:

• Apo-domperidone
• Ava-domperidone
• Dom-domperidone
• Jamp-domperidone
• Mylan-domperidone
• Nu-domperidone
• PHL-domperidone
• PMS-domperidone
• Domperidone-10
• RAN-domperidone
• Domperidone
• Teva-domperidone
• Ratio-domperidone

Managing marketed health product-related adverse reactions depends on healthcare 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 ventricular arrhythmia, sudden cardiac death or other serious or unexpected adverse reactions in patients receiving domperidone should be reported to the respective manufacturer listed below, or Health Canada.

• Apotex Incorporated Telephone: 1-800-667-4708 Telefax: 1-416-401-3819
• Avanstra Inc. Telephone: 1-855-708-3678 Telefax: 1-855-227-5833
• Dominion Pharmacal Telephone: 1-888-550-6060 Telefax: 1-514-340-0164
• Jamp Pharma Corporation Telephone: 1-888-399-9091 Telefax: 1-450-449-1546
• Mylan Pharmaceuticals ULC Telephone: 1-800-575-1379 Telefax: 1-304-285-6409
• Nu-Pharm Inc. Telephone: 1-905-886-2344 Telefax: 1-905-886-0564
• Pharmel Inc. Telephone: 1-888-550-6060 Telefax: 1-514-340-0164
• Pharmascience Inc. Telephone: 1-888-550-6060 Telefax: 1-514-340-0164
• Pro Doc Limitée Telephone: 1-800-575-1379 Telefax: 1-416-236-4363
• Ranbaxy Pharmaceuticals Inc. Telephone: 1-866-840-1340 Telefax: 1-905-602 4216
• Sanis Health Inc. Telephone: 1-866-236-4076 Telefax: 1-905-689-1465
• Teva Canada Limited and ratiopharm Inc. 1-800-268-4127 ext 5005 (English), 1-877-777-9117 (French), Telefax: 1-416-335-4472

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.public@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).

Yours sincerely,

original signed by

Mathi Mathivanan, PhD

Director, Regulatory Affairs

Teva Canada Limited

References: