Download Health Canada Endorsed Important Safety Information on

Health Canada Endorsed Important Safety Information on
domperidone maleate
March 2, 2012
Dear Healthcare 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.
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Domperidone should be initiated at the lowest possible dose, including in
patients with Parkinson’s disease.
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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.
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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 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 (http://www.hc-sc.gc.ca/dhp-mps/medeff/reportdeclaration/index-eng.php). 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: [email protected]
Telephone: 613-954-6522
Fax: 613-952-7738
Yours sincerely
original signed by
Mathi Mathivanan, PhD
Director, Regulatory Affairs
Teva Canada Limited
References:
1.
van Noord C, Dieleman JP, van Herpen G, Verhamme K, Sturkenboom MC. Domperidone and
ventricular arrhythmia or sudden cardiac death: a population-based case-control study in the
Netherlands. Drug Saf. 2010 Nov 1;33(11):1003-1014.
2.
Johannes CB, Varas-Lorenzo C, McQuay LJ, Midkiff KD, Fife D. Risk of serious ventricular
arrhythmia and sudden cardiac death in a cohort of users of domperidone: a nested case-control
study. Pharmacoepidemiol Drug Saf. 2010 Sep;19(9):881-888.