Canadian Adverse Reaction Newsletter, Volume 23 - Issue 4 - October 2013
Cat no H42-4/1-23-4E
Health Products and Food Branch
Marketed Health Products Directorate
Canadian Adverse Reaction Newsletter Editorial Team
In this Issue:
This quarterly publication alerts health professionals to potential signals detected through the review of case reports submitted to Health Canada. It is a useful mechanism to stimulate adverse reaction reporting as well as to disseminate information on suspected adverse reactions to health products occurring in humans before comprehensive risk-benefit evaluations and regulatory decisions are undertaken. The continuous evaluation of health product safety profiles depends on the quality of your reports.
Reporting Adverse Reactions
Canada Vigilance Program
For more information on how to report an adverse reaction, visit the Reporting Adverse Reactions to Drugs and Other Health Products page.
Caveat: Adverse reactions (ARs) to health products are considered to be suspicions, as a definite causal association often cannot be determined. Spontaneous reports of ARs cannot be used to estimate the incidence of ARs because ARs remain underreported and patient exposure is unknown.
Adverse reaction reports make a difference
- Reporting of suspected adverse reactions is a key component in monitoring the safety and effectiveness of marketed health products.
- Detailed reports facilitate a more thorough assessment of the potential safety issue.
- The relationship between information collected by Health Canada and information communicated to health professionals is synergistic, as illustrated in two examples that describe how a safety issue evolved over time.
Every time you report an adverse reaction to Health Canada, you help improve the safety of health products used by Canadians.
Adverse reactions to prescription and nonprescription drugs, biologics (including fractionated blood products, as well as therapeutic and diagnostic vaccines), natural health products and radiopharmaceuticals can be reported to Health Canada (see Reporting an adverse reaction to Health Canada).
Medical device-related adverse incidents and adverse events from a vaccine used in the prevention of infectious disease are reported separately (please see section on How do you report? for more information).
Why should you report?
Reporting of suspected adverse reactions by health professionals and consumers is a key component in monitoring the safety and effectiveness of marketed health products. These reports provide important information concerning previously undetected adverse reactions or changes in marketed health product safety and effectiveness profiles. It is well known that the controlled conditions under which patients use health products in clinical trials do not always reflect the way products will be used in real-world conditions. In addition, some adverse reactions may take a long time to develop or may occur infrequently. Even if an adverse reaction is known, additional reports are important to assess the overall benefit-risk profile of a health product.
Do not assume that someone else will report. If you are aware of an adverse reaction, report it. Duplicate reports of the same case are matched in the Health Canada database and may provide a clearer picture of the adverse reaction.
What should you report?
You do not have to be certain that a health product caused the reaction in order to report it. Adverse reaction reports are, for the most part, only suspected associations. Health Canada wants to know about all suspected adverse reactions, but especially if they are:
- unexpected (not consistent with product information or labelling), regardless of their severity;
- seriousFootnote 1, whether expected or not; or
- related to a new health product (one that has been on the market less than 5 years).
Adverse reaction reports require at least four information items in order to be properly assessed by Health Canada. It only takes a few moments to provide the following:
- patient identifier such as a qualifying descriptor (e.g., sex, age, etc.) or a patient identification number; for reasons of confidentiality, do not use name or initials
- description of the adverse reaction experienced by the patient
- name of the health productFootnote 2 you suspect caused the adverse reaction
- your contact information in case Health Canada requires additional information
Please do not hesitate to report any suspected adverse reaction of clinical concern, even if you are unable to supply any further details.
Quality reporting is key!
Providing as much information as possible will enhance the quality of your adverse reaction report. This includes indicating if a section is not applicable (for example, other health products taken), rather than leaving it blank. Detailed reports will facilitate a more thorough assessment of the potential safety issue. Other useful information to provide, if known, includes:
- patient characteristics (age, sex, height and weight);
- dosing information and indication for use of the suspected health product;
- therapy dates: when the suspected health product was started and stopped;
- changes to therapy with the suspected health product and impact on the patient (e.g., dechallenge/rechallenge information);
- treatment of the adverse reaction (including date the adverse reaction occurred and was resolved, if applicable);
- investigations to exclude alternate causes for the adverse reaction;
- relevant history and pre-existing conditions;
- relevant tests/lab data; and
- other health products taken (including over-the-counter and natural health products) with therapy dates and dosing information.
Please note that information related to the identities of both the patient and the reporter of an adverse reaction are protected as personal information under the Privacy Act, and also under the Access to Information Act in the case of an access to information request.
How do you report?
For information on how to report adverse reactions to prescription and nonprescription drugs, biologics (including fractionated blood products, as well as therapeutic and diagnostic vaccines), natural health products and radiopharmaceuticals, see Reporting an adverse reaction to Health Canada.
Reporting an adverse reaction to Health Canada
- By phone:
- By completing a form:
The Canada Vigilance Adverse Reaction Reporting Form is available on the Health Canada web site. It is also available in the Compendium of Pharmaceuticals and Specialties (CPS).
Fax completed form to 1-866-678-6789 (toll-free); or
Mail completed form using a postage paid label (available at www.health.gc.ca/medeffect or by calling the toll-free phone number above)
For device-related adverse incidents, information on how to complete a report and where to send completed reports is available on Health Canada's web site. Please see the User Problem Reporting for Medical Devices guidance document for more information.
To report adverse events following immunization with a vaccine used in the prevention of infectious disease, please visit the Public Health Agency of Canada's web site.
What happens to your reports?
Adverse reaction reports are carefully assessed along with information collected from a variety of sources (including manufacturers, scientific literature, Phase IV studies, the World Health Organization, the Public Health Agency of Canada, foreign regulatory agencies, etc.) to detect potential health product safety signals. A signal is considered to be the preliminary indication of a product-related issue. Signals are carefully evaluated to confirm or disprove the potential association between a health product and an adverse reaction.
When you report an adverse reaction, you contribute to the ongoing collection of safety information that occurs once health products are on the market. Your report may contribute to:
- the identification of previously unrecognized rare, or serious adverse reactions;
- changes in product safety information (e.g. through an update to the Canadian product monograph);
- other regulatory actions such as the issuance of a health product advisory or the withdrawal of a product from the Canadian market;
- international data regarding benefits and risks of health products; and
- increasing the safe use of health products by all Canadians.
How is new safety information communicated back to you?
New safety information may be communicated by Health Canada and/or manufacturers to health professionals and the public via:
- health product advisories (recently issued health professional and consumer advisories can be found at the end of this publication);
- Canadian product monograph updates; and
- the Canadian Adverse Reaction Newsletter (CARN).
The following two examples (Fig. 1 and Fig. 2) show the relationship between information collected by Health Canada (including adverse reaction reports, published literature and other types of health product safety information) and information provided to health professionals (through advisories, product monograph updates and CARN).
The review of marketed health products is an ongoing process. All data are assessed over time to detect potential safety signals; thus, continued adverse reaction reporting can provide valuable information that supports the monitoring of marketed health products.
Fig. 1: Example of how a safety issue involving a pharmaceutical product evolved over time
Medical literature described 3 cases of profound decreases in high-density lipoprotein cholesterol (HDL-C) levels in patients treated with rosiglitazone. (2004)
Health Canada published an article in CARN called Rosiglitazone (Avandia): decreased high-density lipoprotein cholesterol levels which described the published literature reports, as well as an adverse reaction report submitted to Health Canada involving rosiglitazone and decreased HDL-C levels. (2005)
Further studies and case reports published in the literature suggested that, in some patients, severe decreases in HDL-C may involve the interaction of rosiglitazone with fenofibrate or bezafibrate. (2005-2010)
Adverse reaction reports:
Health Canada received 7 additional adverse reaction reports of decreased HDL-C levels in patients using rosiglitazone and fenofibrate concomitantly. (2005-2010)
Health Canada assessed adverse reaction reports, scientific literature and other health product safety information related to the potential drug interaction between rosiglitazone and fenofibrate or bezafibrate. (2010)
Health Canada published an article in CARN to relay new safety information: Rosiglitazone-fenofibrate interaction: severe paradoxical decreased high-density lipoprotein cholesterol levels. (2011)
Canadian product monographs for Avandia, Lipidil products (fenofibrate) and Bezalip (bezafibrate) are updated. (2011)
Monitoring: International reports of liver toxicity suspected of being associated with black cohosh accumulate. No adverse reaction reports of liver dysfunction involving black cohosh have been received by Health Canada. (2005) Communication: Additional information was needed to further characterize the suspected relationship between black cohosh and liver toxicity. Health Canada published an article in CARN called Black cohosh: international reports of liver toxicity describing international concerns. (2005) Health Canada issued an advisory: Health Canada is advising consumers about a possible link between black cohosh and liver damage. (2006) Adverse reaction reports: Health Canada received 6 adverse reaction reports of liver toxicity suspected of being associated with black cohosh. (2005-2009) Monitoring/analysis: Published research showed problems with the herbal identity of some products marketed in the United States as black cohosh. Health Canada requested lab testing of suspected black cohosh products to investigate possible contamination. (2006) Analysis revealed that some of the products identified in the adverse reaction reports did not contain authentic black cohosh. (2007) Outcome: A review was conducted of the herbal authenticity of all licensed products containing black cohosh in Canada. This review resulted in the voluntary withdrawal from the market of several products that did not contain black cohosh. (2008) Health Canada updated the black cohosh monograph. (2009) Communication: Health Canada published an article in CARN to communicate findings: Black cohosh products and liver toxicity: update.(2010)
Fig. 2: Example of how a safety issue involving a natural health product evolved over time
International reports of liver toxicity suspected of being associated with black cohosh accumulate. No adverse reaction reports of liver dysfunction involving black cohosh have been received by Health Canada. (2005)
Additional information was needed to further characterize the suspected relationship between black cohosh and liver toxicity. Health Canada published an article in CARN called Black cohosh: international reports of liver toxicity describing international concerns. (2005)
Health Canada issued an advisory: Health Canada is advising consumers about a possible link between black cohosh and liver damage. (2006)
Adverse reaction reports:
Health Canada received 6 adverse reaction reports of liver toxicity suspected of being associated with black cohosh. (2005-2009)
Published research showed problems with the herbal identity of some products marketed in the United States as black cohosh. Health Canada requested lab testing of suspected black cohosh products to investigate possible contamination. (2006)
Analysis revealed that some of the products identified in the adverse reaction reports did not contain authentic black cohosh. (2007)
A review was conducted of the herbal authenticity of all licensed products containing black cohosh in Canada. This review resulted in the voluntary withdrawal from the market of several products that did not contain black cohosh. (2008)
Health Canada updated the black cohosh monograph. (2009)
Health Canada published an article in CARN to communicate findings: Black cohosh products and liver toxicity: update.(2010)
Quarterly Summary of health professional and consumer advisories
|DateTable 1 footnote [a]||Product||Subject|
Table 1 footnotes
|Aug 6 & 9||Votrient (pazopanib hydrochloride)||Change to frequency of liver test monitoring|
|Aug 6||Nova Max blood glucose test strips||Recall: may give false high results|
|Aug 2||Safeway and Compliments Ibuprofen Liquid Capsules||Recall: labelling error|
|Aug 2||Certain Sandoz products for injection||Possible volume under-fill of some vials|
|July 31||Synthetic calcitonin (salmon) nasal spray||Market withdrawal of all products|
|July 31||Calcimar (synthetic salmon calcitonin-solution for injection)||Increased risk of cancer with long-term use|
|July 29||Rituxan (rituximab)||Hepatitis B virus recurrence: updates on screening and management|
|July 26||Compliments Iron Ferrous Gluconate Tablets||Recall: labelling error|
|July 23||Progesta-Care Body Cream, DHEA 25 Age-Free and DHEA 50 Age-Free||Unauthorized health products removed from sale|
|July 20||Innerget Instant Erection, Innerget Prolonged Performance, Innerget Everlasting Strength and Megaton 2080||Hidden ingredients may pose serious risks to health|
|July 18||Voluven and Volulyte (hydroxyethyl starch)||Increased mortality and severe renal injury|
|July 16||Clinoleic 20%||Potential for the presence of particles|
|July 13||Unauthorized health products||Updated list of products from Veslon Cosmetics and Super Discount Distributing|
|July 12||Medtronic MiniMed Insulin Reservoirs||Recall: potential risk of a leak in the reservoir|
|July 8||Aclasta (zoledronic acid 5 mg/100mL)||Volume overfill in vials|
|July 6||Veslon Aqueous Chlorhexidine Gluconate Solution||Unauthorized health product for sale|
|July 5||Designer drugs||Reminder that these drugs are dangerous and illegal|
|June 27||"Poppers" (products containing alkyl nitrites)||May pose serious risks to health|
|June 24||Apo-Cephalex (cephalexin)||Recall: possible reduced efficacy|
|June 24||Hydroxyethyl starch solutions||Not recommended for use in some critically ill patients|
|June 21||AmBisome (liposomal amphotericin B for injection)||Recall: risk of bacterial contamination|
|June 21||ACET-650 suppositories||Recall: mislabelling and potential overdose risk|
|June 20||Paradigm and Polyfin Insulin Infusion Sets||Potential of under- or over-delivery of insulin|
|June 19||Ketoconazole||Risk of potentially fatal liver toxicity|
|June 10||Intralipid 10%, 20% and 30% fat emulsion||Missing French label information|
|June 6||Codeine-containing products||Recommended for use only in patients aged 12 and over|
|June 6||Safeway Extra Strength Ibuprofen||Recall: labelling error|
|June 5||Eight products used as "poppers"||May pose serious risks to health|
|June 4||ExtenZe Plus and ExtenZe Maximum Strength||Hidden ingredients may pose serious risks to health|
|May 30||Amlodipine, Ciprofloxacin, Lamotrigine, Norfloxacin and Telmisartan||Recall: quality issues with various lots|
|May 30||Stiff Nights and Stiff 4 Hours||Hidden ingredients may pose serious risks to health|
|May 29||Cetrotide (cetrorelix for injection)||Increased reconstitution time for four lots|
|May 27 & 30||Champix (varenicline tartrate) and Zyban (bupropion hydrochloride)||Revision to the product monographs|
|May 25||Apo-Clindamycin, Clindamycine-150, Clindamycine-300 (clindamycin hydrochloride)||Potential contamination with quetiapine fumarate|
|May 24||GW501516||Serious risks associated with use of the unauthorized product|
|May 23||Children's Little Remedies for Fevers (grape and cherry) and Infant's Little Remedies for Fevers (berry and grape) (acetaminophen)||Recall: concerns with quality|
|May 17 & 18||Co Quetiapine, Riva Quetiapine and Sanis Quetiapine (quetiapine fumarate)||Recall: potential contamination with clindamycin|
|May 17||Magnesium Sulfate Injection USP 50% (50 mL vial)||Recall: potential presence of glass particles|
|May 17||Covidien Surgical Stapler Reloads||One lot of non-sterile devices stolen|
|May 16 & 22||Thalomid (thalidomide)||Risk of developing second cancers|
|May 18 to August 18||Foreign products||8 Foreign Product Alerts (FPAs) were posted during this period|
To receive the Newsletter and health product advisories free by e-mail, subscribe to MedEffect e-Notice.
On page 5 of the French July 2013 CARN, Volume 23, Issue 3, under the section "Incidents liés à des instruments médicaux", please note the following error:
"Selon les articles 59 à 61 du Règlement sur les instruments médicaux, les fabricants et les importateurs ont l'obligation de transmettre un rapport concernant tout incident lié à un instrument médical"
should be corrected to:
"Selon les articles 59 à 61 du Règlement sur les instruments médicaux, les fabricants et les importateurs ont l'obligation de transmettre les rapports d'incidents obligatoires".
Canadian Adverse Reaction Newsletter
Marketed Health Products Directorate
Address Locator 0701D
Ottawa ON K1A 0K9
Patricia Carruthers-Czyzewski, BScPhm, MSc (Editor-in-Chief)
Christianne Scott, BPharm, MBA
Jared Cousins, BSP
Hoa Ly, BSc
Emir Al-Khalili, RPh, BScPhm, MSc
Hélène Perrier, RPh, BSc(Pharm)
Nicoleta Hosszu Ungureanu, MSc
We thank the following members of the Expert Advisory Committee on the Vigilance of Health Products for their review of material for this issue: Colleen J. Metge, BSc(Pharm), PhD; Yola Moride, PhD, FISPE; Rishma Walji, ND, PhD; and Darrel Forsythe, RN, BN, ACCN. We also thank Alexandre Pratt, Kristina Klinovski, BSc, and Rachel Mailhot, students in Biomedical Sciences, Occupational Therapy and Biomedical Sciences, respectively, and Sally Pepper, RPh, BScPhm, for their participation in the production of the newsletter.
Your comments are important to us. Let us know what you think.
Reporting Adverse Reactions
Canada Vigilance Program
© 2013 Her Majesty the Queen in Right of Canada. This publication may be reproduced without permission provided the source is fully acknowledged. The use of this publication for advertising purposes is prohibited. Health Canada does not assume liability for the accuracy or authenticity of the information submitted in case reports.
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