Home > Drugs & Health Products > MedEffect Canada > Canadian Adverse Reaction Newsletter (CARN)

Contact
MHPD-DPSC

This document is also available in PDF format
[carn-bcei_v17n3_e.pdf]
Pages: 4, Size: 571 K, Date: 2007-07-03

Canadian Adverse Reaction Newsletter

Volume 17 . Issue 3 . July 2007

Health Products and Food Branch
Marketed Health Products Directorate

In this Issue:
Benadryl Total: medication incident and stroke
Rosiglitazone and parotid gland enlargement: update
Adverse reaction reporting: education modules
Case presentation: Norethindrone and decreased breast milk production
Summary of advisories

Scope
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 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
Contact Health Canada or a Regional AR Monitoring Office free of charge
Phone: 866-234-2345
Fax: 866-678-6789

Click here for the Adverse Reaction Reporting Form

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.

Benadryl Total: medication incident and stroke

In October 2006, Health Canada received a report of a suspected adverse reaction involving a medication incident related to product labelling and packaging.

A 64-year-old woman consulted her family physician after experiencing an allergic reaction. She was given epinephrine (0.3mg subcutaneously) and was advised to take Benadryl (diphenhydramine) 3 times daily for 3 days. Inadvertently, the patient bought Benadryl Total (diphenhydramine, pseudoephedrine and acetaminophen). She was unaware that this product contained pseudoephedrine and acetaminophen. After the second day of use, the patient experienced a stroke that affected her vision and speech. No other risk factors for stroke were reported other than age and use of pseudoephedrine.

Health products with sound-alike names and look-alike packaging and labelling can cause confusion for both consumers and health professionals and contribute to inappropriate product selection (Fig.1). Such errors may result in serious patient harm.^1,2 Health professionals are reminded that product line extensions can sometimes lead to confusion for their patients in choosing the intended product. Patients are encouraged to always read the product's label carefully and to consult their pharmacist whenever they select self-care products.

Michel Trottier, BScPhm, RPEBC, RPh, Health Canada

Figure 1: Packages of Benadryl (left) and Benadryl Total (right)
Fig. 1: Packages of Benadryl (left) and Benadryl Total (right).

References

Cohen MR. The role of drug packaging and labelling in medication errors. In: Cohen MR, editor. Medication errors. Washington (DC): American Pharmaceutical Association; 1999. p. 13.1.
Kenagy JW, Stein GC. Naming, labelling and packaging of pharmaceuticals. Am J Health Syst Pharm 2001;58(21):2033-41. [ PubMed]

Rosiglitazone and parotid gland enlargement: update

The thiazolidinedione rosiglitazone (Avandia) is an insulin sensitizer that is indicated for use either as monotherapy or in combination with metformin or a sulfonylurea in patients whose type 2 diabetes is inadequately controlled by diet and exercise alone.¹ In the January 2006 issue of the Canadian Adverse Reaction Newsletter, it was reported that Health Canada had received 5 domestic reports of parotid gland enlargement suspected of being associated with the use of rosiglitazone.² As of Dec. 31, 2006, 1 additional domestic report was received. All 6 cases involved patients who experienced visibly evident enlargement of one or both parotid glands while taking the drug. In 4 cases the adverse reaction was alleviated or resolved when the rosiglitazone therapy was stopped; in the remaining 2 cases this information was not provided.

The parotid glands are the largest of the salivary glands and are located in the facial subcutaneous tissue, over the posterior aspect of each mandibular ramus. There is considerable variation in the size of parotid glands of healthy individuals,³ but on clinical examination they are not visible and are not readily palpable. Nontender parotid gland enlargement has been associated with a number of medical disorders (e.g., diabetes mellitus, obesity and hyperlipidemia) and medications (e.g., iodides, phenylbutazone and propylthiouracil).^4, ^5, ^6, ⁷

Rosiglitazone is a highly selective and potent agonist for the peroxisome proliferator-activated receptor gamma (PPARγ).¹ Although rosiglitazone appears to be associated with some effects that are not mediated by PPARγ, binding of rosiglitazone to PPARγ seems to be an important component of its mechanism of action.⁸ In addition, PPARγ-responsive genes participate in the regulation of fatty acid metabolism and in the maturation of preadipocytes, predominantly of subcutaneous origin.¹ Although PPARγ is also implicated in various functions in the parotid glands,^9, ^10, ¹¹ the activity of rosiglitazone in the parotid glands is not fully understood. Further studies are required to confirm whether the drug causes noticeable parotid gland enlargement by acting directly on the parotid tissue through its agonist activity on PPARγ, or indirectly through induction of weight gain or elevation of serum lipid levels, or by another mechanism.

Parotid gland enlargement may be due to diabetes alone and may become clinically evident during treatment with rosiglitazone. When a diabetic patient taking rosiglitazone experiences nontender parotid gland enlargement, the drug may be considered as a possible cause.

Health professionals are encouraged to report any cases of parotid gland enlargement in patients receiving rosiglitazone.

Bruce Eveleigh, MD, Health Canada

References

Avandia (rosiglitazone) [product monograph]. Mississauga (ON): GlaxoSmithKline Inc.; 2006.
Health Canada. Rosiglitazone (Avandia): suspected association with parotid gland enlargement. Can Advers Reaction Newsl 2006;16(1):3.
Medbery R, Yousem DM, Needham MF, et al. Variation in parotid gland size, configuration, and anatomic relations. Radiother Oncol 2000;54(1):87-9. [ PubMed]
Daniels TE. Diseases of the mouth and salivary glands. In: Goldman L, Ausiello D editors. Cecil textbook of medicine. 22nd edition. Philadelphia: Saunders; 2004. p. 2426-32.
Russotto SB. Asymptomatic parotid gland enlargement in diabetes mellitus. Oral Surg Oral Med Oral Pathol 1981;52(6):594-8. [ PubMed]
Gill G. Metabolic and endocrine influences on the salivary glands. Otolaryngol Clin North Am 1977;10(2):363-9. [ PubMed]
Infectious diseases, Mumps. In: Porter RS, Kaplan JL, editors. The Merck manual online. Available: www.merck.com/mmpe/index.html (accessed 2007 Apr 18).
Wagstaff AJ, Goa KL. Rosiglitazone: a review of its use in the management of type 2 diabetes mellitus. Drugs 2002;62(12):1805-37. [ PubMed]
Mukunyadzi P, Ai L, Portilla D, et al. Expression of peroxisome proliferator-activated receptor gamma in salivary duct carcinoma: immunohistochemical analysis of 15 cases. Mod Pathol 2003;16(12):1218-23. [ PubMed]
Slomiany BL, Slomiany A. Activation of peroxisome proliferator-activated receptor gamma impedes Porphyromonas gingivalis lipopolysaccharide interference with salivary mucin synthesis through phosphatidylinositol 3-kinase/erk pathway. J Physiol Pharmacol 2003;54(1):3-15. [ PubMed]
Begum NM, Nakashiro K, Kawamata H, et al. Expression of peroxisome proliferator-activated receptor gamma and the growth inhibitory effect of its synthetic ligands in human salivary gland cancer cell lines. Int J Oncol 2002;20(3):599-605. [ PubMed]

Adverse reaction reporting: education modules

Health Canada has developed 2 new education modules on adverse reaction (AR) reporting of marketed health products (pharmaceuticals, biologics [e.g., fractionated blood products, and therapeutic and diagnostic vaccines], natural health products and radiopharmaceuticals). In addition to the existing module for naturopathic doctors, modules for other health professionals and for consumers are now available on the MedEffect Canada Web site.

The online module Health Professional Reporting of Adverse (Drug) Reactions provides an interactive tool to help health professionals report suspected adverse reactions to Health Canada. The online module for consumers, Reporting Side Effects from Your Medicine: What You Need to Know, comes with a guidebook and provides comprehensive learning tools to help consumers and patients report side effects, either to their health professional or to Health Canada.

MedEffect Canada

MedEffect Canada is Health Canada's resource centre for Canadians to obtain health product safety information and to report adverse reactions.

MedEffect Canada's Web site provides health professionals and the general public centralized access to:

Recent health product safety information, such as health professional and public communications, warnings, advisories and recalls
MedEffect e-Notice subscription
Canadian Adverse Reaction Newsletter
The Adverse Reaction Database, which contains information on suspected adverse reactions to Canadian marketed health products reported to Health Canada
Adverse reaction reporting forms and guidance documents
A learning centre with education modules on how to report adverse reactions
Other relevant information about postmarket monitoring of adverse reactions

Case presentation

Recent Canadian cases are selected based on their seriousness, frequency of occurrence or the fact that the reactions are unexpected. Case presentations are considered suspicions and are presented to stimulate reporting of similar suspected adverse reactions.

Norethindrone (Micronor): suspected association with decreased breast milk production

In Canada norethindrone (Micronor), a progestin-only oral contraceptive, has been marketed since 1972. From the date of marketing to Apr. 20, 2007, Health Canada received 13 domestic reports of decreased puerperal lactation (breast milk production) suspected of being associated with the use of norethindrone. Some reports noted that the infants had lost weight or were not gaining weight. The cases involved postpartum women aged 22-35 years (median 30 years). The age was not specified in 2 cases. Norethindrone therapy was started more than 6 weeks after delivery in 9 cases and less than 6 weeks after delivery in 3 cases; this information was not provided in 1 case. The reaction onset was reported in 9 of the cases and ranged from 3 to 16 days after the start of the norethindrone therapy. Upon withdrawal of the norethindrone therapy, 10 women experienced improved milk production, 3 of whom had used health products to improve lactation (domperidone, fenugreek and blessed thistle).

How to report an adverse reaction?

There are multiple ways to report an adverse reaction (AR) to Health Canada. To report an AR, go to the AR Reporting page on the MedEffect Canada Web site*.

By submitting a suspected AR report, you are contributing to the ongoing collection of safety and effectiveness information that occurs once health products are marketed.

*The Adverse Reaction Reporting Form is also available in the CPS (Canadian Compendium of Pharmaceuticals and Specialties).

Summary of health professional and consumer advisories posted by Health Canada from February 15, 2007 to May 14, 2007

Date	Product	Subject and type
May 11	Depakene & ratio-Valproic	Recall of two Valproic acid drugs, Depakene 500 mg and ratio-Valproic 500 mg -- consumer information
May 3	Urat Madu	Foreign Product Alert - Urat Madu -- consumer information
Apr 24	FiberChoice plus Multivitamins	Foreign Product Alert - FiberChoice plus Multivitamins -- consumer information
Apr 19 & 16	Aranesp and Eprex	Important safety information and new prescribing information for the erythropoiesis-stimulating agents (ESAs), Aranesp (darbepoietin alfa) and Eprex (epoetin alfa) -- consumer information and health professional communication -- Amgen Canada and Janssen-Ortho, Inc.
Apr 18	Actos	Association between Long-Term Treatment with Actos (pioglitazone hydrochloride) Tablets for Type 2 Diabetes Mellitus and Fractures in Women -- consumer information and health professional communication -- Eli Lilly Canada Inc.
Apr 18	Herbal sleep supplement	Herbal sleep supplement found to contain habit-forming drug -- consumer information
Apr 16	Defibrillators	Urgent Medical Device Information - Subset of Implantable Cardiac Defibrillators and Cardiac Resynchronization Therapy Defibrillators -- health professional communication -- Boston Scientific
Apr 13	Lexscl Fat Rapid Loss	Foreign Product Alert - Lexscl Fat Rapid Loss -- consumer information
Apr 13	V.MAX, Rhino Max (Rhino V Max)	Foreign Product Alert - V.MAX, Rhino Max (Rhino V Max) -- consumer information
Apr 13	Lanmei Keili Ji	Foreign Product Alert - Lanmei Keili Ji -- consumer information
Apr 13	Health Products for Weight Loss	Health Canada - It's Your Health - The Safe Use of Health Products for Weight Loss -- consumer information
Apr 10	Iressa	Important Safety Information on Iressa (gefitinib) -- consumer information -- AstraZeneca Canada Inc.
Apr 4	Salivart Oral Moisturizer	Certain lots of Salivart Oral Moisturizer contaminated with mould or yeast -- consumer information
Mar 31	Permax	Health Canada reviewing link between Parkinson's drug Permax and heart valve conditions -- consumer information
Mar 30	Zelnorm	Voluntary suspension of sales of Zelnorm due to cardiovascular ischemic events -- consumer information and health professional communication -- Novartis Pharmaceuticals Canada Inc.
Mar 29	Vigorect Oral Gel Shooter	Health Canada warns Canadians not to use the sexual enhancer Vigorect Oral Gel Shooter due to potential health risks -- consumer information
Mar 27	Trasylol	Association of Trasylol (aprotinin) with hypersensitivity reactions and renal dysfunction -- consumer information and notice to hospitals -- Bayer Inc.
Mar 27	Tamiflu	Changes to Canadian labelling of Tamiflu -- consumer information
Mar 24	XOX For Men	Health Canada warns Canadians not to use the sexual enhancer XOX For Men, due to potential health risks -- consumer information
Mar 16	Patient Restraints	Important Safety Information on the Use of Waist and Torso Patient Restraints -- notice to hospitals
Mar 14	MIAOZI Slimming Capsules	Health Canada advises consumers not to use MIAOZI Slimming Capsules due to potential health risks -- consumer information
Mar 13 & 9	Gadolinium- containing contrast agents	Association of gadolinium-containing contrast agents and Nephrogenic Systemic Fibrosis /Nephrogenic Fibrosing Dermopathy (NSF/NFD) -- consumer information and notice to hospitals
Mar 12 & 7	Omniscan	Association of Omniscan (Gadodiamide) and Nephrogenic Systemic Fibrosis/Nephrogenic Fibrosing Dermopathy (NSF/NFD) -- consumer information and health professional communication -- GE Healthcare Canada
Mar 12	ReNu MultiPlus	Health Canada warns consumers not to use certain lots of ReNu MultiPlus contact lens solution due to potential health risk -- consumer information
Mar 9	Exjade	Association of acute renal failure (severe kidney problems) and reports of cytopenias (low blood cell counts) with Exjade (deferasirox) -- consumer information and health professional communication -- Novartis Pharmaceuticals Canada Inc.
Mar 8 & 7	Medical equipment	Important information concerning unpredictable events in medical equipment due to Daylight Savings Time change -- health professional communication -- consumer information update and United States Advice for Patients
Mar 5	Waist Restraint	Important Safety Information on Pinel Rotating Waist Restraint -- notice to hospitals -- Pinel Medical Inc.
Feb 28	EMPowerPlus	Reports of adverse reactions in patients with serious mental health conditions suspected in association with use of prescription medications and EMPowerPlus -- consumer information
Feb 28 & 23	Rosiglitazone- containing products	Important safety information on rosiglitazone-containing products: Avandia, Avandamet and Avandaryl -- consumer information and health professional communication -- GlaxoSmithKline Inc. (GSK)
Feb 27	Confirm Clearly Smart Pregnancy Test	Association of Confirm Clearly Smart Pregnancy Test and Refills with false-positive results -- consumer information -- Durex Canada, Division of SSL Canada Inc.
Feb 23	Sleepees	Health Canada advises consumers not to use herbal sleep supplement Sleepees which contains a habit-forming drug -- consumer information
Feb 21	Baraclude	Information Regarding Baraclude (entecavir) -- consumer information and health professional communication -- Bristol-Myers Squibb Canada
Feb 16	External Defibrillators	Urgent Medical Device Safety Information and Corrective Action - DDU-100 Series Automatic External Defibrillators -- consumer information and health professional communication -- Defibtech, LLC

To receive the Newsletter and health product Advisories free by email, join Health Canada's MedEffect e-Notice.

Report adverse reactions

Reporting information about adverse reactions may contribute to:

The identification of previously unrecognized rare or serious adverse reactions
Changes in product safety information, or other regulatory actions
International data regarding benefits, risks and effectiveness of health products
Improved health product safety knowledge that benefits all Canadians

Canadian Adverse Reaction Newsletter

Marketed Health Products Directorate
AL 0701C
Ottawa ON K1A 0K9
Tel 613-954-6522
Fax 613-952-7738

Health professionals/consumers report toll free:
Tel 866-234-2345
Fax 866-678-6789

Editorial Staff
Ann Sztuke-Fournier, BPharm (Editor-in-Chief)
Ilhemme Djelouah, BScPhm, DIS, AFSA, Medical Biology (University of Paris V)
Gilbert Roy, BPharm
Michel Trottier, BScPhm, RPEBC, RPh
Jared Cousins, BSP

Acknowledgements
Expert Advisory Committee on Pharmacovigilance, Regional AR Monitoring Offices and Health Canada staff.

Suggestions?
Your comments are important to us. Let us know what you think.

Copyright
Her Majesty the Queen in Right of Canada, 2007. 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.

ISSN 1499-9447; Cat no H42-4/1-17-3E

USPS periodical postage paid at Champlain, NY, and additional locations.

Aussi disponible en français.

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.


	Date Modified: 2007-06-28		Important Notices