Health Product InfoWatch - October 2016
Pub. no 150182
Health Products and Food Branch
Marketed Health Products Directorate
Health Product InfoWatch Editorial Team
- Monthly recap
- New information
- Case report: Green Tea Triple Fat Burner - risk of drug-induced liver injury
- Product monograph update: Aczone (dapsone topical gel 5%)
- Product monograph update: Edarbyclor (azilsartan medoxomil and chlorthalidone)
- Product monograph update: Ferrlecit (sodium ferric gluconate complex in sucrose injection)
- Product monograph update: Intuniv XR (guanfacine)
- Product monograph update: Pomalyst (pomalidomide)
- Product monograph update: Solu-Medrol (methylprednisolone sodium succinate) Act-O-Vial 40 mg
Health products mentioned in this issue
Pharmaceuticals and Biologics
- Aczone (dapsone topical gel 5%)
- Bexsero (multicomponent meningococcal B vaccine [recombinant, adsorbed])
- Edarbyclor (azilsartan medoxomil and chlorthalidone)
- Ferrlecit (sodium ferric gluconate complex in sucrose injection)
- Imipenem and Cilastatin for Injection
- Intuniv XR (guanfacine)
- Pomalyst (pomalidomide)
- Primaxin 500 (imipenem and cilastatin sodium)
- Soliris (eculizumab)
- Solu-Medrol (methylprednisolone sodium succinate) Act-O-Vial 40 mg
- Zarontin (ethosuximide)
Natural Health Products
This monthly publication is intended primarily for healthcare professionals and includes information on pharmaceuticals, biologics, medical devices and natural health products. It provides a summary of key health product safety information published in the previous month by Health Canada, as well as a selection of new health product safety information meant to raise awareness. New information contained in this issue is not comprehensive but rather represents a selection of clinically relevant items warranting enhanced dissemination.
Reporting Adverse Reactions
Canada Vigilance Program
For more information on how to report an adverse reaction, visit the Adverse Reaction and Medical Device Problem Reporting page.
New requirements for over-the-counter acetaminophen product labels
Health Canada has recently revised the Guidance Document - Acetaminophen Labelling Standard to ensure that the labels include:
- clearer instructions on packages highlighting the importance of:
- using the lowest effective dose
- not exceeding the recommended daily maximum (4,000 mg for adults) in a 24-hour period
- using these products for no more than 5 days for pain or 3 days for fever
- not mixing them with alcohol if drinking 3 or more drinks in a day
- the statement "contains acetaminophen" in bold, red text in the top right corner on the front of the package to make it easier for consumers to know that a product contains this drug
- a new Drug Facts table for packages to provide more uniform, easier to find, read and understand product instructions, warnings and other safety information
The revised acetaminophen labelling standard also recommends that all children's liquid products include a calibrated dosing device.
The label changes apply immediately to new products that will be introduced into the Canadian market. The labels of the products already on the market are expected to be updated within 18 months.
Health Canada also issued a Notice to industry advising of a policy to limit the amount of acetaminophen in prescription combination products to no more than 325 mg.
Know your dose
The maximum recommended dose of acetaminophen for adults is 4,000 mg daily (the same as 8 extra strength tablets of 500 mg or 12 regular strength tablets of 325 mg). Taking more than the recommended dose can lead to severe or even fatal liver damage.
If you are looking for consumer resources, Health Canada has prepared the following:
Monthly recap of health product safety information
Health Canada has released an updated Labelling Standard for over-the-counter acetaminophen products to help consumers use these products more safely. Product packages will include clearer instructions and stronger warnings to help reduce the potential for liver damage. Health Canada also issued a Notice to industry advising of a policy to limit the amount of acetaminophen in prescription combination products to no more than 325 mg.
This safety review evaluated the risk of respiratory depression associated with gabapentin. Health Canada's review concluded that there is evidence of a link between the use of gabapentin, in general, and the risk of respiratory depression. Health Canada will work with manufacturers to update the Canadian product monographs to further warn about this risk.
Imipenem and Cilastatin for Injection
The multi-vial carton of Hospira's Imipenem and Cilastatin for Injection, 500 mg/500 mg, has incorrect information regarding the final diluted concentration on the outer side panel. It indicates the diluted concentration is 2.5 mg/mL instead of 5 mg/mL (when prepared as per the instructions in the package insert). Healthcare professionals should consult the package insert for the proper reconstitution and dilution instructions.
Health Canada reminded Canadians of the serious risk of birth defects associated with taking isotretinoin while pregnant. Health professionals and women who are using, or considering using this drug are reminded of the importance of not getting pregnant while taking this treatment.
Primaxin 500 (imipenem and cilastatin sodium)
The label on the outer package of Primaxin 500 (imipenem and cilastatin sodium) contains incorrect information regarding the final diluted concentration after reconstitution. It indicates the diluted concentration is 2.5 mg/mL instead of 5 mg/mL (when prepared as per the instructions in the package insert). Healthcare professionals are directed to consult the package insert or the Canadian product monograph for the proper reconstitution and dilution instructions.
"Rapidcuts Shredded" capsules
All lots of Allmax-brand "Rapidcuts Shredded" capsules (NPN 80041658) were recalled by Healthy Body Services Inc., as a precaution. Two lots were found to contain an undeclared prescription drug (yohimbine hydrochloride).
Sage brand disposable skin cloths
Some lots of various Sage brand single-use, pre-moistened disposable cloths used for cleansing or protecting skin were recalled due to possible contamination with the bacteria Burkholderia cepacia (B.cepacia). The affected cloths are used mainly in healthcare settings such as hospitals, but are also sold nationwide at retail pharmacies and medical supply stores.
Soliris (eculizumab) and Bexsero (multicomponent meningococcal B vaccine [recombinant, adsorbed])
This safety review evaluated the increased risk of hemolysis and low hemoglobin when patients receiving Soliris (eculizumab) were vaccinated with Bexsero (multicomponent meningococcal B vaccine [recombinant, adsorbed]). Health Canada's review concluded that there was an increased risk of low hemoglobin or hemolysis when patients already receiving Soliris were vaccinated with Bexsero. The manufacturer has updated the Canadian product monograph for Soliris to include the risk of hemolysis with vaccines against Neisseria meningitidis and recommendations on timing of vaccination to minimize this risk.
Unauthorized health product "Black Orange"
Health Canada advised Canadians that an unauthorized product, "Black Orange", was seized from Keebo Sports Supplements in Regina, Saskatchewan. The product is sold as a pre-workout stimulant and is labelled to contain ingredients that can pose serious health risks (yohimbine hydrochloride, and the combination of ephedrine and caffeine).
Unauthorized health products
Health Canada advised Canadians that 5 unauthorized products promoted as workout or weight loss supplements were seized from Keebo Sports Supplements in Winnipeg, Manitoba. The products are labelled to contain various prescription and other drug substances that may pose serious risks to the health of Canadians.
Erfa Canada 2012 Inc. and Health Canada have received reports of broken or leaking Zarontin (ethosuximide) soft gel capsules, including reports of patients experiencing a higher frequency of seizures after taking capsules that appeared cloudy, broken, leaking, sticky or clumping together. Pharmacists are reminded to verify the content of each bottle to make sure that there are no defective capsules, and to store the product in a controlled temperature and humidity environment. Health Canada has also communicated this information to Canadians.
New health product safety information
The following topics have been selected to raise awareness and, in some cases, to stimulate reporting of similar adverse reactions.
Recent Canadian or international cases are selected based on their seriousness, frequency of occurrence or the fact that the reactions are unexpected. Case Reports are considered suspicions and are presented to stimulate reporting of similar suspected adverse events.
Green Tea Triple Fat Burner and risk of drug-induced liver injury
Health Canada received a report of a 17-year-old woman who developed liver and kidney injury after using Green Tea Triple Fat Burner. She took the product for 5 days (1 capsule twice daily) for weight management. Initially, she presented to the emergency department (ED) with acute abdominal pain, nausea and excessive vomiting and was given intravenous rehydration and an antiemetic. She returned to the ED the following day and received additional intravenous rehydration. Following discharge from the ED, her symptoms persisted at home and her condition continued to deteriorate. Two days later, she was brought to another ED. Her blood work showed significant liver enzyme increases [e.g., alanine aminotransferase was 64 times the upper limit of normal (ULN)] and significant renal function abnormality (serum creatinine was elevated at 10 times the ULN). She was hospitalized, treated with hemodialysis and underwent additional investigations.
This young woman was previously healthy and stated that she did not consume alcohol or illicit drugs. Her past medical history, including concomitant health products, did not reveal any risk factors for acute liver failure and acute kidney injury.
During her hospitalization, autoimmune and infectious causes of hepatitis were ruled out by negative laboratory testing. Her drug screens were negative. Pathology results for the renal biopsy showed acute tubular necrosis (ATN). Qualitative product testing by the manufacturer and Health Canada laboratories did not identify any known adulterants or contaminants. On discharge from the hospital, the patient's liver and kidney functions returned to baseline. She was prescribed an antihypertensive medication that had been initiated in hospital secondary to the kidney disorder.
Green Tea Triple Fat Burner is a licensed (NPN 80037935), multi-ingredient, natural health product (NHP) authorized as an antioxidant supplement and as an aid in weight management for use in adults. It contains green tea extract (Camellia sinensis), bitter orange (Citrus aurantium), 1,3,7-trimethylxanthine (caffeine) and various vitamins (vitamins B3, B6, B12; vitamin C; vitamin E; and folic acid).
Potential drug-induced liver injury (DILI) has been described with the use of green tea extract products.Footnote a Footnote b Footnote c The product's label, as per Health Canada's Green Tea Extract monograph,Footnote d includes a cautionary statement advising consumers to consult a healthcare professional prior to use if they have a liver disorder or develop symptoms of liver trouble (such as abdominal pain, dark urine, or jaundice). None of the main medicinal ingredients in the Green Tea Triple Fat Burner are known to be nephrotoxic.Footnote e The acute renal injury observed in hospital and the subsequent pathologic finding of ATN was likely caused by the profound hypovolemic dehydration secondary to the DILI.
Green tea extract, bitter orange and caffeine are commonly present in NHPs promoted as weight management supplements.Footnote f NHP-weight management products are regulated as low risk health products and are intended to be used in conjunction with caloric reduction and physical activity. In a recent study, it was found that weight loss products available as dietary supplements in the United States were a common cause of adverse event-related ED visits.Footnote g Healthcare professionals are encouraged to remind patients to disclose the use of all health products, including non-prescription drugs and NHPs.
Healthcare professionals are encouraged to report to Health Canada any adverse reactions suspected of being associated with the use of NHPs used for weight management.
Product monograph updates
The following safety labelling updates, which were recently made to the Canadian product monograph, have been selected for your awareness. A complete list of safety labelling updates for brand name pharmaceutical drugs is available on Health Canada's Web site.
Aczone (dapsone topical gel 5%)
The risk of methemoglobinemia associated with the use of Aczone (dapsone topical gel 5%) for the treatment of acne vulgaris has been included in the Warnings and Precautions, Post-Market Adverse Drug Reactions and Drug Interactions sections of the Canadian product monograph for Aczone.
- Cases of methemoglobinemia with hospitalization have been reported with dapsone gel treatment.
- Dapsone gel should be avoided in patients with glucose-6-phosphate dehydrogenase deficiency or with congenital or idiopathic methemoglobinemia. These patients are more susceptible to drug-induced methemoglobinemia.
- Initial signs and symptoms are characterized by a slate grey cyanosis seen, for example, in buccal mucous membranes, lips, and nail beds.
- Patients should discontinue dapsone gel and seek immediate medical attention in the event of cyanosis.
- Dapsone can also cause elevated methemoglobin levels when used in conjunction with methemoglobin-inducing agents such as sulfonamides or acetaminophen.
Edarbyclor (azilsartan medoxomil and chlorthalidone)
Edarbyclor (azilsartan medoxomil and chlorthalidone) is now contraindicated in patients with refractory hyponatremia. This information has been included in the Contraindications section of the Canadian product monograph (CPM) for Edarbyclor. Additional information on hyponatremia has also been added to the Warnings and Precautions and Dosage and Administration sections of the CPM.
- Edarbyclor is contraindicated in patients with refractory hyponatremia.
- Edarbyclor may cause hyponatremia. Monitor serum electrolytes periodically.
- Correct volume and/or salt depletion prior to administration.
Ferrlecit (sodium ferric gluconate complex in sucrose injection)
The risk of generalized seizures has been included in the Warnings and Precautions and Adverse Reactions sections of the Canadian product monograph for Ferrlecit (sodium ferric gluconate complex in sucrose injection).
- There have been post-marketing reports of seizures in patients receiving Ferrlecit.
- Ferrlecit should be discontinued in patients who experience seizures suspected to be related to treatment.
Intuniv XR (guanfacine)
The risk of hypertensive encephalopathy upon abrupt discontinuation of Intuniv XR (guanfacine) has been included in the Warnings and Precautions section of the Canadian product monograph.
- Patients/caregivers should be instructed not to discontinue Intuniv XR without consulting their physician since elevations in blood pressure and heart rate above original baseline (i.e., rebound) have been reported. In very rare instances, this increase in blood pressure may result in hypertensive encephalopathy.
- To minimize the risk of an increase in blood pressure upon discontinuation, the total daily dose should be tapered by no more than 1 mg every 3 to 7 days. Monitor blood pressure and pulse when reducing the dose or discontinuing the drug.
- Patients/caregivers should be informed about the risk of persistent hypertension following discontinuation, how to identify signs and symptoms (e.g., headaches, feeling confused, nervousness, agitation, and tremors) and to seek immediate medical care.
The risk of reactivation of hepatitis B has been included in the Warnings and Precautions and Adverse Drug Reactions sections of the Canadian product monograph for Pomalyst (pomalidomide).
- Reactivation of hepatitis B, including fatal cases, has been reported rarely in patients receiving Pomalyst in combination with dexamethasone who have previously been infected with the hepatitis B virus (HBV). Some of these cases have progressed to acute hepatic failure, resulting in discontinuation of Pomalyst.
- Caution should be exercised when Pomalyst in combination with dexamethasone is used in patients previously infected with HBV. These patients should be closely monitored for signs and symptoms of active HBV infection throughout therapy.
Solu-Medrol (methylprednisolone sodium succinate) 40 mg and the risk of hypersensitivity in individuals with cow's milk allergy
Solu-Medrol is an intravenous steroid preparation of methylprednisolone sodium succinate.Footnote 1 Intravenous administration of Solu-Medrol is indicated in situations in which a rapid and intense hormonal effect is required. These include the treatment of various conditions such as allergic reactions or inflammation. In some conditions, it may be used as adjunctive therapy. In Canada, Solu-Medrol is available in 500 mg or 1 g Plain Vials or in 40 mg, 125 mg, 500 mg and 1 g Act-O-Vials.Footnote 1 The 40 mg Act-O-Vial formulation contains lactose hydrous as a non-medicinal ingredient (excipient). The lactose hydrous is derived from cow's milk and may contain trace amounts of protein. The other formulations of Solu-Medrol available in Canada do not contain lactose hydrous.
International cases of hypersensitivity to methylprednisolone in patients with a milk allergy have been reported to the market authorization holder,Footnote 2 including cases that have been described in the medical literature.Footnote 3 Footnote 4 Footnote 5 Footnote 6 These published reports describe 11 cases of children with a known cow's milk allergy who were treated for asthma exacerbation or urticaria, and who experienced serious hypersensitivity reactions to intravenous methylprednisolone sodium succinate. Patients' ages ranged from 3 to 15 years, with a median age of 6.5 years.
Certain children may be highly sensitive if exposed to even very low levels of milk protein.Footnote 7 Individuals at a greater risk for severe allergic reactions include those with asthma and those with elevated levels of specific immunoglobulin E to the protein present in cow's milk.Footnote 8
Solu-Medrol Act-O-Vial 40 mg formulation is now contraindicated in patients with a known hypersensitivity to cow's milk or its components or other dairy products. This information has been included in the Contraindications section of the Canadian product monograph.
Key messages for healthcare professionals:
- Solu-Medrol is contraindicated in patients with known hypersensitivity to the ingredients.
- Solu-Medrol 40 mg Act-O-Vials include lactose produced from cow's milk. This dosage form is therefore contraindicated in patients with a known hypersensitivity to cow's milk or its components or other dairy products because it may contain trace amounts of milk ingredients.
Healthcare professionals are encouraged to check for milk allergies prior to the administration of Solu-Medrol 40 mg Act-O-Vials and to report any suspected cases to Health Canada.
Did you know?
Solu-Medrol Act-O-Vial consists of a two-compartment vial containing sterile powder in the lower compartment and clear diluent in the upper compartment. Pressing down on the plastic activator forces diluent into the lower compartment.
- MedEffect™ Canada
- Recalls and Safety Alerts Database
- Summary Safety Reviews
- New Safety Reviews
- Canada Vigilance Adverse Reaction Online Database
- Drug Product Database
- Medical Devices Active Licence Listing
- Licensed Natural Health Products Database
- The Drug and Health Product Register
- Canadian Drug Shortage Database
Your comments are important to us. Let us know what you think by reaching us at InfoWatch_InfoVigilance@hc-sc.gc.ca
Marketed Health Products Directorate
Address Locator 1912C
Ottawa ON K1A 0K9
©2016 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.
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.
Due to time constraints relating to the production of this publication, information published may not reflect the most current information.
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