1. Canada: Diclofenac - Update to Heart and Stroke Related Safety Information and Decrease in the Maximum Recommended Daily Dose for Tablets and Suppositories
Novartis Pharma Canada Inc. (“Novartis Canada”) and Pfizer Canada Inc. (“Pfizer Canada”), in collaboration with Health Canada, informed the public and healthcare professionals of revisions made to the Product Monographs for all diclofenac-containing systemic medicines (tablets and suppositories) including VOLTAREN/VOLTAREN SR (diclofenac sodium), VOLTAREN RAPIDE (diclofenac potassium), ARTHROTEC (diclofenac sodium/misoprostol). This safety update does not refer to topical formulations of diclofenac, such as gel or eye drops.
Health Canada is currently updating the labelling of all systemic formulations of diclofenac-containing medicines as follows:
1. Diclofenac (tablets and suppositories), particularly at higher doses (150 mg per day), is associated with an increased risk of serious cardiovascular adverse events (such as myocardial infarction, stroke or thrombotic events which can be fatal) that is comparable to COX-2 inhibitors. Evidence suggests that the risk may increase with the dose and duration of use.
2. The maximum recommended daily dose of systemic diclofenac has been reduced from 150 mg per day to 100 mg per day for all indications, excluding VOLTAREN RAPIDE which allows for a 200 mg dose only on the first day of treatment for dysmenorrhea. To minimize the potential risk for an adverse cardiovascular event, the lowest effective dose should be used for the shortest possible duration.
3. Treatment with diclofenac is not recommended in patients with pre-existing cardiovascular disease (CVD) or cerebrovascular disease, or presenting risk factors for CVD. For these patients, treatment options other than non-steroidal anti-inflammatory drugs (NSAIDs), particularly COX-2 inhibitors and diclofenac, should be considered first.
Meta-analyses of randomized clinical trials comparing several different NSAIDs suggest that diclofenac systemic formulations, particularly at high doses, is associated with an increased risk of cardiovascular adverse events that is comparable to COX-2 inhibitors. Large population-based observational studies conducted in the general population also support these findings. From January 1, 2008 to December 31, 2012 (approximately 353 X 1000 patient treatment-years), Health Canada received 39 reports of serious cardiovascular events potentially associated with systemic diclofenac use. One of these cases had a fatal outcome. Patients are advised to contact their health care provider if their current daily dose is more than 100 mg per day.
Please refer to the following website in Health Canada for details:http://www.healthycanadians.gc.ca/recall-alert-rappel-avis/hc-sc/../41701a-eng.php
2. Australia: Safety advisory: Non-steroidal anti-inflammatory drugs and diclofenac reviews
Consumers and health professionals are advised that the Therapeutic Goods Administration (TGA) has completed a review of the cardiovascular risks associated with the use of the non-steroidal anti-inflammatory drugs (NSAIDs) diclofenac, naproxen, ibuprofen, celecoxib, etoricoxib, indomethacin, meloxicam and piroxicam. In addition to this review, the TGA has also completed a full safety review of diclofenac.
The reviews involved evaluation of relevant medical literature, assessing input from sponsors and industry stakeholders, and obtaining expert advice from the Advisory Committee on the Safety of Medicines. The full NSAIDs and diclofenac reviews are now available on the TGA website. In summary:-
1. While use of NSAIDs at prescription-only dosages was already known to increase the risk of high blood pressure, heart failure, heart attack and stroke, the TGA NSAIDs review found that these risks also applied to OTC forms of diclofenac, naproxen and ibuprofen.
2. Similarly, the risk of hepatotoxicity (commonly known as liver damage) in relation to use of prescription diclofenac was known, but the TGA's safety review of that medicine found that OTC diclofenac products also carried this risk.
The TGA reviews found that there is a need to raise awareness among consumers and health professionals of the cardiovascular risks associated with NSAIDs and the additional hepatotoxicity risks for diclofenac, including OTC versions of these medicines. The TGA reviews have found that use of OTC NSAIDs is safe when they are used according to the recommended doses for short durations, as instructed on the label. However, inappropriate use or overuse of these medicines can pose a significant health risk. The product labelling for OTC diclofenac, naproxen and ibuprofen does not carry adequate warnings regarding the risks of adverse cardiovascular events or, in the case of diclofenac, hepatotoxicity.
The TGA has developed four options to reduce the risks associated with OTC NSAIDs and is currently undertaking public consultation regarding these alternatives. Health professionals are reminded of the cardiovascular risks associated with treatment with NSAIDs and the additional risk of hepatotoxicity with diclofenac. Avoid using prescription NSAIDs in patients who have previously had myocardial infarction, angina, cardiac failure, hypovolemia, significant peripheral vascular disease or pre-existing significant renal/liver dysfunction. Use these medicines with caution in patients with risks factors for cardiovascular disease, undertaking individual assessment of each patient to ensure the benefits outweigh the risks. Consider advising patients who have risk factors for cardiovascular disease of the increased risks of using NSAIDs, including OTC products, and educating them regarding the signs and symptoms of serious cardiovascular toxicity. Instruct them to seek medical attention immediately if they experience any.
Please refer to the following website in TGA for details:http://www.tga.gov.au/safety/alerts-medicine-nsaid-diclofenac-141007.htm
In Hong Kong, there are 603 registered pharmaceutical products containing NSAIDs, including 247 diclofenac, and 356 other NSAIDs products of ibuprofen, naproxen, indomethacin, mefenamic acid, piroxicam, celecoxib, parecoxib and etoricoxib.
Safety alerts regarding diclofenac and other NSAIDs associated with cardiovascular risks had been issued by various health authorities and were posted on the Drug Office website. Letters to inform local healthcare professionals to draw their attention on the safety of NSAIDs associated with cardiovascular risks, and new warnings on the use of high dose diclofenac for more than four weeks in selected patients were issued and were posted on the Drug Office website on 30 September 2011 and 3 March 2014 respectively.
The above 2 safety issues were discussed by the Registration Committee of the Pharmacy and Poisons Board (the Committee) in February 2013 and May 2014 respectively. In February 2013, the Committee decided that NSAIDs-containing products other than external preparations should include new warnings on cardiovascular risks. In May 2014, the Committee further discussed the safety with high dose of diclofenac and concluded that the Department of Health (DH) would remain vigilant on new announcements related to diclofenac by other health authorities.
So far, DH has received 10 local adverse drug reactions reports concerning NSAIDs, but none of them was related to cardiovascular or hepatotoxicity adverse events. In view of the latest recommendations by Health Canada and TGA, letter to inform local healthcare professionals on the above 2 announcements will be issued, and the safety with hepatotoxicity and high dose of diclofenac will be further discussed by the Committee.
Ends/ Tuesday, October 07, 2014
Issued at HKT 15:30
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