March 1, 2010

Formulary Drug Listing Decisions

Indication (s) of chronic arthritis (e.g., , and ankylosing Piroxicam is used to treat pain and a spondylitis). This labeling change for variety of inflammatory conditions. piroxicam is relevant for the WSIB population, many of whom are pre- DAC Recommendation scribed NSAIDs for treatment of acute, The Drug Advisory Committee (DAC) has short-term pain. recommended that piroxicam be removed Piroxicam was cited as having an from all WSIB formularies following a increased risk of serious skin reactions Health Canada safety review that cited (e.g., Stevens-Johnson syndrome and piroxicam’s, acute, short-term increased toxic epidermal necrolysis) and gas- risk of serious skin conditions and trointestinal problems relative to other gastrointestinal intestinal (GI) problems NSAIDs. compared to other nonsteroidal anti- Drug Profile inflammatory drugs (NSAIDs). There are a number of equally effective NSAIDs (e.g., , ) that Products available can be used for treatment of inflamma- in Canada: The WSIB Decision tory conditions, both on an acute and Apo-Piroxicam, Based on the DAC’s recommendations, the chronic basis. Dom-Piroxicam, WSIB has decided to remove piroxicam Gen-Piroxicam, from all formularies at this time. The DAC recommended that piroxicam Novo-Pirox, Nu-Pirox, be removed from WSIB formularies PMS-Piroxicam, Formulary Status based on a Health Canada review of Pro-Piroxicam studies suggesting an increase in GI Manufacturer: Variety Piroxicam HAS BEEN REMOVED from toxicity and an increased risk of devel- of generic manufac- WSIB formularies at this time. opment of serious skin reactions (which turers has resulted in labeling changes by Recommendation Highlights Health Canada) and on the availability of Piroxicam is a non-selective NSAID that equally effective NSAIDs for treatment has been used in the treatment of pain of inflammatory conditions. and various inflammatory conditions.

A recent review by Health Canada concluded that piroxicam should no longer be used to treat short-term pain and inflammation, although it can still be prescribed for the symptomatic relief of chronic pain and inflammation in patients suffering from certain types

Page 1 of 2 DETAILED DISCUSSION

Background GI toxicity than some other NSAIDs such as indomethacin and , most observa- Piroxicam is a non-selective nonsteroidal tional studies indicate that piroxicam has one anti-inflammatory drug (NSAID) that has been of the highest risks for the development of GI used in the treatment of various inflammatory toxicity. conditions. Non-selective NSAIDs, including piroxicam, exert their effects by inhibiting all Stevens-Johnson syndrome (SJS) and toxic forms of cyclooxygensase, an that epidermal necrolysis (TEN) are severe cutane- mediates pain and inflammation. All NSAIDs ous hypersensitivity reactions that cause are associated with an elevated risk of gas- rash, skin peeling, and sores on the mucous trointestinal toxicity and the rare occurrence membranes. These disorders are extremely of serious skin reactions. However, a recent rare, affecting between 1 and 5 people/million safety review by Health Canada determined users. the risks of these serious adverse events may Data from an international case-control be higher with the use of piroxicam relative to study and a population-based registry both other NSAIDs (e.g., ibuprofen and naproxen) concluded that piroxicam was associated in the acute, short-term treatment pain (i.e., with the greatest increase in risk of SJS/TEN during the initial weeks of therapy). compared to other NSAIDs. When the risk for recently initiated use was compared to that for Summary of Committee long-term use of these agents (>8 weeks), the Considerations relative risk of SJS/TEN associated with initial The DAC considered information from a use of piroxicam was significantly increased. Health Canada Safety Review of piroxicam. Based on the review of evidence, Health This review concluded that piroxicam was Canada concluded that the risks associated associated with a short-term increased risk with the short-term use of piroxicam out- of serious skin reactions and gastrointestinal weighed the benefits, given the availability toxicity relative to other NSAIDs during the of alternative NSAIDs. As such, piroxicam is initial weeks of treatment. no longer indicated for the acute, short-term Upper GI symptoms (e.g., dyspepsia) are ex- treatment of pain and inflammation. Piroxicam tremely common, occurring in up to 35% of all can still be prescribed for the treatment of NSAID users. Serious upper GI complications chronic pain and inflammation in patients (e.g., major bleeding, perforation, obstruction) suffering from certain types of chronic arthritis occur less frequently; the annual incidence of (e.g., osteoarthritis, rheumatoid arthritis and complicated GI events in arthritis patients is ). A similar review in approximately 1-1.5%. Upper GI symptoms 2007 in the United Kingdom resulted in the correlate poorly with NSAID-associated ulcers same restrictions for the use of piroxicam. or complications. Based on this evidence, the DAC recom- Evidence from observational studies suggests mended that piroxicam be removed from all that piroxicam may be associated with a WSIB formularies based on (i) the availability higher risk of serious GI toxicity compared to of equally effective NSAIDs for treatment of other NSAIDs. In one such study, ibuprofen inflammatory conditions; (ii) the increased ranked lowest amongst the NSAIDs for GI risk of development of serious skin reactions complications, followed closely by diclofenac. (i.e., SJS/TEN) compared to other NSAIDs; (iii) , tolmetin and piroxicam ranked suggestion of increased GI toxicity; and (iv) highest and indomethacin, naproxen, labeling change for piroxicam in Canada that it and had intermediate risks. Although should not be used for acute, short-term pain a comparison of adverse effects reported in (a large portion of injured workers). randomized controlled trials suggest that piroxicam may be better tolerated in terms of Revised: January 29, 2013

The WSIB will consider all relevant facts and circumstances, and shall make its decision based upon the merits and justice of a particular case.

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