Australia limits or bans use of Cox-2 drugs

The Australian Government has put serious restrictions on Vioxx type drugs (often called with their more technical name, Cox-2 drugs, and includes drugs like Celebrex, Bextra, Arcoxia, Prexige, and dozens of other brand names that vary by country). The Therapeutic Goods Administration (TGA) is the Australian agency equivalent to the Food and Drug Administration (FDA) in the US. It is important to note that the countries in the European Union have only one agency, that is, the European Medicines Agency. Other than these two, almost all other countries have their own independent agencies though they actively coordinate their drug regulation work with agencies like the FDA and EMEA.

TGA has now introduced new measures on the prescribing of Cox-2 inhibitors following the findings of a review into the safety of this family of medicines. After the worldwide recall of Vioxx by Merck in September 2004, drug agencies have been reviewing the whole family. The FDA and EMEA are scheduled to meet next week. (Related article: Status report on Celebrex, Bextra, Arcoxia, and Prexige prior to review)

The TGA will immediately require manufacturers of Cox-2 inhibitors to place new highlighted explicit warnings in product information about the increased risk of cardiovascular adverse events from this group of drugs. The new warning statements are to be highlighted with a black boxed margin. The TGA is also advising people who are taking more than 200mg a day of celecoxib (Celebrex) or more than 15 mg a day of meloxicam (Mobic; Movalis) to review their treatment regime with their doctors. (Related article: FDA puts strong black box warning on Bextra label)

The TGA believes that most Australians using these drugs will be taking low doses that already meet this dosage advice, but some patients, particularly with rheumatoid arthritis or a rare bowel condition, may be taking 400 mg or 800 mg of celecoxib (Celebrex) a day and some patients with arthritis may be taking more than 15 mg of meloxicam a day. (Related article: Pfizer continues to assert safety of Celebrex)

This recommended dose reduction may result in some patients with arthritis having increased symptoms but the review of Cox-2 inhibitors clearly indicated there is an increased risk of heart attacks and strokes with high doses of these drugs.

The TGA determined that the exact size of the risk and the exact duration of therapy associated with increased risk are still unknown, and so have recommended that Cox-2 inhibitors should be prescribed only when other treatments cannot be tolerated or have caused serious adverse effects. While Vioxx showed a very clear cut risk, that has not been the case with other Cox-2 drugs like Celebrex and Bextra. The regulators from EMEA and FDA will have the same challenge next week. There is conflicting information on these drugs and while many doctors and consumer rights groups are demanding that all of these drugs be recalled, Wall Street analysts are betting that FDA and EMEA are likely to do what TGA has done rather than impose an outright ban. (Related article: Largest US HMO bans Bextra)

Concerning meloxicam, there are theoretical grounds for regarding the drug as having reduced cardiovascular risks. The drug has less selective Cox-2 inhibition than celecoxib or rofecoxib (Vioxx). Clinical study data are more meager, with most studies limited to no more than six months duration. The Committee notes that a Prescription Event Monitoring study in the UK and an observational study in Quebec, Canada, provided reassurance that the cardiovascular risk at up to 15 mg is acceptable. (Related article: Merck could have found out Vioxx risks earlier)

The TGA is also taking a few more steps in the interest of public health in Australia:

1. It is proposed to cancel the registration of the drug parecoxib (Dynastat), an injectable version of Bextra, because of the risk of cardiovascular events. Dynastat is marketed in Australia and is approved as a single dose at the time of surgery to reduce post-operative pain;
2. It is proposed to withdraw the indication of management of arthritis of the drug valdecoxib (Valdyne, Dynoral - known in some countries as Bextra) which is converted to parecoxib in the body. Valdecoxib has not been marketed in Australia. Valdecoxib has been associated with an increased risk of cardiovascular events in cardiac by-pass graft patients. The use of Valdecoxib for 5 days as an analgesic in patients without increased cardiovascular risk will remain; it is proposed to greatly limit the approved uses of two other Cox-2 inhibitors which have not yet been marketed in Australia. They are etoricoxib or Arcoxia and lumiracoxib or Prexige. In both instances, ADEC was not sufficiently assured of the safety of these drugs for anything other than short term use in patients without increased cardiovascular risk.
3. Concerning parecoxib and valdecoxib, TGA was not assured from other available data that the safety of parecoxib in other surgical patients or the safety of valdecoxib other than when used for short periods in patients without cardiovascular risk, had been studied adequately.

Recommended article: Pfizer highlights recall risks of Celebrex and Bextra

Source: TGA