European Medicines Agency public statement on valdecoxib and parecoxib sodium. Cardiovascular risks in coronary artery bypass graft surgery and serious adverse skin reactions

15 December 2004

The European Medicines Agency (EMEA) and its Scientific Committee for human medicines have been made aware of new safety information on cardiovascular and serious skin adverse events in relation to the use of valdecoxib and parecoxib sodium.

Cardiovascular safety
Two clinical studies were conducted to evaluate the safety of valdecoxib and parecoxib sodium, in patients following CABG surgery and another study in patients following general surgery.

The first CABG study evaluated the safety of parecoxib sodium/valdecoxib 40 mg BID given for up to 14 days in 462 patients (311 on parecoxib sodium/valdecoxib and 151 on placebo).

The second CABG surgery study evaluated parecoxib sodium (40mg then 20mg bid) /valdecoxib 20 mg bid or placebo/valdecoxib 20 mg bid or placebo/placebo for up to 10 days in 1671 patients (544 receiving parecoxib/valdecoxib, 544 placebo/valdecoxib and 548 placebo/placebo).

Both CABG studies showed a higher rate of serious cardiovascular thromboembolic events (e.g. myocardial infarction, cerebrovascular accident) in the parecoxib sodium/valdecoxib treatment arm compared to the group of patients receiving placebo. This was not observed in a general surgery setting.

Serious Skin Reactions
The EMEA has received new post-marketing reports of serious skin reactions, some with fatal outcome, including erythema multiforme, exfoliative dermatitis, Stevens-Johnson syndrome and toxic epidermal necrolysis in patients receiving valdecoxib. Erythema multiforme has been reported in association with the use of parecoxib sodium.

The reported rate of these reactions appears to be greater for valdecoxib as compared with other COX- 2 selective inhibitors.

Patients appear to be at highest risk for these events early in the course of therapy, the onset of the event occurring in the majority of cases within the first two weeks of treatment.

Patients without a history of sulphonamide allergy may also be at risk for serious skin reactions.

Based on the new data the EMEA wishes to point out the following information:

Information for physicians considering therapy of patients with valdecoxib or parecoxib:

• Valdecoxib and parecoxib are contraindicated in patients following coronary artery bypass graft (CABG) surgery.
  • Prescribers are advised to carefully follow the latest version of the Summary of Product Characteristics, especially regarding the warnings and precautions in patients with a history of cardiovascular disease.
• In post-marketing experience serious skin adverse reactions most of which occurred within the first two weeks starting treatment, have been reported in association with valdecoxib. Erythema multiforme has been reported in association with the use of parecoxib sodium.
  • The reported rate of serious skin events appears to be greater for valdecoxib as compared to other COX-2 selective inhibitors.
  • Patients appear to be at highest risk for these events early in the course of therapy.
  • Patients without a history of sulphonamide allergy are also at risk for such reactions.
  • Therapy should be discontinued at the first appearance of skin rash, mucosal lesions, or any other sign of hypersensitivity.

Information for patients currently being treated with valdecoxib or parecoxib:

• If you are about to have heart bypass surgery, please inform your physician, as you should not be given these medicines.
• These medicines already contain warnings regarding heart problems. If you have any concerns about your treatment, you are advised to consult your physician.
• If you develop itchy skin or ulceration of the skin, mouth, eyes, face, lips or tongue; or skin rash, swelling of the face, lips or tongue, or blistering and peeling, stop taking Bextra/Valdyn or Dynastat/Rayzon and tell your doctor, pharmacist or nurse immediately. Such allergic reactions often occur in the first weeks of treatment.
• The reported rate of serious skin events appears to be greater for valdecoxib as compared to other so-called COX-2 inhibitors.

The Product Information for valdecoxib and parecoxib sodium has now been modified to reflect the above-mentioned information and is appended to this press release.

Note

1. COX-2 inhibitors (cyclo-oxygenase-2 inhibitors) are non-steroidal anti-inflammatory medicines (NSAID). They are approved in the European Union for use in a number of indications.

EMEA public statement on Valdecoxib and parecoxib sodium _cardiovascular risks in coronary artery bypass graft surgery and serious adverse skin reactions

Reference Number: EMEA/204802/2004