More than 1,000 reports of adverse reactions to Merck's osteoarthritis drug, Vioxx (rofecoxib) and eleven deaths have been reported in the UK since its launch in June of 1999.
The Medicines Control Agency (MCA) and the Committee on Safety of Medicines (CSM) said, "Up to July 2000, the MCA/CSM had received a total of 1,120 reports, via the Yellow Card Scheme, of suspected adverse reactions to rofecoxib."
Five patients died following gastrointestinal reactions, three following cardiac failure and three following myocardial infarction, the agencies reported in their newsletter "Current Problems".
An estimated 557,100 prescriptions for Merck's COX-2 inhibitor have been dispensed in the UK up to the end of May 2000, the agencies said. The rate of reported adverse reactions is therefore approximately one per 500 prescriptions.
"Gastrointestinal adverse reactions account for almost half (554) of the reports, of which the majority (84%) were nausea, dyspepsia, diarrhoea and abdominal pain," the agency said.
"However there have been 68 reports (12%) of upper GI perforations, ulceration and bleeds (PUBs). Forty-four (65%) of the patients with PUBs recovered, although five had a fatal outcome."
The agencies also received 177 reports of suspected cardiovascular reactions, including 101 reports of oedema, 31 reports of hypertension and 19 reports of palpitations.
There were 15 reports of cardiac failure, three of which had a fatal outcome, and nine reports of myocardial infarction, three of them fatal. In the majority of these cases, the patient had risk factors for cardiovascular disease.
Psychiatric reactions were also reported, including 28 reports of depression, 14 reports of confusion and 11 reports of hallucinations.
Adverse reactions recognised with other NSAIDs were also reported with rofecoxib. These included angioedema (35 reports), bronchospasm or exacerbation of asthma (25), renal failure (16), and abnormal hepatic function (12).
The newsletter reminded prescribers that rofecoxib is contraindicated in patients with active peptic ulceration, GI bleeding, and severe congestive heart failure. It also noted that "caution should be exercised in patients with a history of cardiac failure, left ventricular dysfunction, or hypertension and in patients with pre-existing oedema for any other reason".
In conclusion, the agencies said, "As with all new drugs, the safety of rofecoxib remains under close review." They pointed out that another COX-2 inhibitor, Pharmacia's celecoxib (Celebrex), had been launched recently and promised to report on its safety profile in a forthcoming bulletin.