Rofecoxib Chemical formula
Synonyms: MK-966; MK-0966; Rofécoxib; Rofecoxibum; Rofekoksibi; Rofekoxib. 4-[p-(Methylsulfonyl)phenyl]-3-phenyl-2(5H)-furanone.
Cyrillic synonym: Рофекоксиб.

💊 Chemical information

Chemical formula: C17H14O4S = 314.4.
CAS — 162011-90-7.
ATC — M01AH02.
ATC Vet — QM01AH02.

💊 Profile

Rofecoxib is an NSAID reported to be a selective inhibitor of cyclo-oxygenase-2 (COX-2). It was given orally for symptomatic relief in the treatment of osteoarthritis and rheumatoid arthritis, and in the management of acute pain, dysmenorrhoea, and migraine but was generally withdrawn worldwide after reports of cardiovascular adverse effects (see below). Rofecoxib has been applied topically in some countries.

Effects on the cardiovascular system.

As of February 2001, the UK CSM had received a small number of reports of myocardial infarction or ischaemia associated with the selective cyclooxygenase-2 (COX-2) inhibitors.1 At that time it noted that COX-2 inhibitors such as rofecoxib did not possess the intrinsic antiplatelet activity associated with aspirin, and consequently did not provide protection against ischaemic cardiac events. Data from a large, randomised study also showed the incidence of myocardial infarction to be greater in patients taking rofecoxib than in those taking naproxen.2 Postmarketing surveillance of rofecoxib continued to provide further case reports of adverse cardiovascular effects. In addition, results of the then unpublished APPROVe study of rofecoxib for prevention of adenomatous polyposis indicated that the risk of myocardial infarction and stroke was markedly increased in patients receiving the drug compared to those on placebo; however, this difference was only apparent after 18 months of treatment. As a result, the study was stopped early and, in September 2004, the manufacturer generally withdrew rofecoxib worldwide. The cardiovascular findings from the APPROVe study were published in 2005;3 the results showed a twofold increase in the risk of adverse cardiovascular events in patients receiving rofecoxib 25 mg daily when compared with those on placebo. More recently, 1-year follow-up data for patients in the APPROVe study has been released. In a statement from the manufacturer,4 it is noted that in the year after rofecoxib was stopped there was no statistically significant difference in the risk of confirmed thrombotic cardiovascular events in those patients who had previously taken rofecoxib compared with those who had been given placebo; however, when data from both the on- and off-treatment periods were considered together, the difference in the risk of cardiovascular events between the rofecoxib and the placebo groups remained significant. Combined data from the on- and off-treatment periods also showed that there was an increased risk of confirmed heart attacks and ischaemic strokes in the rofecoxib group when compared to the placebo group. (The data for ischaemic stroke were later published.5) Similar data, suggesting a 1.5-fold increase in risk of thrombotic events with rofecoxib, were reported from a study of adjuvant use for colorectal cancer.6 A cumulative meta-analysis also indicated an increased risk of myocardial infarction in patients receiving rofecoxib.7 Subsequent investigation by US and European regulatory authorities has confirmed that other COX-2 inhibitors are also associated with some increased cardiovascular risk, as are some non-selective NSAIDs. A review8 of prospective studies evaluating the effect of selective COX-2 inhibitors on blood pressure was unable to determine if there was any association between the use of these drugs and blood pressure elevations. Of the studies considered, a randomised study in elderly, hypertensive patients with osteoarthritis has suggested that the risk of developing increased systolic blood pressure is greater in those patients receiving rofecoxib than in those receiving celecoxib.9 However, the manufacturers of rofecoxib have pointed out that the trial used doses of rofecoxib greater than those recommended for elderly or hypertensive patients.
1. CSM/MCA. COX-2 selective NSAIDs lack antiplatelet activity. Current Problems 2001; 27: 7. Also available at: http:// FILE&dDocName=CON007458&RevisionSelectionMethod= LatestReleased (accessed 08/11/07
2. Bombardier C, et al. Comparison of upper gastrointestinal toxicity of rofecoxib and naproxen in patients with rheumatoid arthritis. N Engl J Med 2000; 343: 1520–8
3. Bresalier RS, et al. Cardiovascular events associated with rofecoxib in a colorectal adenoma chemoprevention trial. N Engl J Med 2005; 352: 1092–1102. Correction. ibid. 2006; 355: 221
4. Merck, USA. Merck announces preliminary analyses of off-drug extension of APPROVe study (issued 11th May, 2006). Available at: 2006_0511.html (accessed 08/11/07
5. Afilalo J, et al. Long-term risk of ischemic stroke associated with rofecoxib. Cardiovasc Drugs Ther 2007; 21: 117–20
6. Kerr DJ, et al. Rofecoxib and cardiovascular adverse events in adjuvant treatment of colorectal cancer. N Engl J Med 2007; 357: 360–9
7. Jüni P, et al. Risk of cardiovascular events and rofecoxib: cumulative meta-analysis. Lancet 2004; 364: 2021–9
8. Johnson DL, et al. Effect of cyclooxygenase-2 inhibitors on blood pressure. Ann Pharmacother 2003; 37: 442–6
9. Whelton A, et al. Cyclooxygenase-2-specific inhibitors and cardiorenal function: a randomized, controlled trial of celecoxib and rofecoxib in older hypertensive osteoarthritis patients. Am J Ther 2001; 8: 85–95.

💊 Preparations

Proprietary Preparations

Arg.: Antidol†; Blokium Cox†; Coxiro†; Foldoxx†; Toloxane†; Vioxx†; Austral.: Vioxx†; Austria: Ceoxx†; Coxxil†; Vioxx†; Belg.: Vioxx†; Braz.: Vioxx†; Canad.: Vioxx†; Chile: Ceoxx†; Cz.: Vioxx†; Denm.: Vioxx†; Vioxxalt†; Fin.: Vioxx†; Fr.: Vioxx†; Ger.: Vioxx†; Gr.: Peroxx†; Vioxx†; Hong Kong: Vioxx†; Hung.: Vioxx†; India: Alrof†; Dolib†; Rofetab†; Rofib; Rofixx†; Rofiz; Versatil†; Irl.: Ceoxx†; Vioxx†; Israel: Vioxx†; Ital.: Arofexx†; Coxxil†; Dolcoxx†; Dolostop†; Miraxx†; Vioxx†; Malaysia: Vioxx†; Mex.: Vioxx†; Neth.: Vioxx†; Norw.: Vioxx†; NZ: Vioxx†; Port.: Ceoxx†; Coxxil†; Vioxx†; S.Afr.: Vioxx†; Singapore: Vioxx†; Spain: Ceoxx†; Vioxx†; Swed.: Vioxx†; Vioxxakut†; Switz.: Vioxx†; Thai.: Vioxx†; UK: Vioxx†; USA: Vioxx†; Venez.: Vioxx†. Multi-ingredient: India: Rofecip Plus†.
Published March 24, 2019.