COX‐2 inhibition and thrombotic tendency: a need for surveillance

Cleland, Leslie G.; James, Michael J.; Stamp, Lisa K.; Penglis, Peter S.

doi:10.5694/j.1326-5377.2001.tb143099.x

Cited by 33 publications

(15 citation statements)

References 13 publications

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“…The analysis, however, does not take into consideration other benefits, such as the reduction in non‐serious GI adverse events, the number of lives (or ‘life‐years’) saved and increases in economic productivity, and less tangible benefits, such as improvement in quality of life, were not evaluated. In addition, the potential costs resulting from possible increases in cardiovascular and renal morbidity associated with COX‐2 inhibitor use were not considered 18,19 . Clearly, further work is required in this area to evaluate fully the costs and benefits of selective COX‐2 inhibitors, but the results of the present study indicate that a significant increase in health expenditure is likely if the putative benefits of this new class of drugs are to be gained.…”

Section: Discussionmentioning

confidence: 99%

“…In addition, the potential costs resulting from possible increases in cardiovascular and renal morbidity associated with COX-2 inhibitor use were not considered. 18,19 Clearly, further work is required in this area to evaluate fully the costs and benefits of selective COX-2 inhibitors, but the results of the present study indicate that a significant increase in health expenditure is likely if the putative benefits of this new class of drugs are to be gained.…”

Section: Tablementioning

confidence: 91%

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Impact of selective cyclooxygenase‐2 inhibitors on anti‐ulcer medication and non‐steroidal anti‐inflammatory drug use in patients with rheumatic disease

Joshua

Oakley

Major

2004

Internal Medicine Journal

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Section: Discussionmentioning

confidence: 99%

Section: Tablementioning

confidence: 91%

Impact of selective cyclooxygenase‐2 inhibitors on anti‐ulcer medication and non‐steroidal anti‐inflammatory drug use in patients with rheumatic disease

Joshua

Oakley

Major

2004

Internal Medicine Journal

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“…Nevertheless it is useful to consider that when Australian population figures from the 1990s are used, there would need to be an increase of only 0.34% to 0.68% in the annual death rate from ischaemic heart disease to balance the deaths per annum from NSAID induced upper gastrointestinal events. 18 …”

Section: Duty Of Care In Therapeutic Practicementioning

confidence: 99%

Applying a research ethics committee approach to a medical practice controversy: the case of the selective COX-2 inhibitor rofecoxib

James

Cleland²

2004

J Med Ethics

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The new class of anti-inflammatory drugs, the COX-2 inhibitors, have been commercially successful to the point of market dominance within a short time of their launch. They attract a price premium on the basis that they are associated with fewer adverse gastric events than traditional anti-inflammatory drugs. This marketing continues even though a pivotal safety study with one of the COX-2 inhibitors, rofecoxib, showed a significant increase in myocardial infarction with rofecoxib use compared with a traditional antiinflammatory drug. This finding has led to a series of publications containing pooled analyses of existing data that both support and refute the possibility of increased cardiovascular risk with COX-2 inhibitors. These medical journal publications have served to obfuscate rather than provide guidance for medical practitioners. Consideration of a research ethics committee approach to this issue suggests that it would deal with the controversy in a straightforward manner-namely, it would simply inform research participants of the trial results with rofecoxib. The certainty of this research ethics committee approach raises the issue of whether it should be applied in normal medical practice outside of the research environment. A consideration of the legal tests for disclosure of information suggests that therapeutic medical practice should mirror that within the research environment, in this case.T raditional non-steroidal anti-inflammatory drugs (NSAIDs) decrease the pain and swelling associated with inflammatory conditions, such as rheumatoid arthritis; however, their chronic use increases the risk of severe gastric side effects, including haemorrhage. The new class of anti-inflammatory drugs known as cyclooxygenase (COX)-2 inhibitors were developed with the aim of decreasing the pain and swelling of inflammation without the increased risk of adverse gastric events.

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“…Both COX-1 and COX-2 are involved in the product ion of prostaglandins and thromboxa nes (Cleland et al 2001).…”

Section: Tolerability: Cardiovascular Effectsmentioning

confidence: 99%

Rofecoxib: an update on physicochemical, pharmaceutical, pharmacodynamic and pharmacokinetic aspects

Ahuja

Singh

2003

Journal of Pharmacy and Pharmacology

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Rofecoxib (MK-966) is a new generation non-steroidal anti-inflammatory agent (NSAID) that exhibits promising anti-inflammatory, analgesic and antipyretic activity. It selectively inhibits cyclooxygenase (COX)-2 isoenzyme in a dose-dependent manner in man. No significant inhibition of COX-1 is observed with rofecoxib up to doses of 1000 mg. The pharmacokinetics of rofecoxib has been found to be complex and variable. Mean oral bioavailability after single dose of rofecoxib (12.5, 25 or 50 mg) is 93% with t m a x varying widely between 2 and 9 h. It is highly plasma-protein bound and is metabolized primarily by cytosolic reductases to inactive metabolites. Rofecoxib is eliminated predominantly by hepatic metabolism with a terminal half-life of approximately 17 h during steady state. Various experimental models and clinical studies have demonstrated rofecoxib to be superior, or at least equivalent, in anti-inflammatory, analgesic and antipyretic efficacy to comparator nonselective NSAIDs in osteoarthritis, rheumatoid arthritis and other pain models. Emerging evidence suggests that rofecoxib may also find potential use as supportive therapy in various pathophysiologic conditions like Alzheimer's disease, and in various malignant tumours and polyps, where COX-2 is overly expressed. Rofecoxib is generally well-tolerated. Analysis of data pooled from several trials suggests that rofecoxib is associated with fewer incidences of clinically symptomatic gastrointestinal ulcers and ulcer complications vis-a Á -vis conventional NSAIDs. However, this gastropreserving effect may be negated by concurrent use of low-dose aspirin for cardiovascular risk reduction. Rofecoxib tends to show similar tolerability for renal and cardiothrombotic events as compared with nonnaproxen nonselective NSAIDs. No clinically significant drug interaction has been reported for rofecoxib except with diuretics, where it reverses their salt-wasting effect and thus can be clinically exploited in electrolyte-wasting disorders. There is only modest information about the physicochemical and pharmaceutical aspects of rofecoxib. Being poorly water soluble, its drug delivery has been improved using varied formulation approaches. Although it is stable in solid state, rofecoxib is photosensitive and base-sensitive in solution form with its degradation mechanistics elucidated. Analytical determinations of rofecoxib and its metabolites in biological fluids employing HPLC with varied types of detectors have been reported. Isolated studies have also been published on the chromatographic and spectrophotometric assay of rofecoxib and its degradants in bulk samples and pharmaceutical dosage forms. The current article provides an updated overview on the physicochemical, pharmaceutical, pharmacokinetic and pharmacodynamic vistas of rofecoxib.

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COX‐2 inhibition and thrombotic tendency: a need for surveillance

Cited by 33 publications

References 13 publications

Impact of selective cyclooxygenase‐2 inhibitors on anti‐ulcer medication and non‐steroidal anti‐inflammatory drug use in patients with rheumatic disease

Impact of selective cyclooxygenase‐2 inhibitors on anti‐ulcer medication and non‐steroidal anti‐inflammatory drug use in patients with rheumatic disease

Applying a research ethics committee approach to a medical practice controversy: the case of the selective COX-2 inhibitor rofecoxib

Rofecoxib: an update on physicochemical, pharmaceutical, pharmacodynamic and pharmacokinetic aspects

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