chemistry

Rofecoxib

Rofecoxib is a chemistry topic covered in the lgStudy science library. This page brings together a partial reference excerpt, illustrations, worked examples, real-world applications and a short study plan, so you can understand Rofecoxib rather than just read about it. In short: Rofecoxib is a COX-2-selective nonsteroidal anti-inflammatory drug (NSAID). It was marketed by Merck & Co. to treat osteoarthritis, rheumatoid arthritis, juvenile rheumatoid arthritis, acute pain conditions, migraine, and dysmenorrhea.

Key takeaways

Rofecoxib belongs to chemistry; place it in that map before memorising details.
Learn the definition first, then one example that makes the definition concrete.
Connect Rofecoxib to a quantity you can measure, compute or draw — that is where exam questions come from.
Reproduce the core statement of Rofecoxib from memory before moving on to harder problems.

Reference excerpt

Rofecoxib is a COX-2-selective nonsteroidal anti-inflammatory drug (NSAID). It was marketed by Merck & Co. to treat osteoarthritis, rheumatoid arthritis, juvenile rheumatoid arthritis, acute pain conditions, migraine, and dysmenorrhea. Rofecoxib was approved in the United States by the Food and Drug Administration (FDA) in May 1999, and was marketed under the brand names Vioxx, Ceoxx, and Ceeoxx. Rofecoxib was available by prescription in both tablets and as an oral suspension. Rofecoxib gained widespread use among physicians treating patients with arthritis and other conditions causing chronic or acute pain. Worldwide, over 80 million people were prescribed rofecoxib at some time. In September 2004, Merck voluntarily withdrew rofecoxib from the market because of concerns about increased risk of heart attack and stroke associated with long-term, high-dosage use. Merck withdrew the drug after disclosures that it withheld information about rofecoxib's risks from doctors and patients for over five years, allegedly resulting in between 88,000 and 140,000 cases of serious heart disease in the United States alone. Rofecoxib was one of the most widely used drugs ever to be withdrawn from the market. In the year before withdrawal, Merck had sales revenue of US$2.5 billion from Vioxx. In 2005, the FDA issued a memorandum concluding that risks for serious cardiovascular (CV) events seem to be as great for nonselective NSAIDs as for COX-2–selective agents such as rofecoxib, according to long-term, controlled clinical trials. Based on data up to 2015, the FDA reasserted the likelihood of an increased risk of serious adverse CV events from COX-2–selective and nonselective NSAIDs, dependent on dose and duration. In November 2017, Massachusetts-based Tremeau Pharmaceuticals announced its plan to return rofecoxib (TRM-201) to market as a treatment for hemophilic arthropathy (HA). Tremeau announced that the FDA had granted an orphan designation for TRM-201 (rofecoxib) for the treatment of HA, and that they had received FDA feedback on their development plan. HA is a degenerative joint disease caused by recurrent intra-articular bleeding. It is the largest cause of morbidity in patients with hemophilia and has no currently approved treatment options in the United States. Traditional NSAIDs are avoided in this population because of their effects on platelet aggregation and risk of gastrointestinal ulcers, and high potency opioids are the current standard of care in treating HA.

Mode of action

Cyclooxygenase (COX) has two well-studied isoforms, called COX-1 and COX-2. COX-1 mediates the synthesis of prostaglandins responsible for protection of the stomach lining, while COX-2 mediates the synthesis of prostaglandins responsible for pain and inflammation. By creating "selective" NSAIDs that inhibit COX-2, but not COX-1, the same pain relief as traditional NSAIDs is offered, but with greatly reduced risk of fatal or debilitating peptic ulcers. Rofecoxib is a selective COX-2 inhibitor, or "coxib". Though the class of coxibs includes several agents, degrees of COX-2 selectivity vary among them, with celecoxib (Celebrex) being the least COX-2 selective, and rofecoxib (Vioxx), valdecoxib (Bextra), and etoricoxib (Arcoxia), being highly COX-2 selective. At the time of its withdrawal, rofecoxib was the only coxib approved in the United States with clinical evidence of its superior gastrointestinal adverse effect profile over conventional NSAIDs. This was largely based on the VIGOR (Vioxx GI Outcomes Research) study, which compared the efficacy and adverse effect profiles of rofecoxib and naproxen.

Pharmacokinetics The therapeutic recommended dosages were 12.5, 25, and 50 mg with an approximate bioavailability of 93%. Rofecoxib crossed the placenta and blood–brain barrier, and took 1–3 hours to reach peak plasma concentration with an effective half-life (based on steady-state levels) around 17 hours. The metabolic products are cis-dihydro and trans-dihydro derivatives of rofecoxib which are primarily excreted through urine.

Efficacy Rofecoxib was approved by the FDA to treat osteoarthritis, rheumatoid arthritis, juvenile rheumatoid arthritis, acute pain conditions, migraine, and dysmenorrhea. When it was marketed, it gained widespread acceptance among physicians treating patients with arthritis and other conditions causing chronic or acute pain.

Premenstrual acne A 2003 placebo-controlled, small, short-term study in India of 80 women with premenstrual acne vulgaris, who were given rofecoxib or placebo for two cycles of 10 days, suggests that "rofecoxib is effective in the management of premenstrual acne.

Fabricated efficacy studies On March 11, 2009, Scott S. Reuben, former chief of acute pain at Baystate Medical Center, Springfield, Mass., revealed that data for 21 studies he had authored for the efficacy of the drug (along with others such as celecoxib) had been fabricated, overstating the analgesic effects of the drugs. No evidence has been found that Reuben colluded with Merck in falsifying his data. Reuben was also a former paid spokesperson for the drug company Pfizer (which owns the intellectual property rights for marketing celecoxib in the United States). The retracted studies were not submitted to either the FDA or the European Union's regulatory agencies prior to the drug's approval. Drug manufacturer Merck had no comment on the disclosure.

Side effects

In addition to the reduced incidence of gastric ulceration, rofecoxib exhibits no effect on bleeding time or platelet aggregation, even at supratherapeutic doses. Aside from these features, rofecoxib exhibits a similar adverse-effect profile to other NSAIDs.

Heart and blood vessels

… excerpt ends here. Continue reading the full article.

Illustrations

Worked examples

Example 1 — a first encounter with Rofecoxib

Start with the simplest possible case. Write down what Rofecoxib claims or describes in one sentence, then invent the smallest concrete situation in which that sentence is true. In chemistry, the smallest case is usually a single object, a single equation or a single measurement. Check that every symbol or term in your sentence has a meaning in that case.

Example 2 — changing one variable

Take the situation from Example 1 and change exactly one quantity: double it, halve it, or set it to zero. Predict what should happen to Rofecoxib before you calculate. Comparing your prediction with the result is the fastest way to find out whether you understand the idea or only the words.

Example 3 — an exam-style question

Typical questions about Rofecoxib ask you to (a) state it precisely, (b) apply it to given data, and (c) explain a limitation. Practise writing all three answers in under five minutes; the third part is what separates a full-mark answer from an average one.

Applications of Rofecoxib

In research: Rofecoxib appears in chemistry research whenever the underlying quantities have to be modelled precisely. Papers usually cite it as a starting assumption and then explore where it breaks down.
In technology and industry: Engineering practice reuses Rofecoxib in design rules, simulations and safety margins. Knowing the idea lets you read a specification sheet and understand why the numbers look the way they do.
In the classroom: Rofecoxib is common in secondary-school and first-year university syllabi. It links to neighbouring topics 4-(Methylsulphonyl)phenyl compounds, Cyclooxygenase-2 inhibitors, Drugs developed by Merck & Co., so understanding it makes those chapters shorter.
In everyday life: Look for Rofecoxib outside the textbook — in sport, cooking, traffic, electronics or the sky above you. An example you found yourself is remembered far longer than one you were given.

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How to study Rofecoxib in 20 minutes

Read the reference excerpt below once, without taking notes.
Close the page and write down what Rofecoxib means in your own words.
Compare your version with the excerpt and mark what you missed.
Work through the three examples above with pen and paper.
Explain Rofecoxib out loud to somebody else — or to Teacher Smith in the lgStudy chat.

Frequently asked questions

What is Rofecoxib in simple terms?

Why does Rofecoxib matter?

Because it connects several chemistry ideas at once: it gives you a definition you can apply, a quantity you can calculate, and a way to check whether a result is plausible.

How should I study Rofecoxib?

Read the excerpt, restate it from memory, then work through the examples and applications listed on this page. The five-step study plan above takes about twenty minutes.

What does this page cover?

It gives you a compact reference excerpt plus original lgStudy explanations, examples, applications and study material on Rofecoxib.