Question

Rofecoxib (VIOXX) is an antagonist of prostaglandins. Prostaglandins are a group of lipids made at sites of tissues (damaged or infected) that are involved in dealing with injury and illness (Yourhormones.info, 2020). This simply means that it eases pain by reducing fever, swelling, and tenderness. Rofecoxib is marketed by Merck under the brand name VIOXX. It is a white to off-white to light yellow powder. It is a nonsteriodial anti-inflammatory (NSAID) drug The drug was initially made and introduced by Merck to the pharmaceutical market, to treat pain associated with osteoarthritis. VIOXX indications and usages are:

Relief of signs and symptoms of rheumatoid arthritis in adults.

For relief of the signs and symptoms of pauciarticular or polyarticular course Juvenile Rheumatoid Arthritis (JRA) in patients 2 years and older and who weigh 10 kg (22 lbs) or more.

For the management of acute pain in adults.

For the treatment of primary dysmenorrhea (painful mensural cramps).

For the acute treatment of migraine attacks with or without aura in adults.

Summary of VIOXX Package insert

The VIOXX package insert begins with the nomenclature of rofecoxib, with a chemical formula of C17H14O4S. VIOXX tablet sizes for oral administration ranges from 12.5mg, 25mg to 50mg. The drug is soluble in alcohol but insoluble in fatty alcohol such as octanol. However, food consumption had no significant effect on the saturation of VIOXX in plasma concentration.

Clinical studies of VIOXX on Osteoarthritis~ Demonstrated significant reduction in joint pain compared to placebo. Analgesic effects of a 50 mg does of VIOXX is similar in comparison to 550mg naproxen or 400mg ibuprofen. VIOXX was effective regardless of presence of aura, gender, race, age, presence of menses or dysmenorrhea. Although, patients with a mean age of 58 administering aspirin or anti platelet drugs, or a recent history of myocardial infarction (another term for heart attack) or stroke were excluded from the study.

A VIGOR study was conducted to evaluate the comparative Gastrointestinal (GI) safety of VIOXX 50mg once daily versus 500mg daily of naproxen. This study showed reduction in the risk development of PUBs-symptomatic ulcers, including PUBs in patients taking VIOXX compared to naproxen. Albeit, VIGOR study showed a higher incidence of adjudicated serious cardiovascular thrombotic events (formation or presence of blood clots) in patients treated with VIOXX 50mg once daily as compared ton patients treated with naproxen 500mg twice daily.

Contraindications

The safety and effectiveness of VIOXX has not been established for cluster headache. There is hypersensitivity of rofecoxib to patients or other components of VIOXX used. This drug cannot be given to patients who have asthma, Urticaria (Hives or allergic type reactions), or any type of NSAIDs prescribed apart from VIOXX. This shows that can be anaphylactic shock exacerbated from taking VIOXX.

Warnings

Usage of VIOXX can cause stomach bleeding, ulceration and perforation. Indigestion (Dyspepsia) can be caused when taking this medication. If a patient has prior history of ulcer or GI bleeding, caution needs to be taken. Rare cases of anaphylaxis and angioedema (painless swelling under the skin) have been reported with patients taking VIOXX. In late pregnancy VIOXX should be avoided.

Precautions

VIOXX cannot be substituted with corticosteroids or to treat corticosteroids (a class of steroid-hormones) insufficiency. Caution should be applied when patients have a history of ischemic (Clogging of arteries) heart disease. There is a risk for developing a cardiovascular thrombosis (Heart disease due to artery clogging) when treated with VIOXX is significantly higher. VIOXX has a lack of platelet effect. Fluid retention, edema and hypertension have been reported in some patients taking VIOXX. This is why it is necessary to find out if patient is taking aspirin.

In the Osteoarthritis (OA) studies performed regardless of causality, spontaneous adverse events in >0.1% to 1.9% of patients treated with VIOXX. Here is a list of cardiovascular system symptoms that occurred:- angina pectorals (Chest pain), atrial fibrillation (irregular fast heart beat), bradycardia, hematoma, irregular heartbeat, palpitation, premature ventricular contraction, tachycardia, venous insufficiency.

These adverse events of cardiovascular events were present but barely reported in patients taking VIOXX. Symptoms are as follow:

Cardiovascular: cerebrovascular accident, congestive heart failure, deep venous thrombosis, hypertensive crisis, myocardial infarction, pulmonary edema, pulmonary embolism, transient ischemic attack, unstable angina.

The recommended dosage of VIOXX is 50 mg once a day, which is the most in quantity provided in oral administration for VIOXX. The information provided for heart attack and shock about this drug is moderate but scattered within the VIOXX package. For the trained intended reader the information is clearer, but if a patient that is not well informed on medical terminology reads the VIOXX package; then there could be important information about the dangers of using this drug. The cardiovascular, GI track, Renal and blood are all connected. If there is a blockage or obstruction in blood vessels there is a strong chance of a heart attack. For a marketing, team this drug's cure offerings could be considered miraculous. For medical personnel and or medical doctors, it is a nightmare waiting to happen on myocardial infarction street. if a patient takes VIOXX to deal with osteoarthritis pain, there are a lot of risks to consider over the reward of easing pain. The patient taking VIOXX risks a doubled chance of getting a heart attack and or death. During the VIGOR study patients were being treated with VIOXX, the numbers of participants reduced by 600 and there were many incomplete trials due to some sort of complication derivative of VIOXX infestation.

THIS IS FOR A DISCUSSION FORUM . PLEASE READ AND MAKE YOUR CONTRIBUTION BELOW

Answer 1

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 US by the US 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 tablet-form 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.

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, there are varying degrees of COX-2 selectivity 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.

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. 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 memo concluding that data from large long-term controlled clinical trials do not clearly demonstrate that COX-2 selective agents (including rofecoxib) have a greater risk of serious CV events than non-selective NSAIDs. The FDA reinforced this position in 2015, stating that the available data support a dose and duration dependent class effect of an increased risk of serious adverse cardiovascular events for COX-2 selective and non-selective NSAIDs.

Possible return to market:

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 due to their effects on platelet aggregation and risk of gastrointestinal ulcers, and high potency opioids are the current standard of care in treating HA.

In March 2019 Tremeau announced that they had hired as chief development officer a former Merck employee who had been a product development team leader and also was responsible for executive oversight for numerous clinical trials for the COX-2 inhibitor VIOXX (rofecoxib). Tremeau also announced an upcoming clinical trial for rofecoxib and were seeking investigators.