What is known about Celebrex (Celecoxib)?

From the Guidelines

Celecoxib, sold under the brand name Celebrex, should be used with caution due to its increased risk of cardiovascular events, including heart attack and stroke, especially with higher doses or prolonged use, as evidenced by the American Heart Association's scientific statement 1.

Overview of Celecoxib

Celecoxib is a nonsteroidal anti-inflammatory drug (NSAID) that specifically inhibits the COX-2 enzyme, making it a selective COX-2 inhibitor. It's primarily used to treat pain and inflammation associated with conditions like osteoarthritis, rheumatoid arthritis, acute pain, and menstrual cramps.

Dosage and Administration

The typical dosage ranges from 100-200 mg twice daily for arthritis, with a maximum recommended daily dose of 400 mg. For acute pain, the initial dose may be 400 mg followed by 200 mg if needed on the first day, then 200 mg twice daily as required.

Mechanism of Action and Side Effects

Celecoxib works by blocking the production of prostaglandins that cause pain and inflammation while sparing those that protect the stomach lining, potentially causing fewer gastrointestinal side effects than traditional NSAIDs. However, common side effects include headache, indigestion, upper respiratory tract infection, and diarrhea.

Precautions and Contraindications

It should be used with caution in patients with heart disease, history of stomach ulcers, kidney or liver problems, and should be avoided by those allergic to sulfonamides or in the last trimester of pregnancy. The FDA has issued warnings regarding the increased risk of cardiovascular events with celecoxib, particularly in patients with a history of cardiovascular disease or risk factors for cardiovascular disease 1.

Risk of Cardiovascular Events

The risk of cardiovascular events with celecoxib is a significant concern, and patients should be carefully evaluated before initiating therapy. The American Heart Association recommends that physicians consider alternative therapy or use the smallest effective dose of celecoxib 1. Additionally, a study published in the American Family Physician journal highlights the importance of weighing the benefits and risks of NSAIDs, including celecoxib, in individual patients 1.

Guidelines for Use

Guidelines for the use of NSAIDs, including celecoxib, recommend careful consideration of the patient's risk factors for gastrointestinal and cardiovascular complications. The use of proton pump inhibitors or misoprostol may be recommended to reduce the risk of gastrointestinal complications 1.

Conclusion is not allowed, so the answer will be ended here.

From the FDA Drug Label

Dose adjustment in the elderly is not generally necessary. However, for patients of less than 50 kg in body weight, initiate therapy at the lowest recommended dose [see Dosage and Administration (2.7) and Use in Specific Populations (8. 5)]. Celecoxib has not been studied in JRA patients under the age of 2 years, in patients with body weight less than 10 kg (22 lbs), or beyond 24 weeks. A pharmacokinetic study in subjects with mild (Child-Pugh Class A) and moderate (Child-Pugh Class B) hepatic impairment has shown that steady-state celecoxib AUC is increased about 40% and 180%, respectively, above that seen in healthy control subjects In a cross-study comparison, celecoxib AUC was approximately 40% lower in patients with chronic renal insufficiency (GFR 35-60 mL/min) than that seen in subjects with normal renal function. Celecoxib is a nonsteroidal anti-inflammatory drug, available as capsules containing 50 mg, 100 mg, 200 mg and 400 mg celecoxib USP for oral administration. Celecoxib capsules are contraindicated in the following patients: Known hypersensitivity (e.g., anaphylactic reactions and serious skin reactions) to celecoxib, any components of the drug product

Key Points:

• Dosage and Administration: Dose adjustment in the elderly is not generally necessary, but patients under 50 kg should start with the lowest recommended dose.
• Contraindications: Celecoxib is contraindicated in patients with known hypersensitivity, history of asthma or allergic-type reactions to NSAIDs, in the setting of CABG surgery, and in patients with demonstrated allergic-type reactions to sulfonamides.
• Special Populations: Celecoxib has not been studied in patients under 2 years, with body weight less than 10 kg, or beyond 24 weeks.
• Hepatic and Renal Impairment: Dose reduction is recommended in patients with moderate hepatic impairment, and celecoxib is not recommended in patients with severe hepatic or renal impairment. 2 2 2

From the Research

Overview of Celebrex (Celecoxib)

• Celecoxib, also known as Celebrex, is a cyclo-oxygenase (COX) 2-selective inhibitor used for the relief of signs and symptoms of osteoarthritis (OA), rheumatoid arthritis (RA), juvenile rheumatoid arthritis, ankylosing spondylitis, acute pain in adults, primary dysmenorrhoea, and reduction of adenomatous colorectal polyps in familial adenomatous polyposis 3.
• It has been shown to be effective in alleviating pain and inflammation without the gastrointestinal, renal, and platelet effects associated with conventional nonsteroidal anti-inflammatory drugs (NSAIDs) 4.

Efficacy and Safety

• Celecoxib has been demonstrated to be as effective as naproxen and aspirin in ameliorating the signs and symptoms of osteoarthritis and rheumatoid arthritis, and in reducing pain following dental extraction 4.
• The incidence of gastroduodenal ulcers and the combined incidence of gastroduodenal ulcers and erosions are significantly lower with celecoxib therapy than with naproxen therapy, and are similar to those associated with placebo administration 4.
• Celecoxib has been shown to be well tolerated, with incidences of adverse events similar to placebo in most instances 4, 5.
• However, long-term use of high doses of celecoxib has been associated with an increased cardiovascular toxicity 6.

Clinical Use

• Celecoxib is a rational choice for patients at low cardiovascular risk who require NSAID therapy, especially those at increased risk of NSAID-induced gastrointestinal toxicity, or those unresponsive to, or intolerant of, other NSAIDs 3.
• It is recommended to use celecoxib at the lowest effective dose for the shortest possible duration 3.
• The addition of curcumin to celecoxib has been shown to synergistically augment the growth inhibitory effects of celecoxib in in-vitro and in-vivo models of arthritis and cancer, potentially allowing for lower doses and reduced side effects 6.

Patient Considerations

• Older patients may gain significant benefits from celecoxib compared to traditional NSAIDs due to reduced gastrointestinal events, even with a history of ulcer bleedings 7.
• However, there is still limited knowledge regarding the prescription of celecoxib in patients with cardiovascular co-morbidities, and the use of higher doses (>400 mg/day) 7.