What is the information about Celebrex (celecoxib), a nonsteroidal anti-inflammatory drug (NSAID)?

From the Guidelines

Celecoxib should be used with caution due to its increased risk of cardiovascular events, and its use should be limited to patients who have not achieved pain control with nonselective NSAIDs, at the lowest possible dose for the shortest time necessary. When considering the use of celecoxib, it is essential to weigh the benefits against the risks for individual patients, taking into account their specific medical history and current health status 1. Celecoxib is a prescription nonsteroidal anti-inflammatory drug (NSAID) that selectively inhibits the COX-2 enzyme, making it effective for treating pain and inflammation while potentially causing fewer gastrointestinal side effects than traditional NSAIDs. It's commonly prescribed for conditions like osteoarthritis, rheumatoid arthritis, acute pain, and menstrual cramps, typically at doses ranging from 100-200 mg once or twice daily, with a maximum of 400 mg daily for most conditions.

Some key points to consider when prescribing celecoxib include:

• Common side effects: headache, indigestion, and upper respiratory tract infection
• Cardiovascular risks: increased risk of heart attack and stroke, especially with higher doses or prolonged use
• Interactions with other medications: blood thinners, some antidepressants, and other NSAIDs
• Precautions: use with caution in patients with heart disease, high blood pressure, kidney problems, or a history of stomach ulcers
• Administration: take with food if stomach upset occurs, and avoid alcohol during treatment to reduce stomach irritation risk

According to the American Heart Association, celecoxib significantly increases the risk of cardiovascular events in a dose-dependent manner 1. The FDA has also issued warnings and advisories regarding the use of celecoxib, recommending that it be used at the lowest effective dose for the shortest duration necessary 1. A study published in Circulation found that celecoxib increases the risk of myocardial infarction, with a rate ratio of 1.42 (1.13 to 1.78; P=0.003) compared to placebo 1.

In terms of gastrointestinal risks, celecoxib has a lower risk of stomach ulcers than traditional NSAIDs, but it is still important to use caution in patients with a history of gastrointestinal problems 1. The use of proton pump inhibitors (PPIs) can decrease the risk of bleeding ulcers in high-risk NSAID or aspirin users, but the effectiveness of PPIs in patients taking celecoxib is not well established 1.

Overall, the use of celecoxib should be carefully considered and monitored, with a focus on minimizing cardiovascular and gastrointestinal risks. Patients should be fully informed of the potential risks and benefits of celecoxib, and alternative treatments should be considered when possible.

From the FDA Drug Label

1. Clinical Pharmacology
2. 1 Mechanism of Action Celecoxib has analgesic, anti-inflammatory, and antipyretic properties. The mechanism of action of celecoxib capsules are believed to be due to inhibition of prostaglandin synthesis, primarily via inhibition of COX-2. Celecoxib is a potent inhibitor of prostaglandin synthesis in vitro. Celecoxib concentrations reached during therapy have produced in vivo effects Prostaglandins sensitize afferent nerves and potentiate the action of bradykinin in inducing pain in animal models. Prostaglandins are mediators of inflammation. Since celecoxib is an inhibitor of prostaglandin synthesis, its mode of action may be due to a decrease of prostaglandins in peripheral tissues.

Key Points:

• Mechanism of Action: Celecoxib works by inhibiting prostaglandin synthesis, primarily via inhibition of COX-2.
• Properties: Celecoxib has analgesic, anti-inflammatory, and antipyretic properties.
• Effects: Celecoxib decreases prostaglandins in peripheral tissues, which mediates inflammation and induces pain.

5.6 Renal Toxicity and Hyperkalemia Renal Toxicity Long-term administration of NSAIDs has resulted in renal papillary necrosis and other renal injury. Renal toxicity has also been seen in patients in whom renal prostaglandins have a compensatory role in the maintenance of renal perfusion In these patients, administration of an NSAID may cause a dose-dependent reduction in prostaglandin formation and, secondarily, in renal blood flow, which may precipitate overt renal decompensation Patients at greatest risk of this reaction are those with impaired renal function, dehydration, hypovolemia, heart failure, liver dysfunction, those taking diuretics, ACE inhibitors or the ARBs, and the elderly.

Warnings and Precautions:

• Renal Toxicity: Long-term administration of celecoxib may result in renal papillary necrosis and other renal injury.
• Hyperkalemia: Increases in serum potassium concentration, including hyperkalemia, have been reported with use of NSAIDs.
• Patient Risk: Patients with impaired renal function, dehydration, hypovolemia, heart failure, liver dysfunction, and those taking certain medications are at greatest risk of renal toxicity.

5.8 Exacerbation of Asthma Related to Aspirin Sensitivity A subpopulation of patients with asthma may have aspirin-sensitive asthma which may include chronic rhinosinusitis complicated by nasal polyps; severe, potentially fatal bronchospasm; and/or intolerance to aspirin and other NSAIDs Because cross-reactivity between aspirin and other NSAIDs has been reported in such aspirin-sensitive patients, celecoxib capsules are contraindicated in patients with this form of aspirin sensitivity

Contraindications:

• Aspirin Sensitivity: Celecoxib is contraindicated in patients with aspirin-sensitive asthma.
• Serious Skin Reactions: Celecoxib is contraindicated in patients with previous serious skin reactions to NSAIDs.

1. Description 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.

Dosage and Administration:

• Capsule Strengths: Celecoxib is available in 50 mg, 100 mg, 200 mg, and 400 mg capsules.
• Administration: Celecoxib can be administered orally. 2 2 2

From the Research

Overview of Celecoxib

• Celecoxib is a cyclo-oxygenase (COX) inhibitor that exhibits relative in vitro and ex vivo selectivity for COX-2 over COX-1 3.
• It is used for the relief of the signs and symptoms of osteoarthritis (OA), rheumatoid arthritis (RA), juvenile rheumatoid arthritis, ankylosing spondylitis, and acute pain in adults 4.
• Celecoxib is the first COX-2 specific inhibitor approved for use in osteoarthritis and rheumatoid arthritis 3.

Efficacy and Safety

• Celecoxib has been shown to be effective in improving the signs and symptoms of osteoarthritis and rheumatoid arthritis, with similar efficacy to conventional nonsteroidal anti-inflammatory drugs (NSAIDs) 3, 5.
• It has also been shown to be effective in reducing pain and improving functional status in patients with osteoarthritis and rheumatoid arthritis 3, 6.
• Celecoxib has a lower incidence of upper gastrointestinal ulceration and complications compared to conventional NSAIDs 3, 5, 6.
• The incidence of gastroduodenal ulcers and the combined incidence of gastroduodenal ulcers and erosions are significantly lower with celecoxib therapy than with naproxen therapy 5.

Pharmacokinetics and Pharmacodynamics

• Celecoxib is absorbed moderately when given orally, with a peak plasma drug concentration occurring after 2 to 4 hours 7.
• It is extensively protein bound, primarily to plasma albumin, and has an apparent volume of distribution of 455+/-166L in humans 7.
• Celecoxib is eliminated following biotransformation to carboxylic acid and glucuronide metabolites that are excreted in urine and faeces, with little drug (2%) being eliminated unchanged in the urine 7.
• It is metabolised primarily by the cytochrome P450 (CYP) 2C9 isoenzyme and has an elimination half-life of about 11 hours in healthy individuals 7.

Special Considerations

• Celecoxib should be used with caution in patients with chronic renal insufficiency, as plasma concentrations (AUC) of celecoxib appear to be 43% lower in these patients compared to individuals with healthy renal function 7.
• It should also be used with caution in patients with mild and moderate hepatic impairment, as the steady-state AUC is increased by approximately 40% and 180% in these patients, respectively 7.
• Celecoxib does not appear to interact with warfarin, ketoconazole or methotrexate; however, clinically significant drug interactions with fluconazole and lithium have been documented 7.