What is the information about Celecoxib (Celebrex)?

From the Guidelines

Celecoxib should be used with caution and at the lowest effective dose for the shortest duration necessary to minimize potential risks, particularly in patients with a history of gastrointestinal or cardiovascular disease, due to its association with increased risk of heart attack, stroke, and gastrointestinal bleeding 1.

Overview of Celecoxib

Celecoxib is a nonsteroidal anti-inflammatory drug (NSAID) that belongs to a specific class called COX-2 inhibitors. It's primarily used to treat pain and inflammation associated with conditions like osteoarthritis, rheumatoid arthritis, acute pain, and menstrual cramps. The typical dosage ranges from 100-200 mg once or twice daily, depending on the condition being treated, with a maximum recommended dose of 400 mg per day.

Mechanism of Action and Benefits

Celecoxib works by selectively blocking the COX-2 enzyme, which is responsible for producing inflammatory prostaglandins, while having less effect on COX-1 enzymes that protect the stomach lining. This selective action gives celecoxib an advantage over traditional NSAIDs by potentially causing fewer gastrointestinal side effects like ulcers and bleeding.

Risks and Side Effects

However, celecoxib still carries cardiovascular risks, including increased risk of heart attack and stroke, especially with long-term use or in patients with existing heart disease. Common side effects include headache, indigestion, upper respiratory tract infection, and diarrhea. Celecoxib should be used with caution in patients with sulfonamide allergies, kidney or liver disease, heart conditions, or a history of stomach ulcers.

Guidelines for Use

According to recent guidelines, such as those from the ESCEO and OARSI, oral NSAIDs, including celecoxib, should only be used intermittently for the shortest period of time and at the lowest possible dose to control pain, owing to their known adverse cardiovascular, hepatic, and renal effects 1. For patients with normal gastrointestinal function, non-selective oral NSAIDs, preferably in combination with a proton pump inhibitor (PPI), or selective COX2 inhibitors like celecoxib are recommended. In those with gastrointestinal complications or increased risk of cardiovascular events, the use of celecoxib and other NSAIDs should be approached with caution, and alternative treatments should be considered.

Key Considerations

• Age is a major risk factor for cardiovascular, cerebrovascular, and gastrointestinal adverse outcomes and should be taken into account when assessing the benefit-to-risk ratio of NSAID usage.
• The ESCEO guidelines recommend the use of topical NSAIDs over oral NSAIDs in patients with OA aged ≥75 years and in those at increased risk.
• Celecoxib is available by prescription only under brand names like Celebrex.

From the FDA Drug Label

1. Clinical Pharmacology 12. 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.
2. 3 Pharmacokinetics Celecoxib exhibits dose-proportional increase in exposure after oral administration up to 200 mg twice daily and less than proportional increase at higher doses. 4 Hypertension NSAIDs, including celecoxib capsules can lead to new onset of hypertension or worsening of preexisting hypertension, either of which may contribute to the increased incidence of CV events.
3. 5 Heart Failure and Edema The Coxib and traditional NSAID Trialists’ Collaboration meta-analysis of randomized controlled trials demonstrated an approximately twofold increase in hospitalizations for heart failure in COX-2 selective-treated patients and nonselective NSAID-treated patients compared to placebo-treated patients
4. 6 Renal Toxicity and Hyperkalemia Renal Toxicity Long-term administration of NSAIDs has resulted in renal papillary necrosis and other renal injury.
5. 7 Anaphylactic Reactions Celecoxib has been associated with anaphylactic reactions in patients with and without known hypersensitivity to celecoxib and in patients with aspirin sensitive asthma
6. 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.

Celecoxib is a nonsteroidal anti-inflammatory drug (NSAID) with analgesic, anti-inflammatory, and antipyretic properties. The mechanism of action is believed to be due to inhibition of prostaglandin synthesis, primarily via inhibition of COX-2.

• Pharmacokinetics: Celecoxib exhibits dose-proportional increase in exposure after oral administration up to 200 mg twice daily and less than proportional increase at higher doses.
• Hypertension: Celecoxib can lead to new onset of hypertension or worsening of preexisting hypertension.
• Heart Failure and Edema: Celecoxib may increase the risk of heart failure and edema.
• Renal Toxicity and Hyperkalemia: Long-term administration of celecoxib may result in renal papillary necrosis and other renal injury.
• Anaphylactic Reactions: Celecoxib has been associated with anaphylactic reactions in patients with and without known hypersensitivity to celecoxib.
• Description: Celecoxib is available as capsules containing 50 mg, 100 mg, 200 mg, and 400 mg celecoxib USP for oral administration 2, 2, 2.

From the Research

Overview of Celecoxib

• Celecoxib is a cyclo-oxygenase (COX)-2 selective inhibitor used for symptomatic relief in the treatment of osteoarthritis, rheumatoid arthritis, and ankylosing spondylitis 3, 4, 5.
• It is also used for the management of acute pain in adults, treatment of primary dysmenorrhoea, and reduction in the number of adenomatous colorectal polyps in familial adenomatous polyposis 5.

Efficacy of Celecoxib

• Celecoxib has been shown to be significantly more effective than placebo and as effective as nonselective NSAIDs and other coxibs for the symptomatic treatment of patients with active osteoarthritis, rheumatoid arthritis, or ankylosing spondylitis 3, 4.
• It has also been found to be effective in treating the signs and symptoms of osteoarthritis of the hip and knee, with improvements in physical function paralleling those in pain relief 4.
• Celecoxib has been shown to be superior to placebo and equivalent to traditional non-steroidal anti-inflammatory drugs (tNSAIDs) in the treatment of rheumatoid arthritis and osteoarthritis 6.

Safety of Celecoxib

• Celecoxib is generally well tolerated, with mild to moderate upper GI complaints being the most common body system adverse events 3.
• The incidence of upper GI ulcer complications with recommended dosages of celecoxib is significantly lower than that with nonselective NSAIDs and similar to that with paracetamol and other coxibs 3, 4.
• However, concomitant administration of celecoxib with low-dose cardioprotective aspirin may negate the GI-sparing advantages of celecoxib over NSAIDs 3.
• There is inconsistent evidence regarding the cardiovascular risk of celecoxib, but it is thought to be small and similar to that of nonselective NSAIDs 3, 5, 7.

Clinical Use of Celecoxib

• Celecoxib is a useful option for therapy in patients at high risk for NSAID-induced GI toxicity, or in those responding suboptimally to or intolerant of NSAIDs 3, 5.
• It is recommended to use celecoxib at the lowest effective dosage for the shortest possible duration after a careful evaluation of the GI, cardiovascular, and renal risks of the individual patient 3, 5, 7.
• Older patients may gain significant benefits from celecoxib compared to tNSAIDs due to reduced gastrointestinal events, even with a history of ulcer bleedings 6.