Celecoxib

Introduction

Celecoxib is a nonsteroidal anti-inflammatory drug, an NSAID, selectively inhibit cyclo-oxygenase-2 (COX-2). As an NSAID, celecoxib is an analgesic, anti-inflammatory and antipyretic.

Clinical indications for indomethacin include:

• rheumatoid arthritis
• alkylosing spondylitis
• osteoarthritis
• gouty arthritis
• acute painful shoulder bursitis or tendinitis

It is also be used in menstrual pain, headaches, dental pain, postoperative and postpartum pain.

Mechanism of Action

• Anti-inflammatory agent
• Non-steroidal anti-inflammatory drug (NSAID)
• Highly selective COX-2 inhibitor

Dosage

For osteoarthritis

Oral: 200 mg daily given as a single dose or in 2 divided doses. If necessary a dose of 200 mg twice daily may be used.

For rheumatoid arthritis

Oral: 100 to 200 mg given twice daily.

For ankylosing spondylitis

Oral: an initial dose of 200 mg daily, as a single or in 2 divided doses. In the USA, the dose may be increased to 400 mg daily after 6 weeks, although if no response is seen at this dose a further 6 weeks, alternative treatments should be considered.

For pain and dysmenorrhea

Oral: an initial dose of 400 mg followed by an additional dose of 200 mg, if necessary, is recommended on the first day; thereafter the dose is 200mg twice daily. In patients with hepatic impairment and in those also taking fluconazole, a potent inhibitor of the cytochrome P450 isoenzyme CYP2C9, the dose of celecoxib should be reduced to half the recommended dose.

Administration in children

For the treatment of juvenile idiopathic arthritis in children aged 2 years and over, the recommended oral doses, based on body-weight, are:

• 10 to 25 kg: 50 mg twice daily
• Over 25 kg: 100 mg twice daily

It is recommended that children who are deficient in the cytochrome P450 isoenzyme CYP2C9 and hence poor metabolizers of celecoxib should be given alternative treatment. The contents of a celecoxib capsule may be sprinkled onto pureed meal if a patient has difficulty swallowing the capsules. The sprinkled capsule should be taken immediately; it remains stable at a temperature of between 2 degrees to 8 degrees for up to 6 hours.

Pharmacokinetics

Peak plasma concentrations occur after 3 hours of an oral dose. Plasma protein binding is about 97%. Celecoxib is metabolized in the liver mainly by the cytochrome P450 isoenzyme CYP2C9. It is eliminated mainly as metabolites in the faeces and urine. The plasma elimination half-life is about 11 hours. Celecoxib is distributed into breast milk.

Side Effects

Common side effects include:

• Abdominal pain, nausea and diarrhea.

Serious side effects may include:

• Heart attacks
• Strokes
• Gastrointestinal perforation
• Gastrointestinal bleeding
• Kidney failure
• anaphylaxis

It is generally accepted that COX-2 inhibitor may cause less gastrotoxicity than that seen with the non-selective inhibition of the traditional NSAIDs. However, reports that upper gastrointestinal perforation, ulceration and bleeds have occurred with celecoxib treatment and should not be used in patients with active gastrointestinal ulceration or bleeding.