Celecoxib

November 7, 2020 Rima Pharmacology 0

  • Celecoxib is non-steroidal anti-inflammatory agent (NSAIDs) used to treat pain and inflammation. Most of the NSAIDs used including aspirin, ibuprofen and indomethacin are associated with GI and bleeding risks. COX-2 inhibitors (coxibs) are introduced to reduce pain and inflammation without associated GI and bleeding risks. Celecoxib is 1st COX-2 inhibitor introduced in market.
  • It was introduced in medical field in 1999.

Indications of Celecoxib

  • Used in osteoarthritis and rheumatoid arthritis.
  • In acute pain and dysmenorrhea.
  • To reduce number of adenomatous colorectal polyps in familial adenomatous polyposis.

Mechanism of action of Celecoxib

Figure 1- Selective inhibition of COX-2 by Celecoxib

  • It selectively inhibits COX-2 (Cyclooxygenase 2) and prevent synthesis of prostaglandins which are important mediator of pain and inflammation in the body.
  • COX-1 and COX-2 are responsible for synthesis of prostaglandins from arachidonic acid. Most of the NSAIDS inhibit both COX-1 and COX-2. Most of the GI related side effects are due to inhibition of COX-1.
  • Celecoxib, however, has a sulfonamide side chain which binds to hydrophilic region near active binding site of only COX-2 and inhibit it. Hence, it helps to reduce pain and inflammation without any GI related side effects.

Pharmacokinetics of Celecoxib

  • It is mostly administered through oral route. Peak plasma concentration is observed after 3 hours of oral administration. When administered with high fat meal, peak plasma levels were delayed for about 1- 2 hours. Co-administration with magnesium and aluminum containing antacid result in reduction in its plasma concentration.
  • Its half-life is about 11 hours.
  • It binds extensively to plasma protein (mainly albumin). It undergoes hepatic metabolism by cytochrome P450 2C9 and very little (around 3%) is excreted unchanged in urine and feces.
  • Around 57% of drug is excreted through feces and 27% through urine.

Adverse effects

Some of the possible side effects include:

  • Cardiovascular complications like stroke and heart attack.
  • Dizziness.
  • Abdominal bloating, diarrhea.
  • Severe allergy or anaphylactic shock.
  • Rashes, sore throat, flu like symptoms.

Contraindications

  • It should be avoided in patients with cardiovascular and cerebrovascular disease.
  • Contraindicated in patients allergic to sulfonamide and NSAIDs.
  • In liver or kidney damage.
  • In pregnancy and breastfeeding mothers.
  • Contraindicated for pediatric use.

Drug Interactions

  • It increases plasma lithium level. Coadministration of Diflucan increases its plasma level.
  • Concurrent administration with warfarin may increase bleeding complications.

References

  1. Antoniou K, Malamas M, Drosos AA. Clinical pharmacology of celecoxib, a COX-2 selective inhibitor. Expert Opin Pharmacother. 2007; 8(11): 1719-32.
  2. Nissen et al. Cardiovascular Safety of Celecoxib, Naproxen, or Ibuprofen for Arthritis. N Engl J Med. 2016; :2519-2529.
  3. Clemett D, Goa KL. Celecoxib: a review of its use in osteoarthritis, rheumatoid arthritis and acute pain. Drugs. 2000; 59(4): 957-80.
  4. https://www.pfizermedicalinformation.ca/en-ca/celebrex/action-and-clinical-pharmacology
  5. Current Therapy in Pain. 2009, Pages 59-72.