Introduction
Celecoxib is a selective cyclooxygenase-2 (COX-2) inhibitor belonging to the nonsteroidal anti-inflammatory drug (NSAID) class. It was first approved by the FDA in 1998 and represents a significant advancement in NSAID therapy due to its reduced gastrointestinal toxicity profile compared to non-selective NSAIDs while maintaining analgesic and anti-inflammatory efficacy.
Mechanism of Action
Celecoxib selectively inhibits cyclooxygenase-2 (COX-2), an enzyme responsible for the conversion of arachidonic acid to prostaglandins, which mediate inflammation, pain, and fever. Unlike traditional NSAIDs that inhibit both COX-1 and COX-2 isoforms, celecoxib's relative selectivity for COX-2 preserves COX-1-mediated prostaglandin production, which helps maintain gastric mucosal protection and platelet function.
Indications
- Osteoarthritis (OA)
- Rheumatoid arthritis (RA)
- Ankylosing spondylitis
- Acute pain
- Primary dysmenorrhea
- Juvenile rheumatoid arthritis (in patients 2 years and older)
Dosage and Administration
Osteoarthritis: 200 mg daily or 100 mg twice daily Rheumatoid arthritis: 100-200 mg twice daily Acute pain/Primary dysmenorrhea: 400 mg initially, followed by 200 mg if needed on first day; subsequent days: 200 mg twice daily as needed Ankylosing spondylitis: 200 mg daily or 100 mg twice daily Special Populations:- Hepatic impairment: Reduce dose by 50% in moderate impairment (Child-Pugh Class B)
- Renal impairment: Use with caution; not recommended in advanced renal disease
- Elderly: Start at lowest recommended dose
- CYP2C9 poor metabolizers: Consider reduced dose
Pharmacokinetics
Absorption: Well absorbed orally, bioavailability approximately 99% Distribution: Volume of distribution ~400 L; highly protein-bound (97%) primarily to albumin Metabolism: Extensive hepatic metabolism via cytochrome P450 2C9 (CYP2C9) Elimination: Primarily fecal excretion (57%) with renal elimination (27%); elimination half-life approximately 11 hoursContraindications
- History of hypersensitivity to celecoxib, sulfonamides, or other NSAIDs
- History of asthma, urticaria, or allergic-type reactions after taking aspirin or other NSAIDs
- Perioperative pain in coronary artery bypass graft (CABG) surgery
- Third trimester of pregnancy
Warnings and Precautions
- Cardiovascular risk: Increased risk of serious cardiovascular thrombotic events, including MI and stroke
- GI risk: Serious GI adverse events including bleeding, ulceration, and perforation
- Hepatic toxicity: Monitor for signs/symptoms of liver dysfunction
- Hypertension: May worsen existing hypertension or contribute to new-onset hypertension
- Heart failure: Fluid retention and edema may occur
- Renal toxicity: Long-term use may result in renal injury
- Anaphylactic reactions: May occur in patients with aspirin-sensitive asthma
Drug Interactions
- ACE inhibitors/ARBs: Reduced antihypertensive effect
- Anticoagulants (warfarin): Increased bleeding risk
- Aspirin: Increased GI toxicity
- CYP2C9 inhibitors (fluconazole): Increased celecoxib exposure
- Lithium: Increased lithium levels
- Diuretics: Reduced diuretic efficacy
- SSRIs/SNRIs: Increased bleeding risk
Adverse Effects
Common (>1%): Dyspepsia, diarrhea, abdominal pain, nausea, headache, peripheral edema Serious:- Cardiovascular: MI, stroke, heart failure
- GI: Bleeding, ulceration, perforation
- Renal: Acute renal failure, interstitial nephritis
- Hepatic: Hepatitis, liver failure
- Dermatologic: Stevens-Johnson syndrome, toxic epidermal necrolysis
- Hematologic: Anemia, platelet inhibition
Monitoring Parameters
- Blood pressure at baseline and periodically during treatment
- Renal function (serum creatinine, BUN) at baseline and periodically
- Liver function tests at baseline and periodically
- Hemoglobin/hematocrit in patients on long-term therapy
- Signs/symptoms of GI bleeding
- Cardiovascular status in high-risk patients
- Signs of hypersensitivity reactions
Patient Education
- Take with food to minimize GI upset
- Report any signs of GI bleeding (black stools, abdominal pain)
- Monitor for signs of cardiovascular events (chest pain, shortness of breath)
- Report signs of allergic reactions (rash, swelling, difficulty breathing)
- Avoid concurrent use of other NSAIDs unless directed by healthcare provider
- Inform all healthcare providers of celecoxib use before any procedures
- Do not use during late pregnancy
- Report any signs of liver problems (nausea, fatigue, jaundice)
References
1. Solomon SD, et al. Cardiovascular risk of celecoxib in 6 randomized placebo-controlled trials: the cross trial safety analysis. Circulation. 2008;117(16):2104-2113. 2. Silverstein FE, et al. Gastrointestinal toxicity with celecoxib vs nonsteroidal anti-inflammatory drugs for osteoarthritis and rheumatoid arthritis: the CLASS study. JAMA. 2000;284(10):1247-1255. 3. Celecoxib [package insert]. New York, NY: Pfizer Labs; 2021. 4. McGettigan P, Henry D. Cardiovascular risk with non-steroidal anti-inflammatory drugs: systematic review of population-based controlled studies. PLoS Med. 2011;8(9):e1001098. 5. American College of Rheumatology. Guidelines for the Management of Osteoarthritis. Arthritis Care Res. 2019;71(1):2-32. 6. FDA Drug Safety Communication: FDA strengthens warning that non-aspirin nonsteroidal anti-inflammatory drugs (NSAIDs) can cause heart attacks or strokes. FDA. 2015.