Celebrex - Drug Monograph

Introduction

Celebrex (celecoxib) is a prescription nonsteroidal anti-inflammatory drug (NSAID) specifically classified as a COX-2 selective inhibitor. It is manufactured by Pfizer and was first approved by the FDA in 1998. Unlike traditional NSAIDs that inhibit both COX-1 and COX-2 enzymes, Celebrex demonstrates preferential inhibition of cyclooxygenase-2 (COX-2), which may offer improved gastrointestinal safety while maintaining anti-inflammatory efficacy.

Mechanism of Action

Celebrex works by selectively inhibiting cyclooxygenase-2 (COX-2), an enzyme responsible for the synthesis of prostaglandins that mediate inflammation, pain, and fever. By preferentially targeting COX-2 over COX-1, celecoxib reduces the production of inflammatory prostaglandins while largely sparing COX-1-mediated prostaglandins that protect gastric mucosa and support platelet function. This selective inhibition mechanism differentiates it from non-selective NSAIDs.

Indications

FDA-approved indications include:

• Osteoarthritis (OA)
• Rheumatoid arthritis (RA)
• Ankylosing spondylitis
• Acute pain
• Primary dysmenorrhea
• Juvenile rheumatoid arthritis in patients 2 years and older

Off-label uses may include:

• Prevention of colorectal adenomatous polyps in specific high-risk populations
• Gout flare management
• Other inflammatory conditions

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, then 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

• Hepatic impairment (Child-Pugh B): Reduce dose by 50%
• Hepatic impairment (Child-Pugh C): Not recommended
• Renal impairment (CrCl <30 mL/min): Use with caution
• Elderly: Start at lowest effective dose
• Pediatric patients (≥2 years): Dosing based on weight

Pharmacokinetics

• Absorption: Well absorbed orally, with peak plasma concentrations occurring at approximately 3 hours. Bioavailability is approximately 99% when taken with food.
• Distribution: Extensive protein binding (~97%), primarily to albumin. Volume of distribution is approximately 400 L.
• Metabolism: Primarily hepatic via cytochrome P450 2C9 (CYP2C9). Major metabolites include inactive carboxylic acid and hydroxyl derivatives.
• Elimination: Primarily fecal excretion (57%) with renal elimination accounting for 27% of dose. Elimination half-life is approximately 11 hours.

Contraindications

• Known hypersensitivity to celecoxib or any component of the formulation
• History of asthma, urticaria, or allergic-type reactions after taking aspirin or other NSAIDs
• Patients in the peri-operative setting of coronary artery bypass graft (CABG) surgery
• Third trimester of pregnancy

Warnings and Precautions

Drug Interactions

• Warfarin: Increased risk of bleeding (monitor INR closely)
• ACE inhibitors/ARBs: Reduced antihypertensive effect
• Diuretics: Reduced diuretic efficacy
• Lithium: Increased lithium levels
• CYP2C9 inhibitors: Fluconazole significantly increases celecoxib levels
• Aspirin: Increased GI risk (though low-dose aspirin may be continued for cardioprotection)
• SSRIs/SNRIs: Increased risk of GI bleeding

Adverse Effects

• Dyspepsia (8.8%)
• Diarrhea (5.6%)
• Abdominal pain (4.1%)
• Nausea (3.5%)
• Headache (15.8%)
• Peripheral edema (2.7%)

• GI bleeding/perforation
• Cardiovascular thrombotic events
• Hepatotoxicity
• Renal impairment/failure
• Severe skin reactions
• Anaphylaxis
• Hypertension exacerbation

Monitoring Parameters

• Efficacy: Pain assessment, functional status, inflammatory markers
• Safety:

- Blood pressure at baseline and regularly during treatment - Renal function (serum creatinine, BUN) at baseline and periodically - Liver function tests at baseline and periodically - Hemoglobin/hematocrit if signs of bleeding occur - GI symptoms monitoring - For patients on anticoagulants: regular INR monitoring - Signs of fluid retention or heart failure

Patient Education

• Take with food or milk to reduce stomach upset
• Report any signs of GI bleeding (black stools, vomiting blood, abdominal pain)
• Monitor for signs of cardiovascular events (chest pain, shortness of breath, weakness)
• Watch for skin reactions or allergic symptoms
• Avoid alcohol consumption during treatment
• Inform all healthcare providers about Celebrex use, especially before surgery
• Do not exceed prescribed dosage
• Report any swelling, weight gain, or changes in urination patterns
• Discuss all other medications (including OTC drugs and supplements) with healthcare provider

References

1. Solomon DH, et al. The comparative safety of analgesics in older adults with arthritis. Arch Intern Med. 2010;170(22):1968-1976. 2. Celebrex [package insert]. New York, NY: Pfizer Inc; 2021. 3. 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. 4. American College of Rheumatology. Guidelines for the Management of Osteoarthritis. Arthritis Care Res. 2019;71(4):461-475. 5. FDA Drug Safety Communication: FDA strengthens warning that non-aspirin nonsteroidal anti-inflammatory drugs (NSAIDs) can cause heart attacks or strokes. Silver Spring, MD: US Food and Drug Administration; 2015. 6. Chan FK, et al. Celecoxib versus diclofenac and omeprazole in reducing the risk of recurrent ulcer bleeding in patients with arthritis. N Engl J Med. 2002;347(26):2104-2110.