Generic Name

Celecoxib

Mechanism

Celecoxib is a selective cyclo‑oxygenase‑2 (COX‑2) inhibitor that attenuates the synthesis of pro‑inflammatory prostaglandins (PGE2, PGI2, and PGF2α) by competitively binding to the COX‑2 enzyme’s catalytic site.
• Reduced edema and pain by limiting prostaglandin‑mediated nociceptor sensitization.
• Preserves COX‑1 activity, thereby minimizing gastrointestinal prostaglandin‑mediated mucosal protection and platelet aggregation.

Pharmacokinetics

• Absorption: Oral bioavailability ~78 %; peak plasma concentrations (Cmax) reached ~2 h post‑dose.
• Distribution: Highly protein‑bound (≈ 95 % to albumin).
• Metabolism: Hepatic microsomal oxidation (primarily CYP2C9) → polar metabolites.
• Elimination: Renal excretion of both parent drug and metabolites; terminal half‑life 11–12 h.
• Drug‑drug interactions: Strong CYP2C9 inhibition; concurrent warfarin may increase INR; inhibit P‑gp substrates.

Indications

• Osteoarthritis of the knee or hip
• Rheumatoid arthritis (flare control)
• Ankylosing spondylitis
• Acute pain (e.g., dental, postoperative)
• Acute gout flare (short‑term use)
• Low‑dose aspirin‑resistant allergic reactions (clinical trial basis)

Contraindications

• Hypersensitivity to celecoxib or other NSAIDs
• History of myocardial infarction or stroke within 3 months
• Uncontrolled hypertension, active GI ulceration or bleeding
• Severe renal impairment (CrCl < 30 mL/min) or hepatic dysfunction
• Pregnancy (especially the 3rd trimester) and lactation
• Warnings:
• ↑ cardiovascular events with prolonged high‑dose therapy
• GI complications (bleeding, ulceration) albeit lower than nonselective NSAIDs
• Renal toxicity (oliguria, edema, AKI) especially in elderly or dehydrated patients

Dosing

• Start low, go slow in patients >65 yr or with comorbidities.
• Avoid concomitant anticoagulants unless necessary.
• Re‑challenge after GI bleed: Use with caution; consider proton‑pump inhibitor (PPI).

Adverse Effects

• Common: Dyspepsia, nausea, abdominal pain, headache, dizziness, edema.
• Serious:
• Cardiovascular: hypertension, heart failure, myocardial infarction, stroke.
• Gastrointestinal: ulceration, bleeding, perforation.
• Renal: tubular dysfunction, proteinuria, acute kidney injury.
• Hepatic: elevated transaminases, rare hepatotoxicity.
• Hypersensitivity: rash, urticaria, anaphylaxis.

Monitoring

• Baseline: CBC, CMP (LFTs, renal profile), BP, weight.
• During therapy:
• BP and weight every visit.
• LFTs, creatinine, eGFR at 3‑month intervals if >12 mo.
• INR when on warfarin.
• Urinalysis for proteinuria in high‑risk patients.
• Post‑GI event: Repeat endoscopy if clinically indicated.

Clinical Pearls

1. Cardiovascular risk stratification: Use the lowest effective dose for the shortest duration; consider concomitant low‑dose aspirin only if clearly indicated.
2. Renal consideration: Initiate therapy with a lower dose in CKD Stage 3–4; monitor eGFR every 6 months.
3. Drug‑interaction vigilance: Patients on CYP2C9 inhibitors (e.g., fluconazole) may have increased celecoxib levels; adjust dose accordingly.
4. “Switch‑off” strategy: In patients with GI intolerance to non‑selective NSAIDs, switch to celecoxib rather than add a PPI, as COX‑2 selectivity alone provides superior GI safety.
5. Pregnancy counseling: Avoid during 3rd trimester; discontinue 30 days before delivery to minimize neonatal respiratory depression.
6. Elderly dosing nuance: For patients >75 yr with multiple comorbidities, start at 100 mg BID and titrate cautiously; avoid >200 mg total daily dose if possible.

These pearls help balance efficacy against potential hazards, ensuring celecoxib is used safely and effectively in clinical practice.