Celecoxib

Mechanism

💊 Common Business Names

Celebrex, Artilog, Solexa, Celecox, Valdy.

🔬 Pharmacological Group

Derived from benzenesulfonamides. Selective COX-2 inhibitor (Coxib).

Mechanism of Action

Celecoxib selectively interferes with the inflammatory pathway induced by COX-2:

• Highly selective inhibition of COX-2: It has an in vitro selectivity for COX-2 approximately 375 times greater than that for COX-1. This is due to its molecular structure that has a rigid hydrophilic sulfonamide side group that fits precisely into the lateral hydrophobic channel characteristic of the active site of COX-2, being too bulky to access the narrow channel of COX-1. By preserving the constitutive activity of COX-1, the synthesis of gastric cytoprotective prostaglandins and the production of thromboxane in platelets are maintained.

Pharmacokinetics

Key Pharmacokinetics

Indicators and dose

Dosage and Adjustment

• Adults:
  • Osteoarthritis: 200 mg orally once a day, or divided into two doses of 100 mg every 12 hours.
  • Rheumatoid Arthritis and Ankylosing Spondylitis: 100 mg to 200 mg orally every 12 hours. Maximum recommended dose: 400 mg/day.
• Pediatrics: Not routinely established for children under 18 years of age; evaluable only in juvenile idiopathic arthritis in children over 2 years of age with doses adjusted to body weight (10-25 kg: 50 mg twice a day; >25 kg: 100 mg twice a day).
• Adjustment in Kidney Failure:
  • Cl_cr 30-59 mL/min: Use with extreme caution, at the minimum effective dose and with periodic monitoring of creatinine and serum potassium.
  • Cl_cr < 30 mL/min: Absolutely contraindicated.
• Adjustment in Liver Failure:
  • Moderate Hepatic Failure (Child-Pugh B): Immediately reduce the recommended dose by half (50%).
  • Severe Liver Failure (Child-Pugh C): Contraindicated.

Security

Molecular Mechanism of Cardiovascular Risk of Coxibs

Platelet cyclooxygenase is exclusively of the COX-1 type, responsible for the synthesis of Thromboxane TXA₂ (a powerful mediator of platelet aggregation and inducer of vasoconstriction). For its part, COX-2 expressed in vascular endothelial cells catalyzes the production of Prostacyclin PGI₂ (a potent inhibitor of platelet aggregation and local vasodilator). Celecoxib potently inhibits endothelial synthesis of PGI₂ but preserves platelet synthesis of TXA₂ intact. This pro-thrombotic imbalance favors the activation of local coagulation cascades and significantly increases the propensity for systemic arterial thrombosis, inducing myocardial and cerebral ischemic events.

Contraindications

• Absolute: Established ischemic heart disease, active coronary artery disease, history of acute myocardial infarction; previous stroke or transient cerebral ischemia; peripheral arterial disease or recent coronary bypass; hypersensitivity to celecoxib or sulfonamides (risk of immunologically mediated cross-reaction); severe renal failure (Cl_cr < 30 mL/min); severe liver failure (Child-Pugh C).
• Relative: Arterial hypertension not optimally controlled; mild to moderate congestive heart failure (NYHA I-II); diabetes mellitus, hyperlipidemia and smoking (cumulative cardiovascular risk profile).

Adverse Effects (ADR)

• Common / Mild: Headache, mild dizziness, insomnia, mild dyspepsia, abdominal pain, fluid retention with peripheral malleolar edema, sinusitis, pharyngitis.
• Rare / Serious: Major cardiovascular atherothrombotic events (myocardial infarction, stroke). Acute renal failure of hemodynamic origin. Severe exfoliative skin rashes (Stevens-Johnson syndrome). Anemia, neutropenia.

Drug Interactions

• Oral Anticoagulants (Warfarin / Acenocoumarol): Although it does not directly interfere with COX-1 homeostatic platelet aggregation, celecoxib can elevate prothrombin times (INR) due to the displacement of plasma proteins and metabolic interaction with warfarin. Requires close monitoring.
• Drugs Metabolized by CYP2D6 (Metoprolol, Venlafaxine, Amitriptyline): Celecoxib moderately inhibits CYP2D6 in vivo, which may cause marked elevations in serum levels of these compounds.
• ACEI and Diuretics: Deleterious nephrotoxic synergism for renal glomerular function.

Pregnancy and Breastfeeding

Classified in FDA Category C/D. Like other prostaglandin synthesis inhibitors, it is contraindicated during the third trimester of pregnancy due to the risk of inducing closure of the fetal ductus arteriosus, oligohydramnios due to fetal renal failure, and uterine inertia during childbirth. Breastfeeding: Compatible; It is excreted in clinically insignificant quantities in breast milk and presents a very low risk profile for the infant.