Celebrex | Pharmacology Mentor

Generic Name

Celebrex

Selective COX‑2 inhibition: Reduces prostaglandin E₂ synthesis, decreasing inflammation and pain.
Reduced gastric prostaglandin: Preservation of COX‑1 activity limits gastrointestinal (GI) mucosal injury compared with non‑selective NSAIDs.
Modest anti‑inflammatory profile: Lower systemic vasodilation and edema relative to conventional NSAIDs.

Parameter	Findings
Absorption	Rapid, ~90 % bioavailability; peak plasma ~1 h post‑dose.
Distribution	Highly protein‑bound (~97 % to albumin). Linear pharmacokinetics.
Metabolism	CYP‑2C9 (primary), minor CYP‑2C19. Extensive first‑pass elimination.
Elimination	Predominantly hepatic; excretion mainly in feces (≈ 80 %) and urine (≈ 16 %).
Half‑life	11 – 12 h (dose‑dependent; 200 mg BID typical).
Special Populations	Reduced CYP‑2C9 activity (e.g., CYP2C9 2/3 alleles) → ↑ exposure; renal decline has minimal impact; hepatic impairment → ↑ plasma levels.

Contraindications:
Known hypersensitivity to celecoxib or other COX‑2 inhibitors.
Active GI ulcer/bleeding.
Severe hepatic impairment (Child‑Pugh C).
Warnings:
Cardiovascular: ↑ risk of myocardial infarction, stroke, heart failure. Avoid high‑dose use (> 200 mg/day) in patients > 65 yrs or with pre‑existing CV disease.
Renal: Overt nephropathy, obstructive uropathy, or oliguria – caution or discontinue.
Reproductive: ACOG recommends avoiding use after 20 weeks gestation; may be safer than conventional NSAIDs.
Drug Interactions: CYP‑2C9 inhibitors (e.g., fluconazole), warfarin (↑ bleeding), methotrexate (↑ toxicity).

Indication	Typical Dose	Form	Notes
OA/RA, AS	200 mg BID (or 400 mg QD for RA not tolerating 200 mg BID)	200 mg oral tablet	Adjust for renal/hepatic impairment.
Post‑op pain	200 mg BID (max 400 mg/day)	Oral	Use for ≤ 2 weeks.
Migraine prophylaxis	400 mg/day (split)	Oral	Non‑approved indication, trial basis.
Note: Initiate on empty stomach for optimal absorption; may be taken with food to reduce GI upset.

Common (≥ 1 %):
Dyspepsia, nausea, headache, abdominal pain, rash, dizziness.
Serious (≤ 0.1 %):
GI ulcer/bleeding, myocardial infarction, stroke, heart failure exacerbation, severe renal impairment, hypersensitivity reactions.
Pregnancy/Neonatal: Use spares pre‑term labor; risk of premature ductus arteriosus closure (≥ 20 weeks gestation).

Baseline: CBC, CMP, BP, urinalysis.
During therapy:
CV: Monitor BP and weight; Educate patients on signs of heart failure.
Renal: eGFR/CrCl at 3‑month intervals for prolonged therapy.
Liver: AST/ALT if hepatic risk factors or signs of liver injury.
GI: Reassess for epigastric pain, melena.
Special Populations: Frequent monitoring in older adults > 65 yrs and in those with CKD stages 3–5.

COX‑2 Selectivity → Lower gastric risk, but not zero—use proton‑pump inhibitor (PPI) prophylaxis in high‑GI‑risk patients (e.g., elderly, concurrent antiplatelets).
Avoid Dose Escalation Post‑first‑Year: Extra‑capsular evidence shows that benefits plateau while CV risk rises after the first year.
CYP‑2C9 Genotyping can guide dose—patients with *CYP2C9* *2/*3 genotype may require a 100 mg BID dose to mitigate over‑exposure and adverse events.
Drug‑Drug Interaction Tip: Co‑administration with warfarin or nitrofurantoin requires periodic INR or renal function checks.
Pregnancy: 200 mg QD may be acceptable earlier in gestation if alternative NSAIDs are contraindicated; however, counsel on the risk of premature closure of the ductus arteriosus.
Post‑operative: Celecoxib can be combined with acetaminophen or opioids to reduce overall NSAID burden while maintaining analgesia (triple‑cocktail approach).

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• *Sources: FDA prescribing information, UpToDate, and major pharmacology texts.*