CELECOXIB
Clinical safety rating: avoid
Positive evidence of fetus risks but benefits may outweigh risks in some cases
Selective cyclooxygenase-2 (COX-2) inhibitor, reducing prostaglandin synthesis involved in inflammation and pain.
| Metabolism | Hepatic via CYP2C9 (major) and CYP3A4 (minor); metabolites include inactive glucuronide conjugates. |
| Excretion | Primarily hepatic metabolism via CYP2C9 to inactive metabolites (hydroxycelecoxib and carboxylic acid metabolite); <3% excreted unchanged in urine; ~27% excreted in feces as metabolites; minimal biliary excretion. |
| Half-life | Terminal elimination half-life is approximately 11 hours (range 8–12 hours) in healthy adults; prolonged in poor CYP2C9 metabolizers (up to 130 hours) and in patients with moderate to severe hepatic impairment. |
| Protein binding | Approximately 97% bound to albumin, primarily to albumin; binding is concentration-independent. |
| Volume of Distribution | Volume of distribution (Vd/F) is approximately 400 L (5.7 L/kg for a 70 kg adult), indicating extensive tissue distribution. |
| Bioavailability | Oral bioavailability is not well-defined due to lack of intravenous formulation; absolute bioavailability unknown, but absorption is rapid and complete; food delays absorption (peak concentration delayed by 1–2 hours) but does not reduce extent. |
| Onset of Action | Oral: analgesic effect begins within 30–60 minutes; peak plasma concentrations at 2–4 hours. |
| Duration of Action | Duration of analgesic effect is approximately 12–24 hours following a single oral dose; for once-daily dosing for osteoarthritis, sustained efficacy over 24 hours with consistent trough levels. |
100 mg orally twice daily or 200 mg orally once daily. Maximum dose 400 mg/day.
| Dosage form | CAPSULE |
| Renal impairment | GFR 30-60 mL/min: no adjustment. GFR <30 mL/min or dialysis: contraindicated due to increased risk of fluid retention and renal toxicity. |
| Liver impairment | Child-Pugh Class A (mild): no adjustment. Child-Pugh Class B (moderate): reduce dose by 50% (maximum 200 mg/day). Child-Pugh Class C (severe): not recommended. |
| Pediatric use | For juvenile rheumatoid arthritis: weight ≥10 kg to ≤25 kg: 50 mg twice daily; weight >25 kg: 100 mg twice daily. Maximum dose 6 mg/kg/day. |
| Geriatric use | Initiate at lowest recommended dose (100 mg/day) in patients <50 kg or frail. Use caution due to increased risk of GI bleeding, renal impairment, and drug interactions. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
ACE inhibitors and ARBs may have diminished antihypertensive effect Increases risk of serious cardiovascular thrombotic events including MI and stroke.
| Breastfeeding | Celecoxib is excreted into breast milk in low amounts (M/P ratio approximately 0.18). Limited data suggest no adverse effects in infants. Caution is advised due to potential for cardiovascular and renal effects in the infant. Use lowest effective dose for shortest duration. |
| Teratogenic Risk | First trimester: NSAIDs including celecoxib are associated with a small increased risk of cardiac defects and gastroschisis. Second trimester: Avoid use due to potential fetal renal impairment and oligohydramnios. Third trimester: Contraindicated due to risk of premature closure of ductus arteriosus, pulmonary hypertension, and oligohydramnios. |
■ FDA Black Box Warning
Increased risk of serious cardiovascular thrombotic events, myocardial infarction, and stroke, which can be fatal. Risk increases with duration of use and in patients with cardiovascular risk factors. Contraindicated for treatment of perioperative pain in coronary artery bypass graft (CABG) surgery.
| Common Effects | rheumatoid arthritis |
| Serious Effects |
Known hypersensitivity to celecoxib or sulfonamides; history of asthma, urticaria, or allergic-type reactions after taking aspirin or NSAIDs; treatment of perioperative pain in CABG surgery; advanced renal disease; third trimester of pregnancy.
| Precautions | Cardiovascular thrombotic events; gastrointestinal bleeding, ulceration, and perforation; hypertension; fluid retention and edema; serious skin reactions (e.g., Stevens-Johnson syndrome); renal toxicity; anaphylactoid reactions; avoid in late pregnancy (may cause premature closure of ductus arteriosus). |
Loading safety data…
| Fetal Monitoring | Monitor maternal blood pressure, renal function, and signs of bleeding. Fetal monitoring includes ultrasound assessment for oligohydramnios and ductus arteriosus patency if used beyond 20 weeks gestation. |
| Fertility Effects | Celecoxib may impair female fertility by inhibiting prostaglandin synthesis, potentially interfering with ovulation and implantation. Reversible upon discontinuation. |
| Food/Dietary |
| Take with food or milk to minimize GI upset. Avoid high-fat meals as they may delay absorption but do not significantly alter total exposure. Do not consume alcohol regularly as it increases risk of gastrointestinal bleeding. Avoid grapefruit juice? No significant interaction known. Antacids containing magnesium or aluminum may decrease celecoxib absorption; separate by at least 2 hours. |
| Clinical Pearls | Celecoxib is a selective COX-2 inhibitor with lower GI ulcer risk than nonselective NSAIDs, but it does not reduce cardiovascular risk; avoid in patients with ischemic heart disease or cerebrovascular disease. Use lowest effective dose for shortest duration. Celecoxib is sulfonamide-based; contraindicated in patients with sulfonamide allergy. Monitor renal function in elderly, volume-depleted, or those on diuretics/ACEi/ARBs. May mask fever in infection. Onset of analgesia is rapid (within 1 hour). |
| Patient Advice | Take with food or milk to reduce stomach upset, but avoid antacids containing magnesium or aluminum (they lower absorption). · Do not take aspirin or other NSAIDs (ibuprofen, naproxen) while on celecoxib unless prescribed. · Report signs of heart attack (chest pain, shortness of breath) or stroke (weakness, slurred speech) immediately. · Stop celecoxib and seek medical help if you develop rash, hives, or swelling (possible sulfa allergy). · Celecoxib may cause fluid retention; monitor for swelling in legs or weight gain, especially if you have high blood pressure or heart failure. · Avoid alcohol while taking this medication as it increases risk of stomach bleeding. · Do not use before or after coronary artery bypass graft (CABG) surgery. |