Selective COX-2 Inhibitors Data - Uses, Dosage, Drug class, Brand name, Warnings, etc

Pharmacology	Inhibition of the COX-2 enzyme isoform is thought to be responsible for the anti-inflammatory effects of NSAIDs, whereas inhibition of COX-1 results in GI and possibly other side effects. A relatively selective COX-2 inhibitor should combine anti-inflammatory, analgesic, and antipyretic efficacies equivalent to older, nonselective NSAIDs with improved safety.
Administration and Adult Dosage	- Celecoxib: • PO for osteoarthritis: 100 mg twice daily or 200 mg daily • PO for rheumatoid arthritis: 100–200 mg twice daily • PO for familial adenomatous polyposis: 400 mg twice daily - Rofecoxib: • PO for osteoarthritis: 12.5–25 mg once daily • PO for acute pain and primary dysmenorrhea: 50 mg/day as needed, to a maximum of 5 days of consecutive use
Special Populations - Pediatric Dosage	- (<18 yr) Safety and efficacy not established for either agent.
Special Populations - Geriatric Dosage	- Celecoxib: Dosage adjustment usually not necessary; use the lowest effective dose; for patients <50 kg, initiate at the lowest recommended dose - Rofecoxib: Dosage adjustment not necessary; initiate with the lowest recommended dose
Dosage Forms	- Celecoxib: Capsule: 100, 200 mg - Rofecoxib: Tablet: 12.5, 25, 50 mg; Suspension: 2.5, 5 mg/mL
Patient Instructions	- This drug can cause headache, upset stomach, or diarrhea - Report edema, rash, unusual weight gain, or signs and symptoms of gastrointestinal bleeding to your physician - Avoid products containing aspirin and nonsteroidal anti-inflammatory drugs unless directed - Take without regard to meals, except take celecoxib 400 mg twice daily with food
Missed Doses	- If taken on a regular schedule, take a missed dose as soon as remembered - If near the time for the next dose, take that dose only; do not double the dose or take extra
Pharmacokinetics - Fate	- Celecoxib: • Absolute bioavailability not studied • Peak plasma levels in 3 hr; high-fat meals delay peak by 1–2 hr with 10–20% increased absorption • Protein Binding: 97% • Metabolism: Predominantly hepatic by CYP2C9 to inactive metabolites • Excretion: <3% unchanged in urine or feces - Rofecoxib: • Bioavailability: 93% • Peak plasma levels in 2–3 hr; high-fat meal delays peak by 1–2 hr with no effect on concentration or absorption • Protein Binding: 87% • Metabolism: Predominantly by cytosolic enzymes with minor P450 involvement to inactive metabolites • Excretion: <1% unchanged in urine
Pharmacokinetics - t¹⁄₂	- Celecoxib: 11 hr - Rofecoxib: 17 hr
Adverse Reactions & Side Effects	- GI toxicity, dyspepsia, abdominal pain, nausea, vomiting, and diarrhea at a rate similar to placebo and less than conventional NSAIDs - Renal and liver effects equivalent to other NSAIDs
Contraindications	- History of aspirin- or NSAID-induced asthma, urticaria, or allergic-type reactions - Celecoxib: Allergy to sulfonamides
Precautions & Warnings	- Use cautiously in patients with pre-existing asthma, renal or hepatic compromise, fluid retention, hypertension, or CHF
Drug Interactions	- May diminish effects of ACE inhibitors, furosemide, and thiazide diuretics - May increase lithium plasma levels - Concurrent use with anticoagulants increases bleeding risk - Celecoxib: CYP2C9 inhibitors (e.g., fluconazole) increase serum concentrations - Rofecoxib: Increases methotrexate serum concentrations (23%) and reduces its renal clearance; rifampin decreases rofecoxib serum levels by 50%
Parameters to Monitor	- Monitor for weight gain, renal function during long-term use, and occult blood loss if on concomitant aspirin or anticoagulant therapy
Class and Drug Brand Name	- Class: Nonsteroidal Anti-Inflammatory Drugs - Brand Names: Celebrex (celecoxib), Vioxx (rofecoxib)
Notes	- Celecoxib: 100 or 200 mg twice daily is as effective as naproxen 500 mg twice daily for osteoarthritis and produces fewer gastroduodenal ulcers than naproxen, diclofenac, or ibuprofen - Rofecoxib: 12.5 or 25 mg is as effective as ibuprofen 800 mg three times daily and diclofenac 50 mg three times daily for osteoarthritis and produces fewer gastroduodenal ulcers than ibuprofen - Parecoxib, an injectable COX-2 inhibitor, is under study for acute pain; doses of 20 and 40 mg are as effective as injectable ketorolac with improved safety - Parecoxib is a prodrug of valdecoxib, an oral drug pending FDA approval

References

Hand of Clinical Drug Data