Nonsteroidal Anti-inflammatory Drug (NSAID), COX-2 Selective

Relief of the signs and symptoms of osteoarthritis; relief of the signs and symptoms of rheumatoid arthritis in adults

C (D after 34 weeks gestation or close to delivery)

In late pregnancy may cause premature closure of the ductus arteriosus. In animal studies, celecoxib has been found to be excreted in milk; it is not known whether celecoxib is excreted in human milk. Because many drugs are excreted in milk, and the potential for serious adverse reactions exists, a decision should be made whether to discontinue nursing or discontinue the drug, taking into account the importance of the drug to the mother.

Hypersensitivity to celecoxib or any component, sulfonamides, aspirin, or other nonsteroidal anti-inflammatory drugs (NSAIDs)

Gastrointestinal irritation, ulceration, bleeding, and perforation may occur with NSAIDs (it is unclear whether celecoxib is associated with rates of these events which are similar to nonselective NSAIDs). Use with caution in patients with a history of GI disease (bleeding or ulcers), decreased renal function, hepatic disease, congestive heart failure, hypertension, or asthma. Anaphylactoid reactions may occur, even with no prior exposure to celecoxib. Use caution in patients with known or suspected deficiency of cytochrome P-450 isoenzyme 2C9.

>10%: Central nervous system: Headache (15.8%)

2% to 10%:

Cardiovascular: Peripheral edema (2.1%)

Central nervous system: Insomnia (2.3%), dizziness (2%)

Dermatologic: Skin rash (2.2%)

Gastrointestinal: Dyspepsia (8.8%), diarrhea (5.6%), abdominal pain (4.1%), nausea (3.5%), flatulence (2.2%)

Neuromuscular & skeletal: Back pain (2.8%)

Respiratory: Upper respiratory tract infection (8.1%), sinusitis (5%), pharyngitis (2.3%), rhinitis (2%)

Miscellaneous: Accidental injury (2.9%)

0.1% to 2%:

Cardiovascular: Hypertension (aggravated), chest pain, myocardial infarction, palpitation, tachycardia, facial edema, peripheral edema

Central nervous system: Migraine, vertigo, hypoesthesia, fatigue, fever, pain, hypotonia, anxiety, depression, nervousness, somnolence

Dermatologic: Alopecia, dermatitis, photosensitivity, pruritus, rash (maculopapular), rash (erythematous), dry skin, urticaria

Endocrine & metabolic: Hot flashes, diabetes mellitus, hyperglycemia, hypercholesterolemia, breast pain, dysmenorrhea, menstrual disturbances, hypokalemia

Gastrointestinal: Constipation, tenesmus, diverticulitis, eructation, esophagitis, gastroenteritis, vomiting, gastroesophageal reflux, hemorrhoids, hiatal hernia, melena, stomatitis, anorexia, increased appetite, taste disturbance, dry mouth, tooth disorder, weight gain

Genitourinary: Prostate disorder, vaginal bleeding, vaginitis, monilial vaginitis, dysuria, cystitis, urinary frequency, incontinence, urinary tract infection,

Hepatic: Elevated transaminases, increased alkaline phosphatase

Hematologic: Anemia, thrombocytopenia, ecchymosis

Neuromuscular & skeletal: Leg cramps, increased CPK, neck stiffness, arthralgia, myalgia, bone disorder, fracture, synovitis, tendonitis, neuralgia, paresthesia, neuropathy, weakness

Ocular: Glaucoma, blurred vision, cataract, conjunctivitis, eye pain

Otic: Deafness, tinnitus, earache, otitis media

Renal: Increased BUN, increased creatinine, albuminuria, hematuria, renal calculi

Respiratory: Bronchitis, bronchospasm, cough, dyspnea, laryngitis, pneumonia, epistaxis

Miscellaneous: Allergic reactions, flu-like syndrome, breast cancer, herpes infection, bacterial infection, moniliasis, viral infection, increased diaphoresis

<0.1% (limited to severe): Congestive heart failure, ventricular fibrillation, pulmonary embolism, syncope, cerebrovascular accident, gangrene, thrombophlebitis, thrombocytopenia, ataxia, acute renal failure, intestinal obstruction, pancreatitis, intestinal perforation, gastrointestinal bleeding, colitis, esophageal perforation, sepsis, sudden death

Symptoms may include epigastric pain, drowsiness, lethargy, nausea, and vomiting; gastrointestinal bleeding may occur. Rare manifestations include hypertension, respiratory depression, coma, and acute renal failure.

Treatment is symptomatic and supportive; forced diuresis, hemodialysis and/or urinary alkalinization may not be useful

Celecoxib may be a cytochrome oxidase P-450 isoenzyme 2C9 substrate and an inhibitor of isoenzyme 2D6

Increased effect: Inhibitors of isoenzyme 2C9 may result in significant increases in celecoxib concentrations. Coadministration of drugs by 2D6 may result in increased serum concentrations of these agents. Fluconazole increases celecoxib concentrations two-fold. Lithium concentrations may be increased by celecoxib. Celecoxib may be used with low-dose aspirin, however rates of gastrointestinal bleeding may be increased with coadministration. May increase INR when used concurrently with warfarin (case reports).

Inhibits prostaglandin synthesis by decreasing the activity of the enzyme, cyclooxygenase-2 (COX-2), which results in decreased formation of prostaglandin precursors. Celecoxib does not inhibit cyclooxygenase-1 (COX-1) at therapeutic concentrations.

Distribution: V_d (apparent): 400 L

Protein binding: 97% (albumin)

Metabolism: Metabolized by cytochrome P-450 isoenzyme 2C9 (CYP 2C9)

Bioavailability, absolute: Has not been determined

Half-life: 11 hours

Time to peak: 3 hours

Elimination: In urine as metabolites (<3% unchanged drug)

Adults: Oral:

Rheumatoid arthritis: 100-200 mg twice daily

Dosing adjustment in renal impairment: No specific dosage adjustment is recommended

Dosing adjustment in hepatic impairment: Reduced dosage is recommended (AUC may be increased by 40% to 180%)

Dosing adjustment for elderly: No specific adjustment is recommended. However, the AUC in elderly patients may be increased by 50% as compared to younger subjects. Use the lowest recommended dose in patients weighing <50 kg.

Peak concentrations are delayed and AUC is increased by 10% to 20% when taken with a high-fat meal; celecoxib may be taken without regard to meals

Periodic LFTs

May cause dizziness and insomnia; may rarely, cause anxiety, depression, nervousness, or somnolence

Effects of benzodiazepines and antidepressants may be altered. Lithium concentrations may be increased by celecoxib via decreased renal lithium clearance; dose adjustment may be needed.

No information available to require special precautions

Nonselective NSAIDs are known to reversibly decrease platelet aggregation via mechanisms different than observed with aspirin. According to the manufacturer, celecoxib, at single dose up to 800 mg and multiple doses of 600 mg twice daily, had no effect on platelet aggregation or bleeding time. Comparative NSAIDs (naproxen 500 mg twice daily, ibuprofen 800 mg three times daily or diclofenac 75 mg twice daily) significantly reduced platelet aggregation and prolonged the bleeding times.

Do not take more than recommended dose. May be taken with food to reduce GI upset. Do not take with antacids. Avoid alcohol, aspirin, and OTC medication unless approved by prescriber. You may experience dizziness, confusion, or blurred vision (avoid driving or engaging in tasks requiring alertness until response to drug is known); anorexia, nausea, vomiting, taste disturbance, gastric distress (small frequent meals, frequent mouth care, sucking lozenges, or chewing gum may help). GI bleeding, ulceration, or perforation can occur with or without pain; it is unclear whether celecoxib has rates of these events which are similar to nonselective NSAIDs. Stop taking medication and report immediately stomach pain or cramping, unusual bleeding or bruising, or blood in vomitus, stool, or urine. Report persistent insomnia; skin rash; unusual fatigue or easy bruising or bleeding; muscle pain, tremors, or weakness; sudden weight gain; changes in hearing (ringing in ears); changes in vision; changes in urination pattern; or respiratory difficulty. Pregnancy/breast-feeding precautions: Inform prescriber if you are or intend to be pregnant. Consult prescriber if breast-feeding.

Capsule: 100 mg, 200 mg

Geis GS, et al, "Efficacy and Safety of Celecoxib, A Specific COX-2 Inhibitor, in Patients With Rheumatoid Arthritis," Arthritis Rheum, 1998, 41(9 Suppl):S316:1699.

Karim A, et al, "Celecoxib, A Specific COX-2 Inhibitor, Lacks Significant Drug-Drug Interactions With Methotrexate or Warfarin," Arthritis Rheum, 1998, 41(9 Suppl):S315:1698.

Lane NE, "Pain Management in Osteoarthritis: The Role of COX-2 Inhibitors," J Rheumatol, 1997, 24(Suppl 49):20-4.

Lipsky PE and Isakson PC, "Outcome of Specific COX-2 Inhibition in Rheumatoid Arthritis," J Rheumatol, 1997, 24(Suppl 49):9-14.

Mengle-Gaw L, et al, "A Study of the Platelet Effects of SC-58635, A Novel COX-2 Selective Inhibitor," Arthritis Rheum, 1998, 41(9 Suppl):S93:374.

Needleman P and Isakson PC, "The Discovery and Function of COX-2," J Rheumatol, 1997, 24(Suppl 49):6-8.

Simon LS, et al, "Preliminary Study of the Safety and Efficacy of SC-58635, A Novel Cyclo-oxygenase 2 Inhibitor: Efficacy and Safety in Two Placebo-Controlled Trials in Osteoarthritis and Rheumatoid Arthritis, and Studies of Gastrointestinal and Platelet Effects," Arthritis Rheum, 1998, 41:1591-1602.