Celecoxib: uses, appearance and warnings

Celecoxib is indicated Celecoxib is a nonsteroidal anti-inflammatory drug indicated for: Osteoarthritis (OA) ( 1.1 ) Rheumatoid Arthritis (RA) ( 1.2 ) Juvenile Rheumatoid Arthritis (JRA) in patients 2 years and older ( 1.3 ) Ankylosing Spondylitis (AS) ( 1.4 ) Acute Pain (AP) ( 1.5 ) Primary Dysmenorrhea (PD) ( 1.6 ) 1.1 Osteoarthritis (OA) For the management of the signs and symptoms of OA [ see Clinical Studies (14.1) ] . 1.2 Rheumatoid Arthritis (RA) For the management of the signs and symptoms of RA [ see Clinical Studies (14.2) ] . 1.3 Juvenile Rheumatoid Arthritis (JRA) For the management of the signs and symptoms of JRA in patients 2 years and older [ see Clinical Studies (14.3) ] . 1.4 Ankylosing Spondylitis (AS) For the management of the signs and symptoms of AS [ see Clinical Studies (14.4) ] . 1.5 Acute Pain For the management of acute pain in adults [ see Clinical Studies (14.5) ] . 1.6 Primary Dysmenorrhea For the management of primary dysmenorrhea [ see Clinical Studies (14.5) ] .

Celecoxib capsules: 50 mg are white capsules, with "OE" imprinted on the cap and "50" on the body. 100 mg are white capsules, with "OE" imprinted on the cap and "100" on the body. 200 mg are white capsules, with "OE" imprinted on the cap and "200" on the body. Celecoxib capsules: 50 mg, 100 mg, 200 mg ( 3 )

Celecoxib 50 mg capsules are white, with "OE" imprinted on the cap and "50" on the body, supplied as: NDC 83301-0028-1 bottle of 60 with child-resistant closure Celecoxib 100 mg capsules are white, with "OE" imprinted on the cap and "100" on the body, supplied as: NDC 83301-0011-3 bottle of 30 with child-resistant closure NDC 83301-0011-1 bottle of 100 with child-resistant closure NDC 83301-0011-2 bottle of 500 Celecoxib 200 mg capsules are white, with "OE" imprinted on the cap and "200" on the body, supplied as: NDC 83301-0012-3 bottle of 30 with child-resistant closure NDC 83301-0012-1 bottle of 100 with child-resistant closure NDC 83301-0012-2 bottle of 500 Storage Store at room temperature 20° to 25°C (68° to 77°F); excursions permitted from 15° to 30°C (59° to 86°F) [ See USP Controlled Room Temperature ]. Dispense in tight (USP), child-resistant containers.

Celecoxib is contraindicated in the following patients: Known hypersensitivity (e.g., anaphylactic reactions and serious skin reactions) to celecoxib, any components of the drug product [ see Warnings and Precautions (5.7 , 5.9) ] . History of asthma, urticaria, or other allergic-type reactions after taking aspirin or other NSAIDs. Severe, sometimes fatal, anaphylactic reactions to NSAIDs, have been reported in such patients [ see Warnings and Precautions (5.7 , 5.8) ] . In the setting of CABG surgery [ see Warnings and Precautions (5.1) ] . In patients who have demonstrated allergic-type reactions to sulfonamides [ see Warnings and Precautions (5.7) ] . Known hypersensitivity to celecoxib, or any components of the drug product or sulfonamides. ( 4 ) History of asthma, urticaria, or other allergic-type reactions after taking aspirin or other NSAIDs. ( 4 ) In the setting of CABG surgery. ( 4 )

Hepatotoxicity: Inform patients of warning signs and symptoms of hepatotoxicity. Discontinue if abnormal liver tests persist or worsen, or if clinical signs and symptoms of liver-disease develop (5.3). Hypertension: Patients taking some antihypertensive medications may have an impaired response when taking NSAIDs. Monitor blood pressure (5.4, 7). Heart Failure and Edema: Avoid use of celecoxib in patients with severe heart failure unless benefits outweigh risks (5.5). Renal Toxicity: Monitor renal function in patients with renal/hepatic impairment, heart failure, dehydration, or hypovolemia. Avoid use in advanced renal disease unless benefits outweigh risks (5.6). Anaphylactic Reactions: Seek emergency help if an anaphylactic reaction occurs (5.7). Exacerbation of Asthma Related to Aspirin Sensitivity: Celecoxib is contraindicated in aspirin-sensitive asthma. Monitor patients with pre-existing asthma (without aspirin sensitivity) (5.8). Serious Skin Reactions: Discontinue celecoxib at the first appearance of skin rash or other signs of hypersensitivity (5.9). Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS): Discontinue and evaluate clinically (5.10). Fetal Toxicity: Limit NSAID use between ~20–30 weeks’ gestation because of oligohydramnios/fetal renal dysfunction; avoid from ~30 weeks onward due to premature ductus arteriosus closure (5.11, 8.1). Hematologic Toxicity: Monitor hemoglobin or hematocrit in patients with any signs or symptoms of anemia (5.12, 7). 5.1 Cardiovascular Thrombotic Events Clinical trials of several cyclooxygenase-2 (COX-2) selective and nonselective NSAIDs of up to three years duration have shown an increased risk of serious cardiovascular (CV) thrombotic events, including myocardial infarction (MI) and stroke, which can be fatal. Based on available data, it is unclear that the risk for CV thrombotic events is similar for all NSAIDs. The relative increase in serious CV thrombotic events over baseline conferred by NSAID use appears to be similar in those with and without known CV disease or risk factors for CV disease. However, patients with known CV disease or risk factors had a higher absolute incidence of excess serious CV thrombotic events, due to their increased baseline rate. Some observational studies found that this increased risk of serious CV thrombotic events began as early as the first weeks of treatment. The increase in CV thrombotic risk has been observed most consistently at higher doses. In the APC (Adenoma Prevention with Celecoxib) trial, there was about a threefold increased risk of the composite endpoint of cardiovascular death, MI, or stroke for the celecoxib 400 mg twice daily and celecoxib 200 mg twice daily treatment arms compared to placebo. The increases in both celecoxib dose groups versus placebo-treated patients were mainly due to an increased incidence of myocardial infarction [ see Clinical Studies (14.7) ] . A randomized controlled trial entitled the Prospective Randomized Evaluation of Celecoxib Integrated Safety vs. Ibuprofen or Naproxen (PRECISION) was conducted to assess the relative cardiovascular thrombotic risk of a COX-2 inhibitor, celecoxib, compared to the non-selective NSAIDs naproxen and ibuprofen. Celecoxib 100 mg twice daily was non-inferior to naproxen 375 to 500 mg twice daily and ibuprofen 600 to 800 mg three times daily for the composite endpoint of the Antiplatelet Trialists' Collaboration (APTC), which consists of cardiovascular death (including hemorrhagic death), non-fatal myocardial infarction, and non-fatal stroke [ see Clinical Studies (14.6) ] . To minimize the potential risk for an adverse CV event in NSAID-treated patients, use the lowest effective dose for the shortest duration possible. Physicians and patients should remain alert for the development of such events, throughout the entire treatment course, even in the absence of previous CV symptoms. Patients should be informed about the symptoms of serious CV events and the steps to take if they occur. There is no consistent evidence that concurrent use of aspirin mitigates the increased risk of serious CV thrombotic events associated with NSAID use. The concurrent use of aspirin and an NSAID, such as celecoxib, increases the risk of serious gastrointestinal (GI) events [ see Warnings and Precautions (5.2) ] . Status Post Coronary Artery Bypass Graft (CABG) Surgery Two large, controlled clinical trials of a COX-2 selective NSAID for the treatment of pain in the first 10 to 14 days following CABG surgery found an increased incidence of myocardial infarction and stroke. NSAIDs are contraindicated in the setting of CABG [ see Contraindications (4) ] . Post-MI Patients Observational studies conducted in the Danish National Registry have demonstrated that patients treated with NSAIDs in the post-MI period were at increased risk of reinfarction, CV-related death, and all-cause mortality beginning in the first week of treatment. In this same cohort, the incidence of death in the first year post-MI was 20 per 100 person years in NSAID-treated patients compared to 12 per 100 person years in non-NSAID exposed patients. Although the absolute rate of death declined somewhat after the first year post-MI, the increased relative risk of death in NSAID users persisted over at least the next four years of follow-up. Avoid the use of celecoxib in patients with a recent MI unless the benefits are expected to outweigh the risk of recurrent CV thrombotic events. If celecoxib is used in patients with a recent MI, monitor patients for signs of cardiac ischemia. 5.2 Gastrointestinal Bleeding, Ulceration, and Perforation NSAIDs, including celecoxib cause serious gastrointestinal (GI) adverse events including inflammation, bleeding, ulceration, and perforation of the esophagus, stomach, small intestine, or large intestine, which can be fatal. These serious adverse events can occur at any time, with or without warning symptoms, in patients treated with celecoxib. …

The following adverse reactions are discussed in greater detail in other sections of the labeling: Cardiovascular Thrombotic Events [ see Warnings and Precautions (5.1) ] GI Bleeding, Ulceration and Perforation [ see Warnings and Precautions (5.2) ] Hepatotoxicity [ see Warnings and Precautions (5.3) ] Hypertension [ see Warnings and Precautions (5.4) ] Heart Failure and Edema [ see Warnings and Precautions (5.5) ] Renal Toxicity and Hyperkalemia [ see Warnings and Precautions (5.6) ] Anaphylactic Reactions [ see Warnings and Precautions (5.7) ] Serious Skin Reactions [ see Warnings and Precautions (5.9) ] Hematologic Toxicity [ see Warnings and Precautions (5.12) ] Most common adverse reactions in arthritis trials (> 2% and > placebo) are: abdominal pain, diarrhea, dyspepsia, flatulence, peripheral edema, accidental injury, dizziness, pharyngitis, rhinitis, sinusitis, upper respiratory …

See Table 3 for clinically significant drug interactions with celecoxib. Table 3: Clinically Significant Drug Interactions with Celecoxib Drugs that Interfere with Hemostasis Clinical Impact: Celecoxib and anticoagulants such as warfarin have a synergistic effect on bleeding. The concomitant use of celecoxib and anticoagulants have an increased risk of serious bleeding compared to the use of either drug alone. Serotonin release by platelets plays an important role in hemostasis. Case-control and cohort epidemiological studies showed that concomitant use of drugs that interfere with serotonin reuptake and an NSAID may potentiate the risk of bleeding more than an NSAID alone. …