General: CELEBREX cannot be expected to substitute for corticosteroids or to treat corticosteroid insufficiency. Abrupt discontinuation of corticosteroids may lead to disease exacerbation of corticosteroid-responsive illness. Patients on prolonged corticosteroid therapy should have their therapy tapered slowly if a decision is made to discontinue corticosteroids.
The pharmacological activity of CELEBREX in reducing inflammation, and possibly fever, may diminish the utility of these diagnostic signs in detecting infectious complications of presumed non-infectious, painful conditions.
Hepatic Effects: Borderline elevations of one or more liver tests may occur in up to 15% of patients taking NSAIDs, and notable elevations of ALT or AST (approximately three or more times the upper limit of normal) have been reported in approximately 1% of patients in clinical trials with NSAIDs. These laboratory abnormalities may progress, may remain unchanged, or may be transient with continuing therapy. Rare cases of severe hepatic reactions, including jaundice and fatal fulminant hepatitis, liver necrosis and hepatic failure (some with fatal outcome) have been reported with NSAIDs, including CELEBREX (see Post-marketing experience under ADVERSE REACTIONS). In controlled clinical trials of CELEBREX, the incidence of borderline elevations (greater than or equal to 1.2 times and less than 3 times the upper limit of normal) of liver tests was 6% for CELEBREX and 5% for placebo, and approximately 0.2% of patients taking CELEBREX and 0.3% of patients taking placebo had notable elevations of ALT and AST.
A patient with symptoms and/or signs suggesting liver dysfunction, or in whom an abnormal liver test has occurred, should be monitored carefully for evidence of the development of a more severe hepatic reaction while on therapy with CELEBREX. If clinical signs and symptoms consistent with liver disease develop, or if systemic manifestations occur (e.g., eosinophilia, rash, etc.), CELEBREX should be discontinued.
Rare cases of severe hepatic reactions, including fulminant hepatitis (some with fatal outcome), liver necrosis, hepatic failure (some with fatal outcome or requiring liver transplant), have been reported with celecoxib).
Hematological Effects: Anemia is sometimes seen in patients receiving CELEBREX. In controlled clinical trials the incidence of anemia was 0.6% with CELEBREX and 0.4% with placebo. Patients on long-term treatment with CELEBREX should have their hemoglobin or hematocrit checked if they exhibit any signs or symptoms of anemia or blood loss. CELEBREX does not generally affect platelet counts, prothrombin time (PT), or partial thromboplastin time (PTT), and does not appear to inhibit platelet aggregation at indicated dosages (see Pharmacology: Clinical Studies: Special Studies: Platelets under Actions).
Pre-existing Asthma: Patients with asthma may have acetyl salicylic acid -sensitive asthma. The use of acetyl salicylic acid in patients with acetyl salicylic acid -sensitive asthma has been associated with severe bronchospasm which can be fatal. Since cross reactivity, including bronchospasm, between acetyl salicylic acid and other non-steroidal anti-inflammatory drugs has been reported in such acetyl salicylic acid - sensitive patients, CELEBREX should not be administered to patients with this form of acetyl salicylic acid sensitivity and should be used with caution in patients with pre-existing asthma.
CYP 2D6 inhibition: Celecoxib has shown to be a moderately potent CYP2D6 inhibitor. For drugs that are metabolized by CYP2D6, a dose reduction during initiation of celecoxib treatment or a dose increase upon termination of celecoxib treatment may be necessary (see Interactions).
Information for Patients: Patients should be informed of the following information before initiating therapy with CELEBREX and periodically during the course of ongoing therapy. Patients should also be encouraged to read the NSAID Medication Guide that accompanies each prescription dispensed.
CELEBREX, like other NSAIDs, may cause serious CV side effects, such as MI or stroke, which may result in hospitalization and even death. Although serious CV events can occur without warning symptoms, patients should be alert for the signs and symptoms of chest pain, shortness of breath, weakness, slurring of speech, and should ask for medical advice if they observe any of these signs or symptoms. Patients should be apprised of the importance of this follow-up (see CV Effects under WARNINGS).
CELEBREX, like other NSAIDs, can cause gastrointestinal discomfort and, rarely, more serious side effects, such as ulcers and bleeding, which may result in hospitalization and even death. Although serious GI tract ulcerations and bleeding can occur without warning symptoms, patients should be alert for the signs and symptoms of ulcerations and bleeding, and should ask for medical advice when they observe any signs or symptoms that are indicative of these disorders, including epigastric pain, dyspepsia, melena, and hematemesis. Patients should be apprised of the importance of this follow-up (see Gastrointestinal (GI) Effects: Risk of Gastrointestinal Ulceration, Bleeding, and Perforation under WARNINGS).
Patients should be advised to stop the drug immediately if they develop any type of rash and contact their physicians as soon as possible. CELEBREX is a sulfonamide and can cause serious skin side effects, such as exfoliative dermatitis, SJS, and TENS, which may result in hospitalizations and even death. These reactions can occur with all NSAIDs, even non-sulfonamides. Although serious skin reactions may occur without warning, patients should be alert for the signs and symptoms of skin rash and blisters, fever, or other signs of hypersensitivity, such as itching, and should ask for medical advice when observing any indicative signs or symptoms. Patients with prior history of sulfa allergy should not take CELEBREX.
Patients should promptly report signs or symptoms of unexplained weight gain or edema to their physicians.
Patients should be informed of the warning signs and symptoms of hepatotoxicity (e.g., fatigue, lethargy, pruritus, jaundice, right upper quadrant tenderness, and "flu-like" symptoms). Patients should be instructed that they should stop therapy and seek immediate medical therapy if these signs and symptoms occur.
Patients should be informed of the signs and symptoms of an anaphylactoid reaction (e.g., difficulty breathing, swelling of the face or throat). Patients should be instructed to seek immediate emergency assistance if they develop any of these signs and symptoms (see Anaphylactoid Reactions under WARNINGS).
Patients should be informed that in late pregnancy CELEBREX should be avoided because it may cause premature closure of the ductus arteriosus.
Laboratory Tests: Because serious GI tract ulcerations and bleeding can occur without warning symptoms, physicians should monitor for signs or symptoms of GI bleeding.
Patients on long-term treatment with NSAIDs, should have a CBC and a chemistry profile checked periodically. If clinical signs and symptoms consistent with liver or renal disease develop, systemic manifestations occur (e.g., eosinophilia, rash, etc) or if abnormal liver tests or renal tests persist or worsen, CELEBREX should be discontinued.
In controlled clinical trials, elevated BUN occurred more frequently in patients receiving CELEBREX compared with patients on placebo. This laboratory abnormality was also seen in patients who received comparator NSAIDs in these studies. The clinical significance of this abnormality has not been established.
Use in Children: Safety and effectiveness in pediatric patients below the age of 18 years have not been evaluated.
Use in Elderly: Of the total number of patients who received CELEBREX in clinical trials, more than 3,300 were 65-74 years of age, while approximately 1,300 additional patients were 75 years and over. No substantial differences in effectiveness were observed between these subjects and younger subjects.
In clinical studies comparing renal function as measured by the GFR, BUN and creatinine, and platelet function as measured by bleeding time and platelet aggregation, the results were not different between elderly and young volunteers.
However, as with other NSAIDs, including those that selectively inhibit COX-2, there have been more spontaneous post-marketing reports of fatal GI events and acute renal failure in the elderly than in younger patients (see Gastrointestinal (GI) Effects: Risk of GI Ulceration, Bleeding, and Perforation under WARNINGS).