Celebrex (Celecoxib) Contraindications and Precautions
- coronary artery bypass graft surgery (CABG)
- NSAID hypersensitivity
- salicylate hypersensitivity
- sulfonamide hypersensitivity
- acute bronchospasm
- alcoholism
- anemia
- angina
- anticoagulant therapy
- asthma
- bone marrow suppression
- breast-feeding
- cardiac disease
- cerebrovascular disease
- children
- corticosteroid therapy
- dehydration
- edema
- elderly
- GI bleeding
- GI disease
- GI perforation
- heart failure
- hepatic disease
- hypertension
- hypovolemia
- immunosuppression
- jaundice
- myocardial infarction
- nasal polyps
- peptic ulcer disease
- peripheral edema
- peripheral vascular disease
- pregnancy
- renal disease
- renal failure
- renal impairment
- stroke
- thrombophlebitis
- tobacco smoking
- urticaria
Celebrex Contraindications/Precautions
Celecoxib is contraindicated in patients with known hypersensitivity to the drug, its components, or sulfonamide hypersensitivity (celecoxib contains a sulfonamide side chain). However, celecoxib does not contain the aromatic amine or the N1-substituent that are present in sulfonamide antibiotics. Conflicting information exists regarding whether or not cross-sensitivity exists between all sulfonamide-containing medications, including celecoxib. Of 6 patients with positive hypersensitivity results to sulfamethoxazole, all tolerated an oral celecoxib challenge of 10 mg and then 100 mg 1 hour later. Additionally, 5 of the 6 patients continued to receive celecoxib uneventfully; 1 stopped therapy after 12 days due to GI adverse events. The other patient’s physician did not prescribe celecoxib due to a perceived risk. A meta-analysis of 11,008 patients from 14 trials demonstrated that the incidence of allergic reactions with celecoxib was not significantly different from placebo or active comparators (i.e., other NSAIDs). The subset of patients with a history of sulfonamide hypersensitivity had a 3- to 6-fold higher incidence of dermatologic reactions in general than did the entire arthritis trial cohort. Although the incidence of dermatologic reactions occurred with greater frequency in patients with sulfonamide hypersensitivity, the trend was consistent across all treatment groups (i.e., celecoxib, placebo, NSAIDs).
Celecoxib is contraindicated in patients with salicylate hypersensitivity or NSAID hypersensitivity who have experienced asthma, urticaria, or other allergic reactions after taking aspirin or other NSAIDs. Severe, rarely fatal, anaphylactoid reactions to NSAIDs have been reported in such patients. A study of patients with history of a cutaneous reaction to NSAIDs demonstrated that the safety profile of more selective COX-2 inhibitors varies by drug. Of the NSAID-sensitive patients treated with celecoxib, one-third (33.3%) had a reaction. Celecoxib should not be used in patients with aspirin-sensitive asthma or the aspirin triad because of the approximate 5% cross-sensitivity that occurs between aspirin and NSAIDs. The triad typically occurs in patients with asthma who experience rhinitis with or without nasal polyps, or who experience severe, potentially fatal, acute bronchospasm after taking aspirin or other NSAIDs. In one report, celecoxib did not induce bronchospasm in 27 patients with asthma and aspirin intolerance. However, the authors recommend that selective COX-2 inhibitors only be given to patients with aspirin-sensitive asthma in a trial setting until more information is available.
Because serious GI tract ulceration and bleeding can occur without warning or symptoms, patients receiving celecoxib should be monitored for signs and symptoms of GI bleeding. NSAIDs, including those that selectively inhibit COX-2, should be prescribed with extreme caution in patients with a prior history of GI bleeding, GI perforation, or ulcerative GI disease. Most spontaneous reports of fatal GI events are in elderly or debilitated patients and therefore, special care should be taken in treating this population. The incidence of adverse experiences tended to be higher in elderly patients; however, no substantial differences in effectiveness have been observed between elderly and younger patients. As compared with younger adults, patients over 65 years of age had a 40% higher maximum serum concentration and a 50% higher systemic exposure. To minimize the potential risk for an adverse GI event, the lowest effective dose should be used for the shortest possible duration. Initiate therapy at the lowest recommended dose for patients that weigh less than 50 kg. For high risk patients, alternate therapies that do not involve NSAIDs should be considered. Studies have shown that patients with a prior history of peptic ulcer disease and/or GI bleeding and who use NSAIDs have a greater than 10-fold higher risk for developing a GI bleed than patients with neither of these risk factors. In addition to a past history of ulcer disease, other factors that increase the risk for GI bleeding include concurrent oral corticosteroid therapy or anticoagulant therapy, longer duration of NSAID therapy, tobacco smoking, alcoholism, older age, and poor general health status. The CLASS trial (Celecoxib Long-term Arthritis Study), which combined 2 studies of celecoxib (400 mg twice daily) in comparison with diclofenac (75 mg twice daily) or ibuprofen (800 mg 3 times daily) in 8059 patients with osteoarthritis or rheumatoid arthritis, reports data from the first 6 months (the maximum duration of follow-up for the 2 trials was 15 and 12 months, respectively). No significant difference between the groups in the incidence of complicated ulcers (e.g., ulcer perforation, gastric-outlet obstruction, or upper GI bleeding) was noted (0.8% in the celecoxib group vs. 1.5% in either NSAID group). When the annualized incidence of complicated and symptomatic ulcers was combined, the rate was similar for celecoxib (1.2%) and diclofenac (1.3%), but the rate for ibuprofen was significantly higher (1.9%). The data reported need to be interpreted carefully, as the published trial is different from the original protocol with regard to design, outcomes, follow-up duration, and analysis. The FDA was concerned that celecoxib could interfere with the benefits of COX 2 in ulcer healing. As a result, the prespecified primary outcome measure was ulcer related complications. Based on the primary outcome measure, there was no statistical difference between the groups. Furthermore, no statistically significant differences between the groups were found when an alternative definition of ulcer complications that addressed more serious bleeding was used. Thus, more data are needed to clarify any potential difference between celecoxib and other NSAIDs with regard to gastrointestinal adverse effects.
Hepatic disease decreases the metabolism of celecoxib in subjects with mild to moderate hepatic impairment. Dosage should be reduced for moderate hepatic impairment. Celecoxib has not been studied in patients with severe hepatic impairment (Child-Pugh Class C), and therefore, is not recommended. In patients taking NSAIDs, elevations of liver tests can occur and in rare cases, progress to severe hepatic reactions. A patient with symptoms and/or signs suggesting liver dysfunction (e.g., jaundice), 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 celecoxib.
Celecoxib, like all NSAIDs, may exacerbate hypertension and congestive heart failure and may cause an increased risk of serious cardiovascular thrombotic events, myocardial infarction, and stroke, which can be fatal. The risk may increase with duration of use, and patients with cardiovascular disease or risk factors for cardiovascular disease (e.g., high blood pressure) may be at greater risk. Caution is recommended when administering celecoxib to patients with cardiac disease, peripheral vascular disease, cerebrovascular disease (e.g., stroke, transient ischemic attack), pre-existing renal disease, fluid retention, hypertension, or edema. Fluid retention, angina pectoris, chest pain (unspecified), myocardial infarction, pulmonary embolism, stroke, thrombophlebitis, and peripheral edema have occurred. Due to the lack of data on the safety of celecoxib in patients with cerebrovascular disease, a large, multicenter, placebo-controlled clinical trial to explore the cardiovascular safety of celecoxib in patients with cardiac disease and osteoarthritis is in the planning stages. No information is available regarding the use of celecoxib in patients with advanced kidney disease such as renal failure; therefore, treatment with celecoxib is not recommended. Clinical trials with celecoxib have demonstrated renal effects (e.g., sodium, potassium, and fluid retention and decreases in renal function) and mild increases in blood pressure and peripheral edema similar to those observed with comparator NSAIDs. Renal toxicity has also been seen in patients in whom renal prostaglandins have a compensatory role in the maintenance of renal perfusion. In these patients, administration of an NSAID may cause a dose-dependent reduction in prostaglandin formation and, secondarily, in renal blood flow, which may precipitate overt renal decompensation. Patients at greatest risk of this reaction are those with renal impairment, renal failure, heart failure, liver dysfunction, hypovolemia (dehydration), those taking diuretics and ACE inhibitors, or older patients. Discontinuation of NSAID therapy is usually followed by recovery. Patients should be rehydrated before starting therapy with celecoxib. Close monitoring of renal function and blood pressure throughout the duration of celecoxib use is advisable.
Celecoxib is contraindicated for the treatment of peri-operative pain in the setting of coronary artery bypass graft surgery (CABG). An increased incidence of myocardial infarction and stroke was found through analysis of data regarding the use of another COX-2 selective NSAID for the treatment of pain in the first 10—14 days after CABG surgery.
Anemia is sometimes seen in patients receiving celecoxib and could potentially worsen pre-existing anemia. Patients on long-term treatment with celecoxib should have their hemoglobin or hematocrit assessed if they exhibit any signs or symptoms of anemia or blood loss. Celecoxib 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.
The pharmacological activity of celecoxib in reducing inflammation, and possibly fever, may diminish the utility of these diagnostic signs in detecting unsuspected infection that may accompany coexisting painful conditions. NSAIDs should be used with caution in patients with immunosuppression or neutropenia. NSAIDs may mask the signs of infection such as fever or pain in patients with bone marrow suppression.
Celecoxib is classified as FDA pregnancy category risk C; there have been no studies of celecoxib in pregnant women. Celecoxib should be used during pregnancy only if the potential benefit to the mother justifies the potential risk to the fetus; its use should especially be avoided during the third trimester. Celecoxib may delay closure of the ductus arteriosis. No studies have been conducted to evaluate the effect of celecoxib on the closure of the ductus arteriosus in humans [consider pregnancy category D (3rd trimester)]. The effects of celecoxib on labor and delivery in pregnant women are unknown.
Celecoxib appears to be excreted in human milk, as indicated by data from one patient. Due to the potential for serious adverse reactions in nursing infants from celecoxib, a decision should be made whether to discontinue breast-feeding or to discontinue the drug, taking into account the importance of the drug to the mother.
Safety and effectiveness in children below the age of 18 years has not been evaluated.
[ Last revised: 8/4/2005 12:32:00 PM ]
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