FDA Safety Labeling Changes: Celebrex
News Author: Yael Waknine
From Medscape Medical News
Nov. 9, 2005 — The U.S. Food and Drug Administration (FDA) has approved safety labeling revisions to advise that celecoxib therapy is linked to risks for cardiovascular, gastrointestinal, renal, and dermatologic adverse events.
Celecoxib (Celebrex) Linked to Multiple Adverse Events
On July 29, the FDA approved safety labeling revisions for the nonsteroidal anti-inflammatory (NSAID) drug celecoxib (Celebrex capsules, made by Pfizer Global Pharmaceuticals) to warn of contraindications and warnings associated with this class of drugs and to emphasize the need to minimize its use to the lowest effective dose for the shortest possible duration.
Use of a NSAID similar to celecoxib for pain management during the first 10 to 14 days after coronary artery bypass graft (CABG) surgery has been linked to an increased risk for myocardial infarction (MI) and stroke; use of celecoxib in this setting is therefore contraindicated.
The FDA also warned that chronic use of celecoxib may be linked to an increased risk for serious and potentially fatal cardiovascular thrombotic events, MI, and stroke. As with other NSAIDs, these risks may increase in the presence of existing cardiovascular disease and/or related risk factors.
The warning was based on results of the Prevention of Sporadic Colorectal Adenomas with Celecoxib trial in 1,356 patients, showing that use of 400 mg of celecoxib twice daily was linked to a 3.4-fold increase in the composite risk of cardiovascular death, MI, or stroke, relative to placebo (95% confidence interval [CI], 1.4 - 8.5). In patients receiving 200 mg of celecoxib twice daily, the relative risk was 2.4 (95% CI, 1.0 - 6.4).
The FDA notes that there is no consistent evidence that concurrent use of low-dose aspirin mitigates the increased risk for serious cardiovascular thrombotic events associated with celecoxib use.
Also, data from the Celecoxib Long-Term Arthritis Safety Study (CLASS) of 8,000 patients have linked concomitant use of low-dose aspirin and 400 mg of celecoxib twice daily to an increased risk for serious gastrointestinal adverse events compared with celecoxib alone (2.19% vs 0.78%). This risk was further increased in the elderly (3.06% vs 1.40%).
A 400-mg dose of celecoxib twice daily is twofold and fourfold the recommended dose for osteoarthritis and rheumatoid arthritis, respectively, and the approved dose for familial adenomatous polyposis.
As with all NSAIDs, use of celecoxib can lead to the onset of new hypertension or worsening of preexisting disease, either of which may lead to an increased incidence of cardiovascular events.
Fluid retention and edema have also been observed in patients receiving NSAIDs, such as celecoxib. In the CLASS study, the Kaplan-Meier cumulative rates of peripheral edema at nine months in patients receiving 400 mg of celecoxib twice daily, 800 mg of ibuprofen three times daily, and 75 mg of diclofenac twice daily were 4.5%, 6.9%, and 4.7%, respectively.
The FDA advises that celecoxib be prescribed with caution in patients with fluid retention or heart failure. Because concurrent use of NSAIDs may impair response to treatment with thiazides or loop diuretics, close monitoring of blood pressure is recommended.
In the CLASS study, hypertension was observed in 2.4%, 4.2%, and 2.5%, respectively, in patients receiving celecoxib, ibuprofen, and diclofenac.
Celecoxib and other NSAIDs are also associated with an increased risk for serious and potentially fatal gastrointestinal adverse events, particularly in the elderly. Bleeding, ulceration, and perforation of the stomach or intestines may occur at any time during therapy and without warning symptoms; only one in five patients who develop a serious upper gastrointestinal tract adverse event while receiving NSAID therapy is symptomatic.
The FDA notes that the risk of developing a gastrointestinal bleed is 10-fold greater in patients with a prior history of peptic ulcer disease and/or gastrointestinal bleeding, and NSAIDs should therefore be prescribed with extreme caution in this population.
Other factors that increase the risk of bleeding include concomitant use of oral corticosteroids, anticoagulants, longer duration of therapy, smoking, alcohol consumption, advanced age, and poor general health status. Because most spontaneous reports of fatal gastrointestinal events are in elderly or debilitated patients, special care should be taken in treating this population.
Papillary necrosis and other renal injuries have been observed with long-term administration of celecoxib and other NSAIDs. In patients for whom renal prostaglandins have a compensatory role in the maintenance of renal perfusion, NSAIDs may cause a dose-dependent reduction in prostaglandin formation that may precipitate overt renal decompensation.
Patients with impaired renal function, heart failure, liver dysfunction, the elderly, and those taking diuretics and angiotensin-converting enzyme inhibitors are at greatest risk for this reaction. Discontinuation of NSAID therapy is usually followed by recovery to the pretreatment state.
The FDA notes that no controlled clinical trials of celecoxib in patients with advanced renal disease have been performed; its use is therefore not recommended in this population. If celecoxib therapy must be initiated, close monitoring of renal function is advised.
As a sulfonamide, celecoxib can cause serious and potentially fatal dermatologic adverse events, such as exfoliative dermatitis, Steven Johnson syndrome, and toxic epidermal necrolysis. These can occur without warning and in patients with no history of sulfa allergy. The FDA advises discontinuation of celecoxib therapy at the first appearance of skin rash or any other sign of hypersensitivity.
Celecoxib capsules are indicated for the relief of signs and symptoms associated with rheumatoid arthritis in adults, osteoarthritis, and ankylosing spondylitis; treatment of acute pain in adults; treatment of primary dysmenorrhea; and for use as an adjunct to usual care to reduce the number of adenomatous colorectal polyps in familial adenomatous polyposis.
From Medscape Medical News
Nov. 9, 2005 — The U.S. Food and Drug Administration (FDA) has approved safety labeling revisions to advise that celecoxib therapy is linked to risks for cardiovascular, gastrointestinal, renal, and dermatologic adverse events.
Celecoxib (Celebrex) Linked to Multiple Adverse Events
On July 29, the FDA approved safety labeling revisions for the nonsteroidal anti-inflammatory (NSAID) drug celecoxib (Celebrex capsules, made by Pfizer Global Pharmaceuticals) to warn of contraindications and warnings associated with this class of drugs and to emphasize the need to minimize its use to the lowest effective dose for the shortest possible duration.
Use of a NSAID similar to celecoxib for pain management during the first 10 to 14 days after coronary artery bypass graft (CABG) surgery has been linked to an increased risk for myocardial infarction (MI) and stroke; use of celecoxib in this setting is therefore contraindicated.
The FDA also warned that chronic use of celecoxib may be linked to an increased risk for serious and potentially fatal cardiovascular thrombotic events, MI, and stroke. As with other NSAIDs, these risks may increase in the presence of existing cardiovascular disease and/or related risk factors.
The warning was based on results of the Prevention of Sporadic Colorectal Adenomas with Celecoxib trial in 1,356 patients, showing that use of 400 mg of celecoxib twice daily was linked to a 3.4-fold increase in the composite risk of cardiovascular death, MI, or stroke, relative to placebo (95% confidence interval [CI], 1.4 - 8.5). In patients receiving 200 mg of celecoxib twice daily, the relative risk was 2.4 (95% CI, 1.0 - 6.4).
The FDA notes that there is no consistent evidence that concurrent use of low-dose aspirin mitigates the increased risk for serious cardiovascular thrombotic events associated with celecoxib use.
Also, data from the Celecoxib Long-Term Arthritis Safety Study (CLASS) of 8,000 patients have linked concomitant use of low-dose aspirin and 400 mg of celecoxib twice daily to an increased risk for serious gastrointestinal adverse events compared with celecoxib alone (2.19% vs 0.78%). This risk was further increased in the elderly (3.06% vs 1.40%).
A 400-mg dose of celecoxib twice daily is twofold and fourfold the recommended dose for osteoarthritis and rheumatoid arthritis, respectively, and the approved dose for familial adenomatous polyposis.
As with all NSAIDs, use of celecoxib can lead to the onset of new hypertension or worsening of preexisting disease, either of which may lead to an increased incidence of cardiovascular events.
Fluid retention and edema have also been observed in patients receiving NSAIDs, such as celecoxib. In the CLASS study, the Kaplan-Meier cumulative rates of peripheral edema at nine months in patients receiving 400 mg of celecoxib twice daily, 800 mg of ibuprofen three times daily, and 75 mg of diclofenac twice daily were 4.5%, 6.9%, and 4.7%, respectively.
The FDA advises that celecoxib be prescribed with caution in patients with fluid retention or heart failure. Because concurrent use of NSAIDs may impair response to treatment with thiazides or loop diuretics, close monitoring of blood pressure is recommended.
In the CLASS study, hypertension was observed in 2.4%, 4.2%, and 2.5%, respectively, in patients receiving celecoxib, ibuprofen, and diclofenac.
Celecoxib and other NSAIDs are also associated with an increased risk for serious and potentially fatal gastrointestinal adverse events, particularly in the elderly. Bleeding, ulceration, and perforation of the stomach or intestines may occur at any time during therapy and without warning symptoms; only one in five patients who develop a serious upper gastrointestinal tract adverse event while receiving NSAID therapy is symptomatic.
The FDA notes that the risk of developing a gastrointestinal bleed is 10-fold greater in patients with a prior history of peptic ulcer disease and/or gastrointestinal bleeding, and NSAIDs should therefore be prescribed with extreme caution in this population.
Other factors that increase the risk of bleeding include concomitant use of oral corticosteroids, anticoagulants, longer duration of therapy, smoking, alcohol consumption, advanced age, and poor general health status. Because most spontaneous reports of fatal gastrointestinal events are in elderly or debilitated patients, special care should be taken in treating this population.
Papillary necrosis and other renal injuries have been observed with long-term administration of celecoxib and other NSAIDs. In patients for whom renal prostaglandins have a compensatory role in the maintenance of renal perfusion, NSAIDs may cause a dose-dependent reduction in prostaglandin formation that may precipitate overt renal decompensation.
Patients with impaired renal function, heart failure, liver dysfunction, the elderly, and those taking diuretics and angiotensin-converting enzyme inhibitors are at greatest risk for this reaction. Discontinuation of NSAID therapy is usually followed by recovery to the pretreatment state.
The FDA notes that no controlled clinical trials of celecoxib in patients with advanced renal disease have been performed; its use is therefore not recommended in this population. If celecoxib therapy must be initiated, close monitoring of renal function is advised.
As a sulfonamide, celecoxib can cause serious and potentially fatal dermatologic adverse events, such as exfoliative dermatitis, Steven Johnson syndrome, and toxic epidermal necrolysis. These can occur without warning and in patients with no history of sulfa allergy. The FDA advises discontinuation of celecoxib therapy at the first appearance of skin rash or any other sign of hypersensitivity.
Celecoxib capsules are indicated for the relief of signs and symptoms associated with rheumatoid arthritis in adults, osteoarthritis, and ankylosing spondylitis; treatment of acute pain in adults; treatment of primary dysmenorrhea; and for use as an adjunct to usual care to reduce the number of adenomatous colorectal polyps in familial adenomatous polyposis.
posted by Ricardo Pocurull at 5:39 AM
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