The Coxib and traditional NSAID Trialists’ Collaboration meta-analysis of randomized controlled trials demonstrated an approximately two-fold increase in hospitalizations for heart failure in COX-2 selective-treated patients and nonselective NSAID-treated patients compared to placebo-treated patients. In a Danish National Registry study of patients with heart failure, NSAID use increased the risk of MI, hospitalization for heart failure, and death.
Additionally, fluid retention and edema have been observed in some patients treated with NSAIDs. Use of celecoxib may blunt the CV effects of several therapeutic agents used to treat these medical conditions (e.g., diuretics, ACE inhibitors, or angiotensin receptor blockers [ARBs]) [ see Drug Interactions ( 7) ].
In the CLASS study [see Clinical Studies ( 14.7)], the Kaplan-Meier cumulative rates at 9 months of peripheral edema in patients on celecoxib capsules 400 mg twice daily (4-fold and 2-fold the recommended OA and RA doses, respectively), ibuprofen 800 mg three times daily and diclofenac 75 mg twice daily were 4.5%, 6.9% and 4.7%, respectively.
Avoid the use of celecoxib capsules in patients with severe heart failure unless the benefits are expected to outweigh the risk of worsening heart failure. If celecoxib capsules are used in patients with severe heart failure, monitor patients for signs of worsening heart failure.
Long-term administration of NSAIDs has resulted in renal papillary necrosis and other renal injury.
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 impaired renal function, dehydration, hypovolemia , heart failure, liver dysfunction, those taking diuretics, ACE inhibitors or the ARBs, and the elderly. Discontinuation of NSAID therapy is usually followed by recovery to the pretreatment state.
No information is available from controlled clinical studies regarding the use of celecoxib capsules in patients with advanced renal disease. The renal effects of celecoxib may hasten the progression of renal dysfunction in patients with preexisting renal disease.
Correct volume status in dehydrated or hypovolemic patients prior to initiating celecoxib capsules. Monitor renal function in patients with renal or hepatic impairment, heart failure, dehydration, or hypovolemia during use of celecoxib capsules [ see Drug Interactions ( 7) ] . Avoid the use of celecoxib capsules in patients with advanced renal disease unless the benefits are expected to outweigh the risk of worsening renal function. If celecoxib capsules are used in patients with advanced renal disease, monitor patients for signs of worsening renal function.
Increases in serum potassium concentration, including hyperkalemia, have been reported with use of NSAIDs, even in some patients without renal impairment. In patients with normal renal function, these effects have been attributed to a hyporeninemic- hypoaldosteronism state.
Celecoxib has been associated with anaphylactic reactions in patients with and without known hypersensitivity to celecoxib and in patients with aspirin sensitive asthma. Celecoxib is a sulfonamide and both NSAIDs and sulfonamides may cause allergic type reactions including anaphylactic symptoms and life-threatening or less severe asthmatic episodes in certain susceptible people [see Contraindications ( 4) and Warnings and Precautions ( 5.8) ].
Seek emergency help if any anaphylactic reaction occurs.
A subpopulation of patients with asthma may have aspirin-sensitive asthma which may include chronic rhinosinusitis complicated by nasal polyps; severe, potentially fatal bronchospasm; and/or intolerance to aspirin and other NSAIDs. Because cross-reactivity between aspirin and other NSAIDs has been reported in such aspirin-sensitive patients, celecoxib capsules are contraindicated in patients with this form of aspirin sensitivity [ see Contraindications ( 4) ]. When celecoxib capsules are used in patients with preexisting asthma (without known aspirin sensitivity), monitor patients for changes in the signs and symptoms of asthma.
Serious skin reactions have occurred following treatment with celecoxib capsules, including erythema multiforme, exfoliative dermatitis, Stevens-Johnson Syndrome (SJS), toxic epidermal necrolysis (TEN), drug reaction with eosinophilia and systemic symptoms (DRESS), and acute generalized exanthematous pustulosis (AGEP). These serious events may occur without warning and can be fatal.
Inform patients about the signs and symptoms of serious skin reactions, and to discontinue the use of celecoxib capsules at the first appearance of skin rash or any other sign of hypersensitivity. Celecoxib capsules are contraindicated in patients with previous serious skin reactions to NSAIDs [ see Contraindications ( 4) ].
Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) has been reported in patients taking NSAIDs such as celecoxib. Some of these events have been fatal or life-threatening. DRESS typically, although not exclusively, presents with fever, rash, lymphadenopathy, and/or facial swelling. Other clinical manifestations may include hepatitis, nephritis, hematological abnormalities, myocarditis, or myositis. Sometimes symptoms of DRESS may resemble an acute viral infection. Eosinophilia is often present. Because this disorder is variable in its presentation, other organ systems not noted here may be involved. It is important to note that early manifestations of hypersensitivity, such as fever or lymphadenopathy, may be present even though rash is not evident. If such signs or symptoms are present, discontinue celecoxib and evaluate the patient immediately.
Premature Closure of Fetal Ductus Arteriosus
Avoid use of NSAIDs, including celecoxib capsules, in pregnant women at about 30 weeks gestation and later. NSAIDs, including celecoxib, increase the risk of premature closure of the fetal ductus arteriosus at approximately this gestational age.
Oligohydramnios/Neonatal Renal Impairment
Use of NSAIDs, including celecoxib, at about 20 weeks gestation or later in pregnancy may cause fetal renal dysfunction leading to oligohydramnios and, in some cases, neonatal renal impairment. These adverse outcomes are seen, on average, after days to weeks of treatment, although oligohydramnios has been infrequently reported as soon as 48 hours after NSAID initiation. Oligohydramnios is often, but not always, reversible with treatment discontinuation. Complications of prolonged oligohydramnios may, for example, include limb contractures and delayed lung maturation. In some postmarketing cases of impaired neonatal renal function, invasive procedures such as exchange transfusion or dialysis were required.
If NSAID treatment is necessary between about 20 weeks and 30 weeks gestation, limit celecoxib use to the lowest effective dose and shortest duration possible. Consider ultrasound monitoring of amniotic fluid if celecoxib treatment extends beyond 48 hours. Discontinue celecoxib if oligohydramnios occurs and follow up according to clinical practice [ see Use in Specific Populations ( 8.1) ].
Anemia has occurred in NSAID-treated patients. This may be due to occult or gross blood loss, fluid retention, or an incompletely described effect on erythropoiesis. If a patient treated with celecoxib capsules has any signs or symptoms of anemia, monitor hemoglobin or hematocrit.
In controlled clinical trials the incidence of anemia was 0.6% with celecoxib capsules and 0.4% with placebo. Patients on long-term treatment with celecoxib capsules should have their hemoglobin or hematocrit checked if they exhibit any signs or symptoms of anemia or blood loss.
NSAIDs, including celecoxib capsules, may increase the risk of bleeding events. Co-morbid conditions such as coagulation disorders or concomitant use of warfarin, other anticoagulants, antiplatelet drugs (e.g., aspirin), SSRIs and serotonin norepinephrine reuptake inhibitors (SNRIs) may increase this risk. Monitor these patients for signs of bleeding [ see Drug Interactions ( 7) ].
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