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Risk of GI ulceration, bleeding and perforation with NSAID: Serious GI toxicity such as bleeding, ulceration and perforation can occur at any time with or without warning symptoms in patients treated with NSAID therapy. Although minor upper GI problems (e.g. dyspepsia) are common, usually developing early in therapy, prescribers should remain alert for ulceration and bleeding in patients treated with NSAIDs even in the absence of previous GI tract symptoms.
Studies to date have not identified any subset of patients not at risk of developing peptic ulceration with bleeding. Patients with prior history of serious GI events and other risk factors associated with peptic ulcer disease (e.g. alcoholism, smoking and corticosteroid therapy) are at increased risk. Elderly or debilitated patients seem to tolerate ulceration or bleeding less than other individuals and account for most spontaneous reports for fatal GI events.
Cardiovascular Effects: Cardiovascular Thrombotic Events: Celecoxib may cause an increased risk of serious CV thrombotic events, myocardial infarction (MI), and stroke, which can be fatal. All NSAIDs may have a similar risk. This risk may increase with dose and duration of use. The relative increase of this risk appears to be similar in those with or without known CV disease or CV risk factors. However, patients with CV disease or CV risk factors may be at greater risk in terms of absolute incidence, due to their increased rate at baseline. To minimize the potential risk for an adverse CV event in patients treated with Celecoxib, the lowest effective dose should be used for the shortest duration possible. Physicians and patients should remain alert for the development of such events, even in the absence of previous CV symptoms. Patients should be informed about the signs and symptoms of serious CV toxicity and the steps to take if they occur (see Pharmacology under Actions).
Celecoxib is not a substitute for Acetylsalicylic acid for prophylaxis of CV thromboembolic diseases because of the lack of effect on platelet function. Because Celecoxib does not inhibit platelet aggregation, anti-platelet therapies (e.g. Acetylsalicylic acid) should not be discontinued.
Hypertension: As with all NSAIDs, Celecoxib can lead to the onset of new hypertension or worsening of pre-existing hypertension, either of which may contribute to the increased incidence of CV events. Patients taking angiotensin converting enzyme (ACE) inhibitors, Thiazide diuretics or Loop diuretics may have impaired response to these therapies when taking NSAIDs. NSAIDs, including Celecoxib, should be used with caution in patients with hypertension. Blood pressure should be monitored closely during the initiation of therapy with Celecoxib and throughout the course of therapy (see Pharmacology under Actions).
Fluid Retention and Edema: As with other drugs known to inhibit prostaglandin synthesis, fluid retention and edema have been observed in some patients taking Celecoxib. Therefore, patients with pre-existing congestive heart failure (CHF) or hypertension should be closely monitored. Celecoxib should be used with caution in patients with compromised cardiac function, pre-existing edema, or other conditions predisposing to, or worsened by, fluid retention including those taking diuretic treatment or otherwise at risk of hypovolemia.
Gastrointestinal (GI) Effects: Upper and lower GI perforations, ulcers or bleeds can occur in patients treated with Celecoxib. These serious adverse events can occur at any time, with or without warning symptoms, in patients treated with Celecoxib.
Patients most at risk of developing these types of GI complications with NSAIDs are the elderly, patients with CV disease, patients using concomitant glucocorticoids, antiplatelet drugs (such as Aspirin), or other NSAIDs, patients using alcohol or patients with a prior history of, or active, GI disease, such as ulceration, GI bleeding or inflammatory conditions. Other factors that increase the risk of GI bleeding in patients treated with NSAIDs include longer duration of NSAID therapy; concomitant use of oral corticosteroids, antiplatelet drugs (such as Aspirin), anticoagulants, or selective serotonin reuptake inhibitors (SSRIs); smoking; use of alcohol; older age; and poor general health status. Most spontaneous reports of fatal GI events have been in elderly or debilitated patients.
Strategies to Minimize the GI Risks in NSAID-treated Patients: Use the lowest effective dosage for the shortest possible duration.
Avoid administration of more than one NSAID at a time.
Avoid use in patients at higher risk unless benefits are expected to outweigh the increased risk of bleeding. For such patients, as well as those with active GI bleeding, consider alternate therapies other than NSAIDs.
Remain alert for signs and symptoms of GI ulceration and bleeding during NSAID therapy.
If a serious GI adverse event is suspected, promptly initiate evaluation and treatment, and discontinue Celecoxib until a serious GI adverse event is ruled out.
In the setting of concomitant use of low-dose aspirin for cardiac prophylaxis, monitor patients more closely for evidence of GI bleeding.
Renal Effects: NSAIDs including Celecoxib may cause renal toxicity. Patients at greatest risk for renal toxicity are those with impaired renal function, heart failure, liver dysfunction, and the elderly. Such patients should be carefully monitored while receiving treatment with Celecoxib. Caution should be used when initiating treatment in patients with dehydration. It is advisable to rehydrate patients first and then start therapy with Celecoxib.
Advanced Renal Disease: Renal function should be closely monitored in patients with advance renal disease who are administered Celecoxib (see Dosage & Administration).
Anaphylactoid Reactions: As with NSAIDs in general, anaphylactoid reactions can occur in patients exposed to Celecoxib (see Contraindications).
Serious Skin Reactions: Serious skin reactions, some of them fatal, including drug reaction with eosinophilia and systemic symptoms (DRESS syndrome), exfoliative dermatitis, Stevens-Johnsons syndrome, and toxic epidermal necrolysis, can be observed very rarely in association with the use of Celecoxib. Patients appear to be at highest risk for these events early in the course of therapy, the onset of the event occurring in the majority of cases within the first month of treatment. Celecoxib should be discontinued at the first appearance of skin rash, mucosal lesions, or any other sign of hypersensitivity.
Hepatic Effects: Patients with severe hepatic impairment (Child-Pugh Class C) have not been studied. The use of Celecoxib in patients with severe hepatic impairment is not recommended. Celecoxib should be used with caution when treating patients with moderate hepatic impairment (Child-Pugh Class B), and initiated half the recommended dose (see Dosage & Administration). Rare cases of severe hepatic reactions, including fulminant hepatitis (some with fatal outcome), liver necrosis, and hepatic failure (some with fatal outcome or requiring liver transplant), can be observed with Celecoxib.
A patient with symptoms and/or signs of liver dysfunction, or in whom an abnormal liver function test has occurred, should be monitored carefully for evidence of the development of a more severe hepatic reaction while on therapy with Celecoxib.
Use with Oral Anticoagulants: The concomitant use of NSAIDs with oral anticoagulants increases the risk of bleeding and should be given with caution. Oral anticoagulants include warfarin/coumarin-type and novel oral anticoagulants (e.g. Apixaban, Dabigatran, and Rivaroxaban). In patients on concurrent therapy with warfarin or similar agents, serious bleeding events, some of them fatal, may occur. Because of increase in prothrombin time (INR) have been reported, anticoagulation/INR should be monitored in patients taking a warfarin/coumadin-type anticoagulant after initiating treatment with Celecoxib or changing the dose (see Interactions).
General: By reducing inflammation, Celecoxib may diminish the utility of diagnosis signs, such as fever, in detecting infections. The concomitant use of Celecoxib and a non-Aspiring NSAID should be avoided.
CYP2D6 Inhibition: Celecoxib inhibits CYP2D6. Although it is not a strong inhibitor of the enzyme, a dose reduction may be necessary for individually dose-titrated medicinal products that are metabolized by CYP2D6 (see Interactions).
Warning to prescriber when prescribing COX-2 inhibitors to patients with risk factors of heart disease, hypertension (high blood pressure), hyperlipidemia, diabetes, smoking patients and patient with peripheral arterial disease.
Effects on Ability to Drive and Use Machines: The effect of Celecoxib on ability to drive or use machinery has not been studied, but based on its pharmacodynamic properties and overall safety profile it is unlikely to have an effect.
