Source: Registered Drug Product Database (NG) Publisher: Getz Pharma (Pvt.) Limited, 29-30/27, Korangi Industrial Area Karachi 74900, Pakistan, Tel: (92-21) 111-111-511, Fax: (92-21) 5057592 Drug product manufacturer: Getz Pharma (Pvt.) Limited, 29-30/27, Korangi Industrial Area Karachi 74900, Pakistan, Tel: (92-21) 111-111-511, Fax: (92-21) 5057592
Celecoxib is contraindicated in:
Chronic use of celecoxib may cause an increased risk of serious adverse cardiovascular thrombotic events, myocardial infarction and stroke, which can be fatal. All NSAIDs, both COX-2 selective and nonselective, may have a similar risk. Patients with known cardiovascular disease or risk factors for cardiovascular disease may be at greater risk. To minimize the potential risk for an adverse cardiovascular event in patients treated with celecoxib, the lowest effective dose should be used for the shortest duration possible.
Celecoxib cannot be expected to substitute for corticosteroids or to treat corticosteroid insufficiency. Abrupt discontinuation of corticosteroids may lead to exacerbation of corticosteroid-responsive illness. Patients on prolonged corticosteroid therapy should have their therapy tapered slowly if a decision is made to discontinue corticosteroids.
Serious gastrointestinal toxicity such as bleeding, ulceration, and perforation of the stomach, small intestine or large intestine, can occur at any time, with or without warning symptoms, in patients treated with nonsteroidal anti-inflammatory drugs (NSAIDs). Minor upper gastrointestinal problems, such as dyspepsia, are common and may also occur at any time during NSAID therapy. With longer duration of use of NSAIDs, there is a trend for increasing the likelihood of developing a serious GI event at some time during the course of therapy. However, even short-term therapy is not without risk. Therefore, physicians and patients should remain alert for ulceration and bleeding, even in the absence of previous GI tract symptoms.
NSAIDs should be prescribed with extreme caution in patients with a prior history of ulcer disease or gastrointestinal bleeding. To minimize the potential risk for an adverse GI event, the lowest effective dose should be used for the shortest possible duration.
Fluid retention and edema have been observed in some patients taking celecoxib. Therefore, celecoxib should be used with caution in patients with fluid retention, hypertension, or heart failure.
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 cardiovascular events. Patients taking thiazides 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.
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 celecoxib. If clinical signs and symptoms consistent with liver disease develop, or if systemic manifestations occur (e.g., eosinophilia, rash, etc.), celecoxib should be discontinued.
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. Patients at greatest risk of this reaction are those with impaired renal function, heart failure, liver dysfunction, those taking diuretics, ACE-inhibitors, angiotensin II receptor antagonists, and the elderly. Discontinuation of NSAID therapy is usually followed by recovery to the pre-treatment state. Caution should be used when initiating treatment with celecoxib in patients with considerable dehydration. It is advisable to rehydrate patients first and then start therapy with celecoxib.
Anemia is sometimes seen in patients receiving celecoxib. Patients on long-term treatment with celecoxib should have their hemoglobin or hematocrit checked 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 inhibit platelet aggregation at indicated dosages.
Patients appear to be at highest risk for serious skin reactions early in the course of therapy. The onset of these events occurring in the majority of the 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.
Treatment with celecoxib in FAP has not been shown to reduce the risk of gastrointestinal cancer or the need for prophylactic colectomy or other FAP-related surgeries. Therefore, the usual care of FAP patients should not be altered because of the concurrent administration of celecoxib.
As with NSAIDs in general, anaphylactoid reactions have occurred in patients without known prior exposure to celecoxib. Celecoxib should not be given to patients with the aspirin triad. This symptom complex typically occurs in asthmatic patients who experience rhinitis with or without nasal polyps, or who exhibit severe, potentially fatal bronchospasm after taking aspirin or other NSAIDs.
Celecoxib is a sulfonamide and can cause serious skin adverse events such as exfoliative dermatitis, Stevens-Johnson syndrome and toxic epidermal necrolysis (TEN), which can be fatal. These serious events can occur without warning and in patients without prior known sulfa allergy. Patients should be informed about the signs and symptoms of serious skin manifestations and use of the drug should be discontinued at the first appearance of skin rash or any other sign of hypersensitivity.
The pharmacological activity of celecoxib in reducing inflammation, and possibly fever, may diminish the utility of these diagnostic signs in detecting infectious complications of presumed noninfectious, painful conditions.
The concomitant use of celecoxib with any dose of non-aspirin NSAID should be avoided due to the potential for increased risk of adverse reactions.
Celecoxib metabolism is predominantly mediated via cytochrome P450 2C9 in the liver. Co-administration of celecoxib with drugs that are known to inhibit 2C9 should be done with caution. Patients who are known or suspected to be P450 2C9 poor metabolizers based on a previous history should be administered celecoxib with caution as they may have abnormally high plasma levels due to reduced metabolic clearance.
Reports suggest that NSAIDs may diminish the antihypertensive effect of Angiotensin Converting Enzyme (ACE) inhibitors and angiotensin II antagonists. This interaction should be given consideration in patients taking celecoxib concomitantly with ACE inhibitors and angiotensin II antagonists.
Clinical studies, as well as post marketing observations, have shown that NSAIDs can reduce the natriuretic effect of furosemide and thiazides in some patients. This response has been attributed to inhibition of renal prostaglandin synthesis.
Celecoxib can be used with low dose aspirin. However, concomitant administration of aspirin with celecoxib may result in an increased rate of GI ulceration or other complications, compared to use of celecoxib alone. Because of its lack of platelet effects, celecoxib is not a substitute for aspirin for cardiovascular prophylaxis.
Concomitant administration of fluconazole at 200 mg q.d. resulted in a two-fold increase in celecoxib plasma concentration. This increase is due to the inhibition of celecoxib metabolism via P450 CYP2C9 by fluconazole. Celecoxib should be introduced at the lowest recommended dose in patients receiving fluconazole.
Clinical studies showed that the mean steady-state lithium plasma levels increased approximately 17% in subjects receiving lithium 450 mg b.i.d. with celecoxib 200 mg b.i.d. as compared to subjects receiving lithium alone. Patients on lithium treatment should be closely monitored when celecoxib is introduced or withdrawn.
Anticoagulant activity should be monitored, particularly in the first few days, after initiating or changing celecoxib therapy in patients receiving warfarin or similar agents, since these patients are at an increased risk of bleeding complications.
Co-administration of celecoxib with an aluminum and magnesium-containing antacid resulted in a reduction in plasma celecoxib concentrations. No dose adjustment is required.
Oral glucocorticoids should be used with caution since they increase the risk of GI side effects such as ulceration and bleeding. This is especially the case in older (>65 years of age) individuals.
Celecoxib should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. In late pregnancy, starting at 30 weeks gestation, celecoxib should be avoided because it may cause premature closure of the ductus arteriosus.
Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing infants from celecoxib, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.
Patients who experience dizziness, vertigo or somnolence while taking celecoxib should refrain from driving or operating machinery.
The following adverse drug reactions have been reported during therapy of celecoxib:
Most common:
Gastrointestinal: Abdominal pain, diarrhea, dyspepsia, flatulence, nausea.
Central and peripheral nervous system: Dizziness, headache, hypertonia.
Respiratory: Pharyngitis, rhinitis, sinusitis, upper respiratory tract infection.
Others: Back pain, insomnia, rash.
Less common:
Gastrointestinal: Constipation, dysphagia, esophagitis, gastritis, gastroenteritis, gastroesophageal reflux, hemorrhoids, melena, dry mouth, stomatitis, vomiting.
Cardiovascular: Aggravated hypertension, angina pectoris, coronary artery disorder, myocardial infarction, palpitation, tachycardia.
Respiratory: Bronchitis, bronchospasm, bronchospasm aggravated, coughing, dyspnea, laryngitis, pneumonia.
Central, peripheral nervous system: Leg cramps, hypertonia, hypoesthesia, migraine, neuralgia, neuropathy, paresthesia, vertigo.
Psychiatric: Anorexia, anxiety, appetite increased, depression, nervousness, somnolence, tiredness.
Reproductive: Breast fibroadenosis, breast neoplasm, breast pain, dysmenorrhea, menstrual disorder, vaginal hemorrhage, vaginitis, prostatic disorder.
Liver and biliary system: Hepatic function abnormal, SGOT increased, SGPT increased.
Musculoskeletal: Arthralgia, bone disorder, myalgia, neck stiffness, tendonitis.
Metabolic and nutritional: BUN increased, CPK increased, diabetes mellitus, hypercholesterolemia, hyperglycemia, hypokalemia, NPN increase, creatinine increased, alkaline phosphatase increased, weight increase.
General: Allergy aggravated, allergic reaction, asthenia, chest pain, cyst NOS, edema generalized, face edema, fatigue, fever, hot flushes, influenza-like symptoms, pain, peripheral pain, anemia, ear abnormality, earache, photosensitivity reaction, pruritus, dermatitis, taste perversion, otitis media, blurred vision, eye pain, glaucoma, urinary tract infection.
Very rare:
Congestive heart failure, pulmonary embolism, vasculitis cerebrovascular accident, gastrointestinal bleeding, colitis with bleeding, esophageal perforation, pancreatitis, hepatitis, thrombocytopenia, agranulocytosis, aplastic anemia, pancytopenia, leukopenia, hypoglycemia, hyponatremia, aseptic meningitis, ataxia, acute renal failure, interstitial nephritis, erythema multiforme, exfoliative dermatitis, Stevens-Johnson syndrome, toxic epidermal necrolysis, anaphylactoid reaction, angioedema.
Not applicable.
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