Pharmacology: Celecoxib is a nonsteroidal anti-inflammatory drug that exhibits anti-inflammatory, analgesic, and antipyretic activities in animals. The mechanism of action of celecoxib is believed to be related to inhibition of cyclooxygenase-2 (COX-2). COX-2 is expressed at high levels in inflamed tissues where it is induced by mediators of inflammation. COX-2 has the same catalytic activity as COX-1. COX-1 is expressed constitutively in most tissues including the gastrointestinal tract, kidney, lungs, brain, and platelets. The prostaglandins produced in these tissues play key roles in the maintenance of physiological functions including platelet aggregation and maintenance of the gastrointestinal mucosal barrier. At therapeutic concentrations celecoxib inhibits COX-2 and does not inhibit COX-1. rx canada pharmacy

Pharmacokinetics: The pharmacokinetics of celecoxib have been evaluated in approximately 1500 individuals. In addition to healthy, young and elderly volunteers (male and female), pharmacokinetic measurements have been done in patients and also in special populations including individuals with hepatic or renal impairment. rx canada pharmacy

Absorption: Peak plasma levels of celecoxib occur approximately 3 hours after an oral dose. Both peak plasma levels (C _max) and area under the curve (AUC) are roughly dose proportional across the clinical dose range of 100 to 200 mg studied. Under fasting conditions, at higher doses, there is a less than proportional increase in C _max and AUC which is thought to be due to the low solubility of the drug in aqueous media. Because of the low solubility, absolute bioavailability studies have not been conducted. With multiple dosing, steady-state conditions are reached on or before day 5. rx canada pharmacy

The pharmacokinetic parameters of celecoxib in a group of healthy subjects are shown in Table I. rx canada pharmacy

Food Effects: When celecoxib capsules were taken with a high fat meal, peak plasma levels were delayed for about 1 to 2 hours with an increase in total absorption (AUC) of 10 to 20%. Coadministration of celecoxib with an aluminum- and magnesium-containing antacid resulted in a reduction in plasma celecoxib concentrations with a decrease of 37% in C _max and 10% in AUC. Celecoxib capsules can be administered without regard to the timing of meals. rx canada pharmacy

Distribution: In healthy subjects, celecoxib is highly protein bound (approximately 97%) within the clinical dose range. In vitro studies indicate that celecoxib binds primarily to albumin and, to a lesser extent, a 1-acid glycoprotein. The apparent volume of distribution at steady state (V _ss/F) is approximately 400 L, suggesting extensive distribution into the tissues. Celecoxib is not preferentially bound to red blood cells. rx canada pharmacy

Metabolism: Celecoxib metabolism is primarily mediated via cytochrome P450 2C9. Three metabolites, a primary alcohol, the corresponding carboxylic acid and its glucuronide conjugate, have been identified in human plasma. These metabolites are inactive as COX-1 or COX-2 inhibitors. 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. rx canada pharmacy

Excretion: Celecoxib is eliminated predominantly by hepatic metabolism with little (<3%) unchanged drug recovered in the urine and feces. Following a single oral dose of radiolabeled drug, approximately 57% of the dose was excreted in the feces and 27% was excreted into the urine. The primary metabolite in both urine and feces was the carboxylic acid metabolite (73% of dose) with low amounts of the glucuronide also appearing in the urine. It appears that the low solubility of the drug prolongs the absorption process making terminal half-life (t _1/2) determinations more variable. The effective half-life is approximately 11 hours under fasted conditions. The apparent plasma clearance (CL/F) is about 500 mL/min. rx canada pharmacy

Special Populations: Geriatrics: At steady state, elderly subjects (over 65 years old) had a 40% higher C _max and a 50% higher AUC compared to the young subjects. In elderly females, celecoxib C _max and AUC are higher than those for elderly males, but these increases are predominantly due to lower body weight in elderly females. Dose adjustment in the elderly is not generally necessary. However, for patients of less than 50 kg in body weight, initiate therapy at the lowest recommended dose. rx canada pharmacy

Race: Meta-analysis of pharmacokinetic studies has suggested an approximately 40% higher AUC of celecoxib in black patients compared to caucasians. The cause and clinical significance of this finding is unknown. rx canada pharmacy

Hepatic Insufficiency: A pharmacokinetic study in subjects with mild (Child-Pugh Class I) and moderate (Child-Pugh Class II) hepatic impairment has shown that steady-state celecoxib AUC is increased about 40% and 180%, respectively, above that seen in healthy control subjects. Therefore, celecoxib capsules should be introduced at a reduced dose in patients with moderate hepatic impairment. Patients with severe hepatic impairment have not been studied. The use of celecoxib in patients with severe hepatic impairment is not recommended.. rx canada pharmacy

Renal Insufficiency: In a cross-study comparison, celecoxib AUC was approximately 40% lower in patients with chronic renal insufficiency (GFR 35-60 mL/min) than that seen in subjects with normal renal function. No significant relationship was found between GFR and celecoxib clearance. Patients with severe renal insufficiency have not been studied. rx canada pharmacy

Clinical Studies: Osteoarthritis (OA): The clinical effectiveness of celecoxib in the treatment of the signs and the symptoms of OA of the knee and hip was demonstrated in placebo- and active-controlled clinical trials of up to 12 weeks duration, involving approximately 4200 patients. Celecoxib demonstrated significant reductions in joint pain and disease activity, and also improvement in patient functional activity and health-related quality of life compared to placebo. Clinically significant effects on joint pain were seen as early as 24 hours after the first dose of celecoxib. Doses of 200 mg b.i.d. provided no additional efficacy above that seen with 100 mg b.i.d. In the repeated dose OA studies with 100 mg b.i.d. of celecoxib, pain was significantly decreased by the end of the first day of dosing, continued to be significantly less than placebo and was comparable to naproxen 500 mg b.i.d., diclofenac 75 mg b.i.d., and ibuprofen 800 mg t.i.d. rx canada pharmacy

A total daily dose of 200 mg has been shown to be equally effective when administered as 100 mg b.i.d. or 200 mg once daily. Response to celecoxib was independent of age, gender, severity, or duration of OA. Celecoxib has shown continued efficacy at doses of up to 400 mg a day in a long-term (up to 12 months) open label study of 2500 patients. rx canada pharmacy

In patients with OA, treatment with celecoxib 100 mg b.i.d. or 200 mg once daily resulted in improvement in functional activity as demonstrated by an improvement in pain, stiffness, function and total WOMAC (Western Ontario and McMaster Universities Osteoarthritis Index) scores. Improvement in quality of life, as measured by the MOS-SF-36 (Short Form 36 Item Health Survey) has been shown by improvements in Physical Function, Role Physical, Bodily Pain, Vitality and Social Functioning domains. rx canada pharmacy

Rheumatoid Arthritis (RA): The clinical effectiveness of celecoxib in the treatment of the signs and the symptoms of RA was demonstrated in placebo- and active-controlled clinical trials of up to 24 weeks in duration, involving approximately 2100 patients. Celecoxib demonstrated significant reductions in joint tenderness and pain, joint swelling, disease activity, and morning stiffness compared to placebo. Improvements were demonstrated in the ACR20 Index for RA (American College of Rheumatology 20% Responder Index), patient functional activity, and health-related quality of life compared to placebo. Celecoxib doses of 100 mg b.i.d. and 200 mg b.i.d. were similar in efficacy and both were comparable to naproxen 500 mg b.i.d. Although celecoxib 100 mg b.i.d. and 200 mg b.i.d. provided similar efficacy overall, some patients derive additional benefit from the 200 mg b.i.d. dose. Doses of 400 mg b.i.d. provided no additional efficacy above that seen with 100 to 200 mg b.i.d. rx canada pharmacy

Additional studies demonstrated that celecoxib 200 mg b.i.d. was comparable to diclofenac 75 mg b.i.d. and ibuprofen 800 mg t.i.d. Response to celecoxib was independent of age, gender, severity, or duration of RA. In an open label study of up to 12 months in approximately 1900 RA patients, celecoxib has shown continued efficacy. rx canada pharmacy

In patients with RA, treatment with celecoxib 200 mg b.i.d. resulted in improvement in functioning as shown by an improvement in the Health Assessment Questionnaire (HAQ) functional disability index. Improvement in quality of life as measured by the MOS-SF-36 has been shown by improvements in Physical Function, Role Physical Bodily Pain, Vitality and Social Functioning domains. Compared to celecoxib 100 mg b.i.d., celecoxib 200 mg b.i.d. resulted in greater improvement in the HAQ disability index and the MOS-SF-36 domains of Physical Function and Bodily Pain. rx canada pharmacy

Special Studies: Gastroduodenal Ulceration: Scheduled upper gastrointestinal endoscopic evaluations were performed in over 4500 arthritis patients who were enrolled in 5 controlled randomized 12 to 24-week trials using active comparators, 2 of which also included placebo controls. Twelve-week endoscopic ulcer data are available on approximately 1400 patients and 24-week endoscopic ulcer data are available on 184 patients on celecoxib at doses ranging from 50 to 400 mg b.i.d. NSAID comparators included naproxen 500 mg b.i.d., diclofenac 75 mg b.i.d., and ibuprofen 800 mg t.i.d. rx canada pharmacy

In active-controlled studies, the endoscopic gastroduodenal ulceration rate observed with all doses of celecoxib was less than what was seen with the NSAID comparator (see Tables II, III and IV) and, in placebo-controlled studies, was similar to that seen with placebo (see Table II). Studies were designed to detect differences between celecoxib and the NSAID comparator, therefore were not powered to detect small differences relative to placebo. Moreover, celecoxib doses above the highest recommended therapeutic dose of 200 mg b.i.d. were evaluated, and demonstrated that with supratherapeutic doses (2 to 4 times the recommended dose), the incidence of endoscopic ulcers was similar to placebo. Duration of observation had no impact on the celecoxib gastroduodenal ulcer rate, as shown in a 24-week trial in which the celecoxib endoscopic ulcer rate was significantly lower than diclofenac SR and comparable to ulcer rates observed with placebo in other studies.. rx canada pharmacy

In all 3 studies that included naproxen 500 mg b.i.d., and in the study that included ibuprofen 800 mg t.i.d., celecoxib was associated with a statistically significantly lower incidence of endoscopic ulcers over the study period. Two studies compared celecoxib with diclofenac 75 mg b.i.d.; one study revealed a statistically significantly higher prevalence of endoscopic ulcers in the diclofenac group at the study endpoint (6 months on treatment), and 1 study revealed no statistically significant difference between cumulative endoscopic ulcer incidence rates in the diclofenac and celecoxib groups after 1, 2, and 3 months of treatment. There was no consistent relationship between the incidence of gastroduodenal ulcers and the dose of celecoxib over the range studied. rx canada pharmacy

Table II summarizes the incidence of endoscopic ulcers in two 12-week studies that enrolled patients in whom baseline endoscopies revealed no ulcers. rx canada pharmacy

The correlation between findings of endoscopic studies, and the relative incidence of clinically serious upper gastrointestinal events that may be observed with different products, has not been fully established. (see Warnings, Gastrointestinal). rx canada pharmacy

Use with ASA: Approximately 11% of patients (440/4000) enrolled in 4 of the 5 endoscopic studies were taking ASA (£ 325 mg/day). In the celecoxib groups, the endoscopic ulcer rate appeared to be higher in subjects taking both celecoxib and ASA than in subjects taking only celecoxib. However, the increased rate of ulcers in these ASA users was less than the endoscopic ulcer rates observed in the active comparator groups, with or without ASA. rx canada pharmacy

Platelets: In 4 clinical trials involving 118 subjects, celecoxib did not affect platelet function. Celecoxib at single doses up to 800 mg and multiple doses of 600 mg b.i.d. for up to 7 days duration (i.e., 3 times the highest recommended therapeutic dose), had no effect on platelet aggregation and bleeding time compared to placebo. In contrast, the NSAIDs naproxen 500 mg b.i.d., ibuprofen 800 mg t.i.d., and diclofenac 75 mg b.i.d. significantly reduced platelet aggregation and prolonged bleeding time. rx canada pharmacy


Indications: For acute and chronic use in the relief of the signs and symptoms of osteoarthritis and rheumatoid arthritis in adults. rx canada pharmacy

Contraindications: In patients with known hypersensitivity to celecoxib. rx canada pharmacy

Celecoxib should not be given to patients who have demonstrated allergic-type reactions to sulfonamides. rx canada pharmacy

Celecoxib should not be given to patients who have experienced asthma, urticaria, or allergic-type reactions after taking ASA or other NSAIDs. Severe, rarely fatal, anaphylactic-like reactions to NSAIDs have been reported in such patients (see Warnings, Anaphylactoid Reactions, and Precautions, Hypersensitivity Reactions). rx canada pharmacy

Celecoxib is not recommended for use with other NSAIDs because of the absence of any evidence demonstrating synergistic benefits and the potential for additive side effects. rx canada pharmacy


Warnings: Gastrointestinal: Celecoxib exhibited a low incidence of gastroduodenal ulceration and serious clinically significant gastrointestinal events within clinical trials. However, prospective long-term studies required to compare the incidence of serious, clinically significant gastrointestinal adverse events in patients taking celecoxib vs comparator NSAID products have not been performed. Therefore, the following general warnings for NSAIDs should be borne in mind. rx canada pharmacy

Serious gastrointestinal toxicity, such as peptic ulceration, perforation and bleeding, sometimes severe and occasionally fatal, can occur at any time, with or without warning symptoms, in patients treated with NSAIDs. Minor upper gastrointestinal problems, such as dyspepsia, are common, and may also occur at any time during NSAID therapy. Therefore, physicians should remain alert for ulceration and bleeding in patients treated with NSAIDs, even in the absence of previous gastrointestinal tract symptoms. Patients should be informed about the signs and/or symptoms of serious gastrointestinal toxicity and the steps to take if they occur. The utility of periodic laboratory monitoring has not been demonstrated, nor has it been adequately assessed. Only 1 in 5 patients who develop a serious upper gastrointestinal adverse event on NSAID therapy is symptomatic. It has been demonstrated that upper gastrointestinal ulcers, gross bleeding or perforation, caused by NSAIDs, appear to occur in approximately 1% of patients treated for 3 to 6 months, and in about 2 to 4% of patients treated for 1 year. These trends continue thus, increasing the likelihood of developing a serious gastrointestinal event at some time during the course of therapy. However, even short-term therapy is not without risk. rx canada pharmacy

It is unclear, at the present time, how these above rates apply to celecoxib (see Pharmacology, Clinical Studies--Special Studies). Among 5285 patients who received celecoxib in controlled clinical trials of 1 to 6 months duration (most were 3-month studies) at a daily dose of 200 mg or more, 2 (0.04%) experienced significant upper gastrointestinal bleeding, at 14 and 22 days after initiation of dosing. Approximately 40% of these 5285 patients were in studies that required them to be free of ulcers by endoscopy at study entry. Thus it is unclear if this study population is representative of the general population. Prospective, long-term studies required to compare the incidence of serious, clinically significant gastrointestinal adverse events in patients taking celecoxib vs comparator NSAID products have not been performed. rx canada pharmacy

NSAIDs should be prescribed with extreme caution in patients with a prior history of ulcer disease or gastrointestinal bleeding. Most spontaneous reports of fatal gastrointestinal events are in elderly or debilitated patients and therefore special care should be taken in treating this population. To minimize the potential risk for an adverse gastrointestinal event, the lowest effective dose should be used for the shortest possible duration. For high risk patients, alternate therapies that do not involve NSAIDs should be considered. rx canada pharmacy

Studies have shown that patients with a prior history of peptic ulcer disease and/or gastrointestinal bleeding and who use NSAIDs, have a greater than 10-fold higher risk for developing a gastrointestinal bleed than patients with neither of these risk factors. It is unclear how this finding applies to celecoxib. In addition to a past history of ulcer disease, pharmacoepidemiological studies have identified several other cotherapies or comorbid conditions that may increase the risk for gastrointestinal bleeding such as: treatment with oral corticosteroids, treatment with anticoagulants, longer duration of NSAID therapy, smoking, alcoholism, older age and poor general health status. rx canada pharmacy

Anaphylactoid Reactions: As with NSAIDs in general, anaphylactoid reactions may occur in patients without known prior exposure to celecoxib. In postmarketing experience, very rare cases of anaphylactic reactions and angioedema have been reported in patients receiving celecoxib. Celecoxib should not be given to patients with the ASA 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 ASA or other NSAIDs (see Contraindications and Precautions, Hypersensitivity Reactions). Emergency help should be sought in cases where an anaphylactoid reaction occurs. rx canada pharmacy

Advanced Renal Disease: No information is available regarding the use of celecoxib in patients with advanced kidney disease. Therefore, treatment with celecoxib is not recommended in these patients. If celecoxib therapy must be initiated, close monitoring of the patient's kidney function is advisable (see Precautions, Renal Function). rx canada pharmacy

Cross-sensitivity: Patients sensitive to any one of the NSAIDs may be sensitive to any of the other NSAIDs also. rx canada pharmacy

Allergies to sulfonamides: See Contraindications. rx canada pharmacy

Aseptic Meningitis: In occasional cases, with some NSAIDs, the symptoms of aseptic meningitis (stiff neck, severe headaches, nausea and vomiting, fever or clouding of consciousness) have been observed. Patients with autoimmune disorders (systemic lupus erythematosus, mixed connective tissues diseases, etc.) seem to be predisposed. Therefore, in such patients, the physician must be vigilant to the development of this complication. rx canada pharmacy

Pregnancy: There are no studies in pregnant women. Celecoxib should be used during pregnancy only if the potential benefit outweighs the potential risk to the fetus. No studies to evaluate the effect of celecoxib on the closure of the ductus arteriosus in humans have been carried out, therefore use of celecoxib during the third trimester of pregnancy should be avoided. rx canada pharmacy

Lactation: Celecoxib is excreted in rat milk at concentrations similar to those in plasma. Studies of celecoxib excretion in human milk have not been conducted, therefore, the benefit of celecoxib treatment in nursing mothers should be weighed against the potential risk to the newborn. rx canada pharmacy

Children: Safety and effectiveness in pediatric patients below the age of 18 years have not been evaluated. rx canada pharmacy

Precautions: General: Celecoxib cannot be expected to substitute for corticosteroids or to treat corticosteroid insufficiency. Abrupt discontinuation of corticosteroids may lead to exacerbation ofresponsive illness. Patients on prolonged corticosteroid therapy should have their therapy tapered slowly if a decision is made to discontinue corticosteroids. rx canada pharmacy

Gastrointestinal: There is no definitive evidence that the concomitant administration of histamine H ₂-receptor antagonists and/or antacids will either prevent the occurrence of gastrointestinal side effects or allow the continuation of celecoxib when and if these adverse reactions appear. rx canada pharmacy

Renal Function: 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 a 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, heart failure, liver dysfunction, those taking diuretics and ACE inhibitors, and the elderly. Discontinuation of NSAID therapy is usually followed by recovery to the pretreatment state. Clinical trials with celecoxib have shown renal effects similar to those observed with comparator NSAIDs. rx canada pharmacy

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. rx canada pharmacy

Genitourinary Tract: Some NSAIDs are known to cause persistent urinary symptoms (bladder pain, dysuria, urinary frequency), hematuria or cystitis. The onset of these symptoms may occur at any time after the initiation of therapy with an NSAID. Some cases have become severe on continued treatment. Should urinary symptoms occur, treatment with celecoxib must be stopped immediately to obtain recovery. This should be done before any urological investigations or treatments are carried out. rx canada pharmacy

Hepatic Function: Borderline elevations of one or more liver tests may occur in up to 15% of patients taking NSAIDs, and notable elevations of ALT or AST (approximately 3 or more times the upper limit of normal) have been reported in approximately 1% of patients in clinical trials with NSAIDs. These laboratory abnormalities may progress, may remain unchanged, or may be transient with continuing therapy. Rare cases of severe hepatic reactions, including jaundice and fatal fulminant hepatitis, liver necrosis and hepatic failure (some with fatal outcome) have been reported with NSAIDs. In controlled clinical trials of celecoxib, the incidence of borderline elevations of liver tests was 6% for celecoxib and 5% for placebo, and approximately 0.2% of patients taking celecoxib and 0.3% of patients taking placebo had notable elevations of ALT and AST. rx canada pharmacy

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. rx canada pharmacy

Fluid and Electrolyte Balance: Fluid retention and edema have been observed in some patients taking celecoxib (see Adverse Effects). Therefore, as with other nonsteroidal anti-inflammatory drugs, the possibility of precipitating congestive heart failure in elderly patients or those with compromised cardiac function should be borne in mind. Celecoxib should be used with caution in patients with heart failure, hypertension, or other conditions predisposing to fluid retention. rx canada pharmacy

With nonsteroidal anti-inflammatory treatment there is a potential risk of hyperkalemia, particularly in patients with conditions such as diabetes mellitus or renal failure, elderly patients, or in patients receiving concomitant therapy with b-adrenergic blockers, angiotensin converting enzyme inhibitors or some diuretics. Serum electrolytes should be monitored periodically during long-term therapy, especially in those patients who are at risk. rx canada pharmacy

Hematology: Anemia is sometimes seen in patients receiving celecoxib. In controlled clinical trials the incidence of anemia was 0.6% with celecoxib and 0.4% with placebo. 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 appear to inhibit platelet aggregation at indicated dosages (see Pharmacology, Clinical Studies--Special Studies, Platelets). rx canada pharmacy

Blood dyscrasias (such as neutropenia, leukopenia, thrombocytopenia, aplastic anemia and agranulocytosis) associated with the use of NSAIDs are rare, but could occur with severe consequences. rx canada pharmacy

Infection: In common with other anti-inflammatory drugs, celecoxib may mask the usual signs of infection. rx canada pharmacy

Ophthalmology: Blurred and/or diminished vision has been reported with the use of NSAIDs. If such symptoms develop, celecoxib should be discontinued and an ophthalmologic examination performed; ophthalmologic examination should be carried out at periodic intervals in any patient receiving celecoxib for an extended period of time. rx canada pharmacy

Occupational Hazards: CNS: Some patients may experience drowsiness, dizziness, vertigo, insomnia or depression with the use of NSAIDs. If patients experience these side effects, they should exercise caution in carrying out activities that require alertness. rx canada pharmacy

Hypersensitivity Reactions: Patients with asthma may have ASA-sensitive asthma. The use of ASA in patients with ASA-sensitive asthma has been associated with severe bronchospasm which can be fatal. Since cross reactivity, including bronchospasm, between ASA and other NSAIDs has been reported in such ASA-sensitive patients, celecoxib should not be administered to patients with this form of ASA sensitivity and should be used with caution in patients with pre-existing asthma. rx canada pharmacy

Drug interactions: General: Celecoxib metabolism is predominantly mediated via cytochrome P450 2C9 in the liver. Coadministration of celecoxib with drugs that are known to inhibit 2C9 should be done with caution. rx canada pharmacy

In vitro studies indicate that celecoxib, although not a substrate, is a relatively weak inhibitor of cytochrome P450 2D6. Therefore, there is a potential for an in vivo drug interaction with drugs that are metabolized by P450 2D6. rx canada pharmacy

In vitro studies indicate that celecoxib is not an inhibitor of cytochrome P450 2C9, 2C19 or 3A4.. rx canada pharmacy

ASA or other NSAIDs: Celecoxib can be used with low dose ASA. However, concomitant administration of ASA with celecoxib may result in an increased rate of gastrointestinal ulceration or other complications, compared to use of celecoxib alone (see Pharmacology, Clinical Studies--Special Studies). Because of its lack of platelet effects, celecoxib is not a substitute for ASA for cardiovascular prophylaxis. rx canada pharmacy

Anticoagulants: 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. The effect of celecoxib on the anticoagulant effect of warfarin was studied in a group of healthy subjects receiving daily doses of 2 to 5 mg of warfarin (dose sufficient to prolong prothrombin times to 1.2 to 1.7 times their baseline values). In these subjects, celecoxib did not alter the anticoagulant effect of warfarin as determined by prothrombin time. However, in postmarketing experience, bleeding events have been reported, predominantly in the elderly, in association with increases in prothrombin time in patients receiving celecoxib concurrently with warfarin. rx canada pharmacy

Oral Hypoglycemics: The effect of celecoxib on the pharmacokinetics and/or pharmacodynamics of glyburide and tolbutamide has been studied and clinically important interactions have not been found. rx canada pharmacy

Diuretics: Clinical studies, as well as postmarketing 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. Although prospective studies of celecoxib with diuretics have not been conducted, no adverse reactions indicative of elevations in blood pressure were seen in clinical trials in which arthritis patients were taking celecoxib concurrently with diuretics (n=485). No adverse reactions indicative of sodium retention or renal impairment were seen in clinical trials in patients taking celecoxib concurrently with diuretics. rx canada pharmacy

Antihypertensives: Reports suggest that NSAIDs may diminish the antihypertensive effects of Angiotensin Converting Enzyme (ACE) inhibitors. This interaction should be given consideration. Although prospective studies of celecoxib with ACE inhibitors have not been conducted, no adverse reactions indicative of elevations in blood pressure were seen in clinical trials in which arthritis patients were taking celecoxib concurrently with ACE inhibitors (n=305). rx canada pharmacy

Glucocorticoids: Oral glucocorticoids should be used with caution since they increase the risk of gastrointestinal side effects suchulceration and bleeding. This is especially the case in older (>65 years of age) individuals. rx canada pharmacy

Antacids: Coadministration of celecoxib with an aluminum- andcontaining antacid resulted in a reduction in plasma celecoxib concentrations with a decrease of 37% in C _max and 10% in AUC. rx canada pharmacy

Methotrexate: Celecoxib did not have a significant effect on the pharmacokinetics of methotrexate. rx canada pharmacy

Lithium: In a study conducted in healthy subjects, 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. rx canada pharmacy

Fluconazole: Concomitant administration of fluconazole at 200 mg once daily resulted in a 2-fold increase in celecoxib plasma concentration. This increase is due to the inhibition of celecoxib metabolism via P450 2C9 by fluconazole (see Pharmacology, Pharmacokinetics--Metabolism). Celecoxib should be introduced at the lowest recommended dose in patients receiving fluconazole. rx canada pharmacy

Ketoconazole: Celecoxib did not have a significant effect on the pharmacokinetics of ketoconazole. rx canada pharmacy

Phenytoin: Celecoxib did not have a significant effect on the pharmacokinetics of phenytoin. rx canada pharmacy

Other Drug Interactions : No drug interaction data are available for celecoxib and the coadministration of the following products: acetaminophen, alcohol, aminoglycosides, bone marrow depressants, butemide, cholestyramine, colchicine, corticosteroids, cyclosporine, digoxin, gold compounds, indapamide, insulin, nephrotoxic agents, NSAIDs, oral contraceptives, potassium supplements, probenicid, valproic acid, zidovudine. rx canada pharmacy

Laboratory Tests: During the controlled clinical trials, there was an increased incidence of hyperchloremia in patients receiving celecoxib compared with patients on placebo. Other laboratory abnormalities that occurred more frequently in the patients receiving celecoxib included hypophosphatemia, and elevated urea. These laboratory abnormalities were also seen in patients who received comparator NSAIDs in these studies. The clinical significance of these abnormalities has not been established. rx canada pharmacy

Adverse Effects: Of the celecoxib-treated patients in controlled trials, approximately 4250 were patients with OA, approximately 2100 were patients with RA, and approximately 1050 were patients with postsurgical pain. More than 8500 patients have received a total daily dose of celecoxib of 200 mg (100 mg b.i.d. or 200 mg once daily) or more, including more than 400 treated at 800 mg (400 mg b.i.d.). Approximately 3900 patients have received celecoxib at these doses for 6 months or more; approximately 2300 of these have received it for 1 year or more and 124 of these have received it for 2 years or more. rx canada pharmacy

Geriatrics: Celecoxib has been extensively studied in elderly patients. Of the total number of patients who received celecoxib in clinical trials, more than 2100 patients were 65 to 74 years of age, while approximately 800 additional patients were 75 years and over. While the incidence of adverse experiences tended to be higher in elderly patients, no substantial differences in safety and effectiveness were observed between these subjects and younger patients. In gastrointestinal endoscopy studies involving over 800 elderly patients, the rate of gastroduodenal ulceration was not different in elderly patients compared to the young. Other reported clinical experience has not identified differences in response between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out. rx canada pharmacy

In clinical studies comparing renal function as measured by the GFR, urea and creatinine, and platelet function as measured by bleeding time and platelet aggregation, the results were not different between elderly and young volunteers. rx canada pharmacy

Adverse Events from Controlled Trials: Table V lists all adverse events, regardless of causality, occurring in ³2% of patients receiving celecoxib from 12 controlled studies conducted in patients with osteoarthritis and rheumatoid arthritis that included a placebo and/or a positive control group. rx canada pharmacy

In placebo- or active-controlled clinical trials, the discontinuation rate due to adverse events was 7.1% for patients receiving celecoxib and 6.1% for patients receiving placebo. Among the most common reasons for discontinuation due to adverse events in the celecoxib treatment groups were dyspepsia and abdominal pain (cited as reasons for discontinuation in 0.8 and 0.7% of celecoxib patients, respectively). Among patients receiving placebo, 0.6% discontinued due to dyspepsia and 0.6% withdrew due to abdominal pain. rx canada pharmacy

The following adverse events occurred in 0.1 to 1.9% of patients regardless of causality: Celecoxib (100 to 200 mg b.i.d. or 200 mg once daily). rx canada pharmacy

Gastrointestinal: constipation, diverticulitis, dry mouth, dysphagia, eructation, esophagitis, gastritis, gastroenteritis, gastroesophageal reflux, hemorrhoids, hiatal hernia, melena, stomatitis, tenesmus, tooth disorder, vomiting. rx canada pharmacy

Cardiovascular: aggravated hypertension, angina pectoris, coronary artery disorder, myocardial infarction. rx canada pharmacy

General: allergy aggravated, allergic reaction, asthenia, chest pain, cyst NOS, edema generalized, face edema, fatigue, fever, hot flushes, influenza-like symptoms, pain, peripheral pain. rx canada pharmacy

Resistance Mechanism Disorders: herpes simplex, herpes zoster, infection bacterial, infection fungal, infection soft tissue, infection viral, moniliasis, moniliasis genital, otitis media. rx canada pharmacy

Central, Peripheral Nervous Systems: leg cramps, hypertonia, hypoesthesia, migraine, neuralgia, neuropathy, paresthesia, vertigo. rx canada pharmacy

Female Reproductive: breast fibroadenosis, breast neoplasm, breast pain, dysmenorrhea, menstrual disorder, vaginal hemorrhage, vaginitis. rx canada pharmacy

Male Reproductive: prostatic disorder. rx canada pharmacy

Hearing and Vestibular: deafness, ear abnormality, earache, tinnitus. rx canada pharmacy

Heart Rate and Rhythm: palpitation, tachycardia. rx canada pharmacy

Liver and Biliary Systems: ALT increased, AST increased, hepatic function abnormal. rx canada pharmacy

Metabolic and Nutritional: urea increased, CPK increased, diabetes mellitus, hypercholesterolemia, hyperglycemia, hypokalemia, NPN increase, creatinine increased, alkaline phosphatase increased, weight increase. rx canada pharmacy

Musculoskeletal: arthralgia, arthrosis, bone disorder, fracture accidental, myalgia, neck stiffness, synovitis, tendinitis. rx canada pharmacy

Platelets (bleeding or clotting): ecchymosis, epistaxis, thrombocythemia. rx canada pharmacy

Psychiatric: anorexia, anxiety, appetite increased, depression, nervousness, somnolence. rx canada pharmacy

Hemic: anemia. rx canada pharmacy

Respiratory: bronchitis, bronchospasm, bronchospasm aggravated, coughing, dyspnea, laryngitis, pneumonia. rx canada pharmacy

Skin and Appendages: alopecia, dermatitis, nail disorder, photosensitivity reaction, pruritus, rash erythematous, rash maculopapular, skin disorder, skin dry, sweating increased, urticaria. rx canada pharmacy

Application Site Disorders: cellulitis, dermatitis contact, injection site reaction, skin nodule. rx canada pharmacy

Special Senses: taste perversion. rx canada pharmacy

Urinary System: albuminuria, cystitis, dysuria, hematuria, micturition frequency, renal calculus, urinary incontinence, urinary tract infection. rx canada pharmacy

Vision: blurred vision, cataract, conjunctivitis, eye pain, glaucoma. rx canada pharmacy

The following serious adverse events have occurred rarely (< 0.1%) in patients taking celecoxib, regardless of causality. rx canada pharmacy

Cardiovascular: syncope, congestive heart failure, ventricular fibrillation, pulmonary embolism, cerebrovascular accident, peripheral gangrene, thrombophlebitis. rx canada pharmacy

Gastrointestinal: intestinal obstruction, intestinal perforation, gastrointestinal bleeding, colitis with bleeding, esophageal perforation, pancreatitis, cholelithiasis, ileus. rx canada pharmacy

Hemic and Lymphatic: Thrombocytopenia. rx canada pharmacy

Nervous System: ataxia. rx canada pharmacy

Renal: acute renal failure. rx canada pharmacy

General: sepsis, sudden death. rx canada pharmacy

Overdose: Symptoms: Symptoms following acute NSAID overdoses are usually limited to lethargy, drowsiness, nausea, vomiting, and epigastric pain, which are generally reversible with supportive care. Gastrointestinal bleeding can occur. Hypertension, acute renal failure, respiratory depression and coma may occur, but are rare. Anaphylactoid reactions have been reported with therapeutic ingestion of NSAIDs, and may occur following an overdose. rx canada pharmacy



Treatment: Patients should be managed by symptomatic and supportive care following an NSAID overdose. There are no specific antidotes. No information is available regarding the removal of celecoxib by hemodialysis, but based on its high degree of plasma protein binding (>97%) dialysis is unlikely to be useful in overdose. Emesis and/or activated charcoal (60 to 100 g in adults, 1 to 2 g/kg in children) and/or osmotic cathartic may be indicated in patients seen within 4 hours of ingestion with symptoms or following a large overdose. Forced diuresis, alkalinization of urine, hemodialysis, or hemoperfusion may not be useful due to high protein binding. rx canada pharmacy


Dosage: Osteoarthritis: The recommended daily dose is 200 mg administered as a single dose or as 2 divided doses, with or without food.. rx canada pharmacy

Rheumatoid Arthritis: The recommended starting dose is 100 mg twice per day, with or without food, which may be increased to 200 mg twice per day as needed. rx canada pharmacy

Information for the Patient: See Blue Section--Information for the Patient Celebrex. rx canada pharmacy


Supplied: 100 mg: Each white capsule, with printed blue markings of 7767 on the cap and 100 on the body, contains: celecoxib 100 mg. Nonmedicinal ingredients: croscarmellose sodium, lactose monohydrate, magnesium stearate, povidone and sodium lauryl sulfate; shell: edible ink (indigotine [E132]), gelatin and titanium dioxide (E171). Bottles of 100 and 500. rx canada pharmacy

200 mg: Each white capsule, with printed gold markings of 7767 on the cap and 200 on the body, contains: celecoxib 200 mg. Nonmedicinal ingredients: croscarmellose sodium, lactose monohydrate, magnesium stearate, povidone and sodium lauryl sulfate; shell: edible ink (ferric oxide [E172]), gelatin and titanium dioxide (E171). Bottles of 100 and 500. rx canada pharmacy


Store at room temperature (15 to 30°C).

Canada Pharmacy- Celebrex - Celebrex Side Effects - Celebrex Information