Rancelex Capsules 200 mg

Rancelex Capsules 200 mg

celecoxib

Manufacturer:

Ranbaxy

Distributor:

DKLL
Full Prescribing Info
Contents
Celecoxib.
Description
Each capsule contains Celecoxib 200 mg.
Celecoxib is chemically designated as 4-[5-(4-methylphenyl)-3-(trifluoromethyl)-1H-pyrazol1-yl] benzenesulfonamide and is a diaryl-substituted pyrazole. The empirical formula for celecoxib is C17H14F3N3O2S, and the molecular weight is 381.38.
Excipients/Inactive Ingredients: Lactose monohydrate, Povidone, Colloidal anhydrous silica, Sodium lauryl sulfate, Croscarmellose sodium, Purified water, Magnesium stearate, and empty gelatin capsules shell white.
Action
Pharmacology: Pharmcodynamics: Mechanism of Action: Celecoxib is a nonsteroidal anti-inflammatory drug that exhibits anti-inflammatory, analgesic, and antipyretic activities in animal models. The mechanism of action of celecoxib is believed to be due to inhibition of prostaglandin synthesis, primarily via inhibition of cyclooxygenase-2 (COX-2), and at therapeutic concentrations in humans, celecoxib does not inhibit the cyclooxygenase-1 (COX-1) isoenzyme. In animal colon tumor models, celecoxib reduced the incidence and multiplicity of tumors.
Platelets: No effect on reduction of platelet aggregation or increase in bleeding time has been reported with celecoxib at single doses up to 800 mg and multiple doses of 600 mg twice daily for up to 7 days duration (higher than recommended therapeutic doses).
Because of its lack of platelet effects, celecoxib is not a substitute for aspirin for cardiovascular prophylaxis. It is not known if there are any effects of celecoxib on platelets that may contribute to the increased risk of serious cardiovascular thrombotic adverse events associated with the use of celecoxib.
Fluid Retention: Inhibition of PGE2 synthesis may lead to sodium and water retention through increased reabsorption in the renal medullary thick ascending loop of Henle and perhaps other segments of the distal nephron. In the collecting ducts, PGE2 appears to inhibit water reabsorption by counteracting the action of antidiuretic hormone.
Pharmacokinetics: Absorption: Peak plasma levels of celecoxib occur approximately 3 hrs after an oral dose. Under fasting conditions, both peak plasma levels (Cmax) and area under the curve (AUC) are roughly dose-proportional up to 200 mg BID; at higher doses there are less than proportional increases in Cmax and AUC. With multiple dosing, steady-state conditions are reached on or before Day 5. The pharmacokinetic parameters of celecoxib in healthy subjects are shown in table. (See Table 1.)

Click on icon to see table/diagram/image

Food Effect: When celecoxib capsules were taken with a high fat meal, peak plasma levels were reported to be delayed for about 1 to 2 hours with an increase into total absorption (AUC) of 10% to 20%. Under fasting conditions, at doses above 200 mg, there is less than a proportional increase in Cmax and AUC, which is thought to be due to the low solubility of the drug in aqueous media.
Coadministration of celecoxib with an aluminum- and magnesium-containing antacids resulted in a reduction in plasma celecoxib concentrations with a decrease of 37% in Cmax and 10% in AUC. Celecoxib, at doses up to 200 mg twice daily, can be administered without regard to timing of meals. Higher doses (400 mg twice daily) should be administered with food to improve absorption.
Distribution: Celecoxib is highly protein bound (~97%) within the clinical dose range. Celecoxib has been reported to bind primarily to albumin and, to a lesser extent, α1 acid glycoprotein. The apparent volume of distribution at steady state (Vss/F) is approximately 400 L, suggesting extensive distribution into the tissues. Celecoxib is not preferentially bound to red blood cells.
Metabolism: Celecoxib metabolism is primarily mediated via CYP2C9. 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.
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 reported to be excreted in the feces and 27% 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 (t½) 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.
Pharmacogenomics: CYP2C9 activity is reduced in individuals with genetic polymorphisms that lead to reduced enzyme activity, such as those homozygous for the CYP2C9*2 and CYP2C9*3 polymorphisms. Limited data from published reports that included a total of 8 subjects with the homozygous CYP2C9*3/*3 genotype showed celecoxib systemic levels that were 3- to 7-fold higher in these subjects compared to subjects with CYP2C9*1/*1 or *I/*3 genotypes. The pharmacokinetics of celecoxib have not been reported in subjects with other CYP2C9 polymorphisms, such as *2, *5, *6, *9 and *11. It is estimated that the frequency of the homozygous *3/ *3 genotype is 0.3% to 1.0% in various ethnic groups (see Dosage & Administration and Use in Special Populations under Precautions).
Geriatric: At steady state, elderly subjects (over 65 years old) had reported a 40% higher Cmax and a 50% higher AUC compared to the young subjects. In elderly females, celecoxib Cmax 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 (see Dosage & Administration and Precautions).
Pediatric: The oral clearance (unadjusted for body weight) of celecoxib has been reported to increase less than proportionally to increasing weight, with 10 kg and 25 kg patients predicted to have 40% and 24% lower clearance, respectively, compared with a 70 kg adult RA patient.
Race: An approximately 40% higher AUC of celecoxib has been reported in Blacks compared to Caucasians. The cause and clinical significance of this finding is unknown.
Hepatic Insufficiency: The steady-state celecoxib AUC is reported to increase by about 40% and 180%, in subjects with mild (Child-Pugh Class A) and moderate (Child-Pugh Class B) hepatic impairment, respectively. Therefore, the daily recommended dose of celecoxib capsules should be reduced by approximately 50% in patients with moderate (Child-Pugh Class B) hepatic impairment. 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 (see Dosage & Administration and Precautions).
Renal Insufficiency: The celecoxib AUC is approximately 40% lower in patients with chronic renal insufficiency (GFR 35-60 mL/min) than in subjects with normal renal function. No significant relationship has been reported between GFR and celecoxib clearance. Patients with severe renal insufficiency have not been studied. Similar to other NSAIDs, celecoxib is not recommended in patients with severe renal insufficiency (see Precautions).
Indications/Uses
Carefully consider the potential benefits and risks of celecoxib and other treatment options before deciding to use celecoxib. Use the lowest effective dose for the shortest duration consistent with individual patient treatment goals (see Precautions).
Osteoarthritis (OA): Celecoxib is indicated for relief of the signs and symptoms of OA.
Rheumatoid Arthritis (RA): Celecoxib is indicated for relief of the signs and symptoms of RA.
Ankylosing Spondylitis (AS): Celecoxib is indicated for the relief of signs and symptoms of AS.
Acute Pain (AP): Celecoxib is indicated for the management of AP in adults.
Primary Dysmenorrhea (PD): Celecoxib is indicated for the treatment of PD.
Management of Low Back Pain.
Dosage/Direction for Use
Celecoxib capsules 200 mg may not be suitable for all dosages recommendations and therefore, other suitable available strengths and dosage forms should be used in such cases.
Use lowest effective dose for the shortest duration consistent with treatment goals for the individual patient. These doses can be given without regard to timing of meals.
Osteoarthritis: For relief of the signs and symptoms of OA the recommended oral dose is 200 mg per day administered as a single dose.
Rheumatoid Arthritis: For relief of the signs and symptoms of RA there commended oral dose is 200 mg twice daily.
Ankylosing Spondylitis: For the management of the signs and symptoms of AS, the recommended dose of celecoxib is 200 mg daily (once per day). If no effect is observed after 6 weeks, a trial of 400 mg daily may be worthwhile. If no effect is observed after 6 weeks on 400 mg daily, a response is not likely and consideration should be given to alternate treatment options.
Management of Acute Pain and Treatment of Primary Dysmenorrhea: The recommended dose of celecoxib is 400 mg initially, followed by an additional 200 mg dose if needed on the first day. On subsequent days, the recommended dose is 200 mg twice daily as needed.
Low Back Pain (LBP): The recommended dose of celecoxib is 200 mg or 400 mg daily, administered as a 200 mg single dose, or as 100 or 200 mg twice per day. Some patients may benefit from a total daily dose of 400 mg.
Special Populations: Hepatic insufficiency: The daily recommended dose of celecoxib in patients with moderate hepatic impairment (Child-Pugh Class B) should be reduced by 50%. The use of celecoxib in patients with severe hepatic impairment is not recommended (see Precautions and Pharmacology: Pharmacodynamics and Pharmacokinetics under Actions).
Poor Metabolizers of CYP2C9 Substrates: Patients who are known or suspected to be poor CYP2C9 metabolizers based on genotype or previous history/experience with other CYP2C9 substrates (such as warfarin, phenytoin) should be administered celecoxib with caution. Consider starting treatment at half the lowest recommended dose in poor metabolizers (i.e. CYP2C9*3/*3). (See Pharmacology: Pharmacodynamics and Pharmacokinetics under Actions.)
Overdosage
There is no clinical experience of overdose. Doses up to 2400 mg/day for up to 10 days in 12 patients did not result in serious toxicity.
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.
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.
Contraindications
Known hypersensitivity to celecoxib, aspirin, other NSAIDs or to any of the excipients.
In patients who have demonstrated allergic-type reactions to sulfonamides.
In patients who have experienced asthma, urticaria, or allergic-type reactions after taking aspirin or other NSAIDs including COX-2 inhibitors (see Precautions).
Peri-operative pain in the setting of coronary artery bypass graft (CABG) surgery (see Precautions).
Patients with estimated creatinine clearance <30 ml/min.
Inflammatory bowel disease.
Congestive heart failure (NYHA II-IV).
Established ischaemic heart disease, peripheral arterial disease and/or cerebrovascular disease.
Warnings
Cardiovascular and Gastrointestinal Risks: Cardiovascular Risk: Celecoxib may cause an increased risk of serious cardiovascular thrombotic events, myocardial infarction, and stroke, which can be fatal. All nonsteroidal anti-inflammatory drugs (NSAIDs) may have a similar risk. This risk may increase with duration of use. Patients with cardiovascular disease or risk factors for cardiovascular disease may be at greater risk (see Precautions).
Celecoxib is contraindicated for the treatment of peri-operative pain in the setting of coronary artery bypass graft (CABG) surgery (see Contraindications and Precautions).
Gastrointestinal Risk: NSAIDs, including celecoxib, cause an increased risk of serious gastrointestinal adverse events including bleeding, ulceration, and perforation of the stomach or intestines, which can be fatal. These events can occur at any time during use and without warning symptoms. Elderly patients are at greater risk for serious gastrointestinal events (see Precautions).
Special Precautions
Cardiovascular Thrombotic Events: 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 non-selective, may have a similar risk. Patients with known CV disease or risk factors for CV disease may be at greater risk. 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 consistent with individual patient treatment goals. 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/or symptoms of serious CV toxicity and the steps to take if they occur.
There is no consistent evidence that concurrent use of aspirin mitigates the increased risk of serious CV thrombotic events associated with NSAID use. The concurrent use of aspirin and celecoxib does increase the risk of serious GI events.
An increased incidence of myocardial infarction and stroke has been reported with a different COX-2 selective NSAID for the treatment of pain in the first 10-14 days following CABG surgery (see Contraindications).
Patients with significant risk factors for cardiovascular events (e.g. hypertension, hyperlipidaemia, diabetes mellitus, smoking) should only be treated with celecoxib after careful consideration.
COX-2 selective inhibitors are not a substitute for acetylsalicylic acid for prophylaxis of cardiovascular thrombo-embolic diseases because of their lack of antiplatelet effects. Therefore, antiplatelet therapies should not be discontinued.
Hypertension: As with all NSAIDs, celecoxib can lead to the onset of new hypertension or worsening of preexisting hypertension, either of which may contribute to the increased incidence of CV 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.
Congestive Heart Failure and Edema: Fluid retention and edema have been reported in some patients taking NSAIDs, including celecoxib (see Adverse Reactions). The use of celecoxib is contraindicated in patient with congestive heart failure (see Contraindications).
Gastrointestinal (GI) Effects: Risk of GI Ulceration, Bleeding, and Perforation: NSAIDs, including celecoxib, can cause serious gastrointestinal events including bleeding, ulceration, and perforation of the stomach, small intestine or large intestine, which can be fatal. These serious adverse events can occur at anytime, with or without warning symptoms, in patients treated with NSAIDs. Only one in five patients who develop a serious upper GI adverse event on NSAID therapy is symptomatic. 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.
NSAIDs should be prescribed with extreme caution in patients with a prior history of ulcer disease or gastrointestinal bleeding. Patients with a prior history of peptic ulcer disease and/or gastrointestinal bleeding who use NSAIDs have a greater than 10-fold increased risk for developing a GI bleed compared to patients with neither of these risk factors. Other factors that increase the risk of GI bleeding in patients treated with NSAIDs include concomitant use of oral corticosteroids or anticoagulants, longer duration of NSAID therapy, smoking, use of alcohol, older age, and poor general health status. Most spontaneous reports of fatal GI 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 GI event, the lowest effective dose should be used for the shortest duration consistent with individual patient treatment goals. Physicians and patients should remain alert for signs and symptoms of GI ulceration and bleeding during celecoxib therapy and promptly initiate additional evaluation and treatment if a serious GI adverse event is suspected. For high-risk patients, alternate therapies that do not involve NSAIDs should be considered (see Contraindications).
Hepatic Effects: Borderline elevations of one or more liver-associated enzymes 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 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, including celecoxib (see Adverse Reactions).
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.
Renal Effects: 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, 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 pretreatment state.
No information regarding the use of celecoxib in patients with advanced renal disease is available. Therefore, treatment with celecoxib is not recommended in these patients with advanced renal disease. If celecoxib therapy must be initiated, close monitoring of the patient's renal function is advisable.
Anaphylactoid Reactions: As with NSAIDs in general, anaphylactoid reactions have occurred in patients without known prior exposure to celecoxib. Rare cases of anaphylactic reactions and angioedema have been reported in patients receiving 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 (see Contraindications). Emergency help should be sought in cases where anaphylactoid reaction occurs.
Skin Reactions: Celecoxib is a sulfonamide and can cause serious skin adverse events such as exfoliative dermatitis, Stevens-Johnson syndrome (SJS), 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.
Corticosteroid Treatment: 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.
Hematological Effects: 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 (see Pharmacology: Pharmacodynamics and Pharmacokinetics under Actions).
Preexisting Asthma: Patients with asthma may have aspirin-sensitive asthma. The use of aspirin in patients with aspirin-sensitive asthma has been associated with severe bronchospasm, which can be fatal. Since cross reactivity, including bronchospasm, between aspirin and other nonsteroidal anti-inflammatory drugs has been reported in such aspirin-sensitive patients, celecoxib should not be administered to patients with this form of aspirin sensitivity and should be used with caution in patients with preexisting asthma.
Laboratory Tests: Because serious GI tract ulcerations and bleeding can occur without warning symptoms, physicians should monitor for signs or symptoms of GI bleeding. Patients on long-term treatment with NSAIDs should have a CBC and a chemistry profile checked periodically. If abnormal liver tests or renal tests persist or worsen, celecoxib should be discontinued.
Elevated BUN has been reported in patients receiving celecoxib. This laboratory abnormality has also been reported in patients on other NSAIDs. The clinical significance of this abnormality has not been established.
Inflammation: 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.
Others: Celecoxib inhibits CYP2D6. Patients known to be CYP2C9 poor metabolisers should be treated with caution.
Lactose: This product contains lactose. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.
Renal Insufficiency: Celecoxib is not recommended in patients w/ severe renal insufficiency (see previous text and Pharmacology: Pharmacokinetics under Actions).
Labor and Delivery: Celecoxib did not delay labor or parturition at oral doses up to 100 mg/kg in rats (approximately 7-fold human exposure as measured by the AUC0-24 at 200 mg BID). The effects of celecoxib on labor and delivery in pregnant women are unknown.
Use in Pregnancy: See Use in Pregnancy & Lactation.
Use in Children: The long-term cardiovascular toxicity in children exposed to celecoxib has not been evaluated and it is unknown if long-term risks may be similar to that seen in adults exposed to celecoxib or other COX-2 selective and non-selective NSAIDs (see Warnings and previously mentioned text).
Celecoxib has not been studied in patients under the age of 2 years, in patients with body weight less than 10 kg (22 lbs).
Use in the Elderly: No substantial differences in effectiveness have been reported between elderly patients aged ≥65 years of age and younger subjects. However, as with other NSAIDs, including those that selectively inhibit COX-2, more fatal GI events and acute renal failure have been reported in the elderly than in younger patients. (See previously mentioned text.)
Use In Pregnancy & Lactation
Pregnancy: There are no studies in pregnant women. Studies in animals have shown reproductive toxicity. The relevance of these data for humans is unknown.
Celecoxib as with other drugs inhibiting prostaglandin synthesis, may cause uterine inertia and premature closure of the ductus arteriosus and should be avoided during the third trimester of pregnancy.
Celecoxib should be used during pregnancy only if the potential benefit to the mother justifies the potential risk to the fetus.
Lactation: Celecoxib is excreted in the milk of lactating rats at concentrations similar to those in plasma.
Adverse Reactions
The following ADRs have been reported with celecoxib: see Table 2.

Click on icon to see table/diagram/image

Other reported adverse effects are back pain, injury-accidental, diverticulitis, gastroenteritis, gastroesophageal reflux, hemorrhoids, hiatal hernia, dry mouth, tenesmus, coronary artery disorder, cyst NOS, edema generalized, face edema, fatigue, fever, hot flushes, pain, peripheral pain, hypoesthesia, migraine, vertigo, deafness, CPK increased, hypercholesterolemia, hyperglycemia, hypokalemia, NPN increased, alkaline phosphatase increased, arthrosis, myalgia, synovitis, tendinitis, epistaxis, thrombocytothermia, anorexia, appetite increased, nervousness, bronchitis, bronchospasm aggravated, laryngitis, pneumonia, rash erythematous, rash maculopapular, skin disorder, skin dry, sweating increased, cellulitis, dermatitis contact, Albuminuria, cystitis, dysuria, hematuria, micturition frequency, renal calculus, syncope, congestive heart failure, ventricular fibrillation, cerebrovascular accident, peripheral gangrene, thrombophlebitis, intestinal obstruction, gastrointestinal bleeding, colitis with bleeding, esophageal perforation, ileus, cholelithiasis, agranulocytosis, aplasticanemia, hypoglycemia, suicide, sepsis, sudden death.
Drug Interactions
General: Celecoxib metabolism is predominantly mediated via cytochrome P450 (CYP) 2C9 in the liver. Co-administration of celecoxib with drugs that are known to inhibit CYP2C9 should be done with caution. Significant interactions may occur when celecoxib is administered together with drugs that inhibit CYP2C9.
Celecoxib is an inhibitor of CYP2D6. Therefore, there is a potential for an in vivo drug interaction with drugs that are metabolized by CYP2D6. During celecoxib treatment, the plasma concentrations of the CYP2D6 substrate dextromethorphan have been reported to be increased by 136%. The plasma concentrations of drugs that are substrates of this enzyme may be increased when celecoxib is used concomitantly. Examples of drugs which are metabolised by CYP2D6 are antidepressants (tricyclics and SSRIs), neuroleptics, anti-arrhythmic drugs, etc. The dose of individually dose-titrated CYP2D6 substrates may need to be reduced when treatment with celecoxib is initiated or increased if treatment with celecoxib is terminated.
Warfarin: 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 has been reported in healthy subjects receiving daily 2-5 mg doses of warfarin. In these subjects, celecoxib did not alter the anticoagulant effect of warfarin as determined by prothrombin time. However, serious bleeding events, some of which were fatal, have been reported, predominantly in the elderly, in association with increases in prothrombin time in patients receiving celecoxib concurrently with warfarin.
Lithium: The mean steady-state lithium plasma levels have been reported to increase approximately 17% in subjects receiving lithium 450 mg twice daily with celecoxib 200 mg twice daily as compared to subjects receiving lithium alone. Patients on lithium treatment should be closely monitored when celecoxib is introduced or withdrawn.
Aspirin: Celecoxib can be used with low-dose aspirin. However, concomitant administration of aspirin with celecoxib increases the rate of GI ulceration or other complications, compared to use of celecoxib alone (see Precautions). Because of its lack of platelet effects, celecoxib is not a substitute for aspirin for cardiovascular prophylaxis (see Pharmacology: Pharmacodynamics and Pharmacokinetics under Actions).
ACE-inhibitors and Angiotensin II Antagonists: 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 (see Pharmacology: Pharmacodynamics and Pharmacokinetics under Actions).
Fluconazole: A two-fold increase in celecoxib plasma concentration has been reported after concomitant administration of fluconazole 200 mg once daily due to the inhibition of celecoxib metabolism via P450 2C9 by fluconazole (see Pharmacology: Pharmacodynamics and Pharmacokinetics under Actions). Celecoxib should be introduced at the lowest recommended dose in patients receiving fluconazole.
Furosemide: NSAIDs can reduce the natriuretic effect of furosemide and thiazides in some patients. This response has been attributed to inhibition of renal prostaglandin synthesis.
Methotrexate: Celecoxib has been reported to have no effect on the pharmacokinetics of methotrexate in rheumatoid arthritis patients (see Pharmacology: Pharmacodynamics and Pharmacokinetics under Actions).
Concomitant NSAID Use: 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.
Storage
Store below 30°C.
ATC Classification
M01AH01 - celecoxib ; Belongs to the class of non-steroidal antiinflammatory and antirheumatic products, coxibs.
Presentation/Packing
Cap 200 mg (opaque, white to off white hard gelatin capsules imprinted with "CC" on cap and "200" on body of capsule shell with black ink, containing white to off white granular powder and/or compacted mass) x 3 x 10's.
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