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COXIBEST-200

Quick Overview

 


Our aim is to reach out to the globe withinshortest possible time frame


To promote this objective, not only we distribute and market our Analgesic range of products globally through our distribution channels but we also undertake ‘contract manufacturing’& ‘formulation development ’of our wide range of generic products such as Coxibest 200 which contains  Celecoxib..200 mg.


 

COXIBEST-200

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Each capsule contains:

Celecoxib.............200 mg

Excipients   q.s

Approved colours used for empty capsule shell

CHEMICAL NAME:

4-[5-(4-methylphenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl] benzenesulfonamide

CATEGORY:

Sulfa non-steroidal anti-inflammatory drug (NSAID) and selective COX-2 inhibitor

DESCRIPTION: Celecoxib capsule contains Celecoxib, a nonsteroidal anti-inflammatory drug. The molecular formula for Celecoxib is C17H14F3N3O2S, and the molecular weight is 381.38.

CLINICAL PHARMACOLOGY

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, it reduced the incidence and multiplicity of tumors.

Pharmacokinetic  Actions

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.

Food Effects: When celecoxib capsules taken with a high fat meal, peak plasma levels can be delayed for about 1 to 2 hours with an increase in 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.

In healthy adult volunteers, the overall systemic exposure (AUC) of celecoxib was equivalent when celecoxib was administered as intact capsule or capsule contents sprinkled on applesauce. There were no significant alterations in Cmax, Tmax or t1/2 after administration of capsule contents on applesauce.

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.

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.

Distribution:

 In healthy subjects, celecoxib is highly protein bound (~97%) within the clinical dose range. In vitro studies indicate that celecoxib binds primarily to albumin and to a lesser extent, a1-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.

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 (t1/2) 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.

Geriatric: At steady state, elderly subjects (over 65 years old) had 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.

Pediatric: The steady state pharmacokinetics of celecoxib administered as an investigational oral suspension was evaluated in 152 JRA patients 2 years to 17 years of age weighing =10 kg with pauciarticular or polyarticular course JRA and in patients with systemic onset JRA. Population pharmacokinetic analysis indicated that the oral clearance (unadjusted for body weight) of celecoxib increases 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.

Twice-daily administration of 50 mg capsules to JRA patients weighing =12 to =25 kg and 100 mg capsules to JRA patients weighing >25 kg should achieve plasma concentrations similar to those observed in a clinical trial that demonstrated the non-inferiority of celecoxib to naproxen 7.5 mg/kg twice daily (see Dosage and Administration (2.3). Celecoxib has not been studied in JRA patients under the age of 2 years, in patients with body weight less than 10 kg (22 lbs), or beyond 24 weeks.

Race: Meta-analysis of pharmacokinetic studies has suggested an approximately 40% higher AUC of celecoxib in Blacks compared to Caucasians. The cause and clinical significance of this finding is unknown. In animal colon tumor models, celecoxib reduced the incidence and multiplicity of tumors.

INDICATIONS AND USAGE

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.

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.

Juvenile Rheumatoid Arthritis (JRA)

Celecoxib is indicated for relief of the signs and symptoms of JRA in patients 2 years and older.

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.

Familial Adenomatous Polyposis (FAP)

Celecoxib is indicated to reduce the number of adenomatous colorectal polyps in FAP, as an adjunct to usual care (e.g., endoscopic surveillance, surgery). It is not known whether there is a clinical benefit from a reduction in the number of colorectal polyps in FAP patients. It is also not known whether the effects of celecoxib treatment will persist after celecoxib is discontinued. The efficacy and safety of celecoxib treatment in patients with FAP beyond six months have not been studied.

DOSAGE AND ADMINISTRATION

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 or as 100 mg twice daily.

Rheumatoid Arthritis

For relief of the signs and symptoms of RA the recommended oral dose is 100 to 200 mg twice daily.

Juvenile Rheumatoid Arthritis

For the relief of the signs and symptoms of JRA the recommended oral dose for pediatric patients (age 2 years and older) is based on weight. For patients =10 kg to =25 kg the recommended dose is 50 mg twice daily. For patients >25 kg the recommended dose is 100 mg twice daily.

For patients who have difficulty swallowing capsules, the contents of a celecoxib capsule can be added to applesauce. The entire capsule contents are carefully emptied onto a level teaspoon of cool or room temperature applesauce and ingested immediately with water. The sprinkled capsule contents on applesauce are stable for up to 6 hours under refrigerated conditions (2-80 C/ 35-450 F).

Ankylosing Spondylitis (AS)

For the management of the signs and symptoms of AS, the recommended dose of Celecoxib is 200 mg daily in single (once per day) or divided (twice per day) doses. 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.

Familial Adenomatous Polyposis

Usual medical care for FAP patients should be continued while on celecoxib. To reduce the number of adenomatous colorectal polyps in patients with FAP, the recommended oral dose is 400 mg twice per day to be taken with food.

Special Populations

Hepatic insufficiency: The daily recommended dose of celecoxib capsules 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

Poor Metabolizers of CYP2C9 Substrates: Patients who are known or suspected to be poor CYP2C9 metabolizers based on previous history/experience with other CYP2C9 substrates (such as warfarin, phenytoin) should be administered with caution. Consider starting treatment at half the lowest recommended dose in poor metabolizers. Consider using alternative management in JRA patients who are poor metabolizers.

CONTRA-INDICATIONS

Celecoxib is contraindicated:

•In patients with known hypersensitivity to celecoxib, aspirin or other NSAIDs.

•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. Severe anaphylactoid reactions to NSAIDs, some of them   fatal, have been reported in such patients

•For the treatment of peri-operative pain in the setting of coronary artery bypass graft (CABG) surgery.

WARNINGS AND 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. In the reported APC (Adenoma Prevention with celecoxib) trial, the hazard ratio for the composite endpoint of cardiovascular death, MI or stroke was 3.4 (95% CI 1.4 – 8.5) for celecoxib 400 mg twice daily and 2.8 (95% CI 1.1 – 7.2) with celecoxib 200 mg twice daily compared to placebo. Cumulative rates for this composite endpoint over 3 years were 3.0% (20/671 subjects) and 2.5% (17/685 subjects), respectively, compared to 0.9% (6/679 subjects) with placebo treatment. The increases in both celecoxib dose groups versus placebo-treated patients were mainly due to an increased incidence of myocardial infarction.

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.

Two large, controlled, clinical trials of a different COX-2 selective NSAID for the treatment of pain in the first 10–14 days following CABG surgery found an increased incidence of myocardial infarction and stroke.

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. The rates of hypertension from the CLASS trial in the celecoxib, ibuprofen and diclofenac-treated patients were 2.4%, 4.2% and 2.5%, respectively.

Congestive Heart Failure and Edema

Fluid retention and edema have been observed in some patients taking NSAIDs, including celecoxib. In the CLASS study, the Kaplan-Meier cumulative rates at 9 months of peripheral edema in patients on celecoxib 400 mg twice daily (4-fold and 2-fold the recommended OA and RA doses, respectively, and the approved dose for FAP), ibuprofen 800 mg three times daily and diclofenac 75 mg twice daily were 4.5%, 6.9% and 4.7%, respectively. Celecoxib should be used with caution in patients with fluid retention or heart failure.

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 any time, 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. Complicated and symptomatic ulcer rates were 0.78% at nine months for all patients in the CLASS trial and 2.19% for the subgroup on low-dose ASA. Patients 65 years of age and older had an incidence of 1.40% at nine months, 3.06% when also taking ASA. 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.

Hepatic Effects

Borderline elevations of one or more liver-associated enzymes may occur in upto 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, including celecoxib. In controlled clinical trials of celecoxib, the incidence of borderline elevations (greater than or equal to 1.2 times and less than 3 times the upper limit of normal) of liver associated enzymes 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.

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. Clinical trials with celecoxib have shown renal effects similar to those observed with comparator NSAIDs.

No information is available from controlled clinical studies regarding the use of celecoxib in patients with advanced renal disease. 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. It 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. Emergency help should be sought in cases where an 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.

Pregnancy

In late pregnancy, starting at 30 weeks gestation, celecoxib should be avoided because it may cause premature closure of the ductus arteriosus.

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. 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 inhibit platelet aggregation at indicated dosages

Disseminated Intravascular Coagulation (DIC)

Celecoxib should be used only with caution in pediatric patients with systemic onset JRA due to the risk of disseminated intravascular coagulation.

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.

In controlled clinical trials, elevated BUN occurred more frequently in patients receiving celecoxib compared with patients on placebo. This laboratory abnormality was also seen in patients who received comparator NSAIDs in these studies. The clinical significance of this abnormality has not been established.

GI Cancer in Familial Adenomatous Polyposis

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. In particular, the frequency of routine endoscopic surveillance should not be decreased and prophylactic colectomy or other FAP-related surgeries should not be delayed.

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.

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.

ADVERSE REACTIONS

Of the celecoxib-treated patients in the pre-marketing controlled clinical trials, approximately 4,250 were patients with OA, approximately 2,100 were patients with RA, and approximately 1,050 were patients with post-surgical pain. More than 8,500 patients received a total daily dose of celecoxib of 200 mg (100 mg twice daily or 200 mg once daily) or more, including more than 400 treated at 800 mg (400 mg twice daily). Approximately 3,900 patients received celecoxib at these doses for 6 months or more; approximately 2,300 of these have received it for 1 year or more and 124 of these have received it for 2 years or more.

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. The adverse reaction information from clinical trials does, however, provide a basis for identifying the adverse events that appear to be related to drug use and for approximating rates.

WARNING: CARDIOVASCULAR AND GASTROINTESTINAL RISKS

Cardiovascular Risk

•Coxibest, may cause an increased risk of serious cardiovascular thrombotic events, myocardial infarction, and stroke, which can be fatal. All 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.

•Celecoxib is contraindicated for the treatment of peri-operative pain in the setting of coronary artery bypass graft (CABG) surgery.

Gastrointestinal Risk

•NSAIDs, including COXIBEST, 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 (GI) events.

DRUG INTERACTIONS

•Concomitant use of celecoxib and warfarin may result in increased risk of bleeding complications.

•Concomitant use of celecoxib increases lithium plasma levels.

•Concomitant use of celecoxib may reduce the antihypertensive effect of ACE Inhibitors and angiotensin II antaonists

•Use caution with drugs known to inhibit P450 2C9 or metabolized by 2D6 due to the potential for increased plasma levels

USE IN SPECIFIC POPULATIONS

Pregnancy

Pregnancy Category C.

Pregnancy category D from 30 weeks of gestation onward.

Teratogenic effects: Celecoxib at oral doses =150 mg/kg/day (approximately 2-fold human exposure at 200 mg twice daily as measured by AUC 0–24), caused an increased incidence of ventricular septal defects, a rare event and fetal alterations, such as ribs fused, sternebrae fused and sternebrae misshapen when rabbits were treated throughout organogenesis. A dose-dependent increase in diaphragmatic hernias was observed when rats were given celecoxib at oral doses =30 mg/kg/day (approximately 6-fold human exposure based on the AUC 0-24 at 200 mg twice daily) throughout organogenesis. There are no studies in pregnant women. Celecoxib should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Nonteratogenic effects: Celecoxib produced pre-implantation and post-implantation losses and reduced embryo/fetal survival in rats at oral dosages =50 mg/kg/day (approximately 6-fold human exposure based on the AUC 0-24 at 200 mg twice daily). These changes are expected with inhibition of prostaglandin synthesis and are not the result of permanent alteration of female reproductive function, nor are they expected at clinical exposures. No studies have been conducted to evaluate the effect of celecoxib on the closure of the ductus arteriosus in humans. Therefore, use of celecoxib during the third trimester of pregnancy should be avoided.

Labor and Delivery

Celecoxib produced no evidence of delayed labor or parturition at oral doses up to 100 mg/kg in rats (approximately 7-fold human exposure as measured by the AUC 0–24 at 200 mg BID). The effects of celecoxib on labor and delivery in pregnant women are unknown.

Nursing Mothers

Limited data from 3 published reports that included a total of 12 breastfeeding women showed low levels of celecoxib in breast milk. The calculated average daily infant dose was 10–40 mcg/kg/day, less than 1% of the weight-based therapeutic dose for a two-year old-child. A report of two breastfed infants 17 and 22 months of age did not show any adverse events. Caution should be exercised when celecoxib is administered to a nursing woman.

Pediatric Use

Celecoxib is approved for relief of the signs and symptoms of Juvenile Rheumatoid Arthritis in patients 2 years and older. Safety and efficacy have not been studied beyond six months 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. NSAIDs including celecoxib should be used only with caution in patients with systemic onset JRA, due to the risk of disseminated intravascular coagulation. Patients with systemic onset JRA should be monitored for the development of abnormal coagulation tests. Alternative therapies for treatment of JRA should be considered in pediatric patients identified to be CYP2C9 poor metabolizers.

Geriatric Use

Of the total number of patients who received celecoxib in pre-approval clinical trials, more than 3,300 were 65–74 years of age, while approximately 1,300 additional patients were 75 years and over. No substantial differences in effectiveness were observed between these subjects and younger subjects. In clinical studies comparing renal function as measured by the GFR, BUN creatinine and platelet function as measured by bleeding time and platelet aggregation, the results were not different between elderly and young volunteers. However, as with other NSAIDs, including those that selectively inhibit COX-2, there have been more spontaneous post-marketing reports of fatal GI events and acute renal failure in the elderly than in younger patients.

Hepatic Insufficiency

The daily recommended dose of celecoxib capsules 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.

Renal Insufficiency

Celecoxib is not recommended in patients with severe renal insufficiency and poor Metabolizers of CYP2C9 Substrates.

Patients who are known or suspected to be poor CYP2C9 metabolizers based on 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. Alternative management should be considered in JRA patients identified to be CYP2C9 poor metabolizers.

OVERDOSAGE

Doses upto 2400 mg/day for up to 10 days in 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.

Packing: Blister of 10 capsules.

Storage: Store in a dry place below 300 C.

 
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