Coxbitor 200/Coxbitor 400

Celecoxib.

Coxbitor 200: Each Capsule contains: Celecoxib 200 mg.
Coxbitor 400: Each capsule contains: Celecoxib 400 mg.

Pharmacotherapeutic group: M01AH Coxibs.
Pharmacology: Pharmacodynamics: The mechanism of action of celecoxib is via inhibition of prostaglandin synthesis primarily by inhibition of cyclooxygenase 2 (COX-2). At therapeutic concentrations in humans, celecoxib does not inhibit cyclooxygenase 1 (COX-1). COX-2 is induced in response to inflammatory stimuli. This leads to the synthesis and accumulation of inflammatory prostanoids, in particular prostaglandin E2, causing inflammation, edema and pain. Celecoxib acts as an anti-inflammatory, analgesic, and antipyretic agent in animal models by blocking the production of inflammatory prostanoids via COX-2 inhibition. In animal colon tumor models, celecoxib reduced the incidence and multiplicity of tumors.
In vivo and ex vivo studies show that celecoxib has a very low affinity for the constitutively expressed cyclooxygenase 1 enzyme (COX-1). Consequently, at therapeutic doses, celecoxib has no effect on prostanoids synthesized by activation of COX-1 thereby not interfering with normal COX-1 related physiological processes in tissues, particularly stomach, intestine and platelets.
Pharmacokinetics: Celecoxib is absorbed from the gastrointestinal tract; peak plasma concentrations being achieved after about 3 hours. Protein binding is about 97%. Celecoxib is metabolized in the liver mainly by the cytochrome P450 isoenzyme CYP2C9; the three identified metabolites are inactive as inhibitors of COX-1 or COX-2 enzymes. It is eliminated mainly as metabolites in the feces and urine; less than 3% is recovered as unchanged drug. The effective terminal half-life is about 11 hours.
Coxbitor 200: Celecoxib is distributed into breast milk. The pharmacokinetics of celecoxib may vary in different ethnic groups; it has been stated that the area under the curve is elevated in patients of Afro-Caribbean origin, although any clinical significance is unclear.

Treatment of rheumatoid arthritis, osteoarthritis, and ankylosing spondylitis. Celecoxib is also used in the management of acute pain and dysmenorrhea.
Coxbitor 200: Celecoxib is an NSAID reported to be a selective inhibitor of cyclooxygenase-2 (COX-2). It is used in the treatment of juvenile idiopathic arthritis, and in the adjunctive treatment of adenomatous colorectal polyps.

Osteoarthritis: Adult: 200 mg daily given as a single dose or in 2 divided doses; or as prescribed by the physician.
Coxbitor 200: If necessary, a dose of 200 mg twice daily may be used.
Rheumatoid arthritis: Adult: 100 to 200 mg given twice daily; or as prescribed by the physician.
Treatment of pain and dysmenorrhea: Adult: an initial dose of 400 mg followed by an additional dose of 200 mg, if necessary, is recommended on the first day; thereafter the dose is 200 mg twice daily; or as prescribed by the physician.
Treatment of ankylosing spondylitis: Adult: an initial dose of 200 mg daily, as a single dose or in 2 divided doses.
Coxbitor 400: 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.
Coxbitor 200: As an adjunctive treatment of adenomatous colorectal polyps: Adult: may be given in doses of 400 mg twice daily with food.
Reduced doses are recommended in patients with hepatic impairments. Or as prescribed by a physician.

Clinical experience of overdose is limited. Single doses up to 1200 mg and multiple doses up to 1200 mg twice daily have been administered to healthy subjects without clinically significant adverse effects. In the event of suspected overdose, appropriate supportive medical care should be provided. Dialysis is unlikely to be an efficient method of drug removal because of high protein binding of the drug.

Coxbitor 200: Absolute contraindications: Not to be given to those patients who have history of:
Stroke: cerebrovascular accident, CVA.
Heart attack: Myocardial infarction, MI.
Coronary artery bypass graft: CABG.
Uncontrolled hypertension.
Congestive heart failure (CHF) NYHA II-IV.
Therapy is contraindicated in patients with moderate to severe heart failure (NYHA class II to IV), inflammatory bowel disease, and renal impairment associated with a creatinine clearance of less than 30 mL/minute. Celecoxib should also not be used in patients with severe hepatic impairment (Child-Pugh category C). Caution is recommended when using celecoxib in dehydrated patients; rehydration may be advisable before giving celecoxib. Celecoxib treatment may need to be stopped if signs or symptoms of organ toxicity develop.
Coxbitor 400: 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 of 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.

Coxbitor 400: Absolute contraindications: Not to be given to those patients who have history of: Stroke: cerebrovascular accident, CVA; Heart attack: Myocardial Infarction, MI; Coronary artery bypass graft: CABG; Uncontrolled hypertension; Congestive heart failure (CHF) NYHA II-IV. COX-2 inhibitors are not to be given to patients with allergy to NSAIDs and those with asthma. Exercise caution when prescribing Selective COX-2 inhibitors in patients with ischemic heart disease and those with risk factors for heart disease; hypertension; hyperlipidaemia, diabetes, smoking and patients with peripheral arterial disease. Considering association between cardiovascular risk and exposure to COX-2 inhibitors, doctors are advised to use the lowest effective dose for the shortest duration of treatment.
Intake of COX-2 inhibitors should be stopped with appearance of skin rash and signs of hypersensitivity.
If not yet warning statement should include potential gastrointestinal (gastric and liver) and renal toxicities.

Coxbitor 200: Celecoxib should not be used after coronary artery bypass surgery as there may be an increased risk of adverse effects such as myocardial infarction and stroke. It should be used with caution, if at all, in patients with a history of ischemic heart disease, peripheral arterial disease, or cerebrovascular disease; it should also be used with caution in patients with significant risk factors for cardiovascular disease such as hypertension, hyperlipidemia, and diabetes mellitus. Celecoxib is not given to patients with allergy to NSAIDs and those with asthma. Use the lowest effective dose for the shortest duration of treatment. Intake of celecoxib should be stopped with appearance of skin rash and signs of hypersensitivity.
Coxbitor 400: 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 APC (Adenoma Prevention with Celecoxib) trial, the hazard ratio for the composite endpoint or cardiovascular death, MI, or stroke. All NSAIDs, both COX-2 selective and non-selective, may have a similar risk. Patients with known 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 NSAIDs use. The concurrent use of aspirin and celecoxib does increase the risk of serious GI events.
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 thiazide 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 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 observed in some patients taking NSAIDs.
Gastrointestinal (GI) Effects Risk of GI Ulceration, Bleeding and Perforation: NSAID 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. 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.
Hepatic Effects: 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.
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 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 greater 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.
Anaphylactoid Reactions: This symptom complex typically occurs in asthmatic patients who experience rhinitis with or without nasal polyps, or who exhibits severe, potentially fatal bronchospasm after taking aspirin or other NSAIDs.
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.
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.
Hepatic insufficiency: The daily recommended dose of celecoxib in patients with moderate hepatic impairment (Child-Pugh Class B) should be reduced by 50%. 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 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. Consider using alternative management in patients who are poor metabolizers.
Use in the Elderly (> 65 years of age): In the elderly, frail and debilitated, the dosage should be reduced to the lowest level providing control of symptoms and adjusted when necessary.

Coxbitor 200: 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.
Studies in rats show that celecoxib is excreted in milk at concentrations similar to those in plasma. Administration of celecoxib to lactating women has shown very low transfer of celecoxib into breast milk. Because of the potential for adverse reactions in nursing infants from celecoxib, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the expected benefit of the drug to the mother.
Coxbitor 400: Celecoxib, as with other drug inhibiting prostaglandin synthesis, may cause uterine inertia and premature closure of the ductus arteriosus during the last trimester. Celecoxib is contraindicated in pregnancy and in women who can become pregnant. If a woman becomes pregnant during treatment, celecoxib should be discontinued.
Administration of celecoxib to a limited number of lactating women has shown a very low transfer of celecoxib into breast milk. Women who take celecoxib should not breastfeed.
Pregnancy: In late pregnancy, starting at 30 weeks gestation, celecoxib should be avoided because it may cause premature closure of the ductus arteriosus.

Serious skin reactions such as exfoliative dermatitis, Stevens-Johnson syndrome, and toxic epidermal necrolysis have been reported with celecoxib. Other hypersensitivity reactions, including anaphylaxis and angioedema, have also occurred. Celecoxib should be stopped at the first signs of hypersensitivity. Some of these reactions have been seen in patients with a history of allergic reactions to sulfonamides and the use of celecoxib is contraindicated in such patients.

The metabolism of celecoxib is mediated mainly by the cytochrome P450 isoenzyme CYP2C9. Use with other drugs that inhibit or induce or are metabolized by this isoenzyme may result in changes in plasma concentration of celecoxib; fluconazole has increased plasma concentrations of celecoxib and it is recommended that the dose of celecoxib should be halved when given with fluconazole. Celecoxib is an inhibitor of the isoenzyme CYP2D6 and the potential therefore exists for an effect on drugs metabolized by this enzyme.

Store at temperatures not exceeding 30°C.

Nonsteroidal Anti-Inflammatory Drugs (NSAIDs)

M01AH01 - celecoxib ; Belongs to the class of non-steroidal antiinflammatory and antirheumatic products, coxibs.

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