Each capsule contains: Celecoxib 200 mg.
Pharmacology: Celecoxib is a new class of agent which acts through a unique mechanism as a specific cyclo-oxygenase-2 inhibitor (SCI). Cyclooxygenase-2 (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, oedema and pain. Celecoxib acts as an anti-inflammatory, analgesic and antipyretic agent by blocking the production of inflammatory prostanoids via COX-2 inhibition. In vivo and ex vivo studies show that celecoxib has a very low affinity for the constitutively expressed cyclo-oxygenase-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 the stomach, intestine, platelets and kidney.
Further Information from Clinical Trials: Consensus criteria for the definition, in biological terms of COX-2 specificity, have recently been agreed and include the need to demonstrate absence of COX-1 type adverse events, particularly drug-induced gastroduodenal ulceration, serious upper gastrointestinal (UGI) events (bleeds, perforation, gastric outlet obstruction) and lack of inhibition of COX-1-dependent platelet aggregatory activity.
Pharmacokinetics: Absorption: The pharmacokinetics of celecoxib have been evaluated in approximately 1500 individuals. When given under fasting conditions celecoxib is well absorbed reaching peak plasma concentrations after approximately 2-3 hours. Oral bioavailability from capsules is about 99% relative to administration in suspension (optimally available oral dosage form). Under fasting conditions, both peak plasma levels (Cmax) and area under the curve (AUC) are roughly dose proportional up to 200 mg twice daily; at higher doses there are less than proportional increases in Cmax and AUC.
Distribution: Plasma protein binding, which is concentration independent, is about 97% at therapeutic plasma concentrations and celecoxib is not preferentially bound to erythrocytes in the blood.
Food Effects: Dosing with food (high fat meal) delays absorption of celecoxib resulting in a Tmax of about 4 hours and increases bioavailability by about 20%.
Metabolism: Celecoxib metabolism is primarily mediated via cytochrome P450 2C9. Three metabolites, inactive as COX-1 or COX-2 inhibitors, have been identified in human plasma i.e., a primary alcohol, the corresponding carboxylic acid and its glucuronide conjugate. Cytochrome P450 2C9 activity is reduced in individuals with genetic polymorphisms that lead to reduced enzyme activity, such as those homozygous for the CYP2C9*3 polymorphism.
Excretion: Elimination of celecoxib is mostly by hepatic metabolism with less than 1% of the dose excreted unchanged in urine. After multiple dosing elimination half life is 8-12 hours and the rate of clearance is about 500 mL/min. With multiple dosing steady state plasma concentrations are reached before day 5. The intersubject variability on the main pharmacokinetic parameters (AUC, Cmax, elimination half-life) is about 30%. The mean steady state volume of distribution is about 500 L/70 g in young healthy adults indicating wide distribution of celecoxib into the tissues. Preclinical studies indicate that the drug crosses the blood brain barrier.
It is used in the treatment of rheumatoid arthritis, osteoarthritis, and ankylosing spondylitis. Celecoxib is also used in the management of acute pain and dysmenorrhoea.
Favocox Capsule should be used at the lowest effective dose for shortest possible time.
Osteoarthritis: The recommended dose is 200 mg daily given by mouth as a single dose or in 2 divided doses. If necessary a dose of 200 mg twice daily may be used.
Rheumatoid Arthritis: The dose is 100 to 200 mg given twice daily.
Ankylosing Spondylitis: An initial dose of 200 mg daily, as a single dose or in 2 divided doses. If necessary, the dose may be increased to 400 mg daily after 6 weeks, although if no response is seen at this dose after a further 6 weeks, alternative treatments should be considered.
Pain and Dysmenorrhoea: 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.
Elderly: Treatment should be begun at the lowest recommended dose.
Hepatic Impairment: Doses of celecoxib should be reduced by 50% in patients with moderate hepatic impairment.
Mode of administration: Oral.
There is no clinical experience of overdose. Single doses up to 1200 mg and multiple doses up to 600 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.
Favocox Capsule is contraindicated: In patients with severe heart failure and For the treatment of peri-operative pain in the setting of coronary artery bypass graft surgery.
History of hypersensitivity to the active substance or to any of the excipients.
Known hypersensitivity to sulphonamides.
Patients who have experienced asthma, acute rhinitis, nasal polyps, angioneurotic oedema, urticaria or other allergic-type reactions after taking acetylsalicylic acid or NSAIDs including COX-2 (cyclooxygenase-2) inhibitors.
In pregnancy and in women of childbearing potential unless using an effective method of contraception. Celecoxib has been shown to cause malformations in the two animal species studied. The potential for human risk in pregnancy is unknown, but cannot be excluded.
Breast feeding.
Severe hepatic dysfunction (serum albumin < 25 g/L or Child-Pugh score ≥ 10).
Patients with estimated renal creatinine clearance < 30 ml/minute.
Severe congestive heart failure (NYHA III-IV).
Children under 18 years old.
In rare case, Favocox Capsule has been associated with serious liver injury.
Celecoxib contains a sulfonamide moiety. In clinical trials, Celecoxib did not induce bronchospasm in patients with asthma. However, Celecoxib has not been evaluated in patients in whom attacks of asthma, urticaria or acute rhinitis have been precipitated by aspirin or nonsteroidal anti-inflammatory agents. Use in such patients should be avoided until further information is available.
(1) Cardiovascular Risk: NSAIDs may cause an increased risk of serious cardiovascular thrombotic events, myocardial infarction, and stroke, which can be fatal. This risk may increase with duration of use. Patients with cardiovascular disease or risk factors for cardiovascular disease may be at greater risk.
(2) Gastrointestinal Risk: NSAIDS 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.
(3) Celecoxib are not a substitute for acetylsalicylic acid for prophylaxis of cardiovascular thrombo-embolic diseases because of their lack of effect on platelets function.
(4) Given the association between cardiovascular risk and exposure to celecoxib, doctors are advised to use the lowest effective dose for the shortest possible duration of treatment.
(5) Celecoxib should be used with caution in patients with history of cardiac failure or hypertension, since it may result in fluid retention.
(6) Serious skin reactions, including exfoliative dermatitis, Stevens-Johnson syndrome, and toxic epidermal necrolysis, have been reported in association with the use of NSAIDs including celecoxib during postmarketing surveillance.
(7) 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 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.
(8) Advanced Renal Disease: No information is available from controlled clinical studies regarding the use of Favocox Capsule in patients with advanced renal disease. Therefore, treatment with Favocox Capsule is not recommended in these patients with advanced renal disease. If therapy must be initiated, close monitoring of the patient's renal function is advisable.
Pregnancy: There is no information on use in pregnant women. Celecoxib should not be used during pregnancy especially in the 3rd trimester.
Lactation: Studies in rats show that celecoxib is excreted in milk at concentrations similar to those in plasma. Since no studies have been conducted in humans, Celecoxib should not be used during breastfeeding.
Gastrointestinal: Abdominal pain, diarrhea, dyspepsia, flatulence, nausea, constipation, gastritis, vomiting, intestinal perforation, colitis with bleeding, esophageal perforation, gastrointestinal bleeding, pancreatitis, ileus.
CNS: Headache, dizziness.
Psychiatric: Insomnia, somnolence, confusion, anxiety.
Respiratory: Pharyngitis, rhinitis, sinusitis, upper respiratory tract infection.
Skin: Rash, urticaria, photosensitivity reaction, dermatitis, erythema multiforme, Stevens-Johnson syndrome.
Vascular Disorders: Aggravated hypertension, cerebral ischemia, vasculitis.
Cardiovascular: Myocardial infarction, congestive heart failure, palpitation.
Blood and Lymphatic: Ecchymosis, epistaxis, thrombocytopenia, anaemia.
Others: Peripheral edema, hypertension, tinnitus, blurred vision, acute renal failure, flushes.
General: Celecoxib metabolism is predominantly mediated via cytochrome P-450 2C9 in the liver. Co-administration of celecoxib with drugs that are known to inhibit 2C9 should be done with caution. In vitro studies indicate that celecoxib, although not a substrate, is an inhibitor of cytochrome P-450 2D6. Therefore, there is a potential for an in vivo drug interaction with drugs that are metabolized by P-450 2D6.
ACE-Inhibitors: Reports suggest that NSAIDs may diminish the antihypertensive effect of angiotensin converting enzyme (ACE) inhibitors. This interaction should be given consideration in patients taking Celecoxib concomitantly with ACE-inhibitors.
Furosemide: Clinical studies, as well as post-marketing observations, have shown that NSAIDs can reduce the natriuretic effect of furosemide and thiazides in some patients. This response has been attributed to inhibition of renal prostaglandin synthesis.
Aspirin: Celecoxib can be used with low dose aspirin. However, concomitant administration of aspirin with Celecoxib may result in an increased rate of Gl ulceration or other complications, compared to use Celecoxib alone (see Pharmacology under Actions). Because of its lack of platelet effects, Celecoxib is not a substitute for aspirin for cardiovascular prophylaxis.
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 P-450 2C9 by fluconazole. Celecoxib should be introduced at the lowest recommended dose in patients receiving fluconazole.
Lithium: In a study conducted in healthy subjects, mean steady-state lithium plasma levels increased approximately 17% in subjects receiving lithium 450 mg twice a day with Celecoxib 200 mg twice a day as compared to subjects receiving lithium alone. Patients on lithium treatment should be closely monitored when Celecoxib is introduced or withdrawn.
Methotrexate: In an interaction study of rheumatoid arthritis patients taking methotrexate, Celecoxib did not have a significant effect on the pharmacokinetics of methotrexate.
Warfarin: The effect of celecoxib on the anticoagulant effect of warfarin was studied in a group of healthy subjects receiving daily doses of 2-4 mg of warfarin. In these subjects, celecoxib did not alter the anticoagulant effect of warfarin as determined by prothrombin time. However, caution should be used when administering Celecoxib with warfarin since these patients are at increased risk of bleeding complications.
M01AH01 - celecoxib ; Belongs to the class of non-steroidal antiinflammatory and antirheumatic products, coxibs.
Favocox cap 200 mg
100's;30's
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