COXIRON 60 MG: Each film coated tablet contains Etoricoxib 60 mg.
COXIRON 90 MG: Each film coated tablet contains Etoricoxib 90 mg.
COXIRON 120 MG: Each film coated tablet contains Etoricoxib 120 mg.
Pharmacology: Etoricoxib is a nonsteroidal anti-inflammatory drug (NSAID) that exhibits anti-inflammatory, analgesic, and antipyretic activities. Etoricoxib is a potent, orally active, highly selective cyclooxygenase-2 (COX-2) inhibitor within and above the clinical dose range. Two isoforms of cyclooxygenase have been identified: cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2). COX-1 is responsible for prostaglandin-mediated normal physiologic functions such as gastric cytoprotection and platelet aggregation. Inhibition of COX-1 non-selective NSAIDs has been associated with gastric damage and platelet inhibition. COX-2 has been shown to be primarily responsible for the synthesis of prostanoid mediators of pain, inflammation, and fever. Selective inhibition of COX-2 by etoricoxib decreases these clinical signs and symptoms with decreased gastrointestinal toxicity and without effects on platelet function. Etoricoxib produced dose-dependent inhibition of COX-2 without inhibition of COX-1 at doses up to 150 mg daily.
Platelet function: Multiple doses of etoricoxib up to 150 mg administered daily up to nine days had no effect on bleeding time. Similarly, bleeding time was not altered in a single dose with etoricoxib 250 mg or 500 mg. There was no inhibition of ex-vivo arachidonic acid or collagen induced platelet aggregation at steady state with doses of etoricoxib up to 150 mg. These findings are consistent with the COX-2 selectivity of etoricoxib.
Etoricoxib is indicated for: Symptomatic relief in the treatment of osteoarthritis (OA).
Relief of chronic musculoskeletal pain.
Relief of acute pain associated with dental surgery.
Etoricoxib is administered orally. Etoricoxib may be taken with or without food.
Arthritis: Osteoarthritis: The recommended dose is 60 mg once daily.
Analgesia: Acute pain associated with dental surgery: The recommended dose is 120 mg once daily. Etoricoxib 120 mg should be used only for the acute symptomatic period.
Chronic musculoskeletal pain: The recommended dose is 60 mg once daily.
Doses greater than those recommended for each indication have either not demonstrated additional efficacy or have been studied. Therefore, the dose for each indication is the maximum recommended dose.
Elderly, gender, race: No dosage adjustment in etoricoxib is necessary for the elderly or based on gender or race.
Hepatic insufficiency: In patients with mild hepatic insufficiency (Child-Pugh score 5-6), a dose of 60 mg once daily should not be exceeded. In patients with moderate hepatic insufficiency (Child-Pugh score 7-9), the dose should be reduced; a dose of 60 mg every other day should not be exceeded, administration of 30 mg once daily can also be considered. There are no clinical or pharmacokinetic data in patients with severe hepatic insufficiency (Child-Pugh score >9) (see Warnings and Precautions).
Renal insufficiency: In patients with advanced renal disease (creatinine clearance <30 mL/min), treatment with etoricoxib is not recommended. No dosage adjustment is necessary for patients with lesser degrees of renal insufficiency (creatinine clearance ≥30 mL/min) (see Warning and Precautions).
No overdoses of etoricoxib were reported during clinical trials. Administration of etoricoxib at single doses up to 500 mg and multiple doses up to 150 mg/day for 21 days did not result in significant toxicity.
In the event of overdose, it is reasonable to employ the usual supportive measures, e.g., remove unabsorbed material from the gastrointestinal tract, employ clinical monitoring, and institute supportive therapy, if required.
Etoricoxib is not dialysable by hemodialysis; it is not known whether etoricoxib is dialysable by peritoneal dialysis.
Etoricoxib is contraindicated in patients with: Hypersensitivity to any component of this product.
Congestive heart failure (NYHA II-IV).
Established ischemic heart disease, peripheral artery disease and/or cerebrovascular disease (including patients who have recently undergone coronary artery bypass graft surgery or angioplasty).
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. Elderly patients and patients with cardiovascular disease or risk factors for cardiovascular disease may be at greater risk (see as follows and Precautions).
Etoricoxib is contraindicated for the treatment of peri-operative pain in the setting of coronary artery bypass graft (CABG) surgery (see as follows and Precautions).
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 (see as follows and Precautions).
Asthma and skin reaction: Etoricoxib is contraindicated to patients who have experienced asthma, urticaria, or allergic-type reactions after taking aspirin or other NSAIDs (see as follows and Precautions).
Congestive heart failure and edema: Etoricoxib should be used with caution in patients with fluid retention or heart failure (see as follows and Precautions).
Hepatic effects: Patients with symptoms and/or signs suggesting liver dysfunction, or in whom an abnormal liver test has occurred, should be evaluated for evidence of the development of a more severe hepatic reaction while on therapy with etoricoxib (see as follows and Precautions).
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 (see as follows and Precautions).
Cardiovascular thrombotic effects: Several COX-2 and nonselective NSAIDs have shown an increased risk of serious cardiovascular (CV) thrombotic events, myocardial infarction, and stroke, which can be fatal. All NSAIDs both COX-2 selective and nonselective, 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 a NSAID, the lowest effective dose should be used for the shortest duration possible. 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 events 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 NSAIDs does increase the risk of serious GI events (see Gastrointestinal effects as follows).
The use of COX-2 selective NSAIDs for the treatment of pain in the first 10-14 days following CABG surgery found an increased incidence of myocardial infarction and stroke (see Contraindications).
Hypertension: NSAIDs, including etoricoxib, can lead to onset of new hypertension or worsening of pre-existing 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 etoricoxib, should be used with caution in patients with hypertension. Blood pressure (BP) should be monitored closely during the initiation of NSAIDs treatment and throughout the course of therapy.
Congestive heart failure: Fluid retention and edema have been observed in some patients taking NSAIDs. Etoricoxib should be used with caution in patients with fluid retention or heart failure.
Gastrointestinal effects - risk of ulceration, bleeding, and perforation: NSAIDs, including etoricoxib, can cause serious gastrointestinal (GI) adverse events including inflammation, 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. Upper GI ulcers, gross bleeding or perforation caused by NSAIDs occur in approximately 1% of patients treated for 3-6 months, and in about 2-4% of patients treated for 1 year. These trends continue with longer duration of use, 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 those 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 for GI bleeding in patients treated with NSAIDs include concomitant use of oral corticosteroids or anticoagulants, longer duration of NSAIDs 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 in this population.
To reduce the risk of gastrointestinal effect on NSAIDs therapy, the lowest effective dose must be given and short-term therapy. Doctor and patient must be caution on sign and symptoms of ulceration and gastrointestinal bleeding during NSAIDs therapy. If there is serious gastrointestinal effects suspected, evaluate immediately and give additional treatment. For high risk patient, alternative therapy that does not include NSAlDs can be considered.
Selective COX-2 inhibitor class of drugs may be associated with an increased risk of thrombotic events (especially myocardial infarction and stroke). As the cardiovascular risks of selective COX-2 inhibitors may increase with dose and duration of exposure, the shortest duration possible and the lowest effective daily dose should be used. The patient's need for symptomatic relief and response to therapy should be re-evaluated periodically.
Patients with significant risk factors for cardiovascular events (e.g., hypertension, hyperlipidemia, diabetes mellitus, smoking) or peripheral arterial disease should only be treated with etoricoxib after careful consideration.
Selective COX-2 inhibitors are not a substitute for aspirin for cardiovascular prophylaxis because of their lack of effect on platelets. Because etoricoxib, a member of this class, does not inhibit platelet aggregation, antiplatelet therapies should not be discontinued.
There is a further increase in the risk of gastrointestinal adverse effects (gastrointestinal ulceration or other gastrointestinal complications) for etoricoxib, other selective COX-2 inhibitors and NSAIDs, when taken concomitantly with acetylsalicylic acid (even at low doses). The relative differences in gastrointestinal safety between selective COX-2 inhibitors + acetylsalicylic acid vs. NSAlDs + acetylsalicylic acid has not been adequately evaluated in long-term use.
In patients with advanced renal disease, treatment with etoricoxib is not recommended. Clinical experience in patients with estimated creatinine clearance of <30 ml/min is very limited. If therapy with etoricoxib must be initiated in such patients, dose monitoring of the patient's renal function is advisable.
Renal prostaglandins may play a compensatory role in the maintenance of renal perfusion. Therefore, under conditions of compromised renal perfusion, administration of etoricoxib may cause a reduction in prostaglandin formation and, secondarily, in renal blood flow, and thereby impair renal function. Patients at greatest risk of this response are those with pre-existing significantly, impaired renal function, uncompensated heart failure, or cirrhosis. Monitoring of renal function in such patients should be considered. As with other drugs known to inhibit prostaglandin synthesis, discontinuation of therapy with etoricoxib would be expected to be followed by recovery to the pretreatment state.
Caution should be used when initiating treatment with etoricoxib in patients with considerable dehydration, it is advisable to rehydrate patients prior to starting therapy with etoricoxib.
As with other drugs known to inhibit prostaglandin synthesis, fluid retention, edema and hypertension have been observed in some patients taking etoricoxib. The possibility of exacerbating fluid retention, edema or hypertension should be taken into consideration when etoricoxib is used in patients with pre-existing edema, hypertension or heart failure.
Etoricoxib may be associated with more frequent and severe hypertension than some other NSAIDs and selective COX-2 inhibitors, particularly at high doses. Therefore, special attention should be paid to blood pressure monitoring during treatment with etoricoxib. If blood pressure rises significantly, alternative treatment should be considered.
Caution should be exercised in patients with a medical history of ischemic heart disease because of the pharmacodynamic profile of COX-2 selective inhibitors noted previously.
Physicians should be aware that individual patients may develop upper gastrointestinal (GI) ulcers/ulcer complications irrespective of treatment. Upper GI ulcers/ulcer complications have occurred in patients treated with etoricoxib. These events can occur at any time during use and without warning symptoms.
Independent of treatment, patients with a prior history of GI perforation, ulcers and bleeding (PUB) and patients greater than 65 years of age are known to be at a higher risk for a PUB.
Elevations of alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) (approximately three or more times the upper limit of normal) have been reported in patients treated for up to one year with etoricoxib.
A patient with symptoms and/or signs suggesting liver dysfunction, or in whom an abnormal liver function test has occurred, should be evaluated for persistently abnormal liver function tests. If persistently abnormal liver function tests (three times the upper limit of normal) are detected, etoricoxib should be discontinued.
Etoricoxib should be used with caution in patients who have previously experienced acute asthmatic attacks, urticaria, or rhinitis, which were precipitated by salicylates or nonselective cyclooxygenase inhibitors. Since the pathophysiology of these reactions is unknown, physicians should weigh the potential benefits of prescribing etoricoxib versus the potential risks.
Etoricoxib may mask fever, which is a sign of infection. The physician should be aware of this when using etoricoxib in patients being treated for infection.
Use in Children: Safety and effectiveness of etoricoxib in pediatric patients have not been established.
Use in the Elderly: Pharmacokinetics in the elderly (65 years of age and older) are similar to those in the young. No overall differences in safety or effectiveness were observed between elderly and younger patients.
Pregnancy: As with other drugs known to inhibit prostaglandin synthesis, use of etoricoxib should be avoided in late pregnancy because it may cause premature closure of the ductus arteriosus. There are no adequate and well-controlled studies in pregnant women. Etoricoxib should be used during the first two trimesters of pregnancy only if the potential benefit justifies the potential risk to the fetus.
Lactation: Etoricoxib is excreted in the milk of lactating rats. It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk and because of the possible adverse effects of drugs that inhibit prostaglandin synthesis on nursing infants, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.
The following drug-related adverse experiences were reported in patients with osteoarthritis (OA), rheumatoid arthritis (RA) or chronic low back pain treated for up to 12 weeks. These occurred in ≥1% of patients treated with etoricoxib: asthenia/fatigue, dizziness, lower extremity edema, hypertension, dyspepsia, heartburn, nausea, headache, ALT increased, AST increased.
The adverse experience profile was similar in patients with OA or RA treated with etoricoxib for one year or longer.
Compared with diclofenac, hypertension occurred at a higher rate on etoricoxib than on diclofenac.
There was no discernible difference in the rate of serious thrombotic cardiovascular events between patients receiving etoricoxib 60 mg or non-naproxen NSAIDs. However, the rate of these events was higher in patients receiving etoricoxib compared with those receiving naproxen 500 mg twice daily.
The adverse experience profile in ankylosing spondylitis when etoricoxib 90 mg given once daily for up to 1 year was generally similar to that reported in the chronic use in OA, RA and chronic low back pain.
The adverse experience profile in acute gouty arthritis when etoricoxib 120 mg given once daily for eight days was generally similar to that reported in the combined OA, RA and chronic low back pain.
The adverse experience profile in acute analgesia when etoricoxib 120 mg given once daily for one to seven days was generally similar to that reported in the combined OA, RA and chronic low back pain.
Post-marketing experience: The following adverse reactions have been reported in post-marketing experience:
Immune system disorders: hypersensitivity reactions, including anaphylactic/anaphylactoid reactions.
Psychiatric disorders: anxiety, insomnia, confusion, hallucinations.
Nervous system disorders: dysgeusia, somnolence.
Cardiac disorders: congestive heart failure.
Vascular disorders: hypertensive crisis.
Respiratory, thoracic and mediastinal disorders: bronchospasm.
Gastrointestinal disorders: abdominal pain, oral ulcers, peptic ulcers including perforation and bleeding (mainly in elderly patients), vomiting, diarrhea.
Hepatobiliary disorders: hepatitis.
Skin and subcutaneous tissue disorders: angioedema, pruritus, rash, Stevens-Johnson syndrome, urticaria.
Renal and urinary disorders: serial insufficiency, including renal failure, usually reversible upon discontinuation of therapy.
Warfarin: In patients stabilized on chronic warfarin therapy, the administration of etoricoxib 120 mg daily was associated with an increase in prothrombin time international normalized ratio (INR). Standard monitoring of INR values should be conducted when therapy with etoricoxib is initiated or changed, particularly in the first few days, in patients receiving warfarin or similar agents.
Rifampin: Coadministration of etoricoxib with rifampin, a potent inducer of hepatic metabolism, decreased in etoricoxib plasma area under the curve (AUC). This interaction should be considered when etoricoxib is coadministered with rifampin.
Methotrexate: Etoricoxib 120 mg increased methotrexate plasma concentrations and reduced renal clearance of methotrexate. Monitoring for methotrexate-related toxicity should be considered when etoricoxib at doses greater than 90 mg daily and methotrexate are administered concomitantly.
Diuretics, angiotensin converting enzyme (ACE) Inhibitors and angiotensin II antagonists (AIIAs): Reports suggest that NSAIDs including selective COX-2 inhibitors may diminish the antihypertensive effect of diuretics, ACE inhibitors and AIIAs. This interaction should be given consideration in patients taking etoricoxib concomitantly with these products.
Lithium: Reports suggest that non-selective NSAIDs and selective COX-2 inhibitors may increase plasma lithium levels. This interaction should be given consideration in patients taking etoricoxib concomitantly with lithium.
Aspirin: Etoricoxib can be used concomitantly with low-dose aspirin at doses for cardiovascular prophylaxis. However, concomitant administration of low-dose aspirin with etoricoxib results in an increased rate of GI ulceration or other complications compared to use of etoricoxib alone. At steady-state, etoricoxib 120 mg once daily had no effect on the anti-platelet activity of low dose aspirin (81 mg once daily) (see Warnings and Precautions).
Oral contraceptives: Etoricoxib 60 mg given concomitantly with an oral contraceptive ethinyl estradiol (EE) and norethindrone increased the steady-state AUC0-24 hr of EE. Etoricoxib 120 mg given with the same oral contraceptive, either concomitantly or separated by 12 hours, increased the steady-state AUC0-24 hr of EE. This increase in EE concentration should be considered when selecting an appropriate oral contraceptive for use with etoricoxib. An increase in EE exposure can increase the incidence of adverse events associated with oral contraceptives (e.g., venous thrombo-embolic events in women at risk).
Hormone replacement therapy: Administration of etoricoxib 120 mg with hormone replacement therapy consisting of conjugated estrogens increased the mean steady-state AUC0-24hr of unconjugated estrone, equilin and 17-β-estradiol. The effect of the recommended chronic doses of etoricoxib has not been studied. These increases in estrogenic concentration should be taken into consideration when selecting postmenopausal hormone therapy for use with etoricoxib.
Other: In drug-interaction studies, etoricoxib did not have clinically important effects on the pharmacokinetics of prednisone/prednisolone or digoxin. Antacids and ketoconazole (a potent inhibitor of CYP3A4) did not have clinically important effects on the pharmacokinetics of etoricoxib.
Store at temperature below 30°C.
M01AH05 - etoricoxib ; Belongs to the class of non-steroidal antiinflammatory and antirheumatic products, coxibs.
Coxiron FC tab 120 mg
3 × 10's
Coxiron FC tab 60 mg
3 × 10's
Coxiron FC tab 90 mg
3 × 10's
Sign Out
