ARCOXIA Etoricoxib 30mg Film-Coated Tablet 1's

ETORICOXIB (ARCOXIA) is indicated for: Acute and chronic treatment of the signs and symptoms of osteoarthritis (OA) and rheumatoid arthritis (RA); Treatment of ankylosing spondylitis (AS); Relief of chronic low back pain (CLBP): Treatment of acute gouty arthritis; Relief of acute pain; Treatment of primary dysmenorrhea; Treatment of moderate to severe acute post-operative pain associated with dental surgery; Treatment of moderate to severe acute post-operative pain associated with abdominal gynecological surgery.
The decision to prescribe a selective COX-2 inhibitor should be based on an assessment of the individual patient's overall risks (see Precautions).

ETORICOXIB (ARCOXIA) is administered orally. ETORICOXIB (ARCOXIA) may be taken with or without food. ETORICOXIB (ARCOXIA) should be administered for the shortest duration possible and the lowest effective daily dose should be used.
Arthritis: Osteoarthritis: The recommended dose is 30 mg or 60 mg once daily.
Rheumatoid Arthritis: The recommended dose is 90 mg once daily. The minimum effective daily dose is 60 mg once daily. In some patients, 90 mg once daily may provide increased therapeutic benefit.
Ankylosing Spondylitis: The recommended dose is 60 mg or 90 mg once daily. The minimum effective daily dose is 60 mg once daily. In some patients, 90 mg once daily may provide increased therapeutic benefit.
Relief of Chronic Low Back Pain (CLBP): The recommended dose is 60 mg daily.
Acute Pain: For acute pain conditions, the recommended dose is 90 mg or 120 mg once daily. ETORICOXIB (ARCOXIA) should be used only for the acute symptomatic period, limited to a maximum of 8 days treatment.
Acute Gouty Arthritis: The recommended dose is 120 mg once daily.
Primary Dysmenorrhea: The recommended dose is 120 mg once daily.
Post-operative Dental Pain: The recommended dose is 90 mg once daily.
Post-operative Gynecological Pain: The recommended dose is 90 mg once daily. The initial dose should be administered shortly before surgery. The dose can be increased to a maximum 120 mg once daily.
Doses greater than those recommended for each indication have either not demonstrated additional efficacy or have not been studied. Therefore: The dose for OA should not exceed 60 mg daily.
The dose for RA should not exceed 90 mg daily.
The dose for ankylosing spondylitis should not exceed 90 mg daily.
The dose for relief of chronic low back pain should not exceed 60 mg daily.
The dose for acute gout should not exceed 120 mg daily.
The dose for acute pain and primary dysmenorrhea should not exceed 120 mg daily.
The dose for post-operative acute dental surgery pain should not exceed 90 mg daily.
The dose for post-operative acute gynecological surgery pain should not exceed 120 mg daily.
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. (See Precautions.)
Elderly, Gender, Race: No dosage adjustment in ETORICOXIB (ARCOXIA) 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 Precautions.)
Renal Insufficiency: In patients with advanced renal disease (creatinine clearance <30 mL/min), treatment with ETORICOXIB (ARCOXIA) is not recommended. No dosage adjustment is necessary for patients with lesser degrees of renal insufficiency (creatinine clearance ≥30 mL/min). (See Precautions.)
Mode of Administration: ETORICOXIB (ARCOXIA) is administered orally. ETORICOXIB (ARCOXIA) may be taken with or without food.

May be taken with or without food.

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.
Contraindications: Hypersensitivity to the active substance or to any of the excipients.
Active peptic ulceration or active gastro-intestinal (GI) bleeding.
Patients who have experienced bronchospasm, acute rhinitis, nasal polyps, angioneurotic oedema, urticaria, or allergic-type reactions after taking acetylsalicylic acid or NSAIDS including COX-2 (cyclooxygenase-2) inhibitors.
Pregnancy and lactation.
Severe hepatic dysfunction (serum albumin <25 g/L or Child-Pugh score ≥ 10).
Estimated renal creatinine clearance <30 mL/min.
Children and adolescents under 16 years of age.
Inflammatory bowel disease.
Congestive heart failure (NYHA II-IV).
Patients with hypertension whose blood pressure has not been adequately controlled.
Established ischemic heart disease, peripheral arterial disease and/or cerebrovascular disease (including patients who have recently undergone coronary artery bypass graft surgery or angioplasty).

COX-2 inhibitors are not to be given to patients with allergy to NSAIDs.
Exercise caution when prescribing Selective COX-2 inhibitors in patients with ischemic heart disease and those with risk factors for heart disease; hypertension; hyperlipidemia, 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.
Clinical trials suggest that the selective COX-2 inhibitor class of drugs may be associated with an increased risk of thrombotic events (especially MI and stroke), relative to placebo and some NSAIDs (naproxen). 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) 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 difference in gastrointestinal safety between selective COX-2 inhibitors + acetylsalicylic acid vs. NSAIDs + acetylsalicylic acid has not been adequately evaluated in long-term clinical trials.
Long-term administration of NSAIDs has resulted in renal papillary necrosis and other renal injury. Renal prostaglandins may play a compensatory role in the maintenance of renal perfusion. Therefore, under conditions of compromised renal perfusion, administration of ETORICOXIB (ARCOXIA) 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.
Caution should be used when initiating treatment with ETORICOXIB (ARCOXIA) in patients with considerable dehydration. It is advisable to rehydrate patients prior to starting therapy with ETORICOXIB (ARCOXIA).
As with other drugs known to inhibit prostaglandin synthesis, fluid retention, edema and hypertension have been observed in some patients taking ETORICOXIB (ARCOXIA). The possibility of fluid retention, edema or hypertension should be taken into consideration when ETORICOXIB (ARCOXIA) is used in patients with pre-existing edema, hypertension, or heart failure. All Nonsteroidal Antiinflammatory Drugs (NSAIDs), including etoricoxib, can be associated with new onset or recurrent congestive heart failure (see Adverse Reactions).
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.
Physicians should be aware that individual patients may develop upper gastrointestinal (GI) ulcers/ulcer complications irrespective of treatment. Although the risk of GI toxicity is not eliminated with ETORICOXIB (ARCOXIA), the results of the MEDAL Program demonstrate that in patients treated with ETORICOXIB (ARCOXIA), the risk of GI toxicity with ETORICOXIB (ARCOXIA) 60 mg or 90 mg once daily is significantly less than with diclofenac 150 mg daily. In clinical studies with ibuprofen and naproxen, the risk of endoscopically detected upper GI ulcers was lower in patients treated with ETORICOXIB (ARCOXIA) 120 mg once daily than in patients treated with non-selective NSAIDs. While the risk of endoscopically detected ulcers was low in patients treated with ETORICOXIB (ARCOXIA) 120 mg it was higher than in patients treated with placebo. Upper GI ulcers/ulcer complications have occurred in patients treated with ETORICOXIB (ARCOXIA). 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 approximately 1% of patients in clinical trials treated for up to one year with ETORICOXIB (ARCOXIA) 30, 60 and 90 mg daily. In active comparator portions of clinical trials, the incidence of elevated AST and/or ALT in patients treated with ETORICOXIB (ARCOXIA) 60 and 90 mg daily was similar to that of patients treated with naproxen 1000 mg daily, but notably less than the incidence in the diclofenac 150 mg daily group. These elevations resolved in patients treated with ETORICOXIB (ARCOXIA), with approximately half resolving while patients remained on therapy. In controlled clinical trials of ETORICOXIB (ARCOXIA) 30 mg daily versus ibuprofen 2400 mg daily or celecoxib 200 mg daily, the incidence of elevations of ALT or AST was similar.
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 (ARCOXIA) should be discontinued.
When using etoricoxib in the elderly and in patients with renal, hepatic, or cardiac dysfunction, medically appropriate supervision should be maintained. If these patients deteriorate during treatment, appropriate measures should be taken, including discontinuation of therapy.
Serious skin reactions, some of them fatal, including exfoliative dermatitis, Stevens-Johnson syndrome, and toxic epidermal necrolysis, have been reported very rarely in association with the use of NSAIDs and some selective COX-2 inhibitors during post-marketing surveillance (see Adverse Reactions). These serious events may occur without warning. Patients appear to be at highest risk for these reactions early in the course of therapy: the onset of the reaction occurring in the majority of cases within the first month of treatment. Serious hypersensitivity reactions (such as anaphylaxis and angioedema) have been reported in patients receiving etoricoxib (see Adverse Reactions). Some selective COX-2 inhibitors have been associated with an increased risk of skin reactions in patients with a history of any drug allergy. Etoricoxib should be discontinued at the first appearance of skin rash, mucosal lesions, or any other sign of hypersensitivity.
ETORICOXIB (ARCOXIA) may mask fever, which is a sign of infection. The physician should be aware of this when using ETORICOXIB (ARCOXIA) in patients being treated for infection.
Use in Children: Safety and effectiveness of etoricoxib in pediatric patients have not been established.
Use in Elderly: Pharmacokinetics in the elderly (65 years of age and older) are similar to those in the young. In clinical studies, a higher incidence of adverse experiences was seen in older patients compared to younger patients; the relative differences between etoricoxib and control groups were similar in the elderly and the young. Greater sensitivity of some older individuals cannot be ruled out.

In clinical trials, ETORICOXIB (ARCOXIA) was evaluated for safety in 9295 individuals, including 5774 patients with OA, RA or chronic low back pain (approximately 600 patients with OA or RA were treated for one year or longer).
The following drug-related adverse experiences were reported in clinical studies in patients with OA, RA, or chronic low back pain treated for up to 12 weeks. These occurred in ≥1% of patients treated with ETORICOXIB (ARCOXIA) and at an incidence greater than placebo: 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 (ARCOXIA) for one year or longer.
In the MEDAL Study, an endpoint driven CV outcomes trial involving 23,504 patients, the safety of ETORICOXIB (ARCOXIA) 60 or 90 mg daily was compared to diclofenac 150 mg daily in patients with OA or RA (mean duration of treatment was 20 months). In this large trial, only serious adverse events and discontinuations due to any adverse events were recorded. The rates of confirmed thrombotic cardiovascular serious adverse events were similar between ETORICOXIB (ARCOXIA) and diclofenac. The incidence of discontinuations for hypertension-related adverse events was less than 3% in each treatment group; however, ETORICOXIB (ARCOXIA) 60 and 90 mg demonstrated significantly higher rates of discontinuations for these events than diclofenac. The incidence of congestive heart failure adverse events (discontinuations and serious events) and the incidence of discontinuations due to edema occurred at similar rates on ETORICOXIB (ARCOXIA) 60 mg compared to diclofenac; however, the incidences for these events were higher for ETORICOXIB (ARCOXIA) 90 mg compared to diclofenac. The incidence of discontinuations due to atrial fibrillation was higher for etoricoxib compared to diclofenac.
The EDGE and EDGE II studies compared the GI tolerability of etoricoxib 90 mg daily (1.5 to 3 times the doses recommended for OA) and diclofenac 150 mg daily in 7111 patients with OA (EDGE Study; mean duration of treatment 9 months) and 4086 patients with RA (EDGE II; mean duration of treatment 19 months). In each of these studies, the adverse experience profile on ETORICOXIB (ARCOXIA) was generally similar to that reported in the phase IIb/III placebo-controlled clinical studies; however, hypertension and edema-related adverse experiences occurred at a higher rate on etoricoxib 90 mg than on diclofenac 150 mg daily. The rate of confirmed thrombotic cardiovascular serious adverse events occurring in the two treatment groups was similar.
In a combined analysis of phase IIb to V clinical studies of 4 weeks duration or longer (excluding the MEDAL Program Studies), there was no discernible difference in the rate of confirmed thrombotic cardiovascular serious adverse events between patients receiving etoricoxib ≥30 mg or non-naproxen NSAIDs. The rate of these events was higher in patients receiving etoricoxib compared with those receiving naproxen 500 mg twice daily.
In a clinical study for ankylosing spondylitis, patients were treated with ETORICOXIB (ARCOXIA) 90 mg once daily for up to 1 year (N=126). The adverse experience profile in this study was generally similar to that reported in chronic studies in OA, RA and chronic low back pain.
In a clinical study for acute gouty arthritis, patients were treated with ETORICOXIB (ARCOXIA) 120 mg once daily for eight days. The adverse experience profile in this study was generally similar to that reported in the combined OA, RA, and chronic low back pain studies.
In initial clinical studies for acute analgesia, patients were treated with ETORICOXIB (ARCOXIA) 120 mg once daily for one to seven days. The adverse experience profile in these studies was generally similar to that reported in the combined OA, RA, and chronic low back pain studies.
In the additional clinical studies for acute post-operative pain associated with dental and abdominal gynecological surgeries including 1222 patients treated with ETORICOXIB (ARCOXIA) (90 mg or 120 mg), the adverse experience profile was generally similar to that reported in the combined OA, RA, and chronic low back pain studies.
In the combined studies for acute post-operative dental pain, the incidence of post-dental extraction alveolitis (dry socket) reported in patients treated with ETORICOXIB (ARCOXIA) was similar to that of patients treated with active comparators.
Post-marketing experience: The following adverse reactions have been reported in post-marketing experience: Blood and lymphatic system disorders: thrombocytopenia.
Immune system disorders: hypersensitivity reactions, including anaphylactic/anaphylactoid reactions including shock.
Metabolism and nutrition disorders: hyperkalemia.
Psychiatric disorders: anxiety, insomnia, confusion, hallucinations, depression, restlessness.
Nervous system disorders: dysgeusia, somnolence.
Eye disorders: blurred vision.
Cardiac disorders: congestive heart failure, palpitations, angina, arrhythmia.
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, jaundice, hepatic failure.
Skin and subcutaneous tissue disorders: angioedema, pruritus, erythema, rash, Stevens-Johnson syndrome, toxic epidermal necrolysis, urticaria, fixed drug eruption.
Renal and urinary disorders: renal insufficiency, including renal failure (see Precautions).

Warfarin: In subjects stabilized on chronic warfarin therapy, the administration of ETORICOXIB (ARCOXIA) 120 mg daily was associated with an approximate 13% increase in prothrombin time International Normalized Ratio (INR). Standard monitoring of INR values should be conducted when therapy with ETORICOXIB (ARCOXIA) is initiated or changed, particularly in the first few days, in patients receiving warfarin or similar agents.
Rifampin: Co-administration of ETORICOXIB (ARCOXIA) with rifampin, a potent inducer of hepatic metabolism, produced a 65% decrease in etoricoxib plasma area under the curve (AUC). This interaction should be considered when ETORICOXIB (ARCOXIA) is co-administered with rifampin.
Methotrexate: Two studies investigated the effects of ETORICOXIB (ARCOXIA) 60, 90 or 120 mg administered once daily for seven days in patients receiving once-weekly methotrexate doses of 7.5 to 20 mg for rheumatoid arthritis. ETORICOXIB (ARCOXIA) at 60 and 90 mg had no effect on methotrexate plasma concentrations (as measured by AUC) or renal clearance. In one study, ETORICOXIB (ARCOXIA) 120 mg had no effect on methotrexate plasma concentrations (as measured by AUC) or renal clearance. In the other study, ETORICOXIB (ARCOXIA) 120 mg increased methotrexate plasma concentrations by 28% (as measured by AUC) and reduced renal clearance of methotrexate by 13%. Monitoring for methotrexate-related toxicity should be considered when ETORICOXIB (ARCOXIA) 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 (ARCOXIA) concomitantly with these products.
In some patients with compromised renal function (e.g., elderly patients or patients who are volume-depleted, including those on diuretic therapy) who are being treated with non-steroidal anti-inflammatory drugs, including selective COX-2 inhibitors, the co-administration of ACE inhibitors or AIIAs may result in a further deterioration of renal function, including possible acute renal failure. These effects are usually reversible. Therefore, the combination should be administered with caution, especially in the elderly.
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 (ARCOXIA) concomitantly with lithium.
Aspirin: ETORICOXIB (ARCOXIA) can be used concomitantly with low-dose aspirin at doses for cardiovascular prophylaxis. At steady state, etoricoxib 120 mg once daily had no effect on the anti-platelet activity of low-dose aspirin (81 mg once daily). However, concomitant administration of low-dose aspirin with ETORICOXIB (ARCOXIA) increases rate of GI ulceration or other complications compared to use of ETORICOXIB (ARCOXIA) alone. (See Precautions.)
Oral Contraceptives: ETORICOXIB (ARCOXIA) 60 mg given concomitantly with an oral contraceptive containing 35 mcg ethinyl estradiol (EE) and 0.5 to 1 mg norethindrone for 21 days increased the steady state AUC_0-24hr of EE by 37%. ETORICOXIB (ARCOXIA) 120 mg given with the same oral contraceptive concomitantly or separated by 12 hours, increased the steady state AUC_0-24hr of EE by 50 to 60%. This increase in EE concentration should be considered when selecting an 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 thromboembolic events in women at risk).
Hormone Replacement Therapy: Administration of ETORICOXIB (ARCOXIA) 120 mg with hormone replacement therapy consisting of conjugated estrogens (0.625 mg PREMARIN) for 28 days, increased the mean steady state AUC_0-24hr of unconjugated estrone (41%), equilin (76%), and 17-β-estradiol (22%).
The effect of the recommended chronic doses of ETORICOXIB (ARCOXIA) (30, 60 and 90 mg) has not been studied. The effects of ETORICOXIB (ARCOXIA) 120 mg on the exposure (AUC_0-24hr) to these estrogenic components of PREMARIN were less than half of those observed when PREMARIN was administered alone and the dose was increased from 0.625 to 1.25 mg. The clinical significance of these increases is unknown, and higher doses of PREMARIN were not studied in combination with ETORICOXIB (ARCOXIA). These increases in estrogenic concentration should be taken into consideration when selecting post-menopausal hormone therapy for use with ETORICOXIB (ARCOXIA).
Other: In drug-interaction studies, ETORICOXIB (ARCOXIA) 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 (ARCOXIA).

Nonsteroidal Anti-Inflammatory Drugs (NSAIDs)