Biocoxib

Etoricoxib.

Each tablet contains Etoricoxib 90 mg.

Pharmacology: Pharmacodynamics: Etoricoxib is a member of a class of Non-Steroid Anti-Inflammatory Drugs which is highly selective cyclo-oxygenase-2 (COX-2) inhibitor with anti-inflammatory and analgesic properties.
Pharmacokinetics: Absorption: Etoricoxib is well absorbed from the gastrointestinal tract after oral doses. Peak plasma concentrations are reached in about 1 hour in fasted adults.
Distribution: Etoricoxib is approximately 92% bound to plasma protein. At steady state the half-life of etoricoxib is about 22 hours.
Metabolism: The major route of metabolism is via cytochrome P450 isoenzymes including CYP3A4 to from the 6'-hydroxymethyl derivative of etoricoxib, which is then oxidized to the 6'-carboxylic acid derivative, the major metabolite. Both are inactive or only weak cyclo-oxygenase-2 (COX-2) inhibitors.
Excretion: Etoricoxib is excretion mainly via the urine 70% with only 20% of a dose appearing in the faeces.

Acute and chronic treatment of the signs and symptoms of osteoarthritis (OA) and rheumatoid arthritis (RA).
Treatment of ankylosing spondylitis (AS).
Treatment of acute gouty arthritis.
Relief of chronic musculo-skeletal pain, including chronic low back pain.
Relief of acute pain including dental surgery.
Treatment of primary dysmenorrhea.
Treatment of moderate to severe acute post-operative pain associated with abdominal gynecological surgery.

BIOCOXIB (90 mg) is administered orally. BIOCOXIB (90 mg) may be taken with or without food. BIOCOXIB (90 mg) should be administered for the shorted duration possible and the lowest effective daily dose should be used.
Osteoarthritis: The recommended dose is 60 mg once daily.
Rheumatoid Arthritis: The recommended dose is 90 mg once daily.
Ankylosing Spondylitis: The recommended dose is 90 mg once daily.
Acute Gouty Arthritis: The recommended dose is 120 mg once daily.
Chronic musculo-skeletal pain, including chronic low back pain: The recommended dose is 90 mg or 120 mg once daily should be used a maximum of 4 weeks.
Acute pain: For acute pain conditions, BIOCOXIB (90 mg) should be used only for the acute symptomatic period limited to a maximum of 8 days.
Post-operative Dental pain: The recommended dose is 90 mg once daily should be used a maximum of 3 days.
Primary Dysmenorrhea: The recommended dose is 120 mg once daily should be used a maximum of 8 days.
Post-operative abdominal gynecological pain: The recommended dose is 90 mg or 120 mg once daily.

Symptoms: Most reports of toxic signs and symptoms when use NSAIDs overdose are mild to moderate and include GI distress, nausea, vomiting, lethargy, tinnitus, confusion, headache, and blurred vision. Severe poisoning may result in hypertension, acute renal failure, hepatic dysfunction, cardiovascular collapse, and cardiac arrest.
Treatment: Treatment of NSAID toxicity is primarily supportive and symptomatic. In addition to supportive measures, the use of oral activated charcoal may help to reduce the absorption of the NSAID. However, hemodialysis may be necessary in cases of NSAID-induced prolonged or severe renal failure.

BIOCOXIB (90 mg) contraindicated in: Patients with known hypersensitivity to any component of this product.
Patients with moderate to severe heart failure (NYHA II-IV).
Patients with renal impairment associated with a creatinine clearance < 30 ml/min.
Patients with ischemic heart disease, peripheral arterial disease or cerebrovascular disease.
Patients with severe hepatic impairment (Child-Pugh score of 10 or more).
Patients with hypertension whose blood pressure is not controlled.
Patients with active gastro-intestinal ulceration or bleeding.
Patients with inflammatory bowel disease.

Cardiovascular: The cardiovascular safety of etoricoxib has been assessed in the MEDAL program which pooled data from 3 studies involving over 30,000 patients with either osteoarthritis or rheumatoid arthritis. Patients with osteoarthritis were given etoricoxib 60 or 90 mg daily; those with rheumatoid arthritis received 90 mg daily. In all studies, diclofenac 150 mg daily was given as the comparator. After an average treatment duration of 18 months, the rate of thrombotic events such as myocardial infarction, stroke, and sudden or unexplained death with etoricoxib were similar to those for diclofenac. One of the 3 studies showed that there was a non-significant increase in the rate of heart failure with etoricoxib 90 mg daily compared to diclofenac.
In another study that pooled pre-licensing data, the risk of thrombotic events with etoricoxib, given at a dose of at least 60 mg daily, was also found to be similar to that for placebo treatment, ibuprofen 2.4 g daily, diclofenac 150 mg daily and naproxen 1 g daily, although there was a trend towards more events with etoricoxib than with naproxen. The EMEA's Committee for Medicinal Product for Human Use (CHMP) has recommended the inclusion of a warning in the labelling of etoricoxib that it must not be given to patients whose blood pressure is persistently above 140/90 mmHg and inadequately controlled; in addition, high blood pressure should be controlled before starting treatment and monitored for 2 weeks afterwards then regularly thereafter. Etoricoxib should be used the shortest duration possible and lowest effective daily dose. The patient's need for symptomatic relief and response to therapy should be re-evaluated periodically.
Hepatic: NSAIDs should be used with caution in patients with hepatic impairment; NSAIDs should be avoided in severe liver disease (Child-Pugh 10 or more), maximum 60 mg daily in mild hepatic impairment (Child-Pugh score 5 to 6), maximum 60 mg on alternate days or 30 mg once daily in moderate hepatic impairment (Child-Pugh score 7 to 9).
Renal: NSAIDs should be avoided if possible or used with caution in patients with renal impairment; the lowest effective dose should be used for the shortest possible duration, and renal function should be monitored. Sodium and water retention may occur and renal function may deteriorate, possibly leading to renal failure; deterioration in renal function has also been reported after topical use. Avoid if eGFR less than 30 ml/minute/1.73 m².
Gastro-intestinal: It is generally accepted that the inhibition of cyclo-oxygenase-1 (COX-1) plays a role in the adverse gastrointestinal effects of the NSAIDs, and COX-2 by NSAIDs such as etoricoxib may cause less gastrotoxicity than that seen with the non-selective inhibition of the traditional NSAIDs. In addition, etoricoxib should not be used in patients with active gastrointestinal ulceration or bleeding. In a study of the pooled data from 3 randomised clinical studies, etoricoxib (in doses of 60 or 90 mg daily) was associated with significantly less frequent upper gastrointestinal clinical events than diclofenac (150 mg daily). But the adverse gastrointestinal effects may be increased, if used in the elderly patients and have a history of gastrointestinal reaction.

Use in Pregnancy: NSAIDs should be avoided during pregnancy or avoid them unless the potential benefit outweighs the risk. NSAIDs should be avoided during the third trimester because use is associated with a risk of closure of fetal ductus arteriosus in utero and possibly persistent pulmonary hypertension of the newborn. In addition, the onset of labour may be delayed and its duration may be increased.
Use in Lactation: NSAIDs should be used with caution during breast-feeding.

Gastrointestinal: Discomfort, nausea, diarrhoea, bleeding, ulceration.
Immune system: Hypersensitivity (rash, angioedema, bronchospasm).
Central nervous system: Headache, vertigo, dizziness, depression, drowsiness, insomnia.
Dermatologic: Photosensitivity.
Renal: Haematuria, renal failure.
Cardiovascular: Hypertension, congestive heart failure.

Angiotensin Converting Enzyme (ACE) Inhibitors and Angiotensin II Antagonists (AIIAs): NSAIDs may decrease the antihypertensive of ACEI and/or AIIAs. The co-administration medication may be the risk of nephrotoxicity increased. Consider discontinuation of BIOCOXIB (90 mg) if patient is uncontrolled blood pressure. Periodically measure renal function during concomitant use.
Azole antifungals (Fluconazole, Ketoconazole): Increase in BIOCOXIB (90 mg) plasma concentration may occur, increasing the pharmacologic effect and adverse reactions.
Corticosteroid oral (Prednisone): The risk of GI bleeding may be increased. Use corticosteroid oral and BIOCOXIB (90 mg) with caution.
Antiplatelet therapy (Clopidogrel, Prasugrel): The risk of bleeding may be increased. Use antiplatelet and BIOCOXIB (90 mg) with caution.
Anticoagulant (Warfarin): Coadministration with BIOCOXIB (90 mg) may increase the risk of anticoagulant-induced bleeding (eg. GI bleeding). Monitor prothrombin time and International Normalized Ratio (INR) and patients closely, especially the first few days.
Beta-blockers: The antihypertensive effect of beta-blockers with BIOCOXIB (90 mg) may be impaired, possibly because of BIOCOXIB (90 mg) as the NSAIDs inhibition of renal prostaglandin synthesis, thereby allowing unopposed pressure systems. Monitor blood pressure and adjust beta-blocker dose as needed to treat.
Cyclosporin and tacrolimus: Coadministration with BIOCOXIB (90 mg) may increase nephrotoxicity. Monitor renal function frequently and consider avoiding concurrent use.
Diuretics (Thiazides, Potassium-sparing diuretics, Loop diuretics): The effects of diuretics may be decreased, the risk of acute renal failure may be increased when co-administered. Closely monitor renal function if coadministration cannot be avoided. If renal function decreases, consider stopping one or both drugs.
Lithium: Concomitant administration with BIOCOXIB (90 mg) may increase plasma lithium levels. This interaction should be given consideration in patients taking BIOCOXIB (90 mg) concomitantly with lithium.
Methotrexate: Concomitant administration with BIOCOXIB (90 mg) may increase risk of methotrexate toxicity (eg. stomatitis, bone marrow suppression, nephrotoxicity). This interaction should be given low-dose methotrexate in patients taking BIOCOXIB (90 mg) concomitantly.

Do not store above 30°C.

Nonsteroidal Anti-Inflammatory Drugs (NSAIDs)

M01AH05 - etoricoxib ; Belongs to the class of non-steroidal antiinflammatory and antirheumatic products, coxibs.

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