Torixib

Etoricoxib.

TORIXIB (60 MG TABLET): A dark-green, oval, biconvex, film-coated tablet, engraved with "
Click on icon to see table/diagram/image
" logo on one side and "60" on the other side.
 Each film-coated tablet contains Etoricoxib 60 mg.
TORIXIB (90 MG TABLET): A white, oval, biconvex, film-coated tablet, engraved with "
Click on icon to see table/diagram/image
" logo on one side and "90" on the other side.
Each film-coated tablet contains Etoricoxib 90 mg.
TORIXIB (120 MG TABLET): A pale-green, oval, biconvex, film-coated tablet, engraved with "
Click on icon to see table/diagram/image
" logo on one side and "120" on the other side.
Each film-coated tablet contains Etoricoxib 120 mg.

Pharmacology: Pharmacodynamics: Etoricoxib decreases synthesis of prostaglandins due to selective dose-dependent inhibition of cyclooxygenase-2 (COX-2) enzyme within the clinical dose range; has antipyretic, analgesic and anti-inflammatory properties. Etoricoxib does not inhibit cyclooxygenase-1 (COX-1) at therapeutic concentrations.
Pharmacokinetics: Absorption: Etoricoxib is well absorbed from gastrointestinal tract after oral doses. The absolute bioavailability is approximately 100%. Peak plasma concentrations occur in about 1 hour in fasted adults; food delays absorption by about 2 hours, although it has no effect on the extent of absorption.
Distribution: Plasma protein binding is about 92%. The volume of distribution at steady state (V_d) is approximately 120 L.
Metabolism: Etoricoxib is extensively metabolized with less than 2% of a dose recovered in the urine as the parent drug. The major route of metabolism is via cytochrome P450 isoenzymes including CYP3A4 to form 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 cyclooxygenase-2 (COX-2) inhibitors.
Excretion: At steady state the half-life of Etoricoxib is about 22 hours. Excretion is mainly via the urine (70%) with only 20% of a dose appearing in the feces.

Etoricoxib is indicated for: 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.

Recommended Dose and Mode of administration: Etoricoxib is administered orally. Etoricoxib may be taken with or without food. Etoricoxib should be administered for the shortest duration possible and the lowest effective daily dose should be used.
Osteoarthritis: The recommended dose is 30 mg or 60 mg once daily.
Rheumatoid arthritis: 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.
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.
Chronic musculo-skeletal pain, including chronic low back pain: The recommended dose is 60 mg once daily.
Acute pain: For acute pain conditions, the recommended dose is 90 mg or 120 mg once daily. Etoricoxib should be used only for the acute symptomatic period limited to a maximum of 8 days.
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.
Dosage greater than dose recommended for each indication have either not demonstrated additional efficacy or have not been studied. Therefore: The dose for osteoarthritis should not exceed 60 mg daily.
The dose for rheumatoid arthritis should not exceed 90 mg daily.
The dose for ankylosing spondylitis should not exceed 90 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 chronic pain should not exceed 60 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.
Dosage in elderly: No dosage adjustment in Etoricoxib is necessary for the elderly.
Dosage in 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).
Dosage in 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).
Pediatric: Adolescent ≥16 years: Refer to adult dosing. Consider dosage reduction in adolescent <60 kg.

Overdose and Treatment: There have been reports of acute overdosage with etoricoxib, although adverse experiences were not reported in the majority of cases. The most frequently observed adverse experiences were consistent with the safety profile for etoricoxib (e.g. gastrointestinal events, renovascular events).
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 dialyzable by hemodialysis; it is not known whether etoricoxib is dialyzable by peritoneal dialysis.

Etoricoxib is contraindicated in: Patients with known hypersensitivity to Etoricoxib or any component of this product; Patients with active peptic ulceration or gastro-intestinal (GI) bleeding; Patients with severe hepatic dysfunction (Child-Pugh score >9); Patients with estimated creatinine clearance <30 mL/min; Patients who have developed sign of asthma, acute rhinitis, nasal polyps, angioneurotic oedema or urticaria following the administration of aspirin or other non-steroidal anti-inflammatory drugs (NSAIDs); Pregnancy and lactation; Children under 16 years of age; Patients with inflammatory bowel disease; Patients with congestive heart failure (NYHA II-IV); Patients with hypertension whose blood pressure has not been adequately controlled; Patients with established ischemic heart disease, peripheral arterial disease and/or cerebrovascular disease (including patients who recently undergone coronary artery bypass graft surgery or angioplasty).

Based on the Ministry of Public Health's Announcement: 1. Contraindicated in patients with known hypersensitivity to any component of this product, pregnancy and lactation.
2. Contraindicated in patients who have recently undergone coronary artery bypass graft surgery.
3. Contraindicated in patients with cardiovascular or cerebrovascular disease.
4. Contraindicated in patients with un-controlled hypertension.
5. Contraindicated in patients with myocardial infarction or congestive heart failure NYHA II-IV.
6. Contraindicated in patients with history of ischemic heart disease or history of paralysis from cerebrovascular disease.
7. Caution should be used in patients with risk factors for cardiovascular events e.g. hypertension, hyperlipidemia, diabetes mellitus, smoking, elderly.
8. Caution should be used in patients with liver or renal disease.

The selective COX-2 inhibitor class of drugs may be associated with an increased risk of thrombotic events, especially MI and stroke. These 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 and smoking, should only be treated with Etoricoxib after careful consideration.
Selective COX-2 inhibitors, including Etoricoxib, are not a substitute for aspirin for cardiovascular prophylaxis because of their lack of effect on platelets. Therefore, antiplatelet therapies should not be discontinued.
When used Etoricoxib concomitantly with aspirin (even at low dose), there is a further increase in the risk of gastrointestinal adverse effects (gastrointestinal ulceration or other gastrointestinal complications). Gastroprotective (e.g., proton pump inhibitors, misoprostol) is recommended.
Upper gastrointestinal complications including perforations, ulcers or bleedings (PUBs), some of them resulting in fatal outcome, have occurred in patients treated with Etoricoxib.
Use caution with a history or risk of gastrointestinal disease (bleeding or ulcers), concurrent therapy with aspirin or other NSAIDs, anticoagulants and/or corticosteroids, smoking, alcohol, and the elderly or debilitated patients.
Long-term administration of NSAIDs has resulted in renal papillary necrosis and other renal injury. Under conditions of compromised renal perfusion, administration of Etoricoxib may cause a reduction in prostaglandin formation and, secondarily, in renal blood flow, and therapy impaired renal function. Monitoring of renal function should be considered in patients with pre-existing significantly impair renal function, uncompensated heart failure, or cirrhosis.
Caution should be used when initiating treatment with Etoricoxib in patients with considerable dehydration. It is advisable to rehydrate patients prior starting therapy with Etoricoxib.
Monitor renal function closely; discontinue use with persistent or worsening renal function; use is contraindicated with severe renal impairment (CrCl <30 mL/min).
As with other drugs known to inhibit prostaglandin synthesis, fluid retention, edema and hypertension may occur in some patients taking Etoricoxib. Etoricoxib may be associated with more frequent and severe hypertension. Therefore, maintain blood pressure <140/90 mmHg prior to initiation and special attention should be paid to blood pressure monitoring during treatment with Etoricoxib. If blood pressure rises significantly, alternative treatment should be considered.
Elevations of alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) (approximately three or more times the upper limit of normal) may occur, monitor hepatic function closely in patients with previous abnormal hepatic function tests or sign/symptoms of hepatic dysfunction. 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 non-selective cyclooxygenase inhibitors.
Serious skin reactions, some of them fatal, including exfoliative dermatitis, Stevens-Johnson syndrome (SJS), and toxic epidermal necrosis (TEN) have been reported very rarely and serious hypersensitivity reactions such as anaphylaxis and angioedema have been reported in patient receiving Etoricoxib. Etoricoxib should be discontinued at the first appearance of skin rash, mucosal lesions, or any other sign of hypersensitivity.
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 measure should be taken, including discontinued of therapy.
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.
The use of Etoricoxib, as with any drug known to inhibit COX-2, is not recommended in woman attempting to conceive.
Patients who experience dizziness, vertigo or somnolence while taking Etoricoxib should refrain from driving or operating machinery.

Pregnancy: Etoricoxib is contraindicated in women who are pregnant or who may become pregnant.
No data are available on the use of Etoricoxib in pregnant woman and the risk to the human fetus exposed to Etoricoxib is unknown. However, as with other medications inhibiting prostaglandin synthesis, Etoricoxib may cause uterine inertia and premature closure of the ductus arteriosus if used during the last trimester.
In animal studies, reproductive toxicity was shown. While Etoricoxib administration in rats at approximately 1.5 times the daily human dose based on exposure did not result in teratogenicity. A low incidence of cardiovascular malformations and increases in post implantation loss were observed in Etoricoxib-treated rabbits.
Breastfeeding: It is not known whether Etoricoxib is excreted in human milk. However, Etoricoxib is excreted into the milk of lactating rat. The use of Etoricoxib is contraindicated during lactation.

Common: asthenia/fatigue, flu-like disease, dizziness, headache, oedema/fluid retention, lower extremity edema, hypertension, abdominal pain, flatulence, diarrhea, dyspepsia, heartburn, epigastric discomfort, nausea, ALT increased, AST increased, alveolar osteitis.
Uncommon to Rare: Blood and lymphatic system disorders: thrombocytopenia, leucopenia.
Infections and infestation: gastroenteritis, upper respiratory infection, urinary tract infection.
Immune system disorders: hypersensitivity reactions, including angioedema, anaphylactic/anaphylactoid reactions including shock.
Metabolism and nutrition disorders: appetite increase or decrease, weight gain, hyperkalemia.
Psychiatric disorders: anxiety, depression, mental acuity decreased, hallucinations, confusion, restlessness.
Nervous system disorders: dysgeusia, insomnia, paresthesia/hypaesthesis, somnolence.
Eye disorders: blurred vision, conjunctivitis.
Ear and labyrinth disorders: tinnitus, vertigo.
Cardiac disorders: congestive heart failure, non-specific ECG changes, myocardial infarction, palpitations, angina, arrhythmia, atrial fibrillation, tachycardia.
Vascular disorders: flushing, cerebrovascular accident, hypertensive crisis, transient ischaemic attack, vasculitis.
Respiratory, thoracic and mediastinal disorders: cough, dyspnea, epistaxis, bronchospasm.
Gastrointestinal disorders: abdominal distention, acid reflux, bowel movement pattern change, constipation, dry mouth, gastroduodenal ulcer, irritable bowel syndrome, oesophagitis, oral ulcers, peptic ulcers including perforation and bleeding (mainly in elderly patients), vomiting, gastritis, pancreatitis.
Hepatobiliary disorders: hepatitis, jaundice, hepatic failure.
Skin and subcutaneous tissue disorders: ecchymosis, facial oedema, pruritus, erythema, rash, Stevens-Johnson syndrome, toxic epidermal necrolysis, urticaria, fixed drug eruption.
Musculoskeletal, connective tissue and bone disorders: muscular cramp/spasm, musculoskeletal pain/stiffness.
Renal and urinary disorders: proteinuria, renal insufficiency, including renal failure.
General disorders and administration site conditions: chest pain.
Investigations: blood urea nitrogen increased, creatinine phosphokinase increased, haematocrit decreased, haemoglobin decreased, hyperkalaemia, leukocytes decreased, platelets decreased, serum creatinine increased, uric acid increased, blood sodium decreased.
The following serious undesirable effects have been reported in association with the use of NSAIDs and cannot be ruled out for Etoricoxib: nephrotoxicity including interstitial nephritis and nephrotic syndrome, hepatotoxicity, including hepatic failure.

Warfarin: Coadministration of an anticoagulant and an NSAID may increase the risk of serious bleeding. Patients receiving oral anticoagulants should be closely monitored for their prothrombin time INR, particularly in the first few days when therapy with Etoricoxib is initiated or the dose of Etoricoxib is changed.
Rifampin: Concurrent administration of Etoricoxib, a CYP3A4 substrate, and rifampin, a potent CYP3A4 inducer, results in a 65% reduction on Etoricoxib blood concentrations. This increase in Etoricoxib metabolism may lead to symptom recurrence when Etoricoxib and rifampin are co-administered.
Methotrexate: The concomitant use of Etoricoxib and methotrexate may cause increased methotrexate plasma concentrations. Monitor for methotrexate toxicity during therapy if Etoricoxib and methotrexate coadministration is necessary.
Diuretics, Angiotensin Converting Enzyme (ACE) Inhibitors and Angiotensin II Antagonists (AIIAs): 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. 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 NSAIDs, 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. Patients should be adequately hydrated and consideration should be given to monitoring of renal function after initiation of concomitant therapy, and periodically thereafter.
Lithium: NSAIDs, including selective COX-2 inhibitors decrease lithium renal excretion and therefore increase lithium plasma levels. This interaction should be given consideration in patients taking Etoricoxib with lithium. Monitor serum lithium levels frequently and observe for sign and symptoms of lithium toxicity.
Aspirin: Etoricoxib can be used concomitantly with aspirin at doses used for cardiovascular prophylaxis (low-dose aspirin). However, concomitant administration of low-dose aspirin with Etoricoxib may result in an increased rate of GI ulceration or other complications compared to use of Etoricoxib alone. Concomitant administration of Etoricoxib with doses of aspirin above those for cardiovascular prophylaxis or with other NSAIDs is not recommended.
Cyclosporin and tacrolimus: Coadministration of cyclosporin or tacrolimus with any NSAID may increase the nephrotoxic effect of cyclosporin or tacrolimus. Renal function should be monitored when Etoricoxib and either of these drugs is used in combination.
Oral contraceptives: The increase in ethinyl estradiol concentration should be considered when selecting an oral contraceptive for use with Etoricoxib. An increase in ethinyl estradiol 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: The increases in estrogenic concentration should be taken into consideration when selecting post-menopausal hormone therapy for use with Etoricoxib because the increase in estrogen exposure might increase the risk of adverse events associated with HRT.
Digoxin: Coadministration of digoxin and NSAIDs may increase digoxin plasma concentrations and prolong the half-life of digoxin. Patients at high risk of digoxin toxicity should be monitored when Etoricoxib and digoxin are administered concomitantly.
Effect of Etoricoxib on drugs metabolized by sulfotransferases: Etoricoxib inhibits human sulfotransferase activity (particularly that of SULT1E1 substrates) and increases serum ethinyl estradiol, a human sulfotransferase substrate. Therefore, coadministration of Etoricoxib and drugs primarily metabolized by human sulfotransferases (e.g. oral salbutamol and minoxidil) may also increase the exposure of these drugs. Use caution if concurrently administration is required.
Prednisone/prednisolone: Etoricoxib do not have clinically important effects on the pharmacokinetics of prednisone/prednisolone.
Ketoconazole: Ketoconazole do not have clinically important effects on the pharmacokinetics of Etoricoxib.
Antacids: Antacids do not have clinically important effects on the pharmacokinetics of Etoricoxib.

Store below 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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