Hofxib 90

Etoricoxib.

Hofxib 90: White film-coated, biconvex faces, apple shaped tablet, inscribed "PCL" on one side.
Each tablet contains Etoricoxib 90 mg.
Excipients/Inactive Ingredients: Microcrystalline Cellulose and Dibasic calcium phosphate, Povidone K30, Croscarmellose Sodium, Colloidal Silicone Dioxide 200, Magnesium Stearate, Hypromellose E15, Polyethylene glycol 6000, Talc, Titanium dioxide, Purified water, Alcohol 95%, Isopropyl alcohol.

Pharmacology: Pharmacodynamics: Etoricoxib decreases synthesis of prostaglandins due to selective inhibition of cyclooxygenase-2 (COX-2) enzyme; 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 the gastrointestinal tract after oral dose. Peak plasma concentrations occur in about 1 hour in fasted adults; food delays absorption by about 2 hours, it has no affect on the extent of absorption.
Bioavailability is about 100%.
Distribution: Volume of distribution is about 120 L. Plasma protein binding is about 92%.
Metabolism: Etoricoxib is extensively metabolized via hepatic. 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 derivative, the major metabolite. Both are inactive or only weak cyclooxygenase-2 (COX-2) inhibitors and no inhibition of cyclooxygenase-1 (COX-1).
Excretion: Excretion is mainly via the urine 70% with the only 20% of a dose appearing in the faeces. The half-life of etoricoxib is about 22 hours.

HOFXIB 90 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.
The decision to prescribe a selective COX-2 inhibitor should be based on an assessment of the individual patient's overall risks (see Precautions).

HOFXIB 90 is administered orally. HOFXIB 90 may be taken with or without food. HOFXIB 90 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 90 mg once daily.
Ankylosing spondylitis: The recommended dose is 90 mg once daily.
Chronic musculo-skeletal pain, including low back pain: The recommended dose is 60 mg once daily.
Acute pain: For acute pain conditions, HOFXIB 90 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 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 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 (see Precautions).
Elderly, Gender, Race: No dosage adjustment in HOFXIB 90 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 arc 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 clearence <30 mL), treatment with HOFXIB 90 is not recommended. No dosage adjustment is necessary for patients with lesser degrees of renal insufficiency (creatinine clearence ≥30 mL/min). (See Precautions.)

Overdose and Treatment: In clinical studies, administration of HOFXIB 90 at a single doses up to 500 mg and multiple doses up to 150 mg/day for 21 days did not result in significant toxicity. There have been reports of acute overdosage with etoricoxib, although adverse experiences were not reported in the majority 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.

HOFXIB 90 is contraindicated in patient with known hypersensitivity to any component of this product; patients with congestive heart failure (NYHA class II-IV); patient with active peptic ulceration or gastro-intestinal (GI) bleeding; patient with severe hepatic dysfunction (Child-Pugh score >9); patient with severe renal impairment (CrCl <30 mL/minute); patient who have history of allergy-type reaction; asthma, acute rhinitis, nasal polyps, angioedema, urticaria following the administration of aspirin or other NSAIDs (Non-steroidal anti-inflammatory drugs); pregnancy and breastfeeding; children <16 years; patient with inflammatory bowel disease; patient with uncontrolled hypertension (persistently above 140/90 mmHg); patient with ischemic heart disease, peripheral artery disease and/or cerebrovascular disease (including patient who have recently undergone coronary artery bypass graft (CABG) surgery or angioplasty.

Etoricoxib increases risk of serious adverse cardiovascular thrombotic events, including MI and stroke. Risk may be increased with long term use or pre-existing cardiac risk factors (eg. hypertension, hyperlipidemia, diabetes, smoking). Carefully evaluate individual cardiovascular profiles prior to prescribing and periodically reevaluate the need for symptomatic relief and response to therapy.
Discontinue use of etoricoxib if worsening heart failure, edema or uncontrolled/severe hypertension occur. Use the lowest effective dose for shortest duration of time, consistent with individual patient goals, to reduce risk of cardiovascular events; consider alternative therapies for high-risk patients.
Should be aware to use etoricoxib in patients who may develop serious upper GI complications including perforations, ulcers and bleeding have occurred, concurrent therapy with aspirin or other NSAIDs, anticoagulants, and/or corticosteroids, smoking, alcohol, elderly and debilitated patients.
Gastroprotective therapy (eg. proton pump inhibitors, misoprostol) is recommended when etoricoxib is used concomitantly with aspirin (even at low dose).
Etoricoxib does not usually affect Prothrombin time (PTT) or platelet counts; does not inhibit aggregation at approved dose.
Elevations in transaminases (>3 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 function.
Etoricoxib may increase the risk of hyperkalemia, particularly in diabetics and with concomitant use of other agents capable of inducing hyperkalemia. Monitor potassium closely.
Discontinue use of etoricoxib at first appearance of skin rash, mucosal lesions or any other sign of hypersensitivity.
Do not administer etoricoxib to patients with aspirin-sensitive asthma, severe bronchospasm. Use with caution in patients with other forms of asthma.
Risk of MI and stroke may be increased with the use of etoricoxib following coronary artery bypass graft (CABG) surgery. Etoricoxib is not recommended for treatment of perioperative pain in the setting of CABG.
Use etoricoxib with caution in mild to moderate renal impairment. Monitor renal function closely, discontinue use with persistent or worsening renal dysfunction.

Pregnancy: Etoricoxib is contraindicated in women who are pregnant or who may become pregnant. Etoricoxib 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.
Lactation: Contraindicated in breastfeeding. Etoricoxib present in milk in animal studies.

Blood and lymphatic system: Thrombocytopenia.
Infections and infestation: Gastroenteritis, upper respiratory infection, urinary tract infection.
Immune system: Hypersensitivity reactions, angioedema, anaphylactic/anaphylactoid reactions.
Metabolism and nutrition system: Appetite change, weight gain, hyperkalemia.
Psychiatric system: Anxiety, depression, confusion, hallucination.
Nervous system: Insomnia, paresthesia, somnolence.
Eye system: Blurred vision.
Ear and labyrinth system: Tinnitus.
Cardiac system: Congestive heart failure, ECG change, myocardial infarction, angina, arrhythmia.
Vascular system: Flushing, cerebrovascular accident, hypertensive crisis.
Respiratory, thoracic and mediastinal system: Cough, dyspnoea, epistaxis, bronchospasm.
Gastrointestinal system: Abdominal pain, constipation, gastroduodenal ulcer, vomiting, gastritis, peptic ulcer.
Hepatobiliary system: 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 disorder: Muscular cramp/spasm, musculoskeletal pain/stiffness.
Renal and urinary disorders: Proteinuria, renal insufficiency, including renal failure (see Precautions).
General disorders and administration site conditions: Chest pain.

Anticoagulant (Warfarin): Co-administration with etoricoxib may increase the risk of anticoagulant-induced bleeding (eg, GI bleeding). Monitor Prothrombin Time (PTT) and International Normalized Ratio (INR) and patients closely, especially the first few days and instruct patients to watch for signs and symptoms of bleeding.
Rifampin: Rifampin is a potent inducer of CYP isoenzymes. Co-administration with etoricoxib has produced decreased plasma concentration of etoricoxib.
Methotrexate: Concomitant administration with etoricoxib may increase risk of methotrexate toxicity (eg, stomatitis, bone marrow suppression, nephrotoxicity).
Angiotensin Converting Enzyme (ACE) Inhibitors and Angiotensin II Antagonists (AIIAs): Nonsteroidal anti-inflammatory drugs (NSAIDS) may decrease the antihypertensive effects of ACEI and/or AIIAs.
Co-administration may increase the risk of nephrotoxicity. Consider discontinuation of etoricoxib if blood pressure is uncontrolled. Periodically measure renal function during concomitant use.
Diuretics (Thiazides, Potassium-sparing diuretics, Loop diuretics): Co-administration may decrease effects of diuretic and increase the risk of acute renal failure. Closely monitor renal function. If renal function decreases, consider stopping one or both drugs.
Lithium: Concomitant use with etoricoxib may increase serum lithium levels. Monitor for signs of lithium toxicity in patient closely.
Aspirin: The potential for GI side effects, including bleeding may be increased with regular use of full-dose. Etoricoxib can be used concomitantly with low-dose aspirin at doses of cardiovascular prophylaxis.
Cyclosporin and Tacrolimus: Co-administration with etoricoxib may increase nephrotoxicity. Renal function should be monitored when etoricoxib and either of these drugs are used in combination.
Oral contraceptive: Etoricoxib is an inhibitor of human sulfotransferase activity and has been shown to increase the plasma concentration of ethinylestradiol and exposure increase incidence of adverse events associated with oral contraceptive.
Prednisone: The risk of GI bleeding may be increased. Use with caution when concomitantly used.
Azole antifungal (Fluconazole, ketoconazole): Increase etoricoxib plasma concentration may occur, increasing the pharmacologic effects and adverse reaction.
Beta-blocker: The antihypertensive effect of beta-blocker with etoricoxib may be impaired, possibly because of etoricoxib as the NSAIDs inhibition of renal prostaglandin synthesis, thereby allowing unopposed pressure system. Monitor blood pressure and adjust beta-blocker dose as needed to treat.
Effect of etoricoxib on drugs metabolised by sulfotransferases: Etoricoxib is an inhibitor of human sulfotransferase activity, particularly SULT1E1 and has been shown to increase the serum concentration of ethinylestradiol. While knowledge about effects of multiple sulfotransferases in presently limited and the clinical consequences for many drugs are still being examined, it may be prudent to exercise care when administering etoricoxib concurrently with other drugs primarily metabolised by human sulfotransferases (e.g. oral salbutamol and minoxidil).

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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