Ecoxib

Etoricoxib.

ECOXIB (120 mg): Pale-green, asymmetric hexagonal with rounded corners, biconvex film-coated tablet debossed with "ATC" in triangle on one side and "ECOXIB 120" on the other side.
Each film-coated tablet contains Etoricoxib 120 mg.
ECOXIB (90 mg): White, asymmetric hexagonal with rounded corners, biconvex film-coated tablet debossed with "ATC" in triangle on one side and "ECOXIB 90" on the other side.
Each film-coated tablet contains Etoricoxib 90 mg.
ECOXIB (60 mg): Dark green, asymmetric hexagonal with rounded corners, biconvex film-coated tablet debossed with "ATC" in triangle on one side and "ECOXIB 60" on the other side.
Each film-coated tablet contains Etoricoxib 60 mg.

Pharmacology: Pharmacodynamics: 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: Etoricoxib is well absorbed from the gastrointestinal tract after oral doses. 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. Plasma protein binding is about 92%. At steady state the half-life of etoricoxib is about 22 hours. Etoricoxib is extensively metabolised 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 oxidised to the 6'-carboxylic acid derivative, the major metabolite. Both are inactive or only weak cyclo-oxygenase-2 (COX-2) inhibitors. Excretion is mainly via the urine (70%) with only 20% of a dose appearing in the faeces. Studies in animals suggest that etoricoxib may cross the placenta and that some is distributed into breast milk.

ECOXIB 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.

Recommended Dose: ECOXIB is administered orally. ECOXIB may be taken with or without food. ECOXIB 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.
Acute Gouty Arthritis: The recommended dose is 120 mg once daily.
Chronic musculo-skeletal pain, including chronic low back pain: The recommended dose is 60 mg once daily.
Acute Pain: For acute pain conditions, ECOXIB 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.
Primary Dysmenorrhea: The recommended dose is 120 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 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.
Pediatric adolescents ≥16 years: Refer to adult dosing.
Note: Consider dosage reduction in adolescents <60 kg; similar pharmacokinetics have been observed between this population and adults; administered a 33% higher dose.
Renal Impairment: CrCl ≥30 mL/minute: No dosage adjustment necessary.
CrCl <30 mL/minute: Use is contraindicated.
Hepatic Impairment: Etoricoxib 120 mg tablet is not for use in mild and moderate hepatic impairment.
Mild hepatic impairment (Child-Pugh class A): Do not exceed 60 mg once daily.
Moderate hepatic impairment (Child-Pugh class B): Do not exceed 30 mg once daily or 60 mg every other day; use with caution.
Severe hepatic impairment (Child-Pugh class C): Use is contraindicated.
Mode of Administration: Oral: May be administered without regard to meals.

Overdose and treatment: In general, symptoms of NSAID poisoning are mild, and usually include nausea and vomiting, epigastric, pain, tinnitus, headache, drowsiness, blurred vision, and dizziness. Gastrointestinal bleeding may also occur. There have been isolated case reports of more serious toxicity, including seizures, hypotension, apnoea, coma, and renal failure, although usually after ingestion of substantial quantities. Exacerbation of asthma may occur in asthmatics.
Treatment of NSAID overdosage is entirely supportive. The benefit of gastric decontamination is uncertain although activated charcoal may be of benefit within 1 hour of ingestion of a potentially toxic amount. Forced diuresis, haemodialysis, or haemoperfusion are unlikely to be of benefit for NSAID overdosage, although haemodialysis may be required if oliguric renal failure develops.

ECOXIB is contraindicated in: patients with known hypersensitivity to 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 signs 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 disease and/or cerebrovascular disease (including patients who have recently undergone coronary artery bypass graft surgery or angioplasty).

Announcement of the Ministry of Public Health: 1. Do not use ECOXIB (120 mg) if you are allergic to Etoricoxib, in pregnancy and lactation.
2. Do not use in patients who have recently undergone coronary artery bypass grass graft surgery.
3. Do not use in patients with cardiovascular disease or stroke.
4. Do not use in patients with uncontrolled hypertension.
5. Do not use in patients with myocardial infarction or congestive heart failure NYHA II-IV.
6. Do not use in patients with history of ischemic heart disease or paralysis caused by stroke.
7. Use with caution in patients with risk factors for cardiovascular disease such as hypertension, hypercholesterolemia, diabetes, smoking and elderly.
8. Use with caution in patients with liver or kidney impairment.

ECOXIB should be administered for the shortest duration possible and the lowest effective daily dose should be used, to reduce risk of serious gastrointestinal (GI) and cardiovascular adverse events.
Serious (some fatal) upper GI complications including perforations, ulcers, and bleeding have occurred. Use caution with a history of GI disease (bleeding or ulcers), concurrent therapy with aspirin or other NSAIDs, anticoagulants and/or corticosteroids, smoking, alcohol, and the elderly or debilitated patients. When used concomitantly with aspirin (even at low doses), gastroprotective therapy (eg, proton pump inhibitors, misoprostol) is recommended.
NSAIDs are associated with an increased risk of serious (and potentially fatal) adverse cardiovascular thrombotic events, including MI and stroke. Risk may be increased with long-term use or preexisting cardiac risk factors (eg, hypertension, hyperlipidemia, diabetes, smoking). Carefully evaluate individual cardiovascular profiles prior to prescribing and periodically re-evaluate the need for symptomatic relief and response to therapy.
Risk of MI and stroke may be increased with use following coronary artery bypass graft (CABG) surgery; NSAIDs, including COX-2 selective inhibitors, are not recommended for treatment of perioperative pain in the setting of CABG.
New-onset or worsening hypertension may occur; maintain blood pressure <140/90 mm Hg prior to initiation and monitor carefully throughout therapy. New-onset or worsening edema and heart failure may occur; use caution with preexisting edema (any cause), left ventricular dysfunction, or NYHA class I heart failure; use is contraindicated with NYHA class II-IV heart failure. Discontinue use if worsening heart failure, edema, or uncontrolled/severe hypertension occurs; consider alternate therapies for high-risk patients.
Serious hypersensitivity reactions, including anaphylaxis, angioedema, Stevens-Johnson syndrome (SJS), and toxic epidermal necrolysis (TEN) have been (rarely) reported with etoricoxib; discontinue use at first appearance of skin rash, mucosal lesions, or any other sign of hypersensitivity. Do not use in patients who experience bronchospasm, asthma, rhinitis, or urticaria with NSAID or aspirin therapy.
Use with caution in mild-to-moderate hepatic impairment, dosage adjustment recommended. Use is contraindicated in severe hepatic impairment. 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 signs/symptoms of hepatic dysfunction. Severe hepatic reactions (eg, hepatitis, jaundice, liver failure) have (rarely) occurred with use; discontinue if signs or symptoms of hepatic disease develop, if systemic manifestations occur, or with persistent or worsening abnormal hepatic function tests.
NSAID use may compromise existing renal function through a dose-dependent decrease in prostaglandin synthesis, resulting in a reduction in renal blood flow which may cause renal decompensation (usually reversible). Patients with impaired renal function, dehydration, heart failure, liver dysfunction, those taking diuretics, ACE inhibitors, angiotensin II receptor blockers, and the elderly are at greater risk for renal toxicity. Patients should be adequately hydrated prior to initiation of therapy. Monitor renal function closely; discontinue use with persistent or worsening abnormal renal function tests. Use is contraindicated with severe renal impairment (CrCl <30 mL/minute). Long-term NSAID use may result in renal papillary necrosis.

Pregnancy Considerations: Adverse events have been observed in animal reproduction studies.
Etoricoxib is an NSAID that selectively inhibits COX-2 whereas other NSAIDs are nonselective for COX-1 and COX-2. The effects of selective inhibition to the fetus have not been well studied and no specific data for etoricoxib is available. Like other agents in this class that inhibit prostaglandin synthesis, etoricoxib may cause uterine inertia, premature closure of the ductus arteriosus, and adverse fetal events, and may affect fertility. Use during pregnancy is contraindicated; use in women who wish to become pregnant is not recommended.
Breast-Feeding Considerations: It is not known whether etoricoxib is excreted in human milk. Breastfeeding is contraindicated.

1% to 10%: Cardiovascular: Edema, hypertension, palpitations.
Central nervous system: Dizziness, fatigue, headache.
Dermatologic: Bruising.
Gastrointestinal: Abdominal pain, diarrhea, dyspepsia, flatulence, heartburn, nausea.
Hepatic: ALT increased, AST increased.
Neuromuscular & skeletal: Weakness.
Miscellaneous: Alveolar osteitis, flu-like syndrome.
<1%, postmarketing and/or case reports: Abnormal taste, anaphylactic/anaphylactoid reactions, anemia, angina pectoris, angioedema, anxiety, appetite increase/decrease, arrhythmia, atrial fibrillation, blurred vision, bronchospasm, BUN increased, cerebrovascular accident, chest pain, confusion, congestive heart failure, conjunctivitis, constipation, cough, CPK increased, depression, dyspnea, ECG changes, epistaxis, esophagitis, erythema, facial edema, fixed drug eruption, flushing, gastritis, gastroduodenal ulcer, gastroenteritis, gastroesophageal reflux, gastrointestinal bleeding, gastrointestinal perforation, hallucinations, hepatic failure, hepatitis, hyperkalemia, hypersensitivity reactions, hypertensive crisis, hypoesthesia, hyponatremia, insomnia, interstitial nephritis, jaundice, leukopenia, MI, muscle pain, muscle spasm, nephrotic syndrome, oral ulceration, pancreatitis, paresthesia, peptic ulcers, proteinuria, pruritus, rash, renal insufficiency (including renal failure), serum creatinine increased, shock, somnolence, Stevens-Johnson syndrome (SJS), tachycardia, taste abnormal, thrombocytopenia, tinnitus, toxic epidermal necrolysis (TEN), transient ischemic attack, upper respiratory infection, uric acid levels increased, urinary tract infection, urticaria, vasculitis, vertigo, vomiting, weight gain, xerostomia.

Metabolism/Transport Effects: Substrate of CYP3A4 (major); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential.
Avoid Concomitant Use: Avoid concomitant use of Etoricoxib with any of the following: Dexketoprofen; Floctafenine; Ketorolac (Nasal); Ketorolac (Systemic); Morniflumate; Nonsteroidal Anti-Inflammatory Agents; NSAID (COX-2 Inhibitor); Omacetaxine; Pelubiprofen; Phenylbutazone; Talniflumate; Tenoxicam; Zaltoprofen.
Increased Effect/Toxicity: Etoricoxib may increase the levels/effects of: 5-ASA Derivatives; Aliskiren; Aminoglycosides; Aminolevulinic Acid; Anticoagulants; Bisphosphonate Derivatives; Cyclosporine (Systemic); Deferasirox; Desmopressin; Digoxin; Drospirenone; Eplerenone: Estrogen Derivatives; Haloperidol; Lithium; Methotrexate; NSAID (COX-2 Inhibitor); Omacetaxine; Porfimer: Potassium-Sparing Diuretics; Pralatrexate; Quinolone Antibiotics; Tacrolimus (Systemic); Tenofovir Products; Tolperisone; Triflusal; Vancomycin; Verteportin; Vitamin K Antagonists.
The levels/effects of Etoricoxib may be increased by: ACE Inhibitors; Alcohol (Ethyl); Angiotensin II Receptor Blockers; Antidepressants (Tricyclic, Tertiary Amine); Aspirin; Corticosteroids (Systemic); Cyclosporine (Systemic); Dexketoprofen; Felbinac; Floctafenine; Herbs (Anticoagulant/Antiplatelet Properties); Ketorolac (Nasal); Ketorolac (Systemic); Loop Diuretics; Morniflumate; Naftazone; Nonsteroidal Anti-Inflammatory Agents; Pelubiprofen; Phenylbutazone; Probenecid; Selective Serotonin Reuptake Inhibitors; Sodium Phosphates; Talniflumate; Tenoxicam; Thiazide and Thiazide-like Diuretics; Tolperisone; Triflusal; Zaltoprofen.
Decreased Effect: Etoricoxib may decrease the levels/effects of: ACE Inhibitors, Aliskiren; Angiotensin II Receptor Blockers; Beta Blockers; Eplerenone; Hydralazine; Loop Diuretics; Potassium-Sparing Diuretics; Prostaglandins (Ophthalmic); Selective Serotonin Reuptake Inhibitors; Thiazide and Thiazide-like Diuretics.
The levels/effects of Etoricoxib may be decreased by: Bile Acid Sequestrants; Bosentan; CYP3A4 Inducers (Moderate); CYP3A4 Inducers (Strong); Dabrafenib; Deferasirox; Enzalutamide; Mitotane; Siltuximab, St John's Wort; Tocilizumab.

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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