Exib

EXIB TABLETS 90 MG: White, round, biconvex film coated tablet, plain on both sides.
EXIB TABLETS 120 MG: Pale green, round, biconvex film coated tablets, plain on one side and score on the other.
Each film coated tablet contains: See Table 1.

Click on icon to see table/diagram/image

Excipients/Inactive Ingredients: Core tablet: Lactose Monohydrate, Anhydrous Dibasic Calcium Phosphate, Microcrystalline Cellulose PH301, Croscarmellose Sodium, Magnesium Stearate.
Tablet coating: Hypromellose C15, Hypromellose C5, Polyethylene Glycol 6000, Titanium Dioxide (C.I. 77891), Talc, Indigo Carmine Lake (C.I. 73015)**, Yellow Iron Oxide (C.I. 77492)**.
**These two excipients contain in EXIB TABLETS 120 mg only.

Pharmacology: Pharmacodynamics: Etoricoxib is a non-steroidal anti-inflammatory drug (NSAID), selective cyclooxygenase-2 (COX-2) inhibitor, COX-2 is the isoform of cyclooxygenase that has been shown to be induced by pro-inflammatory stimuli and has been postulated to be primarily responsible for the synthesis of prostanoid mediators of pain, inflammation, and fever. Etoricoxib did not inhibit gastric prostaglandin synthesis and had no effect on platelet function.
Pharmacokinetics: Absorption: Orally administered etoricoxib is well absorbed. The absolute bioavailability is approximately 100%. The peak plasma concentration was observed at approximately 1 hour (T_max) after administration to fasted adults. Dosing with food (a high-fat meal) had no effect on the extent of absorption. The rate of absorption was affected, resulting in a 36% decrease in C_max and an increase in T_max by 2 hours.
Distribution: Etoricoxib is approximately 92% bound to human plasma protein. The volume of distribution at steady state was approximately 120 L.
Biotransformation: Etoricoxib is extensively metabolized with less than 1% of a dose recovered in urine as the parent drug. The major route of metabolism to form the 6'-hydroxymethyl derivative is catalyzed by CYP enzymes. CYP3A4 appears to contribute to the metabolism of etoricoxib.
Elimination: It occurs almost exclusively through metabolism followed by renal excretion, 70% in urine and 20% in faeces. Less than 2% was recovered as unchanged drug. The half-life of etoricoxib is approximately 22 hours.

Etoricoxib is indicated in adults and adolescents 16 years of age and older for the symptomatic relief of osteoarthritis, rheumatoid arthritis, ankylosing spondylitis, the pain and signs of inflammation associated with acute gouty arthritis, and the short-term treatment for moderate pain associated with dental surgery.

Recommended dose: Osteoarthritis: 30 mg or 60 mg once daily (maximum 60 mg once daily).
Rheumatoid arthritis: 60 mg or 90 mg once daily (maximum 90 mg once daily).
Ankylosing spondylitis: 60 mg or 90 mg once daily (maximum 90 mg once daily).
Acute gouty arthritis: 120 mg once daily (limited to a maximum of 8 days treatment).
Postoperative dental surgery pain: 90 mg once daily (limited to a maximum of 3 days treatment).
Acute pain conditions: Etoricoxib should be used only for acute symptomatic period.
Elderly patients: No dosage adjustment is necessary.
Pediatric patients: Etoricoxib is contraindicated in children and adolescent under 16 years of age.
Patients with hepatic impairment: Mild hepatic dysfunction (Child-Pugh score 5-6): the maximum oral dose of etoricoxib, regardless of indications is 60 mg once daily.
Moderate hepatic dysfunction (Child-Pugh score 7-9): the maximum oral dose of etoricoxib, regardless of indications is 30 mg once daily.
There is no data in patients with severe hepatic dysfunction (Child-Pugh score >10), etoricoxib should not be given to patients with severe hepatic dysfunction.
Patients with renal impairment: Creatinine clearance ≥30 mL/min: no dosage adjustment is necessary.
Creatinine clearance <30 mL/min: treatment with etoricoxib is contraindicated.
Remarks: For dose 30 mg and 60 mg, use the other preparation.
*Etoricoxib should be used at the lowest effective dose for shortest possible time.
Mode of Administration: Etoricoxib is administered orally. It may be taken with or without food.

In the event of overdose, it is reasonable to employ the usual supportive measures, e.g., remove unabsorbed material from the GI tract, employ clinical monitoring, and institute supportive therapy, if required.

Etoricoxib is contraindicated in patients with severe heart failure and for the treatment of peri-operative pain in the setting of coronary artery bypass graft surgery.
Hypersensitivity to the active substance or to any of the excipients.
Active peptic ulceration or active gastro-intestinal (GI) bleeding.
Patients who, after taking acetylsalicylic acid or NSAIDs including COX-2 (cyclooxygenase-2) inhibitors, experience bronchospasm, acute rhinitis, nasal polyps, angioneurotic oedema, urticaria, or allergic-type reactions.
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 is persistently elevated above 140/90 mmHg and has not been adequately controlled.
Established ischaemic heart disease, peripheral arterial disease, and/or cerebrovascular disease.
The third trimester of pregnancy, because of risks of premature closure of the ductus arteriosus, and prolonged parturition.

In rare cases, etoricoxib has been associated with serious liver injury.

Cardiovascular Risk: NSAIDs may cause an increased risk of serious cardiovascular thrombotic events, myocardial infarction, and stroke, which can be fatal. This risk may increase with duration of use. Patients with cardiovascular disease or risk factors for cardiovascular disease may be at greater risk.
Gastrointestinal Risk: NSAIDs cause an increased risk of serious gastrointestinal adverse events including bleeding, ulceration, and perforation of the stomach or intestines, which can be fatal. These events can occur at any time during use and without warning symptoms. Elderly patients are at greater risk for serious gastrointestinal events.
Renal Effects: Long-term administration of NSAIDs has resulted in renal papillary necrosis and other renal injury. Renal toxicity has also been seen in patients in whom renal prostaglandins have a compensatory role in the maintenance of renal perfusion. In these patients, administration of a NSAID may cause a dose-dependent reduction in prostaglandin formation and, secondarily, in renal blood flow, which may precipitate overt renal decompensation. Patients at greatest risk of this reaction are those with impaired renal function, heart failure, liver dysfunction, those taking diuretics and ACE inhibitors, and the elderly. Discontinuation of NSAID therapy is usually followed by recovery to the pretreatment state.
Advanced Renal Disease: No information is available from controlled clinical studies regarding the use of etoricoxib in patients with advanced renal disease. Therefore, treatment with etoricoxib is not recommended in these patients with advanced renal disease. If therapy must be initiated, close monitoring of the patient's renal function is advisable.
Use in Pregnancy: Etoricoxib are contraindicated for use during the third trimester of pregnancy because of risks of premature closure of the ductus arteriosus and the potential to prolong parturition. Caution is recommended in prescribing Etoricoxib during the first and second trimesters of pregnancy, particularly from the middle to end of the second trimester of pregnancy (onset at approximately 20 weeks) due to possible fetal renal dysfunction leading to oligohydramnios and, in some cases, neonatal renal impairment or failure.
Etoricoxib should not be used during the first two trimesters of pregnancy unless the expected benefits to the mother outweigh the risks to the fetus.
Published studies and postmarketing reports describe maternal Non-Steroidal Anti-Inflammatory Drug (NSAID) use at approximately 20 weeks gestation or later in pregnancy associated with fetal renal dysfunction leading to oligohydramnios, and in some cases, neonatal renal impairment or failure. NSAIDs were shown to cause significant reduction in fetal urine production prior to reduction of amniotic fluid volume. There have also been a limited number of case reports of maternal NSAID use and neonatal renal dysfunction and renal impairment without oligohydramnios, some of which were irreversible, even after treatment discontinuation.
These adverse outcomes are seen, on average, after days to weeks of treatment, although oligohydramnios has been infrequently reported as soon as 48 hours after NSAID initiation.
Complications of prolonged oligohydramnios may for example, include limb contractures and delayed lung maturation. In some postmarketing cases of impaired neonatal renal function, invasive procedures such as exchange transfusion or dialysis were required.
If after careful consideration of the benefit-risk, NSAID treatment is considered necessary to be administered anywhere from the middle (onset at approximately 20 weeks) to the end of the second trimester of pregnancy, the use should be limited to the lowest effective dose and shortest duration possible. It is also recommended that ultrasound monitoring of amniotic fluid be considered if Etoricoxib treatment extends beyond 48 hours and that NSAIDs treatment be discontinued if oligohydramnios occurs, followed by appropriate medical follow up.

Pregnancy: No clinical data on exposed pregnancies are available for etoricoxib. Studies in animals have shown reproductive toxicity. The potential for human risk in pregnancy is unknown. Etoricoxib, as with other medicinal products inhibiting prostaglandin synthesis, may cause uterine inertia and premature closure of the ductus arteriosus during the last trimester. Etoricoxib is contraindicated in pregnancy. If a woman becomes pregnant during treatment, etoricoxib must be discontinued.
Breastfeeding: It is not known whether etoricoxib is excreted in human milk. Etoricoxib is excreted in the milk of lactating rats. Women who use etoricoxib must not breast feed.
Fertility: The use of etoricoxib, as with any drug substance known to inhibit COX-2, is not recommended in women attempting to conceive.

See Table 2.

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Pharmacodynamic interactions: Oral anticoagulants: 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.
Diuretics, ACE inhibitors and Angiotensin II Antagonists: NSAIDs may reduce the effect of diuretics and other antihypertensive drugs. Use with caution in patients taking etoricoxib concomitantly with ACE inhibitors or angiotensin II antagonists, 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.
Acetylsalicylic acid: Concomitant administration of etoricoxib with doses of acetylsalicylic acid 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.
Pharmacokinetic interactions: Lithium: NSAIDs decrease lithium renal excretion and therefore increase lithium plasma levels. If necessary, monitor blood lithium closely and adjust the lithium dosage while the combination is being taken.
Methotrexate: Monitoring for methotrexate-related toxicity is recommended when etoricoxib and methotrexate are administered concomitantly.
Oral contraceptives: Should be considered when selecting an oral contraceptive for use with etoricoxib due to concomitant use of etoricoxib and oral contraceptives can increase concentration of ethinyl estradiol (EE). An increase in EE 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 (HRT): Should be considered 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 hormone replacement therapy.
Digoxin: Patients at high risk of digoxin toxicity should be monitored for this when etoricoxib and digoxin are administered concomitantly.

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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