Etoricoxib

BRANDS / TRADE NAMES OF ETORICOXIB IN KENYA

Arcoxia, MSD (Pty) Ltd

Cox E, Zest Pharma

Coxirav,Ravian Life Sciences Pvt Ltd

Ecofree ,Medisel Kenya Ltd

Etcox, Laso Healthcare Pvt. Ltd

Etocox , Krishna Chemists Ltd

Etorix , Eskayef Bangladesh Ltd.

ETR, Zawadi Healthcare Ltd

Etrib ,NIPRO JMI Pharma Ltd

Oricox, Nextgen Pharmaceuticals (K) Ltd.

Tory , Square Pharmaceuticals Ltd.

Veroxib, Unosource Pharma Limited


Etoricoxib Chemical Structure: Etoricoxib in Kenya, Where to buy,prices
Etoricoxib Chemical Structure

MODE OF ACTION:

Etoricoxib selectively inhibits isoform 2 of the enzyme cyclooxygenase (COX-2). It has approximately 106-fold selectivity for COX-2 inhibition over COX-1. This reduces the generation of prostaglandins (PGs) from arachidonic acid.

INDICATIONS

Etoricoxib is indicated in adults and adolescents 16 years of age and older for the symptomatic relief of osteoarthritis (OA), rheumatoid arthritis (RA), ankylosing spondylitis, and the pain and signs of inflammation associated with acute gouty arthritis.

Etoricoxib is indicated in adults and adolescents 16 years of age and older for the short-term treatment of moderate pain associated with dental surgery.

The decision to prescribe a selective COX-2 inhibitor should be based on an assessment of the individual patient’s overall risks

DOSAGE AND ADMINISTRATION

As the cardiovascular risks of etoricoxib 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, especially in patients with osteoarthritis.

Osteoarthritis

The recommended dose is 30 mg once daily. In some patients with insufficient relief from symptoms, an increased dose of 60 mg once daily may increase efficacy. In the absence of an increase in therapeutic benefit, other therapeutic options should be considered.

Rheumatoid arthritis

The recommended dose is 60 mg once daily. In some patients with insufficient relief from symptoms, an increased dose of 90 mg once daily may increase efficacy. Once the patient is clinically stabilised, down-titration to a 60 mg once daily dose may be appropriate. In the absence of an increase in therapeutic benefit, other therapeutic options should be considered.

Ankylosing spondylitis

The recommended dose is 60 mg once daily. In some patients with insufficient relief from symptoms, an increased dose of 90 mg once daily may increase efficacy. Once the patient is clinically stabilised, down-titration to a 60 mg once daily dose may be appropriate. In the absence of an increase in therapeutic benefit, other therapeutic options should be considered.

Acute pain conditions

For acute pain conditions, Etoricoxib  should be used only for the acute symptomatic period.

Acute gouty arthritis

The recommended dose is 120 mg once daily.

Postoperative dental surgery pain

The recommended dose is 90 mg once daily, limited to a maximum of 3 days. Some patients may require other postoperative analgesia in addition to Etoricoxib  during the three day treatment period.

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 and ankylosing spondylitis should not exceed 90 mg daily.

The dose for acute gout should not exceed 120 mg daily, limited to a maximum of 8 days treatment.

The dose for postoperative acute dental surgery pain should not exceed 90 mg daily, limited to a maximum of 3 days.

Special populations

 

Elderly patients

No dosage adjustment is necessary for elderly patients. As with other drugs, caution should be exercised in elderly patients .

Patients with hepatic impairment

Regardless of indication, in patients with mild hepatic dysfunction (Child-Pugh score 5-6) a dose of 60 mg once daily should not be exceeded. In patients with moderate hepatic dysfunction (Child-Pugh score 7-9), regardless of indication, the dose of 30 mg once daily should not be exceeded.

Clinical experience is limited particularly in patients with moderate hepatic dysfunction and caution is advised. There is no clinical experience in patients with severe hepatic dysfunction (Child-Pugh score ≥10); therefore, its use is contraindicated in these patients .

Patients with renal impairment

No dosage adjustment is necessary for patients with creatinine clearance ≥30 ml/min . The use of Etoricoxib  in patients with creatinine clearance <30 ml/min is contra-indicated .

Paediatric population

Etoricoxib is contra-indicated in children and adolescents under 16 years of age .

Method of administration

Etoricoxib  is administered orally and may be taken with or without food. The onset of the effect of the medicinal product may be faster when Etoricoxib is administered without food. This should be considered when rapid symptomatic relief is needed.

CONTRAINDICATIONS

  • 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.

DRUG INTERACTIONS

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 or the dose of Etoricoxib  is changed .

Diuretics, ACE inhibitors and Angiotensin II Antagonists:

NSAIDs may reduce the effect of diuretics and other antihypertensive drugs. In some patients with compromised renal function (e.g. dehydrated patients or elderly patients with compromised renal function) the co-administration of an ACE inhibitor or Angiotensin II antagonist and agents that inhibit cyclo-oxygenase may result in further deterioration of renal function, including possible acute renal failure, which is 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.

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:

Although this interaction has not been studied with Etoricoxib, 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

The effect of etoricoxib on the pharmacokinetics of other drugs

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 and when the NSAID is withdrawn.

Methotrexate:

Adequate monitoring for methotrexate-related toxicity is recommended when Etoricoxib Tablets and methotrexate are administered concomitantly.

Oral contraceptives:

Etoricoxib 60 mg given concomitantly with an oral contraceptive containing 35 micrograms ethinyl estradiol (EE) and 0.5 to 1 mg norethindrone for 21 days increased the steady state AUC0-24hr of EE by 37%. Etoricoxib 120 mg given with the same oral contraceptive concomitantly or separated by 12 hours, increased the steady state AUC0-24hr of EE by 50 to 60%. This increase in EE concentration should be considered when selecting an oral contraceptive for use with etoricoxib. 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):

Administration of Etoricoxib 120 mg with hormone replacement therapy consisting of conjugated estrogens for 28 days, increased the mean steady state AUC0-24hr of unconjugated estrone (41%), equilin (76%), and 17-β-estradiol (22%).These increases in estrogenic concentration should be taken into consideration when selecting post-menopausal hormone therapy for use with Etoricoxib because the increase in oestrogen exposure might increase the risk of adverse events associated with HRT.

Prednisone/prednisolone:

In drug-interaction studies, Etoricoxib did not have clinically important effects on the pharmacokinetics of prednisone/prednisolone.

Digoxin:

Patients at high risk of digoxin toxicity should be monitored for this when Etoricoxib and digoxin are administered concomitantly.

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 concentrations of ethinyl estradiol. While knowledge about effects of multiple sulfotransferases is 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).

Effect of Etoricoxib on drugs metabolised by CYP isoenzymes

Based on in vitro studies, Etoricoxib is not expected to inhibit cytochromes P450 (CYP) 1A2, 2C9, 2C19, 2D6, 2E1 or 3A4. In a study in healthy subjects, daily administration of Etoricoxib 120 mg did not alter hepatic CYP3A4 activity as assessed by the erythromycin breath test.

Effects of other drugs on the pharmacokinetics of Etoricoxib

The main pathway of Etoricoxib metabolism is dependent on CYP enzymes. CYP3A4 appears to contribute to the metabolism of etoricoxib in vivo. In vitro studies indicate that CYP2D6, CYP2C9, CYP1A2 and CYP2C19 also can catalyse the main metabolic pathway, but their quantitative roles have not been studied in vivo.

Ketoconazole:

Ketoconazole, a potent inhibitor of CYP3A4, dosed at 400 mg once a day for 11 days to healthy volunteers, did not have any clinically important effect on the single-dose pharmacokinetics of 60 mg Etoricoxib (43% increase in AUC).

Voriconazole and Miconazole:

Co-administration of either oral voriconazole or topical miconazole oral gel, strong CYP3A4 inhibitors, with Etoricoxib caused a slight increase in exposure to etoricoxib, but is not considered to be clinically meaningful based on published data.

Rifampicin:

Co-administration of Etoricoxib with rifampicin, a potent inducer of CYP enzymes, produced a 65% decrease in Etoricoxib plasma concentrations. This interaction may result in recurrence of symptoms when Etoricoxib is co-administered with rifampicin. While this information may suggest an increase in dose, doses of etoricoxib greater than those listed for each indication have not been studied in combination with rifampicin and are therefore not recommended.

Antacids:

Antacids do not affect the pharmacokinetics of Etoricoxib to a clinically relevant extent.

ADVERSE EFFECTS:

Infections and infestations

alveolar osteitis , gastroenteritis, upper respiratory infection, urinary tract infection

Blood and lymphatic system disorders

anaemia (primarily associated with gastrointestinal bleeding), leukopenia, thrombocytopenia

Immune system disorders

hypersensitivity, angioedema/anaphylactic /anaphylactoid reactions including shock

Metabolism and nutrition disorders

oedema/fluid retention, appetite increase or decrease, weight gain

Psychiatric disorders

anxiety, depression, mental acuity decreased, hallucinations, confusion, restlessness

Nervous system disorders

dizziness, headache, dysgeusia, insomnia, paresthaesia/hypaesthesia, somnolence

Eye disorders

blurred vision, conjunctivitis

Ear and labyrinth disorders

tinnitus, vertigo

Cardiac disorders

palpitations, arrhythmia

Reporting of suspected adverse reactions

The PPB Department of Pharmacovigilance was set up with a vision to develop, implement and continuously upgrade an appropriate system for detecting, reporting and monitoring adverse drug reactions (ADRs) and other relevant problems with medicines in Kenya. The department strives to ensure the safety and efficacy of pharmaceutical products in Kenya.
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals/ Patients are encouraged to report any suspected adverse reactions via Pharmacovigilance Yellow Form, pv@pharmacyboardkenya.org or clicking below button:

Clinical | Pharmacokinetic data


Pregnancy Category: Not Recommended
Routes of Administration: Oral
Bioavailability: 100%
Protein Binding: 92%
Metabolosim: Hepatic, CYP extensively involved (mainly CYP3A4)
Onset of Action: Not Available
Elimination Half life: 22 hours
Excretion: Renal (70%) and fecal (20%)

Legal Status | Dosage forms & Strengths


Prescription Category:
POM (Prescription only)
Narcotic Drugs and Psychotropic Substances (Control ) Act Schedule:
This drug is not a controlled substance under Narcotic Drugs and Psychotropic Substances (Control ) Act
Dosage Forms | Strengths:
Tablets

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References/ Citation:




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