Etoricoxib

Uses and Administration

Etoricoxib is an NSAID (Refer to) reported to be a selective inhibitor of cyclo-oxygenase-2 (COX-2). It is used in the symptomatic relief of rheumatoid arthritis, osteoarthritis, ankylosing spondylitis, and acute gouty arthritis. Etoricoxib is also used for the short-term treatment of moderate postoperative dental pain.

In osteoarthritis, it is given in a usual dose of 30 mg once daily, increased to 60 mg once daily if necessary. The recommended dose in rheumatoid arthritis and in ankylosing spondylitis is 60 mg once daily, increased to 90 mg once daily if necessary. Higher doses of 120 mg once daily are used in gouty arthritis although such doses should only be used for the acute symptomatic period and for a maximum of 8 days. For postoperative dental pain, the recommended dose of etoricoxib is 90 mg once daily for a maximum of 3 days.

For dosage recommendations in patients with hepatic impairment, see Refer to .

(last reviewed 2010-08-20; last modified 2017-07-18)

References.

(last reviewed 2010-08-20; last modified 2006-05-17)

References

1. Patrignani P, et al.. Clinical pharmacology of etoricoxib: a novel selective COX2 inhibitor.Expert Opin Pharmacother. 2003; 4: 265–84. PubMed

2. Dallob A, et al.. Characterization of etoricoxib, a novel, selective COX-2 inhibitor.J Clin Pharmacol. 2003; 43: 573–85. PubMed

3. Martina SD, et al.. Etoricoxib: a highly selective COX-2 inhibitor.Ann Pharmacother. 2005; 39: 854–62. PubMed

Administration in hepatic impairment

The maximum oral dose of etoricoxib in patients with mild hepatic impairment (Child-Pugh score of 5 to 6), regardless of indication, is 60 mg once daily; those with moderate impairment (Child-Pugh 7 to 9) should be given a maximum of 60 mg every other day or 30 mg once daily. Etoricoxib should not be given to patients with severe hepatic impairment (Child-Pugh 10 or more).

(last reviewed 2010-08-20; last modified 2016-06-28)

Musculoskeletal and joint disorders

The selective cyclo-oxygenase-2 (COX-2) inhibitor etoricoxib is used in the treatment of ankylosing spondylitis (see Spondyloarthropathies, Refer to ), osteoarthritis ( Refer to ), and rheumatoid arthritis ( Refer to ); it is also used in gouty arthritis ( Refer to ). However, in the UK, it is recommended that the use of selective COX-2 inhibitors is limited to patients with good cardiovascular health and at high risk of developing serious gastrointestinal problems if given a non-selective NSAID (see Refer to ).

References.

(last reviewed 2010-08-20; last modified 2017-07-18)

References

1. Cochrane DJ, et al.. Etoricoxib.Drugs. 2002; 62: 2637–51. PubMed

2. Schumacher HR, et al.. Randomised double blind trial of etoricoxib and indometacin in treatment of acute gouty arthritis.BMJ. 2002; 324: 1488–92. PubMed

3. Gottesdiener K, et al.. Results of a randomized, dose-ranging trial of etoricoxib in patients with osteoarthritis.Rheumatology (Oxford). 2002; 41: 1052–61. PubMed

4. Wiesenhutter CW, et al.. Evaluation of the comparative efficacy of etoricoxib and ibuprofen for treatment of patients with osteoarthritis: a randomized, double-blind, placebo-controlled trial.Mayo Clin Proc. 2005; 80: 470–9. PubMed

5. van der Heijde D, et al.. Evaluation of the efficacy of etoricoxib in ankylosing spondylitis: results of a fifty-two-week, randomized, controlled study.Arthritis Rheum. 2005; 52: 1205–15. PubMed

6. Curtis SP, et al.. Etoricoxib in the treatment of osteoarthritis over 52-weeks: a double-blind, active-comparator controlled trial [NCT00242489].BMC Musculoskelet Disord. 2005; 6: 58. PubMed online

7. Bingham CO, et al.. Efficacy and safety of etoricoxib 30 mg and celecoxib 200 mg in the treatment of osteoarthritis in two identically designed, randomized, placebo-controlled, non-inferiority studies.Rheumatology (Oxford). 2007; 46: 496–507. PubMed

8. Croom KF, Siddiqui MAA. Etoricoxib: a review of its use in the symptomatic treatment of osteoarthritis, rheumatoid arthritis, ankylosing spondylitis and acute gouty arthritis.Drugs. 2009; 69: 1513–32. PubMed

9. Bickham K, et al.. Evaluation of two doses of etoricoxib, a COX-2 selective non-steroidal anti-inflammatory drug (NSAID), in the treatment of rheumatoid arthritis in a double-blind, randomized controlled trial.BMC Musculoskelet Disord. 2016; 17: 331. PubMed

Pain

A systematic review1 found that a single 120-mg dose of etoricoxib, given orally, provided effective pain relief after surgery. When compared indirectly, etoricoxib was considered to be at least as effective as other commonly used analgesics.

(last reviewed 2010-08-20; last modified 2016-06-28)

References

1. Clarke R, et al.. Single dose oral etoricoxib for acute postoperative pain in adults. Available in The Cochrane Database of Systematic Reviews; Issue 5. Chichester: John Wiley; 2014 (accessed 25/05/16). PubMed

Adverse Effects, Treatment and Precautions

As for NSAIDs in general, Refer to .

Hypersensitivity reactions including anaphylaxis and angioedema have occurred in patients receiving etoricoxib; it should be stopped at the first signs of hypersensitivity.

Etoricoxib should not be used in patients with ischaemic heart disease, peripheral arterial disease, or cerebrovascular disease. It should be used with caution in patients with significant risk factors for cardiovascular disease such as hypertension, hyperlipidaemia, and diabetes mellitus. Etoricoxib, particularly at high doses, may be associated with more frequent and severe hypertension compared with other NSAIDs and selective cyclo-oxygenase-2 (COX-2) inhibitors; blood pressure monitoring during etoricoxib treatment is recommended. Etoricoxib should not be used in patients with hypertension whose blood pressure is not controlled (see also Effects on the Cardiovascular System, Refer to ).

Etoricoxib is also contra-indicated in patients with inflammatory bowel disease, moderate to severe heart failure (NYHA class II to IV), and renal impairment associated with a creatinine clearance of less than 30 mL/minute. It should be avoided in patients with severe hepatic impairment (Child-Pugh score of 10 or more). Therapy should be stopped if persistently abnormal liver enzyme values are seen. Caution is recommended when using etoricoxib in dehydrated patients; it may be advisable to rehydrate patients before giving etoricoxib.

(last reviewed 2010-08-20; last modified 2010-06-02)

Effects on the cardiovascular system

There have been concerns about the adverse cardiovascular effects of selective cyclo-oxygenase-2 (COX-2) inhibitors after the worldwide withdrawal of rofecoxib (see Refer to ). The cardiovascular safety of etoricoxib has been assessed in the MEDAL programme,1 which pooled data from 3 studies involving over 30 000 patients with either osteoarthritis or rheumatoid arthritis. Patients with osteoarthritis were given etoricoxib 60 or 90 mg daily; those with rheumatoid arthritis received 90 mg daily. In all studies, diclofenac 150 mg daily was given as the comparator; low-dose aspirin (100 mg daily or less) was also allowed where indicated. After an average treatment duration of 18 months, the rates of thrombotic events such as myocardial infarction, stroke, and sudden or unexplained death with etoricoxib were similar to those for diclofenac. (It has been suggested that diclofenac itself may increase the risk of some thrombotic events; for further details, see Refer to .) The programme also found that the rate of some other non-thrombotic cardiovascular events was increased with etoricoxib: one of the 3 studies showed that there was a non-significant increase in the rate of heart failure with etoricoxib 90 mg daily compared with diclofenac; withdrawals due to oedema were also more frequent with high-dose etoricoxib than with diclofenac or etoricoxib 60 mg daily. In addition, the number of patients stopping treatment because of hypertension was higher with both doses of etoricoxib than with diclofenac. Similar results were seen in the other 2 studies.

In another study2 that pooled pre-licensing data, the risk of thrombotic events with etoricoxib, given at a dose of at least 60 mg daily, was also found to be similar to that for placebo treatment, ibuprofen (2.4 g daily), diclofenac (150 mg daily), and naproxen (1 g daily), although there was a trend towards more events with etoricoxib than with naproxen. For details on the relative risk of thrombotic events associated with non-selective NSAIDs, see Refer to .

After a recommendation from the EMEA's Committee for Medicinal Products for Human Use (CHMP),3 licensed product information for etoricoxib states that it must not be given to patients whose blood pressure is persistently above 140/90 mmHg and inadequately controlled; in addition, high blood pressure should be controlled before starting treatment and monitored for 2 weeks afterwards then regularly thereafter.

For discussion and advice on the use of selective COX-2 inhibitors in patients with cardiovascular or cerebrovascular disease, see under Celecoxib, Refer to .

(last reviewed 2010-08-20; last modified 2010-06-02)

References

1. Cannon CP, et al.. Cardiovascular outcomes with etoricoxib and diclofenac in patients with osteoarthritis and rheumatoid arthritis in the Multinational Etoricoxib and Diclofenac Arthritis Long-term (MEDAL) programme: a randomised comparison.Lancet. 2006; 368: 1771–81. PubMed

2. Curtis SP, et al.. Pooled analysis of thrombotic cardiovascular events in clinical trials of the COX-2 selective inhibitor etoricoxib.Curr Med Res Opin. 2006; 22: 2365–74. PubMed

3. EMEA. EMEA recommends strengthening warnings and contraindications for etoricoxib-containing medicines used in the treatment of rheumatoid arthritis and ankylosing spondylitis (issued 26th June, 2008). Available at: Link (accessed 16/07/08)

Effects on the gastrointestinal tract

It is generally accepted that the inhibition of cyclo-oxygenase-1 (COX-1) plays a role in the adverse gastrointestinal effects of the NSAIDs, and that the selective inhibition of the other isoform, COX-2, by NSAIDs such as etoricoxib may cause less gastrotoxicity than that seen with the non-selective inhibition of the traditional NSAIDs. However, licensed product information states that upper gastrointestinal perforation, ulceration, and bleeds, in some cases fatal, have occurred with etoricoxib treatment; consequently, it should be used with caution in patients with a history of, or at risk of developing, such events. In addition, etoricoxib should not be used in patients with active gastrointestinal ulceration or bleeding.

Results from controlled studies have suggested that NSAIDs selective for COX-2 were associated with a lower incidence of serious gastrointestinal effects. In a study1 of the pooled data from 3 randomised clinical studies, etoricoxib (in doses of 60 or 90 mg daily) was associated with significantly less frequent upper gastrointestinal clinical events than diclofenac (150 mg daily). The result was attributed to the lower rate of uncomplicated ulcers with etoricoxib compared with diclofenac; there was no difference in the rate of complicated gastrointestinal events between the 2 drugs. The lower rate of uncomplicated events with etoricoxib compared with diclofenac was not affected by treatment with low-dose aspirin or proton pump inhibitors. An analysis2by the manufacturer, of pooled data from 10 randomised clinical studies, found that etoricoxib (in daily doses of 60, 90, or 120 mg) was associated with a lower combined risk of upper gastrointestinal perforations and bleeding, and symptomatic gastroduodenal ulcers when compared with non-selective NSAIDs (diclofenac 150 mg daily, ibuprofen 2.4 g daily, or naproxen 1 g daily) as a group. This reduced risk was seen even in patients with known risk factors for such complications such as the elderly and those with a history of gastrointestinal reactions.

(last reviewed 2010-08-20; last modified 2009-09-05)

References

1. Laine L, et al.. Assessment of upper gastrointestinal safety of etoricoxib and diclofenac in patients with osteoarthritis and rheumatoid arthritis in the Multinational Etoricoxib and Diclofenac Arthritis Long-term (MEDAL) programme: a randomised comparison.Lancet. 2007; 369: 465–73. PubMed

2. Ramey DR, et al.. The incidence of upper gastrointestinal adverse events in clinical trials of etoricoxib vs. non-selective NSAIDs: an updated combined analysis.Curr Med Res Opin. 2005; 21: 715–22. PubMed

Effects on the kidneys

Limited evidence of the renal toxicity of the selective cyclo-oxygenase-2 (COX-2) inhibitors such as etoricoxib suggests that such NSAIDs appear to have effects on renal function similar to those of the non-selective NSAIDs (see Refer to ).

(last reviewed 2010-08-20; last modified 2007-09-28)

Porphyria

The Drug Database for Acute Porphyria, compiled by the Norwegian Porphyria Centre (NAPOS) and the Porphyria Centre Sweden, classifies etoricoxib as possibly porphyrinogenic; it should be used only when no safer alternative is available and precautions should be considered in vulnerable patients.1

(last reviewed 2010-08-20; last modified 2011-11-14)

References

1. The Drug Database for Acute Porphyria. Available at: Link (accessed 23/10/11)

Interactions

The metabolism of etoricoxib is mediated by the cytochrome P450 isoenzyme CYP3A4. Use with other drugs that inhibit or induce this isoenzyme may result in changes in plasma concentration of etoricoxib. In addition, in vitro studies suggest that several other isoenzymes may also mediate the main metabolic pathway of etoricoxib. Rifampicin, a potent inducer of CYP isoenzymes, has produced decreased plasma concentrations of etoricoxib.

Etoricoxib is an inhibitor of human sulfotransferase activity and has been shown to increase the plasma concentration of ethinylestradiol. Interactions with other drugs, such as oral salbutamol and minoxidil, also metabolised by this enzyme may be a possibility and licensed product information advises care with such combinations.

For interactions associated with NSAIDs in general, see Refer to .

(last reviewed 2010-08-20; last modified 2007-09-28)

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.

(last reviewed 2010-08-20; last modified 2010-06-02)

References.

(last reviewed 2010-08-20; last modified 2010-06-02)

References

1. Agrawal NGB, et al.. Single- and multiple-dose pharmacokinetics of etoricoxib, a selective inhibitor of cyclooxygenase-2, in man.J Clin Pharmacol. 2003; 43: 268–76. PubMed

2. Agrawal NGB, et al.. Pharmacokinetics of etoricoxib in patients with hepatic impairment.J Clin Pharmacol. 2003; 43: 1136–48. PubMed

3. Agrawal NGB, et al.. Pharmacokinetics of etoricoxib in patients with renal impairment.J Clin Pharmacol. 2004; 44: 48–58. PubMed

4. Takemoto JK, et al.. Clinical pharmacokinetic and pharmacodynamic profile of etoricoxib.Clin Pharmacokinet. 2008; 47: 703–20. PubMed

Preparations: Single-Ingredient

The following preparations list represents a compilation of all available salt forms or related substances for this drug product.

The symbol ¤ denotes a preparation which is discontinued or no longer actively marketed.

ARGENTINA: Arcoxia; Cox-Quin;AUSTRALIA: Arcoxia;AUSTRIA: Arcoxia; Auxib¤;BELGIUM: Arcoxia; Ranacox¤;BRAZIL: Arcoxia; Hetori;CHILE: Arcoxia;CHINA: Arcoxia (安康信);CZECH REPUBLIC: Arcoxia;DENMARK: Arcoxia;FINLAND: Arcoxia; Coxiloc; Turox¤;FRANCE: Arcoxia;GERMANY: Arcoxia; Exinef¤;GREECE: Arcoxia; Turox¤;HONG KONG: Arcoxia;HUNGARY: Arcoxia;INDIA: Alcoxib; Coxet; Coxifact; Doricox; E-Trom; Ebov; Ecoxib¤; Eleton; Erofica; Eteron¤; Eticox; Etobus; Etocos; Etody; Etofan; Etolex; Etom; Etori; Etorica; Etosaid; Etoshine; Etosym; Etoxib; Etozox; Etrik; Etro; Etrobax; Ezact; Hicox; Hireto; Ifydrox; Intacoxia; Ixidol; Kingcox; Kretos; L-Kon; M-Kon; Nucoxia; O-Cox;INDONESIA: Arcoxia;IRELAND: Acoxxel¤; Arcoxia;ISRAEL: Arco; Arcoxia;ITALY: Algix; Arcoxia; Exinef; Tauxib;MALAYSIA: Arcoxia;MEXICO: Arcoxia; Doscoxel;NETHERLANDS: Arcoxia; Auxib¤; Ecoxyton; Evetore; Oxidraxib;NORWAY: Arcoxia;NEW ZEALAND: Arcoxia;PHILIPPINES: Arcoxia; Arcoxib¤; Xibra¤;POLAND: Arcoxia; Doloxib; Kostarox; Roticox;PORTUGAL: Arcoxia; Exxiv; Turox;RUSSIAN FEDERATION: Arcoxia (Аркоксиа);SOUTH AFRICA: Arcoxia; Exinef;SINGAPORE: Arcoxia;SPAIN: Acoxxel; Arcoxia; Exxiv;SWEDEN: Arcoxia; Turox;SWITZERLAND: Arcoxia;THAILAND: Arcoxia;UNITED ARAB EMIRATES: Turox;UNITED KINGDOM: Arcoxia;UKRAINE: Arcoxia (Аркоксия);VENEZUELA: Arcoxia;

Preparations: Multi-Ingredient

The following preparations list represents a compilation of all available salt forms or related substances for this drug product.

The symbol ¤ denotes a preparation which is discontinued or no longer actively marketed.

INDIA: Etro-P; Nucoxia-MR; Nucoxia-P; Nucoxia-SP;

Therapeutic Use

• Analgesics Anti-inflammatory Drugs and Antipyretics

Last Updated 1/21/20