Etoricoxib

Structural formula
General
Non-proprietary name	Etoricoxib
other names	5-chloro-6′-methyl-3- [4- (methylsulfonyl) phenyl] -2,3′-bipyridine ( IUPAC )
Molecular formula	C 18 H 15 ClN 2 O 2 S
External identifiers / databases
EC number	682-421-5
ECHA InfoCard	100.207.709
PubChem	123619
DrugBank	DB01628
Wikidata	Q631202
Drug information
ATC code	M01 AH05
Drug class	COX-2 inhibitors
properties
Molar mass	358,84 g · mol -1
safety instructions
	Please note the exemption from the labeling requirement for drugs, medical devices, cosmetics, food and animal feed
GHS labeling of hazardous substances danger
H and P phrases	H: 302-310
	P: ?
	As far as possible and customary, SI units are used. Unless otherwise noted, the data given apply to standard conditions .

Etoricoxib is a drug that is used as a pain reliever from the class of COX-2 inhibitors ( non-steroidal anti-inflammatory drugs , NSAIDs) for the treatment of osteoarthritis, rheumatoid arthritis and acute gout attacks. Etoricoxib has been approved in Germany for people aged 16 and over since September 2004.

Indications

Etoricoxib is approved in Germany for:

arthrosis
Rheumatoid arthritis
Acute gouty arthritis
ankylosing spondylitis
Postoperative toothache (approval since April 2012)

In contrast to other non-steroidal anti-inflammatory drugs , only a relatively low dose is used. The daily dose is 30–120 mg.

Pharmacokinetics

The biological half-life is 22 hours. The preparation floods very quickly and reaches the highest effective level after about an hour. As a result, a very quick onset of action can be expected, according to studies on average after 25 minutes. The approval studies in acute gouty arthritis ran against 3 × 50 mg indomethacin ; the same effectiveness could be shown. In osteoarthritis and rheumatoid arthritis , 3 × 50 mg diclofenac or 2 × 500 mg naproxen were compared, each with the same efficacy result.

Side effects

Like all NSAIDs, the preparation can lead to arterial hypertension and edema .

With regard to the cardiovascular safety profile , only data over a period of 12 to 15 months were known. There an increased risk compared to naproxen was found. The results of the MEDAL study, which was carried out on around 34,000 patients, have been published since November 2006. The actual MEDAL study was carried out with etoricoxib (60 mg and 90 mg) against diclofenac 150 mg. The primary endpoint was cardiovascular thrombotic events (fatal or non-fatal). In this study, no difference was found between diclofenac and etoricoxib in terms of cardiovascular safety. The study ran for a maximum of 3.5 years, with over 12,000 patients treated for 2 years. The study was criticized because of the choice of diclofenac as a comparison substance, since in contrast to naproxen, diclofenac was also known to have an increased cardiovascular risk; thus one has just chosen a comparison substance which itself has a comparatively high level of undesirable side effects in the cardiovascular area.
Etoricoxib caused more dropouts due to edema under 90 mg and more dropouts because of high blood pressure under 60 mg and 90 mg. Diclofenac was more toxic to the liver (study discontinuations approx. 3% vs. 0.3%).

In the gastrointestinal (gastrointestinal tract), etoricoxib was better tolerated than diclofenac, but not in all subgroups.

The MEDAL program is an important pivotal study for etoricoxib in the United States. After evaluating the data, the FDA again rejected the approval.

Another possible side effect of etoricoxib and other COX-2 inhibitors is depression .

Contraindications

Etoricoxib is contraindicated in renal insufficiency (with creatinine clearance below 30 ml / min) and severe hepatic impairment. The same applies to acute stomach ulcers and gastrointestinal bleeding. Dehydrated patients (e.g. competitive athletes with insufficient fluid intake) as well as pregnant and breastfeeding women must also not receive etoricoxib.

After a reassessment of the class of coxibs by the US Food and Drug Administration (FDA) and the European Medicines Agency , the following contraindications were added in 2004:

Patients with arterial hypertension whose blood pressure is not adequately controlled and ischemic heart disease such as
Heart failure ( NYHA II-IV)
Clinically proven coronary artery disease (CHD, e.g. angina pectoris ) and / or cerebrovascular diseases (e.g. stroke )

Trade names

Monopreparations
Arcoxia, Exinef (D, A, CH), Auxib (A)

literature

CP Cannon 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) program: a randomized comparison. In: The Lancet . Volume 368, Number 9549, November 2006, pp. 1771-1781, doi: 10.1016 / S0140-6736 (06) 69666-9 , PMID 17113426 .
PM Kearney et al .: Do selective cyclo-oxygenase-2 inhibitors and traditional non-steroidal anti-inflammatory drugs increase the risk of atherothrombosis? Meta-analysis of randomized trials. In: BMJ. Volume 332, number 7553, June 2006, pp. 1302-1308, doi: 10.1136 / bmj.332.7553.1302 , PMID 16740558 , PMC 1473048 (free full text).

Web links

Trends-in-Medicine (PDF; 326 kB) 2004
Technical information (PDF; 93 kB) 2005

Individual evidence

↑ Template: CL Inventory / not harmonized There is not yet a harmonized classification for this substance . A labeling of 2,3'-bipyridine, 5-chloro-6'-methyl-3- (4- (methylsulfonyl) phenyl) - Template: link text check / apostrophe in the Classification and Labeling Inventory of the European Chemicals Agency (ECHA), is shown, which is derived from a self-classification by the distributor accessed on February 10, 2020.
↑ Carolina Kusnick: Etoricoxib for the therapy of postoperative toothache. In: deutsche-apotheker-zeitung.de. September 23, 2015, accessed January 19, 2020 .
↑ Ralf Baron, Wolfgang Koppert, Michael Strumpf, Anne Willweber-Strumpf: Practical pain medicine, interdisciplinary diagnostics - multimodal therapy . 4th edition. Springer-Verlag, Berlin 2019, ISBN 978-3-662-57486-7 .
^ Sue Hughes: MEDAL: Etoricoxib shows same thrombotic cardiovascular risk as diclofenac . November 13, 2006; Retrieved October 4, 2016.
↑ arznei-telegram 2007; 38: p. 105.
↑ Article 31 Referral, Etoricoxib (CPMP / 1748/04) . CHPM recommendation of February 27, 2004, EC decision of April 28, 2004.
↑ Red List Online, as of August 2009.
↑ AM comp. d. Switzerland, as of August 2009.
↑ AGES-PharmMed, as of August 2009.

[1] Template: CL Inventory / not harmonized There is not yet a harmonized classification for this substance . A labeling of 2,3'-bipyridine, 5-chloro-6'-methyl-3- (4- (methylsulfonyl) phenyl) - Template: link text check / apostrophe in the Classification and Labeling Inventory of the European Chemicals Agency (ECHA), is shown, which is derived from a self-classification by the distributor accessed on February 10, 2020.

[2] Carolina Kusnick: Etoricoxib for the therapy of postoperative toothache. In: deutsche-apotheker-zeitung.de. September 23, 2015, accessed January 19, 2020 .

[3] Ralf Baron, Wolfgang Koppert, Michael Strumpf, Anne Willweber-Strumpf: Practical pain medicine, interdisciplinary diagnostics - multimodal therapy . 4th edition. Springer-Verlag, Berlin 2019, ISBN 978-3-662-57486-7 .

[4] Sue Hughes: MEDAL: Etoricoxib shows same thrombotic cardiovascular risk as diclofenac . November 13, 2006; Retrieved October 4, 2016.

[5] rznei-telegram 2007; 38: p. 105.

[6] Article 31 Referral, Etoricoxib (CPMP / 1748/04) . CHPM recommendation of February 27, 2004, EC decision of April 28, 2004.

[7] Red List Online, as of August 2009.

[8] AM comp. d. Switzerland, as of August 2009.

[9] AGES-PharmMed, as of August 2009.