Etoricoxib

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Etoricoxib
Clinical data
AHFS/Drugs.comInternational Drug Names
Pregnancy
category
  • AU: C
  • Not recommended
Routes of
administration		By mouth
ATC code
Legal status
Legal status
  • AU: S4 (Prescription only)[1]
  • BR: Class C1 (Other controlled substances)[2]
  • UK: POM (Prescription only)
CYP extensively involved (mainly CYP3A4)
Elimination half-life22 hours
ExcretionKidney (70%) and fecal (20%)
Identifiers
  • 5-Chloro-6'-methyl-3-[4-(methylsulfonyl)phenyl]-2,3'-bipyridine
JSmol)
  • O=S(=O)(c3ccc(c2cc(Cl)cnc2c1cnc(cc1)C)cc3)C
  • InChI=1S/C18H15ClN2O2S/c1-12-3-4-14(10-20-12)18-17(9-15(19)11-21-18)13-5-7-16(8-6-13)24(2,22)23/h3-11H,1-2H3 checkY
  • Key:MNJVRJDLRVPLFE-UHFFFAOYSA-N checkY
  (verify)

Etoricoxib, sold under the brand name Arcoxia, is a selective COX-2 inhibitor developed and commercialized by

Non Approvable Letter to Merck and required them to provide additional data.[3]

It was patented in 1996 and approved for medical use in 2002.[4]

Medical uses

Etoricoxib is indicated for "the symptomatic relief of

acute gouty arthritis."[5]

Efficacy

A

Cochrane review assessed the benefits of single-dose etoricoxib in the reduction of acute post-operative pain in adults.[6] Single-dose oral etoricoxib provides four times more pain relief post-operatively than placebo, with equivalent levels of adverse events.[6] Etoricoxib given at a dose of 120 mg is as effective or even better than other analgesics that are commonly used.[6]

Adverse effects

Like all other NSAIDs, the COX-2 inhibitors too have their share of adverse effects. Fixed drug eruption and generalised erythema,[7] acute generalized exanthematous pustulosis (AGEP),[8] erythema multiforme like eruption[9] and drug induced pretibial erythema[10] are among the reported serious side effects.

Mechanism of action

Like any other selective COX-2 inhibitor ("coxib"), etoricoxib selectively inhibits

COX-1.[11] This reduces the generation of prostaglandins (PGs) from arachidonic acid
. The clinical relevance of the drug stems from the role of PGs in the inflammation cascade.

Selective COX-2 inhibitors show less activity on COX-1 compared to traditional

non-steroidal anti-inflammatory drugs (NSAID). This reduced activity is the cause of reduced gastrointestinal side effects, as demonstrated in several large clinical trials performed with different coxibs.[12][13]

Cardiovascular safety and concerns

Etoricoxib's safety on the gastrointestinal tract and cardiovascular was evaluated in the MEDAL Program consisting of three clinical trials: MEDAL (Multinational Etoricoxib Versus Diclofenac Arthritis Long-term Study), EDGE (Etoricoxib versus Diclofenac Sodium Gastrointestinal Tolerability and Effectiveness) and EDGE II.[14] Pooled analysis from these trials shows that etoricoxib has the same rates of thrombotic cardiovascular events as those of diclofenac, including thrombotic events (1.24 events per 100 patient-years with etoricoxib versus 1.3 events per 100 patient-years with diclofenac), arterial thrombotic events (1.05 events per 100 patient-years with etoricoxib versus 1.10 events per 100 patient-years with diclofenac) and risks of heart attack, stroke and death of vascular cause (0.84 per 100 patient-years with etoricoxib versus 0.87 events per 100 patient-years with diclofenac). Rates of upper gastrointestinal events (ulcer, bleeding, perforation, and obstruction) are in favor of the etoricoxib group (0.67 events per 100 patient-years with etoricoxib versus 0.97 events per 100 patient-years with diclofenac), but rates of complicated upper gastrointestinal events are similar between two groups.[15]

Like rofecoxib's VIGOR trial, the MEDAL Program was also criticized, this time due to Merck's choice of comparator group. In a testimony before the FDA Arthritis Advisory Committee, Sidney M. Wolfe pointed out that unlike the VIGOR trial, in which the active comparator was naproxen, three trials in the MEDAL Program used diclofenac as an active comparator. Wolfe showed that when compared etoricoxib to naproxen, which is a nonselective COX inhibitor, etoricoxib significantly increases the risks of cardiovascular events to such a degree that "are similar to rofecoxib/naproxen comparison", but when compared etoricoxib to diclofenac, which inhibits COX-2 more preferentially and has a worse CV safety profile than placebo, the difference was not statistically significant. He also noted the increase in other cardiac events, such as heart failure and high blood pressure.[16]

References

  1. ^ "Prescription medicines: registration of new generic medicines and biosimilar medicines, 2017". Therapeutic Goods Administration (TGA). 21 June 2022. Retrieved 30 March 2024.
  2. ^ Anvisa (31 March 2023). "RDC Nº 784 - Listas de Substâncias Entorpecentes, Psicotrópicas, Precursoras e Outras sob Controle Especial" [Collegiate Board Resolution No. 784 - Lists of Narcotic, Psychotropic, Precursor, and Other Substances under Special Control] (in Brazilian Portuguese). Diário Oficial da União (published 4 April 2023). Archived from the original on 3 August 2023. Retrieved 16 August 2023.
  3. ^ "Merck & Co., Inc. (Jobs) Receives Non Approvable Letter from FDA for Arcoxia (etoricoxib)". BioSpace. Retrieved 15 October 2023.
  4. ISBN 978-3-527-60749-5
    .
  5. ^ "Arcoxia - Article 6 (12) referral - Annex I, II, III, IV" (PDF). European Medicines Agency. 21 November 2008. Retrieved 15 October 2023.
  6. ^
    PMID 24809657
    .
  7. PMID 16880582
    .
  8. PMID 18311467
    .
  9. S2CID 207645594
    .
  10. PMID 26904451
    .
  11. PMID 11160644
    .
  12. PMID 11087881
    .
  13. S2CID 18464206
    .
  14. ^ newera-admin (21 November 2011). "MEDAL Study (Multinational Etoricoxib Versus Diclofenac Arthritis Long-Term Study)". London Pain Clinic. Retrieved 15 October 2023.
  15. S2CID 18464206
    .
  16. ^ "Testimony Concerning Etoricoxib (Arcoxia)". Public Citizen. 12 April 2007. Retrieved 16 October 2023.
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