Etoricoxib

In this article, we will discuss Etoricoxib (General Review). So, let’s get started.

Etoricoxib is a selective inhibitor of COX-2 (cyclooxygenase 2) indicated in the symptomatic relief of osteoarthritis (OA, 30-60mg once daily (od)), rheumatoid arthritis (RA, 90mg od) and the pain and signs of inflammation associated with acute gouty arthritis (120mg od).

Etoricoxib was included in previous CHMP referrals on the safety of COX-2 selective inhibitors in which concluded in 2004 and 2005. Both referral procedures pertained to the safety of the COX-2 inhibitor products, including etoricoxib, with a particular focus on gastrointestinal (GI) and cardiovascular (CV) safety. These led to updates of the product information to include class warnings on the risk of CV thrombotic, GI and severe skin reactions with COX-2 selective inhibitors. In addition to class warnings and contraindications, introduced for all COX-2 selective inhibitors, a contraindication in patients with hypertension whose blood pressure is not adequately controlled was included specifically for etoricoxib
because of evidence of higher rates of cardiorenal events than other COX-2 inhibitor products.

In March 2006, the marketing authorisation holders (MAH) for Arcoxia (etoricoxib) submitted an application to extend the licensed indication to include treatment of ankylosing spondylitis (AS), at a recommended daily dose of 90mg. During the assessment of the procedure, concerns were raised over the long-term safety of etoricoxib 90mg in patients with AS. Following concerns of a possible increased cardiovascular (CV) risk related to the use of the 90mg dose of etoricoxib, France considered that a review of the benefit/risk profile of Arcoxia was needed. Therefore, France sent a notification that was received by the EMEA on 19 September 2007 and a referral under Article 6 (12) of Commission Regulation EC No. 1084/2003 was started on 20 September 2007.

The CHMP reviewed the data submitted by the marketing authorisation holders from clinical trials, drug utilisation studies and spontaneous reporting of adverse drug reactions. The CHMP assessed efficacy data submitted for AS and safety data collected regarding AS, and also in the rheumatoid arthritis population for which the same dose is approved for treatment.

The CHMP concluded on 26 June 2008 that the data confirm the known relatively adverse renovascular safety profile of etoricoxib (hypertension, oedema and congestive heart failure), but similar CV thrombotic risk as diclofenac and some degree of upper GI safety advantage over naproxen and diclofenac (though no particular lower GI safety advantage). There is little direct comparative safety data for individual NSAIDs other than diclofenac and naproxen and it is therefore difficult to determine risks for etoricoxib compared with ibuprofen, ketoprofen or other less-commonly used NSAIDs.

Drug utilisation data showed that some patients with high blood pressure are being initiated on etoricoxib. The CHMP therefore recommends the strengthening of the contraindication in hypertensive patients and alerts prescribers that blood pressure needs to be monitored, especially within 2 weeks of treatment initiation. Healthcare professionals were to be reminded of these measures through a communication letter (DHCP). Data from clinical studies showed clinically meaningful treatment effect for the 90mg etoricoxib once daily dose for AS indications; however, some data are available to indicate that lower doses might also show effect. The CHMP therefore recommends that dose finding studies are explored to conclude if treatment  with 60mg once daily would also be adequate for some patients. Based on the review of the available data, the CHMP considers that the benefits of etoricoxib outweigh the risks in the treatment of ankylosing spondylitis.

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