COX-2 Inhibitor

Products

COX-2 inhibitors (coxibe) are commercially available in the form of film-coated tablets and capsules. The first representatives from this group to be approved in many countries were celecoxib (Celebrex, USA: 1998) and rofecoxib (Vioxx, off label) in 1999. At that time, they rapidly developed into blockbuster drugs. However, due to adverse effects, several drugs had to be withdrawn from the market (see below), and therefore the importance of the drug group is lower today.

Structure and properties

COX-2 inhibitors have a V-shaped structure, with which they fit into the Active Site of the enzyme.

Effects

COX-2 inhibitors (ATC M01AH) have analgesic, anti-inflammatory, and antitumor properties. They are not antiplatelet agents. The effects are due to selective inhibition of the isoenzyme cyclooxygenase-2 (COX-2) and thus inhibition of the synthesis of prostaglandins. Selective inhibition was primarily intended to avoid the gastrointestinal side effects of classical nonselective NSAIDs, which inhibit both COX-1 and COX-2. This is because COX-2, which is inducible by proinflammatory stimuli, seemed to perform mainly pathophysiological functions, whereas COX-1 seemed to be responsible for the physiological functions of prostaglandins. However, it has been shown that severe side effects can also occur with COX-2 inhibitors and that COX-2 also performs physiological functions.

Indications

For symptomatic treatment of inflammation and pain associated with:

  • Osteoarthritis
  • Rheumatoid arthritis
  • Ankylosing spondylitis
  • Juvenile idiopathic arthritis

Dosage

According to the professional information. Depending on the preparation, the drugs are taken once or twice a day.

Active ingredients

Human medicines approved in many countries:

Withdrawn from commerce:

  • Lumiracoxib (Prexige)
  • Rofecoxib (Vioxx)
  • Valdecoxib (Bextra)

Parecoxib (Dynastat), a prodrug of valdecoxib, is still available in some countries but not in many. Veterinary Drugs:

  • Cimicoxib (Cimalgex).
  • Firocoxib (Previcox)
  • Mavacoxib (Trocoxil)
  • Robenacoxib (Onsior)

Contraindications

Numerous precautions must be observed before use. For the full details, please refer to the professional information.

Adverse effects

The most common possible adverse effects include:

COX-2 inhibitors can cause serious cardiovascular side effects such as myocardial infarction. For this reason, rofecoxib (Vioxx) in particular had to be withdrawn from the market. Despite their selectivity, gastric and intestinal ulcers (ulcers) can also occur under COX-2 inhibitors, as with NSAIDs. Severe skin reactions had been observed with valdecoxib (Bextra, also withdrawn from the market).