Withdrawal of COX-2 selective inhibitors rofecoxib and valdecoxib: impact on NSAID and gastroprotective drug prescribing and utilization

Curr Med Res Opin. 2007 Aug;23(8):1859-66. doi: 10.1185/030079907X210561.


Objective: Cyclo-oxygenase-2 (COX-2) inhibitors rofecoxib and valdecoxib were withdrawn from the market because of their association with cardiovascular problems. There is a lack of information on the impact of the COX-2 inhibitors withdrawal on the prescribing and utilization of related drugs. The main objective of this study was to evaluate to what extent prescriptions of non-selective non-steroidal anti-inflammatory drugs (NSAIDs) and gastroprotective drugs changed after the removal of the two COX-2 inhibitors.

Research design and methods: A segmented regression of interrupted time series approach was used to analyze prescription data from July 1, 2003 through December 31, 2005 from a pharmacy claims database maintained by a large pharmacy benefit manager (PBM). Patients continuously eligible for the pharmacy benefit but not enrolled in COX-2 or proton pump inhibitor (PPI) Step Care programs during the study period were included. The number of prescriptions per thousand patients per month for targeted drugs were analyzed and compared.

Results: A total of 175 193 patients were included in the analysis. After the withdrawal of the COX-2 inhibitor, the average monthly non-selective NSAID and PPI prescriptions per thousand patients increased from 13.96 to 19.63 (a change of 40.62%, p < 0.0001) and from 38.67 to 43.33 (a change of 12.05%, p < 0.0001) respectively, whereas COX-2 prescriptions decreased by 54.51% (from 23.61 to 10.74, p < 0.0001). Among non-selective NSAIDs, the five drugs with highest percentage increase were meloxicam (167.12%, from 1.46 to 3.90, p < 0.0001), etodolac (72.06%, from 0.68 to 1.17, p < 0.0001), piroxicam (58.33%, from 0.36 to 0.57, p < 0.0001), nabumetone (52.38%, from 1.26 to 1.92, p < 0.0001), and diclofenac (37.89%, from 1.61 to 2.22, p < 0.0001).

Limitations: This study was restricted to patients with employer-sponsored drug coverage which might not be representative of the national population. Since over-the-counter (OTC) PPI, non-selective NSAID and H2RA were not captured in our claims data, we were unable to examine whether and to what extent the utilization of these drugs has changed. Additionally, the direct impact of these changes on population based outcomes is unknown.

Conclusions: After the withdrawal of COX-2 inhibitors rofecoxib and valdecoxib, there were significant increases in non-selective NSAID and PPI prescriptions but not H2RA and misoprostol. Given the safety concerns with the NSAIDs, further studies are warranted regarding the clinical outcomes associated with the increased use of non-selective NSAIDs with or without gastroprotective agents.

MeSH terms

  • Adolescent
  • Adult
  • Cohort Studies
  • Cyclooxygenase 2 / drug effects*
  • Cyclooxygenase Inhibitors / administration & dosage*
  • Drug Utilization Review*
  • Female
  • Humans
  • Isoxazoles / administration & dosage*
  • Lactones / administration & dosage*
  • Male
  • Middle Aged
  • Proton Pump Inhibitors*
  • Sulfonamides / administration & dosage*
  • Sulfones / administration & dosage*


  • Cyclooxygenase Inhibitors
  • Isoxazoles
  • Lactones
  • Proton Pump Inhibitors
  • Sulfonamides
  • Sulfones
  • rofecoxib
  • valdecoxib
  • Cyclooxygenase 2