Renal safety and tolerability of celecoxib, a novel cyclooxygenase-2 inhibitor

A. Whelton, C. J. Maurath, K. M. Verburg, G. S. Geis

Research output: Contribution to journalArticle

Abstract

The novel cyclooxygenase- (COX)-2 inhibitor celecoxib is an effective treatment for the signs and symptoms of osteoarthritis and rheumatoid arthritis. Conventional treatment for these debilitating conditions routinely involves the use of conventional nonsteroidal anti-inflammatory drugs (NSAIDs), which are nonspecific inhibitors of COX-1 and COX-2. Numerous studies suggest that inhibition of renal prostaglandin synthesis by NSAIDs is deleterious to kidney function, particularly in high-risk patients. As celecoxib inhibits COX-2 and spares COX-1 at therapeutic doses, we hypothesized that it may offer an improved renal safety profile in patients at risk for NSAID-induced renal toxicity. This article represents a post hoc analysis of the renal safety of celecoxib, using the safety database generated during its clinical development program. This analysis includes data from more than 50 clinical studies involving more than 13,000 subjects. Most subjects were enrolled in randomized, controlled trials (of up to 12 weeks' duration); however, more than 5000 subjects received celecoxib for as long as 2 years in a long-term, open-label study at as much as twice the maximum recommended dosage. The overall incidence of renal adverse events after celecoxib was greater than that after placebo but similar to that after NSAIDs. The most common events reported after celecoxib, namely, peripheral edema (2.1%), hypertension (0.8%), and exacerbation of preexisting hypertension (0.6%), were not time- or dose-related. Peripheral edema was not associated with increased weight or blood pressure. Furthermore, there was no evidence of drug-drug interactions between celecoxib and concomitant angiotensin-converting enzyme (ACE) inhibitors, β-blockers, calcium channel blockers, or diuretics. We conclude that celecoxib is well tolerated by patients who may be at risk for NSAID-induced renal toxicity, such as the elderly and those with hypertension or preexisting chronic heart disease.

Original languageEnglish (US)
Pages (from-to)159-175
Number of pages17
JournalAmerican Journal of Therapeutics
Volume7
Issue number3
StatePublished - 2000

Fingerprint

Celecoxib
Cyclooxygenase 2 Inhibitors
Kidney
Safety
Anti-Inflammatory Agents
Pharmaceutical Preparations
Cyclooxygenase 1
Cyclooxygenase 2
Hypertension
Edema
Calcium Channel Blockers
Drug Interactions
Angiotensin-Converting Enzyme Inhibitors
Diuretics
Osteoarthritis
Signs and Symptoms
Prostaglandins

Keywords

  • Analgesic
  • Celecoxib
  • COX-2-specific inhibitors
  • Nephrotoxicity
  • Nonsteroidal anti-inflammatory drugs
  • Renal safety

ASJC Scopus subject areas

  • Pharmacology

Cite this

Whelton, A., Maurath, C. J., Verburg, K. M., & Geis, G. S. (2000). Renal safety and tolerability of celecoxib, a novel cyclooxygenase-2 inhibitor. American Journal of Therapeutics, 7(3), 159-175.

Renal safety and tolerability of celecoxib, a novel cyclooxygenase-2 inhibitor. / Whelton, A.; Maurath, C. J.; Verburg, K. M.; Geis, G. S.

In: American Journal of Therapeutics, Vol. 7, No. 3, 2000, p. 159-175.

Research output: Contribution to journalArticle

Whelton, A, Maurath, CJ, Verburg, KM & Geis, GS 2000, 'Renal safety and tolerability of celecoxib, a novel cyclooxygenase-2 inhibitor', American Journal of Therapeutics, vol. 7, no. 3, pp. 159-175.
Whelton, A. ; Maurath, C. J. ; Verburg, K. M. ; Geis, G. S. / Renal safety and tolerability of celecoxib, a novel cyclooxygenase-2 inhibitor. In: American Journal of Therapeutics. 2000 ; Vol. 7, No. 3. pp. 159-175.
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AB - The novel cyclooxygenase- (COX)-2 inhibitor celecoxib is an effective treatment for the signs and symptoms of osteoarthritis and rheumatoid arthritis. Conventional treatment for these debilitating conditions routinely involves the use of conventional nonsteroidal anti-inflammatory drugs (NSAIDs), which are nonspecific inhibitors of COX-1 and COX-2. Numerous studies suggest that inhibition of renal prostaglandin synthesis by NSAIDs is deleterious to kidney function, particularly in high-risk patients. As celecoxib inhibits COX-2 and spares COX-1 at therapeutic doses, we hypothesized that it may offer an improved renal safety profile in patients at risk for NSAID-induced renal toxicity. This article represents a post hoc analysis of the renal safety of celecoxib, using the safety database generated during its clinical development program. This analysis includes data from more than 50 clinical studies involving more than 13,000 subjects. Most subjects were enrolled in randomized, controlled trials (of up to 12 weeks' duration); however, more than 5000 subjects received celecoxib for as long as 2 years in a long-term, open-label study at as much as twice the maximum recommended dosage. The overall incidence of renal adverse events after celecoxib was greater than that after placebo but similar to that after NSAIDs. The most common events reported after celecoxib, namely, peripheral edema (2.1%), hypertension (0.8%), and exacerbation of preexisting hypertension (0.6%), were not time- or dose-related. Peripheral edema was not associated with increased weight or blood pressure. Furthermore, there was no evidence of drug-drug interactions between celecoxib and concomitant angiotensin-converting enzyme (ACE) inhibitors, β-blockers, calcium channel blockers, or diuretics. We conclude that celecoxib is well tolerated by patients who may be at risk for NSAID-induced renal toxicity, such as the elderly and those with hypertension or preexisting chronic heart disease.

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