Nonnarcotic analgesics: prevalence and estimated economic impact of toxicities.
McGoldrick MD; Bailie GR. Ann Pharmacother, 31(2):221-7 1997 Feb.
This study shows that nonsteroidal anti-inflammatory drugs (NSAIDs) cause about 72.6% of the total toxicities related to the use of NSAIDs, acetaminophen and aspirin. The cost associated with NSAID adverse effects has been estimated at $1.86 billion.
Epidemiology of nonsteroidal anti-inflammatory drug-associated gastrointestinal injury.
Griffin MR. Am J Med 1998 Mar 30;104(3A):23S-29S; discussion 41S-42S.
This study shows that 10% to 20% of individuals aged 65 and older are on a recent or current nonsteroidal anti-inflammatory drug (NSAID) prescription. In Tennessee (USA), 6% of elderly people are prescribed NSAIDs for more than 75% of the year, and 40% of them receive at least one prescription annually. Adverse reactions, particularly to the gastrointestinal system, are frequent, and it has been estimated these drugs are responsible for 28% of all anti-ulcer drug prescriptions in this age group.
Analysis of the costs of NSAID-associated gastropathy. Experience in a US health maintenance organisation.
Johnson RE, Hornbrook MC, Hooker RS, Woodson GT, Shneidman R. Pharmacoeconomics 1997 Jul;12(1):76-88.
This study estimated that for every $1.00 spent on nonsteroidal antiinflammatory drug (NSAID) therapy for the elderly, $0.35 is spent for the treatment of NSAID-induced gastropathy. Overall, the costs of each NSAID-related gastropathy episode was estimated at $2172 (1992 values).
NSAIDs and the elderly. Toxicity and economic implications.
This article warns against routine prescription of nonsteroidal anti-inflammatory drugs (NSAIDs) for noninflammatory conditions to the elderly, due to the potential risks associated with this class of drugs. This practice increases the costs of treatment by a staggering amount when expenses derived from use of gastroprotective agents, laboratory monitoring, and physician consultation and intervention for adverse effects are added to drug costs.
A multicenter study of annual health service utilization and costs in rheumatoid arthritis.
This study estimated that the overall health care costs per patient with rheumatoid arthritis is $2,533 per year (1986 values). These costs include: hospital care ($913), physician costs ($277), medications ($436), laboratory tests ($217), radiographs ($116), assistive devices ($24), and nontraditional therapies ($22). Total costs were not associated with level of self-reported pain.
Inhibition of angiogenesis by nonsteroidal anti-inflammatory drugs: insight into mechanisms and implications for cancer growth and ulcer healing.
Jones MK, et al. Nat Med 1999 Dec;5(12):1418-23.
This study challenges the belief that selective cyclooxygenase 2 (COX-2) inhibitors such as celecoxib and rofecoxib, a new generation of NSAIDs designed to overcome some of side effects associated with traditional NSAIDs, are devoid of gastrointestinal toxicity. NSAIDs reduce pain and inflammation by inhibiting the enzyme cyclooxygenase. This enzyme exists in at least 2 isoforms: COX-1, which participates to the homeostatic regulation of many tissues and produces protective prostaglandines in the stomach, and COX-2, involved in the formation of mediators of pain and inflammation. Unlike NSAIDs, COX-2 inhibitors selectively block the action of the isoenzyme COX-2, while sparing the mucosa-protective enzyme COX-1. The results of this study however, demonstrate that both enzymes are required for the production of new blood vessels and for the maintenance of the integrity of the gastrointestinal lining, making Cox-2 inhibitors potentially capable of causing ulcers and gastrointestinal bleeding as much as traditional NSAIDs.
Cyclooxygenase 2 selective agents and upper gastrointestinal disease. Letter.
Fernandez H and Lesser GT. JAMA Vol. 283 No. 15, April 19, 2000.
This letter comments on the results of a study by Dr. Simon and colleagues suggesting that use of the selective cyclooxygenase 2 (COX-2) inhibitor celecoxib in patients with rheumatoid arthritis is associated with a lower incidence of upper gastrointestinal (GI) ulcers compared to treatment with the conventional nonsteroidal anti-inflammatory drug (NSAID) naproxen. The authors of the letter, however, question several aspects of the study design together with the study's conclusions. First, naproxen was the NSAID chosen for comparison in the study, when other NSAIDs have been associated with lower rates of GI toxicity, and should therefore used as first line agents in patients with arthritis. Second, naproxen was used at the highest recommended dose and its intake was not reduced after the achievement of a treatment response, as common clinical experience recommends. Third, 40% of patients were older than 60 years of age, and had therefore an inherent 3-fold increased risk of developing NSAID-related gastric complications, compared to the general population. Fourth, one third of patients were concomitantly receiving long-term corticosteroid treatment, another factor associated with an increased risk of GI toxicity. In addition, among the patients receiving naproxen, was an 80-year-old woman in whom treatment with high-doses is not indicated. She was the only one to suffer severe complications. The authors conclude that the results of Dr. Simon study cannot indicate that selective COX-2 inhibitors are safer than NSAIDs in patients with arthritis.
Gastropathy due to celecoxib, a cyclooxygenase-2 inhibitor.
Mohammed S, and Croom II DW. N Engl J Med. 1999 Jun 24;340(25):2005-6.
This article reports on the case of a 69-year old woman who developed acute pain in the upper abdomen after initiation of treatment for arthritis with the COX-2 inhibitor celecoxib (Celebrex). Endoscopic evaluation revealed the presence of severe gastropathy with multiple erosions and signs typical of NSAID-induced gastropathy. The authors emphasize that animal studies have shown that COX-2 inhibitors lose their selective action on the isoenzyme COX-2 when used at doses required for anti-inflammatory action, and cause gastric ulcers which cannot be repaired possibly due to interference with the activity of the COX-2 enzyme. This article adds clinical evidence in support of the experimental data indicating that COX-2 inhibitors, like NSAIDs, are toxic to the gastric lining and cause ulcers and bleeding.
COX 2 inhibitor and fulminant hepatic failure.
McCormick PA, Kennedy F, Curry M, Traynor O. Lancet. 1999 Jan 2;353(9146):40-1.
This article reports on the case of a patient who developed fulminant hepatic failure from treatment with the selective COX2 inhibitor Nimesulide.
Gastric perforation associated with the use of celecoxib.
Reuben SS, et al. Anesthesiology. 1999 Nov;91(5):1548-9.
Acute pancreatitis associated with celecoxib.
Baciewicz AM, Sokos DR, King TJ. Ann Intern Med 2000 Apr 18;132(8):680.
Celecoxib-induced acute pancreatitis and hepatitis: a case report.
Carrillo-Jimenez R, Nurnberger M. Arch Intern Med 2000 Feb 28;160(4):553-4.
Are Selective COX-2 Inhibitors Nephrotoxic?
Perazella MA, Eras J. Am J Kidney Dis 2000 May;35(5):937-940.
This article reports on the case of two patients with chronic renal insufficiency who developed acute renal failure within 2 weeks of initiation of treatment with the selective cyclooxygenase-2 enzyme inhibitor celecobix. This finding indicates that even the newer generation of nonsteroidal anti-inflammatory drugs have the potential of inducing acute renal failure in patients at risk for this complication, such as those with heart or liver failure or with chronic renal diseases.
Renal side-effects of cyclo-oxygenase-type-2 inhibitor use.
Lancet. 2000 Feb 26;355(9205):753. Stubanus M, Riegger GA, Kammerl MC, Fischereder M, Kramer BK.
This letter reports on several studies indicating that COX-2 selective inhibitors impair renal function in elderly individuals with or without concurrent medical conditions that may put them at risk of experiencing adverse renal effects. In one study, Swan and colleagues demonstrated a 12% reduction in rate of glomerular filtration in elderly individuals with mild renal dysfunction receiving rofecoxib. Another study by Brooks and colleagues demonstrated an important reduction (60-70%) of urine flow, glomerular filtration rate and sodium excretion in dogs with volume depletion injected with celecoxib. In addition, Whelton and colleagues documented a reduction in sodium excretion after only 2 days of treatment with celecoxib in healthy elderly individuals.
Despite enough evidence suggesting an increased risk of kidney toxicity in at-risk individuals treated with COX-2 inhibitors, all randomized published trials failed to include this patient population in their study, and currently no information is available to guide treatment decisions in this category of patients.
Selective cyclo-oxygenase-2 inhibition with celecoxib elevates blood pressure and promotes leukocyte adherence.
The results of this study indicate that celecoxib produces important increase in blood pressure levels in rats with normal or high baseline blood pressure levels. In the study both normal and hypertensive rats were treated for 3 weeks with celecoxib. Blood pressure levels significantly increased in both groups by an average of more than 33 mmHg. In addition, celecoxib induced weight gain (20% increase in body weight), leukocyte adherence and alteration of renal function. This study indicates that selective suppression of the isoenzyme COX-2 is associated with important changes in the cardiovascular, renal and endocrine systems in animals.
