Clinical and economic comparison of epoetin alfa and darbepoetin alfa.

BACKGROUND: The pharmacoeconomics of erythropoietic therapy for the treatment of anemia is receiving renewed attention due to the current availability of two agents. Epoetin alfa has been the standard of therapy for patients with renal disease and cancer-related anemia for more than a decade. Darbepoetin alfa, an alternative agent, is now approved for anemia resulting from renal disease and cancer chemotherapy. METHODOLOGY: Although direct comparative trials have not been performed with these agents, information published in the last several years regarding their clinical efficacy, safety, and dosing is sufficient, in most cases, to compare costs. With the disclaimer that any efficacy comparison of competing products using published reports has certain limitations, a cost-minimization approach from a provider's perspective was conducted. RESULTS: To provide background for the economic evaluation, pharmacokinetic and pharmacodynamic data for these two agents are discussed. Recent clinical trials in the nephrology and oncology therapeutic areas are summarized, highlighting study designs, dosing regimens, patient entry criteria, study endpoints, and published results. Cost data, based on average wholesale prices (AWP) in 2003, are compared and calculated from available clinical data with an emphasis on efficacy. CONCLUSION: These evaluations largely conclude that epoetin alfa is the better pharmacoeconomic value of the two currently available erythropoietic agents.

Interaction of rofecoxib and celecoxib with warfarin.

The interaction of celecoxib and rofecoxib with warfarin was studied. Patients stable on warfarin therapy and concurrently taking a cyclooxygenase-2 (COX-2) inhibitor comparator (traditional nonsteroidal antiinflammatory medications, salsalate, or acetaminophen) randomly received celecoxib 200 mg/day or rofecoxib 25 mg/day for three weeks. After a one-week washout period, the patients were crossed over to treatment with the opposite COX-2 inhibitor for three more weeks. The International Normalized Ratio (INR) was measured at baseline and at weeks 1, 2, and 3 of therapy with each COX-2 inhibitor by testing blood samples obtained by finger stick. Data for 16 patients were analyzed. The INR increased by 13%, 6%, and 5% on average in patients taking celecoxib at weeks 1, 2, and 3, respectively, and by 5%, 9%, and 5% in patients taking rofecoxib. Changes in the INR were statistically significant at week 1 for celecoxib and at week 2 for rofecoxib. Of the 12 subjects who had a clinically significant > or = 15% change in the INR while receiving either COX-2 inhibitor, 4 showed this change for both agents. Adverse drug reactions were similar for each COX-2 inhibitor, but the rate of edema requiring medical intervention was higher in the rofecoxib group. Significant increases in the INR were observed in patients who were stable on warfarin therapy after the addition of therapy with rofecoxib or celecoxib.

Topical lidocaine does not limit autonomic dysreflexia during anorectal procedures in spinal cord injury: a prospective, double-blind study.

BACKGROUND AND AIMS: Autonomic dysreflexia is a common and potentially dangerous response in patients with spinal cord injury at T6 or above. Acute blood pressure elevation may be precipitated by rectosigmoid distention and anal manipulation. Topical anesthetics are widely recommended to minimize the incidence and severity of autonomic dysreflexia, although no scientific evidence supports or refutes this practice. This study tested whether topical lidocaine would prevent or limit anorectal procedure-associated autonomic dysreflexia. PATIENTS AND METHODS: We enrolled patients with chronic, complete spinal cord injury scheduled for anoscopy and/or flexible sigmoidoscopy. In a double-blind fashion they were randomized to receive either 2% lidocaine jelly (n = 18) or nonmedicated lubricant (control; n = 32) just prior to the procedure. We measured blood pressure before, during, and after procedures. RESULTS: Mean maximal systolic blood pressure increased 35 +/- 25 mmHg in the lidocaine group vs. 45 +/- 30 mmHg in the control group (NS). However, there was a significant difference between anoscopic procedures and flexible sigmoidoscopies without anoscopy (49 +/- 29 vs. 25 +/- 20 mmHg). CONCLUSION: Topical lidocaine did not significantly limit or prevent autonomic dysreflexia in susceptible patients. Both anoscopy and flexible sigmoidoscopy caused significant blood pressure elevation. Anoscopy, which involves stretching of the anal sphincters, was a more potent stimulus for autonomic dysreflexia than flexible sigmoidoscopy, which involves gaseous distention of the rectosigmoid. Anal sphincter stretch and rectosigmoid distention, rather than a mucosal stimulus, are likely nociceptive triggers for procedure-associated autonomic dysreflexia.