Pain comparison after subcutaneous administration of single-dose formulation versus multidose formulation of epogen in hemodialysis patients.

Subcutaneous (s.c.) injection is an approved route of administration for recombinant human erythropoietin (epoetin alfa). However, pain at the injection site with the single-dose formulation has limited its use. With the recent development of a multidose formulation containing benzyl alcohol as a preservative, anecdotal reports have emerged that suggest this product causes less stinging. Using a randomized, triple-blind, placebo-controlled crossover design, this study compared pain perception, intensity, and duration after s.c. injection with a multidose formulation versus single-dose formulation using visual analogue (VAS) and verbal descriptive pain scales (VDS). Twenty-eight hemodialysis patients received s.c. injections of placebo (normal saline) in one arm and either the multidose or single-dose formulation in the opposite arm. One week later, the subjects again received placebo in one arm and the other epoetin alfa formulation in the opposite arm. The VAS and VDS measurements were obtained at time 0 and then every 5 minutes for a period of 30 minutes. Results showed a statistically significant difference in pain perception between formulations at times 0, 10, and 15 minutes for both the VAS and VDS. In conclusion, there was a significant difference in pain perception between formulations with the multidose formulation causing less pain than the single-dose formulation. However, it should be noted that several patients reported no pain with the single-dose formulation. This indicates that individual patient response could be considered when deciding which formulation to use, although it may be difficult to implement an error-free distribution and administration system using the two different formulations.

Accuracy of technicians versus pharmacists in checking syringes prepared for a dialysis program.

The accuracy of pharmacy technicians versus pharmacists in checking drug doses prepared in syringes for a dialysis program was studied. Three pharmacy technicians from the pharmacy of a regional kidney disease program in Minnesota participated in the study after completing a training program and after common preparation errors had been identified by pharmacists. From November 1995 to April 1996, the technicians used labels printed from a database of pharmacist-verified orders to prepare and label i.v. syringes. Four medications were used-epoetin alfa, calcitriol, heparin prepared from beef lung, and heparin prepared from porcine intestinal mucosa. Each syringe was checked by one of nine pharmacists for accuracy of dose and medication, and all errors were recorded. The technicians checked syringes prepared by other technicians and also recorded errors. Accuracy rates (percentages of syringes correctly evaluated) for pharmacists and technicians were compared. A total of 10,608 syringes were checked. Accuracy rates for pharmacists and pharmacy technicians were 99.86% and 99.83%, respectively. Accuracy rates in checking syringes did not differ significantly between pharmacists and technicians in this study setting.

Blood pressure in hemodialysis patients during amelioration of anemia with erythropoietin.

This study analyzed blood pressure in hemodialysis patients treated with epoetin beta in multicenter trials. Antihypertensive drugs were prescribed as usual. Placebo-controlled trials compared epoetin (100 to 150 U/kg; N = 151) with placebo (N = 78) for 82 days. Hemoglobin (108 +/- 18 versus 75 +/- 14 g/L) (mean +/- SD) and diastolic blood pressure (84 +/- 14 versus 78 +/- 15 mm Hg) were greater (P less than 0.05) after epoetin. Clinically important increases in blood pressure (increases in diastolic blood pressure greater than or equal to 10 mm Hg and/or drug therapy) were more frequent with epoetin (58 versus 37%; P = 0.005). A dose-response trial compared epoetin, 25 U/kg (N = 42), 100 U/kg (N = 40), and 200 U/kg (N = 39) for 138 days. Increases in hemoglobin were dose dependent, but clinically important increases in blood pressure were not. In analyses of all patients treated with epoetin (N = 272), no baseline or final level of hemoglobin, or rate of hemoglobin rise, was a threshold for a rise in blood pressure. Patients requiring antihypertensive drugs or having uncontrolled hypertension (diastolic blood pressure greater than 90 mm Hg) at baseline had decreases in blood pressure (P less than 0.05) with antihypertensive therapy. Thus, compared with placebo, 21% of patients had clinically important increases in blood pressure during amelioration of anemia. The baseline or final levels of hemoglobin, the extent or rate of hemoglobin rise, or uncontrolled hypertension or antihypertensive drug use at baseline were not confirmed as risks. Antihypertensive drug therapy was important for blood pressure control.

Suppression of ventricular fibrillation and positive inotropic action of bethanidine sulfate, a chemical analog of bretylium tosylate that is well absorbed orally.

Bethanidine sulfate is a closely related chemical analog of bretylium that has virtually identical pharmacologic and antifibrillatory actions on the ventricle. Unlike bretylium, which is very poorly absorbed from the gut, bethanidine is rapidly and effectively absorbed after oral administration. Bethanidine increased ventricular fibrillation threshold in the normal dog heart from an average control value of 28.5 mA to an average peak value of 66.5 mA, an increase of 150 percent. In the infarcted heart, bethanidine increased ventricular fibrillation threshold from an average postinfarction level of 14.4 mA to an average peak value of 55.3 mA, an increase of 327 percent. Like bretylium, the antifibrillatory action of bethanidine was manifested by the appearance of nonsustained ventricular fibrillation when superthreshold shocks induced episodes of ventricular fibrillation lasting from 2 to 120 seconds and converting spontaneously to sinus rhythm. In contrast, the untreated dog heart must always be defibrillated electrically. The onset of antifibrillatory action began as early as 2 minutes after intravenous administration and 15 to 30 minutes after oral administration; peak action occurred in approximately 60 minutes. Bethanidine had prolonged positive inotropic action in the isolated heart as reflected by an increase in cardiac output and blood pressure lasting up to 60 minutes. Bethanidine lowered coronary vascular resistance and increased coronary blood flow. The oral efficacy and rapid onset of action gives bethanidine a potential role in the prevention of out-of-hospital ventricular fibrillation.