Analysis of the efficacy of measures to reduce pain after subcutaneous administration of epoetin alfa.

Pain at the injection site with subcutaneous administration of epoetin alfa preparations is a common adverse event, and sometimes precludes self-administration. The pain is caused mainly by the vehicle. The present studies were designed to assess whether pain after subcutaneous administration of the vehicle can be influenced by making the solution iso-osmotic, or by diluting the vehicle by the bacteriostatic agent benzyl alcohol saline (BAS). The volumes injected were 1 ml. We also determined whether reduction of the injected volume of 1 ml to 0.33 ml or to 0.1 ml could be of clinical importance. One millilitre of normal saline served as a placebo control. The studies were done in a double-blind, placebo-controlled, randomized order, cross-over fashion in healthy volunteers. Pain scores were obtained from visual analogue pain scales with no divisions and from 5-point verbal descriptive pain scales. Dilution of the vehicle with BAS resulted in significantly less pain (P < 0.0001) after subcutaneous injection, comparable to levels obtained with normal saline. Making the vehicle iso-osmotic had no effects. Injection of smaller volumes of the vehicle was beneficial with 0.1 ml (P < 0.0001), but the reduction to 0.33 ml was not statistically significant.