Consideration of Preventing Local Venous Pain by Dacarbazine.

Local venous pain caused by dacarbazine (DTIC) injection is due to its photodegradation product 5-diazoimidazole-4-carboxamide (Diazo-IC). The production of Diazo-IC can be decreased by protecting the drug from light. Furthermore, the production of Diazo-IC reportedly increases with time; however, there are no studies reporting the association between the injection preparation time and local venous pain caused by the DTIC injection. We evaluated the efficacy of the following: (1) method used to shorten the injection preparation time and (2) method used to change the diluting solution for DTIC. We found that shortening the injection preparation time tended to decrease the local venous pain expression due to DTIC, and Veen F decreased the production of Diazo-IC compared with the normal saline and 5% glucose solution. These results indicate that shortening the injection preparation time may be effective in preventing the local venous pain caused by the DTIC injection; moreover, using Veen F for DTIC may also reduce the pain.

[Methods for reducing dacarbazine photodegradation and its accompanying venous pain].

The anticancer drug dacarbazine (DTIC) is photosensitive, and the photodegradation product 5-diazoimidazole-4-carboxamide (diazo-IC) induces adverse reactions including local venous pain during intravenous injection. In this study we evaluated the effectiveness of colored shields (orange and red) to protect against photodegradation of DTIC as determined by ascertaining the concentration of diazo-IC. Samples were prepared and stored under four conditions: (1) no shield; (2) covered with an aluminum (opaque) shield; (3) covered with an orange shield; and (4) covered with a red shield. The samples were exposed to natural light for a specified time (0, 30, 60, 120, and 180 min) prior to measuring the concentration of diazo-IC by HPLC. We found that after 180 min, the diazo-IC concentration was 5.7±0.6 (S.D.) µg/mL with no shield and 1.9±0.2 µg/mL in both colored shield conditions. This production of diazo-IC under the colored shields was suppressed to a level similar to that under the aluminum shield (1.7±0.2 µg/mL). We also evaluated the effectiveness of NSAIDs (zaltoprofen, loxoprofen sodium, and diclofenac sodium) administered to mice prior to DTIC treatment on venous pain by counting their stretching and writhing reactions. Premedication with zaltoprofen significantly decreased expression of pain behavior in the DTIC-treated mice. These results suggest that storing DTIC under the protection of an orange or red shield is clinically beneficial because the shield prevents DTIC photodegradation, and that NSAIDs such as zaltoprofen are a promising premedication candidate for pain.