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 e‹cacy 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 eŠective in preventing the local venous pain caused by the DTIC injection; moreover, using Veen F for DTIC may also reduce the 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 eŠectiveness 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 speciˆed 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.) mg/mL with no shield and 1.9±0.2 mg/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 mg/mL). We also evaluated the eŠectiveness 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 signiˆcantly 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 beneˆcial because the shield prevents DTIC photodegradation, and that NSAIDs such as zaltoprofen are a promising premedication candidate for pain.
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