Decrease in Venous Irritation by Adjusting the Concentration of Injected Bendamustine

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  • Watanabe Hiroyuki
    Department of Pharmacy, Kyushu University Hospital
  • Ikesue Hiroaki
    Department of Pharmacy, Kyushu University Hospital
  • Tsujikawa Tomoko
    Department of Pharmacy, Kyushu University Hospital
  • Nagata Kenichiro
    Department of Pharmacy, Kyushu University Hospital
  • Uchida Mayako
    Department of Pharmacy, Kyushu University Hospital
  • Suetsugu Kimitaka
    Department of Pharmacy, Kyushu University Hospital
  • Egashira Nobuaki
    Department of Pharmacy, Kyushu University Hospital
  • Muta Tsuyoshi
    Department of Medicine and Biosystemic Science, Kyushu University Graduate School of Medical Sciences
  • Kato Koji
    Department of Medicine and Biosystemic Science, Kyushu University Graduate School of Medical Sciences
  • Takenaka Katsuto
    Department of Medicine and Biosystemic Science, Kyushu University Graduate School of Medical Sciences
  • Ohga Saiji
    Department of Clinical Radiology, Kyushu University Graduate School of Medical Sciences
  • Matsushima Takamitsu
    Department of Medicine and Bioregulatory Science, Kyushu University Graduate School of Medical Sciences
  • Shiratsuchi Motoaki
    Department of Medicine and Bioregulatory Science, Kyushu University Graduate School of Medical Sciences
  • Miyamoto Toshihiro
    Department of Medicine and Biosystemic Science, Kyushu University Graduate School of Medical Sciences
  • Teshima Takanori
    Center for Cellular and Molecular Medicine, Kyushu University Hospital
  • Akashi Koichi
    Department of Medicine and Biosystemic Science, Kyushu University Graduate School of Medical Sciences
  • Oishi Ryozo
    Department of Pharmacy, Kyushu University Hospital

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Intravenous injection of bendamustine often causes venous irritation and also deteriorates the patient’s quality of life. Thus, we evaluated the risk factors associated with venous irritation induced by bendamustine in patients with follicular lymphoma or mantle cell lymphoma. We also evaluated the effectiveness of intervention of changing the preparation procedure for bendamustine. All data were retrospectively collected from the electronic medical record system. In the initial analysis of the total 43 courses of bendamustine therapy, most patients (88%) were administered bendamustine with 250 mL of diluent according to the bendamustine package insert in Japan. The median concentration of bendamustine solution (0.56 mg/mL vs. 0.24 mg/mL) and the incidences of venous irritation (66% vs. 0%, p=0.01) were significantly different between the patients receiving bendamustine at 250 mL and 500 mL of diluent. Based on this result, we proposed changing the final volume of bendamustine dissolution from 250 to 500 mL, which is recommended in other countries. After this intervention, the incidence of venous irritation was significantly reduced from 58 to 20% (p=0.02). The incidence of venous irritation increased in a concentration-dependent manner (≤0.40 mg/mL: 6%; 0.41–0.60 mg/mL: 62%, p<0.001; >0.60 mg/mL: 75%, p<0.001). We conclude that a high concentration bendamustine solution is a risk factor for venous irritation and that 500 mL of diluent is ideal. To further reduce the incidence of venous irritation, the concentration of bendamustine solution is recommended to be 0.40 mg/mL or less.

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