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Stability of octreotide acetate decreases in a sodium bisulfate concentration-dependent manner: compatibility study with morphine and metoclopramide injections
  1. Kouichi Tanabe1,2,
  2. Junko Wada1,
  3. Jun Ohkubo3,
  4. Atsumi Nitta1,
  5. Tomoaki Ikezaki3,
  6. Miyako Takeuchi3,
  7. Aya Handa3,
  8. Mai Tanaka3,
  9. Nozomu Murakami4,
  10. Tatsuhiko Kashii2,
  11. Hidenori Kitazawa3
  1. 1Department of Pharmaceutical Therapy & Neuropharmacology, Faculty of Pharmaceutical Sciences, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama, Japan
  2. 2Department of Medical Oncology, Toyama University Hospital, Toyama, Japan
  3. 3Department of Pharmacy, Saiseikai Takaoka Hospital, Takaoka, Japan
  4. 4Department of General and Digestive Surgery, Himi Municipal Hospital of Kanazawa Medical University, Kanazawa, Japan
  1. Correspondence to Dr Kouichi Tanabe, Department of Medical Oncology, Toyama University Hospital, 2630 Sugitani, Toyama City, Toyama Prefecture 930-0194, Japan; tanabe{at}


Purpose Sodium bisulfate is known to affect the stability of octreotide. However, the critical concentration of sodium bisulfate is not known. Therefore, we assessed the critical concentration of sodium bisulfate needed to preserve the stability of octreotide using actual drugs containing sodium bisulfate.

Methods Although morphine and metoclopramide preparations are considered to be compatible with octreotide, some of their products are known to contain sodium bisulfate. Thus, octreotide was mixed with preparations of sodium bisulfate solutions at serial concentrations and morphine and metoclopramide preparations containing sodium bisulfate, and octreotide stability was then evaluated using high performance liquid chromatography.

Results Octreotide concentrations decreased significantly at a sodium bisulfate concentration of 0.1 mg/mL or higher after 10 days when octreotide was mixed with sodium bisulfate solutions at various concentrations. A significant decrease in octreotide concentrations also occurred when it was mixed with morphine and metoclopramide preparations containing sodium bisulfate and stored for 10 days; however, slight decreases were observed in the mixture with both preparations and were within the clinically acceptable range for morphine preparations.

Conclusions These results indicate that the residual rate of octreotide decreases with time in a sodium bisulfate concentration-dependent manner when octreotide was mixed with morphine or metoclopramide. However, this incompatibility may be clinically acceptable when the final sodium bisulfate concentration is lower than 0.1 mg/mL and the mixed solution is used within 7 days.

  • sodium bisulfate
  • morphine
  • metoclopramide
  • compatibility

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