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Efficacy and Safety of Fentanyl Citrate Patch, Including a Low-Dose 0.5 mg Formulation, in Opioid-Naïve Patients with Cancer Pain

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Background and Objective

The use of transdermal fentanyl for opioid-naïve patients is restricted, however, transdermal fentanyl is a useful opioid analgesic for patients in whom oral administration is difficult or for those with renal failure. In this study, the efficacy and safety of fentanyl citrate patches was evaluated in opioid-naïve patients suffering from cancer pain.


An open-label uncontrolled study was conducted in opioid-naïve patients with cancer pain unable to be controlled by non-opioid analgesics. Fentanyl citrate patches starting at a low dose (0.5 mg/patch, corresponding to 6.25 μg/h fentanyl delivered) were applied once/day for up to 14 days. The analgesic effect was assessed every day from the visual analogue scale pain score and the number of doses of rescue medication. When improvement of the analgesic effect was “significant” or “moderate” at a certain dose for three consecutive days, the patient was classified as a “responder” and was considered to have “completed” the study.


A fentanyl citrate patch was administered to 208 of 209 enrolled patients. In the full-analysis set, 87.0% of the patients were “responders” (95% confidence interval 81.7–91.3%). In 148 patients, the optimum dose was low (0.5 mg in 99, and 1 mg in 49), with patients finishing the study on days 4–8. Following dose escalation to 4 mg, respiratory depression occurred in one patient; however, this was considered a mild adverse event.


A low-dose fentanyl citrate patch was effective in the management of cancer pain in opioid-naïve patients and was well tolerated.

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The authors would like to thank all the patients, investigators, and site staff involved in the study.

Author information

Authors and Affiliations



SY and EU provided advice about the study design, conduct of the study, interpretation of the data, and making a clinical study report. TT, KO, FH, and YT contributed to the study concept and design, the conduct of the study, and data analysis and interpretation. All of the listed authors were involved in critical review and revision of the manuscript and approved the final content.

Corresponding author

Correspondence to Fumitaka Hashimoto.

Ethics declarations


This work was supported by Hisamitsu Pharmaceutical Co., Inc. (Japan), the manufacturer of the fentanyl citrate patch.

Conflict of interest

SY has received honoraria from Hisamitsu Pharmaceutical Co., Inc., The Nakatomi Foundation, Ayumi Pharmaceutical Corporation, Maruho Co., Ltd., Maruishi Pharmaceutical Co., Ltd., Mochida Pharmaceutical Co., Ltd., Teikoku Seiyaku Co., Ltd., Kyowa Kirin Co., Ltd., Eisai Co., Ltd., Takeda Pharmaceutical Co., Ltd., Astellas Pharma Inc., Daiichi Sankyo Co., Ltd., Shionogi & Co., Ltd., Pfizer Japan Inc., Janssen Pharmaceutical K.K., Terumo Corporation, Mundipharma K.K., Taiho Phamaceutical Co., Ltd., Nippon Zoki Pharmaceutical Co., Ltd., MSD K.K., Taisho Toyama Pharmaceutical Co., Ltd., Covidien Japan Inc., AstraZeneca K.K., Mitsubishi Tanabe Pharma Corporation, Baxter Limited, Japan Tobacco Inc., Otsuka Pharmaceutical Factory, Inc., and Daiken Medical Co., Ltd.; and received donations from Hisamitsu Pharmaceutical Co., Inc. EU has received honoraria as a medical consultant from Hisamitsu Pharmaceutical Co., Inc. TT, KO, FH, and YT are employees of Hisamitsu Pharmaceutical Co., Inc.

Ethics approval

This study was conducted in agreement with the principles of the Declaration of Helsinki and its later amendments, and Good Clinical Practice. The institutional review board at each participating center approved the study protocol.


All patients gave written, informed consent to participate.

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The clinical study data are confidential.

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Yamaguchi, S., Uchida, E., Terahara, T. et al. Efficacy and Safety of Fentanyl Citrate Patch, Including a Low-Dose 0.5 mg Formulation, in Opioid-Naïve Patients with Cancer Pain. Clin Drug Investig 40, 1041–1052 (2020).

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