title: Efficacy of nalfurafine hydrochloride in patients with chronic liver disease with refractory pruritus: A randomized, double-blind trial.
abstract: OBJECTIVE
  Patients with chronic liver disease sometimes develop cholestasis, which induces severe whole-body pruritus that may disrupt daily activities and sleep. To determine the efficacy of nalfurafine hydrochloride (5 μg), which is a selective κ-opioid receptor agonist, in improving pruritus, we undertook a double-blind placebo-controlled study in patients with chronic liver disease with refractory pruritus. Nalfurafine hydrochloride at 2.5 μg was also used to evaluate the dose-response relationship.
  
  
  METHODS
  In total, 318 subjects were randomly assigned to receive the placebo or nalfurafine hydrochloride (2.5 or 5 μg) given orally once daily for 84 consecutive days. Pruritus was assessed based on the visual analog scale and pruritus scores.
  
  
  RESULTS
  Changes in the visual analog scale at week 4 (last observation carried forward) were significantly greater in the nalfurafine hydrochloride groups at 28.56 and 27.46 mm in the 2.5 μg and 5 μg groups, respectively, compared to 19.25 mm in the placebo group (P = 0.0022 and 0.0056, respectively). The major adverse drug reactions (ADRs) included pollakiuria (including nocturia), somnolence, insomnia (including middle insomnia), and constipation. Most ADRs were mild.
  
  
  CONCLUSIONS
  Nalfurafine hydrochloride (2.5 or 5 μg daily) was effective in the treatment of refractory pruritus in patients with chronic liver disease. Furthermore, no clinically significant ADRs were observed at either dose.
authors.affiliation: Department of Hepatology, Toranomon Hospital, Tokyo, Japan.
authors.forename: Hiromitsu
authors.initials: H
authors.lastname: Kumada
authors.affiliation: The 4th Department of Internal Medicine, Teikyo University School of Medicine, Mizonokuchi Hospital, Kanagawa, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Miyakawa
authors.affiliation: Department of Neuropsychiatry, Keio University School of Medicine, Tokyo, Japan.
authors.forename: Taro
authors.initials: T
authors.lastname: Muramatsu
authors.affiliation: Toray Industries, Inc., Tokyo, Japan.
authors.forename: Naoki
authors.initials: N
authors.lastname: Ando
authors.affiliation: Toray Industries, Inc., Tokyo, Japan.
authors.forename: Takanori
authors.initials: T
authors.lastname: Oh
authors.affiliation: Juntendo University Urayasu Hospital, Chiba, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Takamori
authors.affiliation: Department of General Internal Medicine, Saitama Medical University Hospital, Saitama, Japan.
authors.forename: Hidetomo
authors.initials: H
authors.lastname: Nakamoto
keywords: VAS; chronic liver disease; double-blind; nalfurafine hydrochloride; pruritus; κ-opioid receptor agonist