title: Efficacy and safety of a novel ĸ-agonist for managing intractable pruritus in dialysis patients.
abstract: BACKGROUND
  Our previous placebo-controlled, prospective, double-blind study demonstrated that a new opioid ĸ-receptor agonist, nalfurafine hydrochloride, effectively reduced treatment-resistant pruritus in 337 hemodialysis patients. Thus, we designed this study to evaluate prospectively the efficacy, safety, addiction liability, and pharmacokinetics of nalfurafine given orally for 1 year.
  
  
  METHODS
  This open-label study examined the effects and adverse drug reactions (ADRs) of 52-week oral administration of nalfurafine hydrochloride (5 µg/day) in 211 hemodialysis patients with a treatment-resistant itch.
  
  
  RESULTS
  Of 211 patients, 145 completed the study as scheduled. The mean pruritus value assessed by the visual analogue scale was 75.2 mm during the pre-observation period, which decreased significantly to 50.9 and 30.9 mm in week 2 and 52, respectively, indicating a long-lasting efficacy. ADRs occurred in 103 patients (48.8%). Frequent ADRs were insomnia (sleep disturbance, 19.4%), constipation (7.1%) and increased blood prolactin (3.3%), similar to previous reports. Regarding addiction liability, it appeared unlikely that nalfurafine hydrochloride was abused. After the start of treatment, plasma drug levels reached a steady state in week 2 with no apparent tendency of systemic accumulation.
  
  
  CONCLUSIONS
  Nalfurafine hydrochloride, orally administered at 5 µg/day for 52 weeks to hemodialysis patients, produced a long-term suppression of pruritus without significant safety problems.
authors.affiliation: Department of Nephrology and Endocrinology, National Defense Medical College, Tokorozawa, Japan. hkumagai@ndmc.ac.jp
authors.forename: Hiroo
authors.initials: H
authors.lastname: Kumagai
authors.forename: Toshiya
authors.initials: T
authors.lastname: Ebata
authors.forename: Kenji
authors.initials: K
authors.lastname: Takamori
authors.forename: Katsumasa
authors.initials: K
authors.lastname: Miyasato
authors.forename: Taro
authors.initials: T
authors.lastname: Muramatsu
authors.forename: Hidetomo
authors.initials: H
authors.lastname: Nakamoto
authors.forename: Masanao
authors.initials: M
authors.lastname: Kurihara
authors.forename: Tomoji
authors.initials: T
authors.lastname: Yanagita
authors.forename: Hiromichi
authors.initials: H
authors.lastname: Suzuki
mesh_terms: D000368:Aged; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007676:Kidney Failure, Chronic / Q000150:complications* / Q000628:therapy; D008297:Male; D008875:Middle Aged; D009019:Morphinans / Q000008:administration & dosage* / Q000009:adverse effects* / Q000493:pharmacokinetics; D017060:Patient Satisfaction; D011446:Prospective Studies; D011537:Pruritus / Q000188:drug therapy* / Q000209:etiology; D017473:Receptors, Opioid, kappa / Q000819:agonists*; D006435:Renal Dialysis; D013141:Spiro Compounds / Q000008:administration & dosage* / Q000009:adverse effects* / Q000493:pharmacokinetics; D011795:Surveys and Questionnaires; D016896:Treatment Outcome
chemical_list: D009019:Morphinans; D017473:Receptors, Opioid, kappa; D013141:Spiro Compounds; C111212:TRK 820