Efficacy and safety of a novel ĸ-agonist for managing intractable pruritus in dialysis patients

Am J Nephrol. 2012;36(2):175-83. doi: 10.1159/000341268. Epub 2012 Aug 3.

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.

Publication types

  • Clinical Trial

MeSH terms

  • Aged
  • Double-Blind Method
  • Female
  • Humans
  • Kidney Failure, Chronic / complications*
  • Kidney Failure, Chronic / therapy
  • Male
  • Middle Aged
  • Morphinans / administration & dosage*
  • Morphinans / adverse effects*
  • Morphinans / pharmacokinetics
  • Patient Satisfaction
  • Prospective Studies
  • Pruritus / drug therapy*
  • Pruritus / etiology
  • Receptors, Opioid, kappa / agonists*
  • Renal Dialysis
  • Spiro Compounds / administration & dosage*
  • Spiro Compounds / adverse effects*
  • Spiro Compounds / pharmacokinetics
  • Surveys and Questionnaires
  • Treatment Outcome

Substances

  • Morphinans
  • Receptors, Opioid, kappa
  • Spiro Compounds
  • TRK 820