A preliminary study of the effect of naldemedine tosylate on opioid-induced nausea and vomiting

  • Junya SatoEmail author
  • Rei Tanaka
  • Hiroshi Ishikawa
  • Tsutomu Suzuki
  • Michihiro Shino
Original Article



Opioid-induced nausea and vomiting (OINV) is induced by opioid receptor stimulation of chemoreceptor trigger zones and vestibular apparatus by opioids. Naldemedine tosylate (NALD) is a peripherally acting non-selective opioid receptor antagonist, used for opioid-induced constipation (OIC). However, the effect of NALD on OINV had not yet been investigated. In this retrospective study, we investigated the secondary effects of NALD on OINV.


Patients who received sustained-release oral morphine or oxycodone preparation were enrolled in the study. Patients who used NALD (0.2 mg) within 2 days of opioid initiation were included in the analysis. The use of rescue antiemetics within 7 days from opioid initiation was defined as OINV expression. Patients who received antiemetics before opioid initiation or those who received chemotherapy around 4 days from opioid initiation were excluded from the analysis. The incidence of OINV was compared between patients who used and did not use NALD.


In total, 982 patients were included in the study. Among them, 89 patients who received NALD and 614 patients who did not receive NALD were analyzed. The incidence of OINV in patients who used NALD was significantly lower than that of patients who did not use NALD (36.0% vs. 47.2%, p = 0.046).


For patients with constipation, using NALD at an early stage of opioid initiation might have secondary benefits, such as relief from OINV, besides improvement of OIC. To confirm the effectiveness of NALD for OINV, the symptom grade and intensity during concomitant use of NALD should be observed in a future study.


Naldemedine tosylate Opioid-induced nausea and vomiting Opioid-induced constipation Peripherally acting morphine antagonists Antiemetics 


Compliance with ethical standards

This study was performed in accordance with the Helsinki standard and approved by the Ethical Review Board of the Shizuoka Cancer Center (30-J90-30-1-3S).

Conflict of interest

The authors declare that they have no conflict of interest.


  1. 1.
    Coluzzi F, Rocco A, Mandatori I, Mattia C (2012) Non-analgesic effects of opioids (2012) opioid-induced nausea and vomiting: mechanisms and strategies for their limitation. Curr Pharm Des 18:6043–6052CrossRefGoogle Scholar
  2. 2.
    Stephenson J, Davies A (2006) An assessment of aetiology-based guidelines for the management of nausea and vomiting in patients with advanced cancer. Support Care Cancer 14:348–353CrossRefGoogle Scholar
  3. 3.
    Welliver M (2015) Histamine, neurokinin, and opioid receptor antagonism for nausea and vomiting. Gastroenterol Nurs 38:389–392. CrossRefGoogle Scholar
  4. 4.
    Japanease Society for palliative Medicine (2014) Clinical guidelines for cancer pain management, 2nd edn. KANAHARA&Co.,Ltd., Tokyo, p 183Google Scholar
  5. 5.
    Mallick-Searle T, Fillman M (2017) The pathophysiology, incidence, impact, and treatment of opioid-induced nausea and vomiting. J Am Assoc Nurse Pract 29:704–710. Google Scholar
  6. 6.
    Hardy JR, O'Shea A, White C, Gilshenan K, Welch L, Douglas C (2010) The efficacy of haloperidol in the management of nausea and vomiting in patients with cancer. J Pain Symptom Manag 40:111–116. CrossRefGoogle Scholar
  7. 7.
    Bruera E, Belzile M, Neumann C, Harsanyi Z, Babul N, Darke A (2000) A double-blind, crossover study of controlled-release metoclopramide and placebo for the chronic nausea and dyspepsia of advanced cancer. J Pain Symptom Manag 19:427–435CrossRefGoogle Scholar
  8. 8.
    Passik SD, Lundberg J, Kirsh KL, Theobald D, Donaghy K, Holtsclaw E, Cooper M, Dugan W (2002) A pilot exploration of the antiemetic activity of olanzapine for the relief of nausea in patients with advanced cancer and pain. J Pain Symptom Manag 23:526–532CrossRefGoogle Scholar
  9. 9.
    Corli O, Roberto A, Corsi N, Galli F, Pizzuto M (2018) Opioid switching and variability in response in pain cancer patients. Support Care Cancer 27:2321–2327. CrossRefGoogle Scholar
  10. 10.
    Streicher JM, Bilsky EJ (2017) Peripherally acting μ-opioid receptor antagonists for the treatment of opioid-related side effects: mechanism of action and clinical implications. J Pharm Pract 31:658–669. CrossRefGoogle Scholar
  11. 11.
    Hale M, Wild J, Reddy J, Yamada T, Arjona Ferreira JC (2017) Naldemedine versus placebo for opioid-induced constipation (COMPOSE-1 and COMPOSE-2): two multicentre, phase 3, double-blind, randomised, parallel-group trials. Lancet Gastroenterol Hepatol 2:555–564. CrossRefGoogle Scholar
  12. 12.
    Luthra P, Burr NE, Brenner DM, Ford AC (2018) Efficacy of pharmacological therapies for the treatment of opioid-induced constipation: systematic review and network meta-analysis. Gut. 68:434–444. CrossRefGoogle Scholar
  13. 13.
    Suzuki T, Sawada T, Kawai K, Ishihara Y (2018) Pharmacological profile of TAN-452, a novel peripherally acting opioid receptor antagonist for the treatment of opioid-induced bowel syndromes. Life Sci 215:246–252. CrossRefGoogle Scholar
  14. 14.
    Lazzari M, Greco MT, Marcassa C, Finocchi S, Caldarulo C, Corli O (2015) Efficacy and tolerability of oral oxycodone and oxycodone/naloxone combination in opioid-naïve cancer patients: a propensity analysis. Drug Des Devel Ther 9:5863–5872. CrossRefGoogle Scholar
  15. 15.
    Suzuki T, Nurrochmad A, Ozaki M, Khotib J, Nakamura A, Imai S, Shibasaki M, Yajima Y, Narita M (2005) Effect of a selective GABA(B) receptor agonist baclofen on the mu-opioid receptor agonist-induced antinociceptive, emetic and rewarding effects. Neuropharmacology 49:1121–1131CrossRefGoogle Scholar
  16. 16.
    Savarese JJ, Goldenheim PD, Thomas GB, Kaiko RF (1986) Steady-state pharmacokinetics of controlled release oral morphine sulphate in healthy subjects. Clin Pharmacokinet 11:505–510CrossRefGoogle Scholar
  17. 17.
    Reder RF, Oshlack B, Miotto JB, Benziger DD, Kaiko RF (1996) Steady-state bioavailability of controlled-release oxycodone in normal subjects. Clin Ther 18:95–105CrossRefGoogle Scholar
  18. 18.
    Campora E, Merlini L, Pace M, Bruzzone M, Luzzani M, Gottlieb A, Rosso R (1991) The incidence of narcotic-induced emesis. J Pain Symptom Manag 6:428–430CrossRefGoogle Scholar
  19. 19.
    Hanks G, Cherny N, Christakis NA, Fallon M, Kaasa S (2003) In: Doyle D, Hanks G, Cherny N, Calman K (eds) Opioid analgesic therapy. Oxford textbook of palliative medicine, 3rd edn. Oxford University Press, Oxford, pp 331–355Google Scholar
  20. 20.
    Murphy DB, Sutton JA, Prescott LF, Murphy MB (1997) Opioid-induced delay in gastric emptying: a peripheral mechanism in humans. Anesthesiology 87:765–770CrossRefGoogle Scholar
  21. 21.
    American Society of Clinical Oncology®, Cancer.Net, Doctor-Approved Patient Information. Accessed 25 Jan 2019
  22. 22.
    Cryer B, Drossman DA, Chey WD, Webster L, Habibi S, Wang M (2017) Analysis of nausea in clinical studies of lubiprostone for the treatment of constipation disorders. Dig Dis Sci 62:3568–3578. CrossRefGoogle Scholar
  23. 23.
    Katakami N, Harada T, Murata T, Shinozaki K, Tsutsumi M, Yokota T, Arai M, Tada Y, Narabayashi M, Boku N (2017) Randomized phase III and extension studies of Naldemedine in patients with opioid-induced constipation and Cancer. J Clin Oncol 35:3859–3866CrossRefGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of PharmacyShizuoka Cancer CenterNagaizumi-cho, Sunto-gunJapan
  2. 2.Addiction Research LaboratoryHoshi UniversityTokyoJapan

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