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Naldemedine: A Review in Opioid-Induced Constipation

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Abstract

Naldemedine [Symproic® (Japan; USA); Rizmoic® (EU)], an orally available peripherally acting μ-opioid receptor antagonist (PAMORA), is approved in several countries for the treatment of opioid-induced constipation. In phase III trials, naldemedine was more effective than placebo at increasing the frequency of bowel movements in patients with constipation induced by opioid treatment for cancer pain or chronic non-cancer pain. Naldemedine was also associated with improvements in patient-rated constipation-related symptoms and quality of life. Naldemedine was generally well tolerated, including over the longer term. Because naldemedine specifically targets opioid receptors in the gastrointestinal (GI) tract and does not cross the blood–brain barrier, it does not cause opioid withdrawal symptoms or interfere with centrally mediated opioid analgesia. Consistent with its mechanism of action, the most commonly reported adverse events were GI in nature. In conclusion, current data indicate that naldemedine is an effective and generally well-tolerated treatment option for opioid-induced constipation in patients with cancer pain or chronic non-cancer pain, with the convenience of once-daily oral dosing.

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References

  1. Viscusi ER. Clinical overview and considerations for the management of opioid-induced constipation in patients with chronic noncancer pain. Clin J Pain. 2019;35(2):174–88.

    Article  PubMed  Google Scholar 

  2. Farmer AD, Drewes AM, Chiarioni G, et al. Pathophysiology and management of opioid-induced constipation: European expert consensus statement. United Eur Gastroenterol J. 2019;7(1):7–20.

    Article  CAS  Google Scholar 

  3. Coyne KS, LoCasale RJ, Datto CJ, et al. Opioid-induced constipation in patients with chronic noncancer pain in the USA, Canada, Germany, and the UK: descriptive analysis of baseline patient-reported outcomes and retrospective chart review. Clinicoecon Outcomes Res. 2014;6:269–81.

    Article  PubMed  PubMed Central  Google Scholar 

  4. Rauck RL, Hong KJ, North J. Opioid-induced constipation survey in patients with chronic noncancer pain. Pain Pract. 2017;17(3):329–35.

    Article  PubMed  Google Scholar 

  5. Andresen V, Layer P. Medical therapy of constipation: current standards and beyond. Visc Med. 2018;34(2):123–7.

    Article  PubMed  PubMed Central  Google Scholar 

  6. Shionogi & Co Ltd. Symproic (naldemedine): Japanese prescribing information. 2017. http://www.pmda.go.jp. Accessed 24 June 2019.

  7. Shionogi & Co Ltd. Symproic® (naldemedine tablets for oral use): US prescribing information. 2019. https://dailymed.nlm.nih.gov. Accessed 24 June 2019.

  8. Shionogi. Rizmoic 200 micrograms film-coated tablets: summary of product characteristics. 2019. https://www.ema.europa.eu. Accessed 24 June 2019.

  9. Kanemasa T, Koike K, Arai T, et al. Pharmacologic effects of naldemedine, a peripherally acting μ-opioid receptor antagonist, in in vitro and in vivo models of opioid-induced constipation. Neurogastroenterol Motil. 2019;31(5):e13563.

    Article  CAS  PubMed  Google Scholar 

  10. Migoya E, Fukumura K, Yamada T, et al. Effect of naldemedine, a peripherally acting μ-opioid receptor antagonist on QT interval [abstract no. 426]. J Pain. 2016;17(Suppl 4):S81.

    Article  Google Scholar 

  11. Fukumura K, Yamada T, Yokota T, et al. The influence of renal or hepatic impairment on the pharmacokinetics, safety, and tolerability of naldemedine. Clin Pharmacol Drug Dev. 2019. https://doi.org/10.1002/cpdd.690.

    Article  PubMed  Google Scholar 

  12. Hale M, Wild J, Reddy J, et al. 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. 2017;2(8):555–64.

    Article  PubMed  Google Scholar 

  13. Katakami N, Harada T, Murata T, et al. Randomized phase III and extension studies of naldemedine in patients with opioid-induced constipation and cancer. J Clin Oncol. 2017;35(34):3859–66.

    Article  CAS  PubMed  Google Scholar 

  14. Webster LR, Nalamachu S, Morlion B, et al. Long-term use of naldemedine in the treatment of opioid-induced constipation in patients with chronic noncancer pain: a randomized, double-blind, placebo-controlled phase 3 study. Pain. 2018;159(5):987–94.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Saito Y, Yokota T, Arai M, et al. Naldemedine in Japanese patients with opioid-induced constipation and chronic noncancer pain: open-label phase III studies. J Pain Res. 2019;12:127–38.

    Article  PubMed  Google Scholar 

  16. Katakami N, Oda K, Tauchi K, et al. Phase IIb, randomized, double-blind, placebo-controlled study of naldemedine for the treatment of opioid-induced constipation in patients with cancer. J Clin Oncol. 2017;35(17):1921–8.

    Article  CAS  PubMed  Google Scholar 

  17. Webster LR, Yamada T, Arjona Ferreira JC. A phase 2b, randomized, double-blind placebo-controlled study to evaluate the efficacy and safety of naldemedine for the treatment of opioid-induced constipation in patients with chronic noncancer pain. Pain Med. 2017;18(12):2350–60.

    Article  PubMed  PubMed Central  Google Scholar 

  18. Tack J, Hale ME, Yamada T, et al. Safety and efficacy of naldemedine in the treatment of opioid-induced constipation in chronic non-cancer pain in subjects with or without inadequate response to laxatives [abstract no. P1738]. United Eur Gastroenterol J. 2018;6(Suppl 8):A700.

    Google Scholar 

  19. Camilleri M, Tack J, Cai B, et al. Naldemedine treatment of opioid-induced constipation improved patient-reported outcomes in subjects with chronic noncancer pain [abstract no. K2]. J Manag Care Spec Pharm. 2017;23(Suppl 3A):S80.

    Google Scholar 

  20. Katakami N, Harada T, Murata T, et al. Randomized phase 3 and extension studies: efficacy and impacts on quality of life of naldemedine in subjects with opioid-induced constipation and cancer. Ann Oncol. 2018;29(6):1461–7.

    Article  PubMed Central  Google Scholar 

  21. Larkin PJ, Cherny NI, La Carpia D, et al. Diagnosis, assessment and management of constipation in advanced cancer: ESMO clinical practice guidelines. Ann Oncol. 2018;29(Suppl 4):iv111–25.

    Article  CAS  PubMed  Google Scholar 

  22. Crockett SD, Greer KB, Heidelbaugh JJ, et al. American Gastroenterological Association institute guideline on the medical management of opioid-induced constipation. Gastroenterology. 2019;156(1):218–26.

    Article  PubMed  Google Scholar 

  23. Becker G, Siemens W. Opioid-induced constipation: reflections on efficacy assessment. Lancet Gastroenterol Hepatol. 2017;2(8):540–1.

    Article  PubMed  Google Scholar 

  24. Yagi Y, Kosugi K, Tanimoto T. Randomized phase III and extension studies of naldemedine in patients with opioid-induced constipation and cancer. J Clin Oncol. 2018;36(10):1049–50.

    Article  CAS  PubMed  Google Scholar 

  25. Luthra P, Burr NE, Brenner DM, et al. Efficacy of pharmacological therapies for the treatment of opioid-induced constipation: systematic review and network meta-analysis. Gut. 2018;38(3):434–44.

    Article  CAS  Google Scholar 

  26. Sridharan K, Sivaramakrishnan G. Drugs for treating opioid-induced constipation: a mixed treatment comparison network meta-analysis of randomized controlled clinical trials. J Pain Symptom Manag. 2018;55(2):468.e1–479.e1.

    Article  Google Scholar 

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Acknowledgements

During the review process, the manufacturer of naldemedine was also offered an opportunity to review this article. Changes resulting from comments received were made on the basis of scientific and editorial merit.

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  1. Springer Nature, Mairangi Bay, Private Bag 65901, Auckland, 0754, New Zealand

    Hannah A. Blair

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  1. Hannah A. Blair
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Correspondence to Hannah A. Blair.

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Funding

The preparation of this review was not supported by any external funding.

Conflict of interest

Hannah Blair is a salaried employee of Adis International Ltd/Springer Nature, is responsible for the article content and declares no relevant conflicts of interest.

Additional information

The manuscript was reviewed by:C. Ostgathe, Palliative Medicine, University of Erlangen, Erlangen, Germany; A. K. Tuteja, Division of Gastroenterology, George E. Wahlen VA Medical Center, University of Utah, Salt Lake City, UT, USA; A. Wald, Division of Gastroenterology and Hepatology, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA.

Additional information for this Adis Drug Evaluation can be found at https://doi.org/10.6084/m9.figshare.8323634.

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Blair, H.A. Naldemedine: A Review in Opioid-Induced Constipation. Drugs 79, 1241–1247 (2019). https://doi.org/10.1007/s40265-019-01160-7

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