Naloxegol for opioid-induced constipation in patients with noncancer pain

New England Journal of Medicine

Volumn 370, Issue 25, 2014, Pages 2387-2396

  Chey, William D ^a   Webster, Lynn ^b   Sostek, Mark ^c   Lappalainen, Jaakko ^c   Barker, Peter N ^c   Tack, Jan ^d  

^a UNIVERSITY OF MICHIGAN MEDICAL SCHOOL   (United States)

^b PRA International   (United States)

^c ASTRAZENECA   (United Kingdom)

^d UNIVERSITY OF LEUVEN   (Belgium)

Author keywords

[No Author keywords available]

Indexed keywords

LAXATIVE; MORPHINE; NALOXEGOL; OPIATE; PLACEBO;

ABDOMINAL PAIN; ADULT; AGED; ARTHRALGIA; ARTHRITIS; ARTICLE; BACKACHE; CONSTIPATION; CONTROLLED STUDY; DEFECATION HABIT; DIARRHEA; DOUBLE BLIND PROCEDURE; DRUG DOSE COMPARISON; DRUG EFFICACY; DRUG FATALITY; DRUG INDUCED DISEASE; DRUG SAFETY; DRUG WITHDRAWAL; FEMALE; FIBROMYALGIA; FLATULENCE; HEADACHE; HUMAN; INTENTION TO TREAT ANALYSIS; MAJOR CLINICAL STUDY; MALE; MIGRAINE; MULTICENTER STUDY; NAUSEA; NEURALGIA; NONCANCER PAIN; OPIOID INDUCED CONSTIPATION; PAIN; PAIN ASSESSMENT; PHASE 3 CLINICAL TRIAL; PRIORITY JOURNAL; RANDOMIZED CONTROLLED TRIAL; TREATMENT DURATION; TREATMENT RESPONSE; UPPER ABDOMINAL PAIN; VERY ELDERLY; VOMITING; WITHDRAWAL SYNDROME;

ADULT; ANALGESICS, OPIOID; CONSTIPATION; DEFECATION; DOSE-RESPONSE RELATIONSHIP, DRUG; DOUBLE-BLIND METHOD; FEMALE; HUMANS; MALE; MIDDLE AGED; MORPHINANS; NARCOTIC ANTAGONISTS; PAIN; POLYETHYLENE GLYCOLS; RECEPTORS, OPIOID, MU;

EID: 84902589936     PISSN: 00284793     EISSN: 15334406     Source Type: Journal    
DOI: 10.1056/NEJMoa1310246     Document Type: Article

References (20)

1. The use of medicines in the United States: review of 2010. Parsippany, NJ: IMS Institute for Healthcare Informatics, 2011.
2. Holzer P. Methylnaltrexone for the management of unwanted peripheral opioid effects. Therapy 2008;5:531-43.
3. Bell TJ, Panchal SJ, Miaskowski C, Bolge SC, Milanova T, Williamson R. The prevalence, severity, and impact of opioid-induced bowel dysfunction: results of a US and European Patient Survey (PROBE 1). Pain Med 2009;10:35-42.
4. Kalso E, Edwards JE, Moore RA, McQuay HJ. Opioids in chronic non-cancer pain: systematic review of efficacy and safety. Pain 2004;112:372-80. (Pubitemid 39550738)
5. Tuteja AK, Biskupiak J, Stoddard GJ, Lipman AG. Opioid-induced bowel disorders and narcotic bowel syndrome in patients with chronic non-cancer pain. Neurogastroenterol Motil 2010;22:424-30, e96.
6. Panchal SJ, Müller-Schwefe P, Wurzelmann JI. Opioid-induced bowel dysfunction: prevalence, pathophysiology and burden. Int J Clin Pract 2007;61:1181-7. (Pubitemid 46934629)
7. Camilleri M. Opioid-induced constipation: challenges and therapeutic opportunities. Am J Gastroenterol 2011;106:835-42, quiz 843.
8. Rachinger-Adam B, Conzen P, Azad SC. Pharmacology of peripheral opioid receptors. Curr Opin Anaesthesiol 2011;24:408-13.
9. Pappagallo M. Incidence, prevalence, and management of opioid bowel dysfunction. Am J Surg 2001;182:Suppl:11S-18S. (Pubitemid 34072942)
10. Reimer K, Hopp M, Zenz M, et al. Meeting the challenges of opioid-induced constipation in chronic pain management - a novel approach. Pharmacology 2009;83:10-7.
11. Holzer P. New approaches to the treatment of opioid-induced constipation. Eur Rev Med Pharmacol Sci 2008;12:Suppl 1:119-27.
12. Diego L, Atayee R, Helmons P, Hsiao G, von Gunten CF. Novel opioid antagonists for opioid-induced bowel dysfunction. Expert Opin Investig Drugs 2011;20:1047-56.
13. Bream-Rouwenhorst HR, Cantrell MA. Alvimopan for postoperative ileus. Am J Health Syst Pharm 2009;66:1267-77.
14. Eldon MA, Song D, Neumann TA, et al. NKTR-118 (oral PEG-naloxol), a PEGylated derivative of naloxone: demonstration of selective peripheral opioid antagonism after oral administration in preclinical models. Presented at the 18th Annual Clinical Meeting of the American Academy of Pain Management, Las Vegas, September 27-30, 2007 (poster).
15. Chenard BL, Maynard GD, Brodbeck RM, Krause JE. G-protein coupled receptor inverse agonists: identification, pharmacological relevance and functional assays. Annu Rep Med Chem 2005;40:383-96.
16. Faassen F, Vogel G, Spanings H, Vromans H. Caco-2 permeability, P-glycoprotein transport ratios and brain penetration of heterocyclic drugs. Int J Pharm 2003;263:113-22. (Pubitemid 37087938)
17. Webster L, Dhar S, Eldon M, Masuoka L, Lappalainen J, Sostek M. A phase 2, double-blind, randomized, placebo-controlled, dose-escalation study to evaluate the efficacy, safety, and tolerability of naloxegol in patients with opioid-induced constipation. Pain 2013;154:1542-50.
18. Farrar JT, Young JP Jr, LaMoreaux L, Werth JL, Poole RM. Clinical importance of changes in chronic pain intensity measured on an 11-point numerical pain rating scale. Pain 2001;94:149-58. (Pubitemid 33016608)
19. Culpepper-Morgan JA, Inturrisi CE, Portenoy RK, et al. Treatment of opioid-induced constipation with oral naloxone: a pilot study. Clin Pharmacol Ther 1992;52:90-5.
20. Himmelsbach CK. The morphine abstinence syndrome, its nature and treatment. Ann Intern Med 1941;15:829-39.