Methylnaltrexone and Gastrointestinal Perforation

Mackey, Ann Corken; Green, Lanh; Greene, Patty; Avigan, Mark

doi:10.1016/j.jpainsymman.2010.01.011

Cited by 59 publications

(34 citation statements)

References 4 publications

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“…Methylnaltrexone should be used with caution in patients with gastrointestinal perforation, severe and persistent diarrhea, and disruptions in blood brain barrier (http:// www.accessdata.fda.gov/drugsatfda_docs/label/ 2014/021964s010lbl.pdf). In addition, there have been case reports of gastrointestinal perforation in association with methylnaltrexone therapy [Mackey et al 2010], and it has been suggested that there should be a titration phase before the recommended dose of methylnaltrexone is used.…”

Section: Methylnaltrexonementioning

confidence: 99%

Opioid-induced constipation: advances and clinical guidance

Nelson

Camilleri

2016

Therapeutic Advances in Chronic Disease

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Currently opioids are the most frequently used medications for chronic noncancer pain. Opioid-induced constipation is the most common adverse effect associated with prolonged use of opioids, having a major impact on quality of life. There is an increasing need to treat opioid-induced constipation. With the recent approval of medications for the treatment of opioid-induced constipation, there are several therapeutic approaches. This review addresses the clinical presentation and diagnosis of opioid-induced constipation, barriers to its diagnosis, effects of opioids in the gastrointestinal tract, differential tolerance to opiates in different gastrointestinal organs, medications approved and in development for the treatment of opioid-induced constipation, and a proposed clinical management algorithm for treating opioid-induced constipation in patients with noncancer pain.

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Section: Methylnaltrexonementioning

confidence: 99%

Opioid-induced constipation: advances and clinical guidance

Nelson

Camilleri

2016

Therapeutic Advances in Chronic Disease

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“…Naloxegol is effective in patients with OIC not responding to traditional laxatives [Garnock-Jones, 2015]. It seems to display a welltolerated profile, as severe AEs were not reported regarding bowel perforation that was noticed in seven patients treated with subcutaneously administered methylnaltrexone [Mackey et al 2010]. However, clinical studies of methylnaltrexone did not report such AEs and confirm its efficacy in patients with OIC [Siemens and Becker, 2016].…”

Section: Discussionmentioning

confidence: 99%

The role of naloxegol in the management of opioid-induced bowel dysfunction

Leppert

Woroń

2016

Therap Adv Gastroenterol

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Opioid-induced constipation (OIC) and other gastrointestinal (GI) symptoms of opioid-induced bowel dysfunction (OIBD) significantly deteriorate patients’ quality of life and may lead to noncompliance with opioid schedule and undertreatment of pain. Although traditional oral laxatives are the first-line treatment of OIC, they do not address OIBD pathophysiology, and display numerous adverse effects. OIC treatment includes prokinetics (lubiprostone), opioid switch, and changing route of opioid administration. Targeted management of OIBD comprises the use of purely peripherally acting μ-opioid receptor antagonists (PAMORA): naloxegol and methylnaltrexone. Naloxegol (NKTR-118) is a polymer conjugate of the opioid antagonist naloxone. The polyethylene glycol limits naloxegol capacity to cross the blood–brain barrier (BBB). Naloxegol is substrate for the P-glycoprotein (P-gp) transporter. The central nervous system penetration of naloxegol is negligible due to reduced permeability and its increased efflux across the BBB, related to P-gp transporter. Naloxegol antagonizes μ- and κ-opioid receptors and displays low affinity to δ-opioid receptors in the GI tract, thereby decreasing OIBD symptoms without reversing central analgesic effects. Naloxegol is metabolised through CYP3A4 to six metabolites, with the majority of the dose (68%) excreted with faeces and less (16%) with urine. The dose of naloxegol equals 25 mg administered orally once daily on a fasting condition. Mild or moderate hepatic impairment has no impact on naloxegol dosing; naloxegol was not studied and is not recommended in patients with hepatic failure. Dose reduction (12.5 mg once daily) and caution is recommended in patients with moderate-to-severe renal impairment. Efficacy (bowel movement in 42–49% of patients not responsive to laxatives) and safety of naloxegol were confirmed in studies conducted in patients with OIC and nonmalignant pain. Naloxegol may be useful for cancer patients with OIC, although studies in this population are lacking.

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“…Nausea, vomiting and flatulence were each reported in over 10% of patients. A reduction in opioid analgesic efficacy has been observed with supra-therapeutic doses (Jagla et al, 2014) (Mackey et al, 2010), some of these patients had an underlying organic GI disorder or surgery (e.g., metastatic colon cancer, volvulus) and during the period approximately 14,000 patients were billed for the medication.…”

Section: Treating Oic With Opioid Antagonistsmentioning

confidence: 99%

Management of opioid-induced constipation

2016

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Up to 40% of patients taking opioids develop constipation. Opioid induced constipation (OIC) may limit the adequate dosing of opioids for pain relief and reduce quality of life.Hence, healthcare providers must inquire about bowel function in patients receiving opioids.The management of OIC includes carefully reevaluating the necessity, type, and dose of opioids at each visit. Lifestyle modification and alteration of aggravating factors, the use of simple laxatives, and when essential, the addition of newer laxatives or opioid antagonists (naloxone, naloxegol or methylnaltrexone) can be used to treat OIC. This review discusses the recent literature regarding the management of OIC and provides a rational approach to assessing and managing constipation in individuals receiving opioids.Abstract word count -115

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Methylnaltrexone and Gastrointestinal Perforation

Cited by 59 publications

References 4 publications

Opioid-induced constipation: advances and clinical guidance

Opioid-induced constipation: advances and clinical guidance

The role of naloxegol in the management of opioid-induced bowel dysfunction

Management of opioid-induced constipation

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