Opioid-induced Constipation In Adults Research Articles

Naldemedine for the treatment of opioid-induced constipation in adults with chronic noncancer pain.

This review aims to summarize the efficacy data for naldemedine, a member of the novel peripherally acting μ-opioid receptor antagonists (PAMORAs), which gained USFDA approval for the treatment of opioid-induced constipation in adults with chronic noncancer pain-related syndromes in 2017. In Phase III trials, patients receiving naldemedine were significantly more likely to meet the primary end point≥3 spontaneous bowel movements/week and an increase of ≥1 spontaneous bowel movement/week from baseline for at least 9/12 weeks compared to placebo (p < 0.0001). The most frequent adverse events were abdominal pain (8%) and diarrhea (7%). Based on available data, naldemedine appears to be an effective and safe first-line therapy for the treatment of opioid-induced constipation in adults with chronic noncancer pain.

Methylnaltrexone: Peripherally Acting μ-Opioid Receptor Antagonist

Opioid-induced constipation (OIC) is a common adverse effect associated with opioid therapy, with many patients never developing tolerance to this effect. There are many traditional laxatives available to help patients combat this symptom, yet OIC may not reliably respond to conventional treatment. Peripherally acting µ-opioid receptor antagonists (PAMORAs) have a place in the treatment of refractory OIC, when traditional laxatives have not resulted in effective laxation. There are a number of PAMORAs now available, and methylnaltrexone is the only PAMORA indicated for the treatment of OIC in adults with advanced illness, as well as for patients with chronic noncancer pain, including patients with chronic pain related to prior cancer treatment who do not require frequent opioid escalation. Advanced practitioners need to have an understanding of how and when to best use these medications for the different indications in patients with advanced illness or chronic noncancer-related pain.

Treatment with Methylnaltrexone in Patients with Opioid-Induced Constipation with or Without Active Cancer (S812)

1.Describe that methylnaltrexone is equally effective in treating opioid-induced constipation in patients with advanced illness with and without active cancer.2.Articulate that treatment with methylnaltrexone does not increase pain scores in patients treated with opioids for pain due to advanced illnesses independent of cause. Subcutaneous (SC) methylnaltrexone is approved for opioid-induced constipation (OIC) in adults with chronic non-cancer pain and OIC in adults with advanced illness or with active cancer who require opioid dosage escalation for palliative care. Post hoc analysis of pooled data from 3 randomized studies of patients with advanced illness and OIC. Patients received single doses of SC MNTX 0.15 or 0.30 mg/kg or placebo (study 301); SC MNTX 0.15 mg/kg or placebo every other day for 2 weeks (study 302); and SC MNTX 8 or 12 mg in patients 38–<62 or ≥62 kg, respectively, or placebo every other day for 2 weeks (study 4000). Data were stratified by those with/without cancer. Efficacy endpoints included laxation ≤4 hours and rescue-free laxation (RFL) ≤24 hours after the first dose; time to RFL; and pain scores. Median baseline opioid use was higher in cancer (MNTX: 190 mg/d, n=198; placebo: 200 mg/d, n=157) versus non-cancer patients (MNTX: 120.0 mg/d, n=82; placebo: 80.0 mg/d, n=80). MNTX significantly increased the percentage of patients with a laxation response ≤4 hours and RFL ≤24 hours after the first dose in cancer (MNTX: 61.1% and 71.2% vs placebo: 15.3% and 41.4%, respectively; P<0.0001) and non-cancer patients (MNTX: 62.2% and 74.4% vs placebo 17.5% and 37.5%, respectively; P<0.0001). MNTX significantly reduced the median time to RFL at 4 hours in cancer (MNTX: 1.1 h, placebo: >4 h; P≤0.0001) and non-cancer patients (MNTX: 1.1 h, placebo: >4 h; P≤0.0001). Mean changes in pain scores were similar (cancer patients, MNTX: −0.4 vs placebo: −0.2; non-cancer patients, MNTX: −0.4 vs placebo: −0.4). MNTX increased laxation responses and improved clinical signs of constipation in OIC patients with/without cancer.

Analysis of Patient-Provider Interactions Regarding the Burden and Treatment of Opioid-Induced Constipation in Adults with Chronic Noncancer Pain.

This analysis of patient-health care provider discussions of opioid-induced constipation (OIC) evaluated the dynamics of interactions, identified communication gaps, and assessed the functional burden of opioid-induced constipation on patients' lives. Retrospective analysis of a Health Insurance Portability and Accountability Act-compliant database of >120,000 patient-provider conversations. Outpatient offices in the United States. Conversations between providers and patients prescribed opioids that occurred in the United States (January 2014-May 2016) and included a discussion of opioid-induced constipation were identified. Demographics and prespecified opioid-induced constipation conversation characteristics were evaluated for these conversations. This analysis included 216 patient-provider discussions. Most patients (76.4% [165/216]) were ≥50 years old. Most conversations were with pain management specialists (39.8% [86/216]) or primary care physicians (36.6% [79/216]). Overall, 64.4% (139/216) of patients reported experiencing symptoms of constipation. Health care providers indicated that symptoms of constipation could be caused by opioid use for 75.5% (105/139) of patients with constipation. In most cases (82.4% [178/216]), providers did not probe about specific constipation symptoms. Few patients (11.5% [16/139]) with OIC discussed the burden of OIC with their providers; burdens reported by patients with OIC included emergency room visits and reduced food or fluid intake. No specific action was recommended for 33.8% (47/139) of patients with constipation. In this analysis, when opioid-induced constipation was discussed, health care providers did not inquire about specific symptoms for most patients, opioids were not cited as a cause of constipation in approximately one-quarter of patients with opioid-induced constipation, and no clear treatment plan or guidance was recommended for one-third of patients. Results of this analysis suggest that more education may be needed to improve patient-provider communication about opioid-induced constipation.

Methylnaltrexone bromide for the treatment of opioid-induced constipation

ABSTRACTIntroduction: The extensive and alarming use of opioids for pain management in patients with chronic pain receiving palliative care is associated with non-tolerable gastrointestinal (GI) adverse effects. Opioid-induced constipation (OIC) is the most common adverse effect impairing patient quality of life (QOL). In addition, OIC is one of the treatment limiting consequences of opioid analgesics. Management of OIC is becoming a challenge since traditional laxatives have limited efficiency. Peripherally acting mu-opioid receptor antagonists (PAMORA) have been developed for the treatment of OIC with methylnaltrexone bromide being the first approved to treat OIC in adults with advanced illness undergoing palliative care.Areas covered: The authors systematically review the clinical evidence for methylnaltrexone bromide including a review of the pharmacokinetic and pharmacodynamic data along with clinical effectiveness and cost-effectiveness. Though there is a need for further long-term clinical investigation, there is a large body of evidence for both its efficacy and safety in the treatment of OIC.Expert opinion: Methylnaltrexone has both subcutaneous injection and oral dosage forms available in the market. The lack of more evidence in specific populations such as pregnant women, pediatrics and elderly still remains. The global consumption of methylnaltrexone shows a projection of increased use since its approval worldwide in 2008.

Spotlight on naldemedine in the treatment of opioid-induced constipation in adult patients with chronic noncancer pain: design, development, and place in therapy.

Opioid-induced constipation (OIC) is an increasingly prevalent problem in the USA due to the growing use of opioids. A novel class of therapeutics, the peripherally acting μ-opioid receptor antagonists (PAMORAs), has been developed to mitigate the deleterious effects of opioids in the gastrointestinal tract while maintaining central analgesia and minimizing opioid withdrawal. This review aimed to summarize the literature on naldemedine, the third PAMORA to gain US Food and Drug Administration (FDA) approval for the treatment of OIC in adults with chronic noncancer pain-related syndromes. Naldemedine has a chemical structure similar to naltrexone, an opioid receptor antagonist, with chemical modifications that limit its ability to cross the blood–brain barrier. Naldemedine was evaluated in two Phase II and three Phase III clinical trials prior to gaining FDA approval. In two pivotal identical Phase III trials, COMPOSE-I (NCT 01965158) and COMPOSE-II (NCT 01993940), patients receiving naldemedine were significantly more likely to respond when compared with placebo (COMPOSE-I: 47.6 vs 34.6%, P=0.002 and COMPOSE-II: 52.5 vs 33.6%, P<0.0001). The most frequent adverse events were abdominal pain (8%) and diarrhea (7%) – rates similar to the other PAMORAs. Based on the available data, naldemedine appears to be an effective and safe drug for the treatment of OIC in adults with chronic noncancer pain.

Naloxegol for managing opioid-induced constipation

Naloxegol is a peripherally acting mu-opioid receptor antagonist for opioid-induced constipation in adults with chronic noncancer pain. This drug's once-daily oral formulation can be used as monotherapy and helps to decrease the constipating effects of opioid therapy; however, it has been associated with abdominal pain.

Opioid-induced constipation in chronic noncancer pain.

Opioid-based management of noncancer pain has become much more prevalent over the last 2 decades and is responsible for a wide range of side-effects, particularly affecting the intestinal tract causing opioid-induced constipation (OIC). This review will consider results of recent clinical trials that have provided evidence of new pharmacological management options for the treatment of OIC. Supportive use of conventional agents, such as stool softeners, osmotic laxatives, and stimulating laxatives in OIC has limited efficacy. The peripheral μ-opioid receptor antagonist (PAMORA) methylnaltrexone (MNTX) was first FDA approved for OIC in patients with advanced illness and later also for OIC in noncancer pain patients; clinical trial results indicated MNTX did not reverse opioid analgesia and did not trigger central opioid withdrawal. Another PAMORA, the orally available naloxegol, has also gained recent FDA approval for the treatment of OIC in adults with chronic, noncancer pain. Lubiprostone, a bicyclical fatty acid acting via activation of intestinal chloride channel-2 (ClC-2), was also approved for OIC treatment in patients with noncancer pain. PAMORA MNTX and naloxegol and the intestinal chloride channel-2 (ClC-2) activator lubiprostone represent additional possible therapeutic options for the management of OIC in patients with chronic noncancer pain.

Naloxegol for Treating Opioid-Induced Constipation n Patients with Non-Cancer Pain (S710)

•Become familiar with the safety and efficacy profile of naloxegol as a treatment for opioid-induced constipation in patients with chronic non-cancer pain.•Understand the mechanism of action of peripherally acting mu-opioid receptor antagonists and how this method of action differs from that of standard laxatives. Opioid-induced constipation (OIC) affects 40%–80% of patients receiving opioids to manage chronic non-cancer pain, which can negatively impact quality of life and effective pain management. OIC results when opioid agonist effects at mu-opioid receptors in the enteric nervous system reduce gastrointestinal (GI) transit and secretions. Over-the-counter laxatives are often ineffective. Naloxegol is an approved, orally administered, peripherally acting mu-opioid receptor antagonist (PAMORA) that specifically targets the mechanism of OIC. To summarize phase 3 clinical trial data for naloxegol. Data were reviewed from two phase 3 randomized, double-blind, 12-week studies conducted in outpatients with non-cancer pain and OIC (KODIAC-04, [NCT01309841]; KODIAC-05, [NCT01323790]) and a 52-week, phase 3 safety study (KODIAC-08 [NCT01336205]). KODIAC-04 (n=652) and KODIAC-05 (n=700) compared the efficacy (primary endpoint: response over 12 weeks) and safety of daily administration of naloxegol 12.5 or 25 mg vs. placebo. A key secondary endpoint included the 12-week response rate in laxative users with OIC symptoms. Both studies reported significantly higher response rates for naloxegol 25 mg vs. placebo in the overall population and among laxative users with OIC symptoms. KODIAC-08 (n=844) compared the safety and tolerability of naloxegol with usual care, and demonstrated a long-term safety profile similar to that seen in the 12-week studies. In all three studies, most common adverse events (AEs) on naloxegol were GI AEs, which occurred early in treatment, were mild or moderate in severity, and resolved during treatment or after discontinuation. Pain scores and opioid doses remained stable. The mechanism of action of naloxegol will be discussed. Naloxegol is a safe and efficacious treatment for OIC in adults with chronic non-cancer pain.

▼Naloxegol for opioid-induced constipation

▼Naloxegol (Moventig—AstraZeneca) is a peripherally acting mu-opioid receptor antagonist licensed for the treatment of opioid-induced constipation in adults who have had an inadequate response to laxative treatment.1 It was launched...

(444) Treatment with naloxegol versus placebo: pain assessment in patients with noncancer pain and opioid-induced constipation

Opioid-induced constipation (OIC) is a deleterious consequence of opioid treatment in patients with chronic pain. Naloxegol is a peripherally acting mu-opioid receptor antagonist with negligible CNS penetration and is FDA-approved for the treatment of OIC in adults with chronic noncancer pain. Two phase 3 randomized, double-blind, 12-week studies investigated the effects of daily oral administration of naloxegol 12.5 or 25 mg vs placebo on pain and opioid use in outpatients with OIC and noncancer pain.

Naloxegol: New treatment for opioid-induced constipation

Naloxegol: New treatment for opioid-induced constipation

Using methylnaltrexone in opioid-induced constipation

Methylnaltrexone (Relistor) is the first peripherally-acting mu (¼)-opioid receptor antagonist to be licensed for the treatment of opioid-induced constipation in adults with advanced illness receiving palliative care, when response to regular laxative therapy has been inadequate. Methylnaltrexone is a new drug in its own classification. It is not classed as a laxative but is designed to target the underlying cause of opioid-induced constipation by reversing the peripheral effects of opioids on the gastrointestinal tract. This article explores the uniqueness of the drug and how it has been used in clinical practice at the London Bridge Hospital.

Relistor approved for opioid-related constipation

FDA has approved the marketing of methylnaltrexone bromide subcutaneous injection for the treatment of opioid-induced constipation in adults receiving palliative care for advanced illness. The product is sold by Wyeth Pharmaceuticals under the brand name Relistor. FDA-approved labeling for