Onset of action of naldemedine in the treatment of opioid-induced constipation in patients with chronic noncancer pain: results from 2 randomized, placebo-controlled, phase 3 trials

Wild, James; Yamada, Tadaaki; Ferreira, Juan Camilo Arjona; Hale, M.

doi:10.1097/j.pain.0000000000001629

Cited by 11 publications

(14 citation statements)

References 18 publications

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“…Rauck et al [39], in a randomized, double-blind trial showed that oral formulation of methylnaltrexone is efficacious and well-tolerated for OIC. Naldemedine is a novel PAMORA recently approved for the treatment of OIC [40][41][42][43][44][45]. Spontaneous BM is achieved earlier with naldemedine (16.1 or 18.3 h) than with placebo (46.7 or 45.9 h, respectively) [41].…”

Section: Peripherally Acting μ-Opioid Receptor Antagonistsmentioning

confidence: 99%

“…Naldemedine is a novel PAMORA recently approved for the treatment of OIC [40][41][42][43][44][45]. Spontaneous BM is achieved earlier with naldemedine (16.1 or 18.3 h) than with placebo (46.7 or 45.9 h, respectively) [41]. Song et al [43] in a meta-analysis have suggested that naldemedine can improve the number of patients achieving spontaneous BM and its frequency.…”

Section: Peripherally Acting μ-Opioid Receptor Antagonistsmentioning

confidence: 99%

“…Naloxegol does not significantly inhibit the activity of CYP1A2, CYP2C9, CYP2D6, CYP3A4, CYP2C19, P-glycoprotein, breast cancer resistance protein, organic anion-transporter (OAT)1, OAT3, organic cation transporter-2, organic anion-transporting polypeptide (OATP)1B1, or OATP1B3, nor does it significantly induce the activity of CYP1A2, CYP2B6, or CYP3A4 [41].…”

Section: Naloxegolmentioning

confidence: 99%

See 2 more Smart Citations

Opioid-Induced Constipation in Oncological Patients: New Strategies of Management

Mesı́a

Echaburu

Gómez

et al. 2019

Curr. Treat. Options in Oncol.

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Opinion statementCancer-associated pain has traditionally been treated with opioid analgesics, often in escalating doses. Opioid-induced constipation (OIC) is a common problem associated with chronic use of opioid analgesics. Typical treatment strategies to alleviate constipation are based on dietary changes, exercise, and laxatives. However, laxatives have a nonspecific action and do not target underlying mechanisms of OIC. This article will review prevalent, clinical presentation and recommendations for the treatment of OIC. An independent literature search was carried out by the authors. We reviewed the literature for randomized controlled trials that studied the efficacy of laxatives, naloxone, and naloxegol in treating OIC. Newer strategies addressing the causal pathophysiology of OIC are needed for a more effective assessment and management of OIC. Finally, traditional recommended therapies are appraised and compared with the latest pharmacological developments. Future research should address whether naloxegol is more efficacious by its comparison directly with first-line treatments, including laxatives.

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Section: Peripherally Acting μ-Opioid Receptor Antagonistsmentioning

confidence: 99%

Section: Peripherally Acting μ-Opioid Receptor Antagonistsmentioning

confidence: 99%

Section: Naloxegolmentioning

confidence: 99%

See 1 more Smart Citation

Opioid-Induced Constipation in Oncological Patients: New Strategies of Management

Mesı́a

Echaburu

Gómez

et al. 2019

Curr. Treat. Options in Oncol.

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“…In an exploratory analysis [32], the onset of action of naldemedine was evaluated in two phase 3, randomized, placebo-controlled trials [29]. Proportion of patients experiencing a SBM within 24 hours of treatment initiation, time from initial dose to first SBM and weekly SBM frequency were assessed.…”

Section: Studies In Non-cancer Patientsmentioning

confidence: 99%

“…Naldemedine had a timely onset of effect, and GI adverse events largely resolved within the first week. These findings should assist clinicians counseling patients with chronic noncancer pain on expectations when initiating naldemedine for OIC [32]. In COMPOSE-4, 193 eligible patients were randomly assigned to naldemedine (n = 97) or placebo (n = 96).…”

Section: Studies In Non-cancer Patientsmentioning

confidence: 99%

The role of naldemedine in the treatment of patients with opioid-induced constipation

Leppert

2019

Palliat Med Pract

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Opioid-induced bowel dysfunction (OIBD) and opioid-induced constipation (OIC) significantly decrease patients' quality of life (QoL), lead to complications and opioid non-compliance resulting in pain exacerbation. Traditional laxatives are first-line preventive and therapeutic measures, although they display limited efficacy and several adverse effects (AE). Non-pharmacology measures, prokinetics, opioid switch, all have little evidence and do not target OIBD and OIC pathophysiology both associated with activation of predominantly µ-opioid receptors mostly peripherally in the gastrointestinal (GI) tract. A combination of prolonged-release (PR) oxycodone with PR naloxone in one tablet with a ratio of 2:1 is available, although limitations include maximal daily dose of 160 mg/80 mg, respectively, and normal liver function. Peripherally acting µ-opioid receptor antagonists (PAMORA) block opioid receptors in the GI tract without compromising analgesia as they do not cross the blood-brain barrier. Currently three drugs are available: methylnaltrexone, naloxegol and naldemedine. Naldemedine has proven efficacy superior to placebo in the treatment of OIC in both cancer and non-cancer patients while improving patient-reported constipation symptoms and patients' QoL. It is well tolerated with mostly mild to moderate intensity GI adverse effects such as abdominal, pain, nausea, and diarrhea, without compromising analgesia. Naldemedine dosing is convenient as it is administered once daily by an oral route. Moreover, naldemedine may be safely used in patients with renal failure and mild to moderate hepatic impairment. Effective prevention and treatment of OIC is of paramount importance in patients receiving long-term opioid therapy.

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The safety and effectiveness of naldemedine for opioid-induced constipation in patients with advanced cancer in real-world palliative care settings: a multicenter prospective observational study

Shimizu,

Maeda,

Kessoku

et al. 2024

Support Care Cancer

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Onset of action of naldemedine in the treatment of opioid-induced constipation in patients with chronic noncancer pain: results from 2 randomized, placebo-controlled, phase 3 trials

Abstract: Naldemedine improves opioid-induced constipation in a timely manner in patients using opioids for noncancer pain; most experienced spontaneous bowel movement within 24 hours of treatment.

Cited by 11 publications

References 18 publications

Opioid-Induced Constipation in Oncological Patients: New Strategies of Management

Opioid-Induced Constipation in Oncological Patients: New Strategies of Management

The role of naldemedine in the treatment of patients with opioid-induced constipation

The safety and effectiveness of naldemedine for opioid-induced constipation in patients with advanced cancer in real-world palliative care settings: a multicenter prospective observational study

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