Naloxegol
Regulatory sources consulted
Approved indications
- Opioid-induced constipation in adults with inadequate response to laxatives.
Contraindications
Absolute
- Known or suspected gastrointestinal obstruction or high risk of recurrent obstruction; hypersensitivity to naloxegol or other opioid antagonists; use with strong CYP3A4 inhibitors.
Clinical warnings
- Major warning · It may cause gastrointestinal perforation, severe abdominal pain, severe diarrhea, or opioid-withdrawal symptoms; these symptoms require urgent assessment. — CIMA AEMPS / FDA label
Drug interactions
- HighStrong CYP3A4 inhibitors
Mechanism: They markedly increase naloxegol exposure.
Recommendation: Concomitant use is contraindicated according to the label.
CIMA AEMPS / FDA label
- ModerateModerate CYP3A4 inhibitors
Mechanism: They increase naloxegol exposure.
Recommendation: Start naloxegol at 12.5 mg and monitor adverse reactions.
CIMA AEMPS / FDA label
- HighStrong CYP3A4 inducers
Mechanism: They markedly reduce naloxegol exposure and may reduce efficacy.
Recommendation: Avoid concomitant use.
CIMA AEMPS / FDA label
- HighOther opioid antagonists
Mechanism: It may increase the risk of additive antagonist effects and opioid withdrawal.
Recommendation: Avoid concomitant use.
CIMA AEMPS / FDA label
Adverse events
Common (≥1%)
Abdominal pain · Diarrhea · Nausea
Rare but serious
Gastrointestinal perforation · Opioid withdrawal
Recent literature (PubMed)
The rise in opioid use for managing chronic and oncologic pain has led to a significant increase in opioid-induced constipation (OIC) that impacts patient quality of life and pain management. In this study, emerging therapies for OIC were criticized for refining advancements and novel treatment options. Key topics included the efficacy of peripherally acting mu-opioid receptor antagonists (PAMORAs) such as methylnaltrexone, naloxegol, and naldemedine, which specifically target opioid-induced gut dysfunction. Other treatment options, including intestinal secretagogues like lubiprostone and linaclotide, selective 5-HT receptor agonists such as prucalopride, and emerging adjunctive therapies like transcutaneous electrical nerve stimulation (TENS) and electroacupuncture were mentioned. Current guidelines from the American Gastroenterological Association (AGA) and the European consensus were criticized. Experts stress the importance of a stepwise approach to managing OIC, considering patient-specific factors and the efficacy of various treatments. While PAMORAs have demonstrated effectiveness in improving bowel function, their high cost and lack of extensive head-to-head comparisons with traditional laxatives are significant concerns. Emerging therapies and adjunctive treatments offer promising results but require further validation through rigorous studies. Future research should focus on long-term outcomes, cost-effectiveness, and comparative effectiveness to better address the complex needs of patients with OIC and refine treatment protocols.
Opioid-induced constipation (OIC) is a common condition in older adults who may not be responsive to traditional laxative therapy. OIC is defined as new or worsening constipation symptoms that occur with initiation of or altering the dose of opioid analgesia. For adult patients with OIC and noncancer pain, we recommend considering nonpharmacologic interventions (eg, dietary measures, increased physical activity, and biofeedback training) and over-the-counter laxatives, followed by prescription opioid receptor antagonists (methylnaltrexone, naloxegol, and naldemedine) if traditional over-the-counter laxatives fail. Other options may include lubiprostone, linaclotide, plecanatide, and prucalopride; however, these are not indicated for OIC specifically or studied in older adults. Because of the complex nature of absorption, distribution, metabolism, and excretion in the aging population, all agents used to treat OIC must be evaluated individually and reevaluated as patients continue to age. This review will serve as a guide to managing OIC in older adults.
Opioid-induced constipation (OIC) is a pervasive and distressing side effect of chronic opioid therapy in patients with cancer pain, significantly impacting their quality of life. Peripherally acting μ-opioid receptor antagonists (PAMORAS) were developed for treatment-resistant OIC but most studies were conducted with non-cancer patients. to discuss two oral formulations of PAMORAs, naldemedine and naloxegol, and to review available evidence of the effectiveness of these drugs for OIC in cancer patients. a comprehensive search to identify primary literature for either naldemedine or naloxegol for OIC in cancer patients. Only three prospective randomized, double-blind, placebo-controlled clinical trials for naldemedine enrolling cancer patients were identified; the results of a subgroup analysis of two of those studies and two non-interventional post marketing surveillance studies of these trials are also reported here. For naloxegol, only two randomized controlled trials were identified; both were unsuccessful in enrolling sufficient patients. An additional four prospective non-interventional observational studies with naloxegol were found that enrolled cancer patients. There were significantly higher rates of responders in the PAMORA groups than in the placebo groups. The most common side effect for both PAMORAs was diarrhea. All studies were industry-funded, and given that only three trials were randomized controlled studies, the overall quality of the studies was lacking. Naldemedine or naloxegol appeared safe and useful in the treatment of OIC in cancer patients and may improve their quality of life. Larger-scale randomized placebo-controlled studies of PAMORAs in cancer patients would strengthen existing evidence.