<p>Naldemedine: A New Option for OIBD</p>

Abstract

Opioid-induced bowel dysfunction (OIBD) is a common complication in longterm opioid users and abusers. It is a burdensome condition, which significantly limits quality of life and is associated with increasing health costs. OIBD affects up to 60% of patients with chronic non-cancer pain and over 80% of patients suffering from cancer pain and is one of the conditions of the most common symptoms associated with opioid maintenance. Given the continued use of opioids for chronic pain management in appropriate patients, OIBD is likely to persist in clinical practice in the coming years. We will herein review its underlying pathophysiological mechanisms and the available treatments. In the last years, pharmaceutical research has focused on the opportunity of targeting peripheral muopioid receptors without affecting their analgesic activity in the central nervous system, and several peripherally acting mu-opioid receptors antagonists (PAMORAs) drugs have been approved. We will mainly focus on naldemedine, discussing its pharmacological properties, its clinical efficacy and side effects. Head-to-head comparisons between naldemedine and the other PAMORAs are not available yet, but some considerations will be discussed based on the pharmacological and clinical data. As a whole, the available data suggest that naldemedine is a valid treatment option for OIBD, as it is a well-tolerated drug that alleviates constipation without affecting analgesia or causing symptoms of opioid withdrawal.

Computational Prediction of Potential Inhibitors of the Main Protease of SARS-CoV-2

“…Most infected COVID-19 patients have been managed in non-critical areas; therefore, in this context, the oral route of administration can be considered feasible, alongside with intravenous injections. Naldemedine, which is an oral peripherally acting μ-opioid receptor antagonist (PAMORA), indicated for opioid-induced constipation (Coluzzi et al, 2020 ), may represent a practicable alternative in less severe COVID-19 patients. Its use, in healthy subjects, was associated with a slight increase in the incidence of diarrhea (Fukumura et al, 2018 ).…”

What to Do and What Not to Do in the Management of Opioid-Induced Constipation: A Choosing Wisely Report

“…In Italy, these medications are indicated for the treatment of OIC in all patients receiving long-term opioid therapy [ 34 ]. Methylnaltrexone is administered by subcutaneous injection and therefore has limited application for OIC given the invasive nature of treatment [ 35 ], whereas naloxegol and naldemedine are available in once-daily oral formulations and therefore have broader utility for the treatment of OIC [ 36 , 37 ]. In placebo-controlled phase III studies (COMPOSE-4 and COMPOSE-5), naldemedine improved the number of spontaneous bowel movements and produced corresponding increases in QoL without influencing opioid analgesia or producing symptoms of opioid withdrawal among individuals with OIC who were taking an opioid for cancer pain [ 38 , 39 ].…”

Impact and Consequences of Opioid-Induced Constipation: A Survey of Patients

“…These include the peripherally acting m-opioid receptors antagonists (PAMORAs) [14][15][16]. PAMORAs are a particularly promising class of agents for OIC [17]. Among these, in addition to methylnaltrexone bromide and naloxegol, naldemedine has recently been approved for OIC.…”

“…Among these, in addition to methylnaltrexone bromide and naloxegol, naldemedine has recently been approved for OIC. These mechanism-based treatments for OIC are valid treatment options, since they are well tolerated, do not affect analgesia, and do not cause symptoms of opioid withdrawal [ 17 ]. In Italy, methylnaltrexone bromide, naloxegol and naldemedine are all reimbursed by the National Healthcare System for OIC in adult patients on chronic opioid therapy who are resistant to at least two laxatives [ 18 ].…”