Abstract
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. Palliat Med Pract 2019; 13, 3: 113–128
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