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Palliative care
Published in Peter Hoskin, Peter Ostler, Clinical Oncology, 2020
Methylnaltrexone is a specific μ-opioid receptor antagonist in the bowel and effective in difficult cases of opioid-induced constipation. If required subcutaneous injection could be given under the supervision of a physician as it may cause acute diarrhoea.
Cancer Pain
Published in Gary W. Jay, Practical Guide to Chronic Pain Syndromes, 2016
Constipation occurs in the majority of those requiring opioids for pain control, and prevention is usually effective using a combination stimulant laxative/softener, such as senna and docusate. As the dose of opioid is increased, the dose of laxative/softener generally needs to be titrated upward. If patients are unable to swallow or are too weak to generate the maneuvers necessary to evacuate the stool, laxative suppositories (such as bisacodyl) are indicated. Dietary changes, bulking agents such as methylcellulose, and increased fluid intake are rarely sufficient to counteract the constipating effects of opioid therapy in people with cancer. Methylnaltrexone is a peripherally acting opioid antagonist that has been shown to reliably reverse the effects of opioid-induced constipation when given subcutaneously at a dose of 0.15 mg/kg. The majority of patients respond within four hours (20).
Investigational opioid antagonists for treating opioid-induced bowel dysfunction
Published in Expert Opinion on Investigational Drugs, 2018
Shilan Mozaffari, Shekoufeh Nikfar, Mohammad Abdollahi
Methylnaltrexone (Relistor) is the first approved PAMORA [13,15]. United States (FDA) has approved methylnaltrexone in 2008 for OIC treatment in patients with long-term use of opioids as palliative care. It is prescribed when other laxatives have no efficacy [13]. Methylnaltrexone is available in the market as a subcutaneous formulation injected every other day in 0.15 and 0.30 mg/kg clinically effective doses [13,14]. The oral and intravenous injection dosage forms are currently under evaluation in clinical trials [14]. As it is a quaternary amine, unlike naltrexone, methylnaltrexone bromide does not cross the blood brain barrier (BBB). Thus, it blocks peripheral mu-opioid receptors in the GI tract [13]. Due to the specific antagonizing effect on peripheral receptors, it is a potentially promising agent for relieving OIC with an acceptable safety and tolerability profile in patients [14]. It is rapidly absorbed after subcutaneous injection. Its onset of action is 30–60 min. Methylnaltrexone is eliminated through kidney with an elimination half-life of 8 h [13].
An update on the use of pharmacotherapy for opioid-induced bowel dysfunction
Published in Expert Opinion on Pharmacotherapy, 2023
Taraneh Mousavi, Shekoufeh Nikfar, Mohammad Abdollahi
Methylnaltrexone is available in 8 mg/0.4 mL, 12 mg/0.6 mL subcutaneous solutions, and 150 mg oral tablets in the United States (US). The recommended adult dosing of methylnaltrexone in OIC patients with advanced illness is based on body weight. That is, 0.15 mg/kg (round dose up to nearest 0.1 mL of volume) for < 38 kg and >114 kg; 8 mg for 38 to < 62 kg; and 12 mg for 62 to 114 kg. OIC patients with chronic non-cancer pain might take methylnaltrexone as oral tablets (450 mg daily) or subcutaneous injections (12 mg daily).
Methylnaltrexone bromide for the treatment of opioid-induced constipation
Published in Expert Opinion on Pharmacotherapy, 2018
Shilan Mozaffari, Shekoufeh Nikfar, Mohammad Abdollahi
To evaluate the safety and tolerability of methylnaltrexone, several studies are designed. Both single and multiple doses of methylnaltrexone are examined to identify the toxicity and adverse effects at each dose. In a study, healthy male volunteers showed dose-dependent adverse effects such as orthostatic hypotension. This adverse effect was self limiting. No significant change in physical and laboratory tests were observed. Therefore methylnaltrexone was shown to be well tolerated at dose of 0.32 mg/kg (intravenous) in healthy volunteers [23]. Multiple administration of intravenous methylnaltrexone with a dose of 0.3 mg/kg every 6 h in 12 consecutive doses was well tolerated in healthy humans. No significant adverse effect or change in opioid analgesic effect was observed [16]. Abdominal pain, diarrhea, nausea and flatulence were the most commonly reported adverse effects [8,17,41–43]. The most frequent adverse effect of methylnaltrexone was abdominal pain. A post-hoc analysis showed that the severity of abdominal pain is mostly mild to moderate. The incidence of abdominal pain decreased after multiple dose administration [2]. The results of two phase-III double-blinded placebo-controlled trials reported pyrexia and vomiting as the most common adverse effects of methylnaltrexone when administered for the treatment of postoperative ileus [44]. Subcutaneous administration of methylnaltrexone in 1034 patients with OIC leads to discontinuation of treatment in 15% of patients. Nine patients experienced serious adverse effects in long-term use [45]. No withdrawal symptoms or change in pain scores were observed [45]. In another trial, 3 of 154 patients experienced serious adverse effects with methylnaltrexone [2]. All examined oral dosages of methylnaltrexone (50, 300, 450 mg) were reported as well-tolerated in OIC patients with non-cancer pain [46]. Besides, the most severe adverse effect reported for methylnaltrexone is GI perforation. It has been observed in several cases with methylnaltrexone treatment. Adult patients with advanced illness and OIC that have the conditions associated with localized or diffuse reduction of structural integrity in the GI tract are more susceptible. Therefore, FDA has contraindicated the drug in patients with known or suspected GI obstruction and patients at increased risk of recurrent obstruction due to the risk of this adverse effect.