Subcutaneous methylnaltrexone for treatment of acute opioid‐induced constipation: Phase 2 study in rehabilitation after orthopedic surgery

Abstract

BACKGROUND:Methylnaltrexone has been shown to be effective for treating opioid-induced constipation (OIC) in chronic settings, but its effects on acute OIC have not been studied.

Definitions and Outcome Measures of Clinical Trials Regarding Opioid-induced Constipation

“…Joswick et al 14 Adults on chronic opioid therapy with OIC, defined as <3 SBMs per week Lichtlen et al 15 Adults on chronic opioid therapy with OIC (ie, <3 spontaneous bowel movements/wk) Mareya et al 16 Adults Z18 y on chronic opioid therapy with OIC, defined as <3 spontaneous bowel movements (SBMs)/week Anissian et al 17 Acute constipation was defined as having no bowel movement for at least 48 h before randomization, difficulty in having a spontaneous bowel movement (straining or sensation of incomplete evacuation or hard, lumpy stools), or the inability to have a spontaneous bowel movement Wirz et al 18 Referring to the definition of constipation as a subjective symptom involving complaints of decreased stool frequency 19,20 and for pragmatic reasons, we defined constipation as the detection of sfi72 in combination with an NRS value for constipation >4 (box 2) 21 Candy et al 22 In general, however, definitions of constipation include a reference to infrequent, difficult, or incomplete bowel evacuation that may lead to pain and discomfort; with stools that can range from small, hard rocks, to a large bulky mass 23-26 Clemens et al 11 Presence of constipation prior to OXN treatment was defined according to the Rome III criteria (20), which is defined by the presence of 2 or more of the following symptoms for a period of at least 3 mo: (i) straining at least 25% of the time;…”

“…69 Therefore, other publications prefer a more patient-centered definition, combining objective measures such as bowel movement (or stool) frequency with PROMs such as pain (during defecation) or feeling "bloated." [11][12][13]17,18,21,27,28,33,34 It is especially well known within the field of palliative care that not every symptom reported as a PROM necessarily needs to be treated. A prominent example is cancer-related anorexia in advanced stages of the disease.…”

“…For 4 of 16 studies (25%) that provided a definition, this was the only measure used [14][15][16]29 (Supplementary Table 1, Supplemental Digital Content 2, http://links.lww.com/JCG/A165). [15][16][17][18][19][21][22][23][24][25][26] Most notably, the majority of studies that provided a definition did neither include the present or recent history of opioid therapy or functional constipation nor the change of bowel habits or defecation patterns in their definition. This leads one to ask how the authors were able to differentiate between OIC and functional constipation.…”

Advances in pharmacotherapy for opioid-induced constipation – a systematic review

“…In the present work OOMs for methylnaltrexone were examined in seven studies with overall 1760 participants ( Table 2) [35,36,[46][47][48][49][50]. Viscusi et al [35] showed that approximately a range of 53 --70% methylnaltrexone patients compared to 35 --41% placebo patients had ‡ 3 RFBMs/week and 1 RFBM increase over baseline; however, the treatment phase was open label in this crossover trial and methylnaltrexone dosing was flexible (pro re nata).…”

“…Median time to RFBM was shortest for the doses 0.15 mg/kg (1.1 h) and 0.3 mg/kg (0.8 h) compared to placebo (> 24 h) (p < 0.0001) [48]. In addition, patients in a postoperative setting received methylnaltrexone after orthopedic procedures in one study [46]. Laxation within 4 h was higher (n = 7, 38.9 vs n = 1, 6.7%, p = 0.021) and time to first BM was significantly lower (15.8 h vs 50.9 h, p = 0.0197) in the methylnaltrexone group.…”