Risk factors for opioid-induced constipation in cancer patients: a single-institution, retrospective analysis.

PURPOSE: To identify risk factors for opioid-induced constipation (OIC). METHODS: This study retrospectively analyzed 175 advanced cancer patients who were receiving pain treatment with opioids and were newly prescribed laxatives for OIC at Seirei Hamamatsu General Hospital between November 2016 and June 2021. For the regression analysis of factors associated with OIC, variables were extracted manually from clinical records. The effect of newly prescribed laxatives for OIC was evaluated as "effective" in cases where the number of spontaneous bowel movements increased at least once in the first 3 days. The OIC was defined based on Rome IV diagnostic criteria. Multivariate logistic regression analysis was performed to identify risk factors for OIC. Optimal cutoff thresholds were determined using receiver operating characteristic analysis. Values of P < 0.05 (two-tailed) were considered significant. RESULTS: Significant factors identified included body mass index (BMI) (odds ratio [OR] = 0.141, 95% confidence interval [CI] = 0.027-0.733; P = 0.020), chemotherapy with taxane within 1 month of evaluation of laxative effect (OR = 0.255, 95% CI = 0.068-0.958; P = 0.043), use of naldemedine (OR = 2.791, 95% CI = 1.220-6.385; P = 0.015), and addition or switching due to insufficient prior laxatives (OR = 0.339, 95% CI = 0.143-0.800; P = 0.014). CONCLUSION: High BMI, chemotherapy including a taxane within 1 month of evaluation of laxative effect, no use of naldemedine, and addition or switching due to insufficient prior laxatives were identified as risk factors for OIC in advanced cancer patients with cancer pain.

Opioid-induced constipation in patients with cancer pain in Japan (OIC-J study): a post hoc subgroup analysis of patients with lung cancer.

OBJECTIVE: To evaluate the opioid-induced constipation burden in the subgroup of patients with lung cancer who participated in the observational Opioid-Induced Constipation in Patients with Cancer Pain in Japan (OIC-J) study. METHODS: The prospective, observational study, OIC-J, included 212 patients with various tumour types, 33% of whom had lung cancer. The incidence of opioid-induced constipation was evaluated using several diagnostic criteria, as well as the physician's diagnosis and patient's subjective assessment. Following initiation of opioids, patients recorded details of bowel movements (i.e. date/time, Bristol Stool Scale form, sensations of incomplete evacuation or anorectal obstruction/blockage and degree of straining) in a diary for 2 weeks. Relationships between patient characteristics and opioid-induced constipation onset and effects of opioid-induced constipation on quality of life were explored. RESULTS: In total, 69 patients were included in this post hoc analysis. The incidence of opioid-induced constipation varied (39.1-59.1%) depending on which diagnostic criteria was used. Diagnostic criteria that included a quality component or a patient's feeling of bowel movement as an evaluation item (i.e. Rome IV, physician's diagnosis, Bowel Function Index, patient's assessment) showed higher incidences of opioid-induced constipation than recording the number of spontaneous bowel movements alone. Opioid-induced constipation occurred rapidly after initiating opioids and had a significant impact on Patient Assessment of Constipation Symptoms total score (P = 0.0031). Patient baseline characteristics did not appear to be predictive of opioid-induced constipation onset. CONCLUSIONS: In patients with lung cancer, opioid-induced constipation can occur quickly after initiating opioids and can negatively impact quality of life. Early management of opioid-induced constipation, with a focus on quality-of-life improvement and patient's assessments of bowel movements, is important for these patients.

Prevalence and Risk Factors for Opioid-Induced Constipation in an Older National Veteran Cohort.

Objectives: This research describes the prevalence and covariates associated with opioid-induced constipation (OIC) in an observational cohort study utilizing a national veteran cohort and integrated data from the Center for Medicare and Medicaid Services (CMS). Methods: A cohort of 152,904 veterans with encounters between 1 January 2008 and 30 November 2010, an exposure to opioids of 30 days or more, and no exposure in the prior year was developed to establish existing conditions and medications at the start of the opioid exposure and determining outcomes through the end of exposure. OIC was identified through additions/changes in laxative prescriptions, all-cause constipation identification through diagnosis, or constipation related procedures in the presence of opioid exposure. The association of time to constipation with opioid use was analyzed using Cox proportional hazard regression adjusted for patient characteristics, concomitant medications, laboratory tests, and comorbidities. Results: The prevalence of OIC was 12.6%. Twelve positively associated covariates were identified with the largest associations for prior constipation and prevalent laxative (any laxative that continued into the first day of opioid exposure). Among the 17 negatively associated covariates, the largest associations were for erythromycins, androgens/anabolics, and unknown race. Conclusions: There were several novel covariates found that are seen in the all-cause chronic constipation literature but have not been reported for opioid-induced constipation. Some are modifiable covariates, particularly medication coadministration, which may assist clinicians and researchers in risk stratification efforts when initiating opioid medications. The integration of CMS data supports the robustness of the analysis and may be of interest in the elderly population warranting future examination.

Rates of appropriate laxative prophylaxis for opioid-induced constipation in veterans with lung cancer: a retrospective cohort study.

PURPOSE: Opioid-induced constipation (OIC) is the most common side effect in patient-prescribed opioids for cancer pain treatment. Current guidelines recommend routine prescription of a laxative for preventing OIC in all patients prescribed an opioid unless a contraindication exists. We determined patterns of prescription of laxative agents in patients with lung cancer initiating opioids. METHODS: We performed a retrospective cohort study evaluating the prescription of laxatives for OIC to adult patients with incident lung cancer seen in the Veteran's Affairs (VA) system, between January 1, 2003, and December 31, 2016. Exposure to laxative agents was categorized as follows: none, docusate monotherapy, docusate plus another laxative, and other laxatives only. Prevalence of OIC prophylaxis was analyzed using descriptive statistics. Linear regression was performed to identify time trends in the prescription of OIC prophylaxis. RESULTS: Overall, 130,990 individuals were included in the analysis. Of these, 87% of patients received inadequate prophylaxis (75% no prophylaxis and 12% docusate alone), while 5% received OIC prophylaxis with the unnecessary addition of docusate to another laxative. Through the study period, laxative prescription significantly decreased, while all other categories of OIC prophylaxis were unchanged. We noted an inverse relationship with OIC prophylaxis and likelihood of a diagnosis of constipation at 3 and 6 months. CONCLUSIONS: In this study of veterans with lung cancer, almost 90% received inadequate or inappropriate OIC prophylaxis. Efforts to educate physicians and patients to promote appropriate OIC prophylaxis in combination with systems-level changes are warranted.

Association between opioid usage and rectal dysfunction in constipation: A cross-sectional study of 2754 patients.

BACKGROUND: Opioid use has reached epidemic proportions. In contrast to the known effect of opioids on gut transit, the effect on rectal sensorimotor function has not been comprehensively investigated. METHODS: Cross-sectional (hypothesis-generating) study of anorectal physiology studies in 2754 adult patients referred to a tertiary unit (2004-2016) for investigation of functional constipation (defined by "derived" Rome IV core criteria). Statistical associations between opioid usage, symptoms, and anorectal physiological variables were investigated. Opioids were sub-classified as prescriptions for mild-moderate or moderate-severe pain. KEY RESULTS: A total of 2354 patients (85.5%) were classified as non-opioid users, 162 (5.9%) as opioid users for mild-moderate pain, and 238 (8.6%) for moderate-severe pain. Opioids for moderate-severe pain were associated with increased symptomatic severity (Cleveland Clinic constipation score 18.5 vs 15.1; mean difference 2.9 [95%-CI 2.3-3.6]; P < .001), rectal hyposensitivity (odds ratio 1.74 [95%-CI 1.23-2.46]; P = .002), functional evacuation disorders (odds ratio 1.73 [95%-CI 1.28-2.34]; P < .001), and delayed whole-gut transit (odds ratio 1.68 [95%-CI 1.19-2.37]; P = .003). Differences in anorectal variables between opioid users for mild-moderate pain and non-opioid users were not statistically significant. Hierarchical opioid use (non vs mild-moderate vs moderate-severe) was associated with decreasing proportions of patients with no physiological abnormality on testing (40.2% vs 38.1% vs 29.2%) and increasing proportions with both delayed whole-gut transit and rectal sensorimotor dysfunction (16.6% vs 17.5% vs 28.5%). CONCLUSIONS AND INFERENCES: Opioid use is over-represented in patients referred for investigation of constipation. Opioids for moderate-severe pain are associated with rectal sensorimotor abnormalities. Further studies are required to determine whether this association indicates causation.

Multidisciplinary intervention incorporating pharmacists in management of opioid-naïve patients with moderate to severe cancer pain.

OBJECTIVE: This study aims to investigate the impact of intervention of multidisciplinary team incorporating pharmacists for management of opioid-naïve patients with moderate to severe cancer pain. METHODS: A retrospective cohort study was conducted to compare pre- and post-multidisciplinary intervention groups in opioid-naïve patients with moderate to severe cancer pain. Primary outcome was the proportions of appropriate pain assessment and opioid titration. Secondary outcomes were pain intensity (PI), length of hospital stay, opioid escalation index percentage (OEI%) and incidences of opioid-related adverse events. RESULTS: A total of 400 patients were included in the study (pre-intervention, n = 200; post-intervention, n = 200). Continuous improvement in pain assessment and titration was recorded after intervention. Though no substantial differences existed between groups in PI on the day of discharge, post-intervention group was associated with reduced length of hospital stay as well as decreased proportion of subjects with OEI% >5%. As for safety, significant decreases in constipation and vomiting were seen. CONCLUSION: Findings suggest that interventions of multidisciplinary team incorporating pharmacists could improve cancer pain management for opioid-naïve patients. Pharmacists should be considered as an important member of a multidisciplinary team in good pain management.

More opioids, more constipation? Evaluation of longitudinal total oral opioid consumption and self-reported constipation in patients with cancer.

PURPOSE: Opioid-induced constipation (OIC) is a distressing physical symptom for patients with cancer taking opioids. Total opioid consumption may contribute to developing worsening OIC-related symptoms. We completed a retrospective analysis examining the association of total daily opioid consumption on self-reported constipation in patients with cancer. METHODS: In over 5 clinic visits, we collected self-reported constipation scores and 24-h oral morphine equivalents (OME). We examined the association between OME and the presence of constipation (i.e., score > 3) and the relationship of OME between patients with or without constipation. RESULTS: Of 297 patients with cancer, we observed 57.8% with constipation and 42.4% without constipation at the first clinic visit. Age was similar in both groups (54.2 ± 14.5 vs. 56.4 ± 14.8 years [mean ± SD]) and the majority of patients were women (63.7% vs. 61.1%). The most common cancer type in patients with constipation was non-colorectal gastrointestinal (n = 25, 14.6%), while in patients without constipation was colorectal gastrointestinal (n = 25; 19.8%). Across visits, we observed weak or no association between OME and self-reported constipation (r = 0.01-0.27). At the first visit, higher mean OME was seen in patients who self-reported constipation (133.4 vs 76; p < 0.05). Age, sex, metastatic disease, and stimulant laxative use were not associated with constipation. CONCLUSIONS: We observed weak to no association between OME and constipation in patients with cancer. These results suggest a lack of a clear association between total opioid consumption and self-reported constipation.

Incidence of opioid-induced constipation in Japanese patients with cancer pain: A prospective observational cohort study.

This multicenter, prospective, observational cohort study assessed opioid induced constipation (OIC) in Japanese patients with cancer. Eligible patients had stable cancer and an ECOG PS of 0-2. OIC incidence based on the Rome IV diagnostic criteria was determined by patient diary entries during the first 14 days of opioid therapy. The proportion of patients with OIC was calculated for each 1-week period and the overall 2-week study period. Secondary measurements of OIC included the Bowel Function Index (BFI) score (patient assessment administered by physician), spontaneous bowel movements (SBMs) per week (patient assessment), and physician assessments. Medication for constipation was allowed. Two hundred and twenty patients were enrolled. The mean morphine-equivalent dose was 22 mg/day. By Rome IV criteria, the cumulative incidence of OIC was 56% (95% CI: 49.2%-62.9%); week 1, 48% (95% CI: 40.8%-54.6%); week 2, 37% (95% CI: 30.1%-43.9%). The cumulative incidence of OIC was lower in patients who received prophylactic agents for constipation (48% [95% CI: 38.1%-57.5%]) than in patients who did not (65% [95% CI: 55.0%-74.2%]). The cumulative incidences of OIC were 59% (95% CI: 51.9%-66.0%), 61% (95% CI: 54.3%-68.1%), and 45% (95% CI: 38.0%-51.8%) based on BFI scores, physician assessments, and SBM frequency, respectively. Frequency of BMs/week before starting opioids was the most influential factor for the occurrence of OIC. Utilization of prophylactic agents for constipation was associated with a modest effect on reducing the incidence of OIC. The incidences of OIC reported were variable depending on the diagnostic tool involved.

The Evolving Role of Long-Term Pharmacotherapy for Opioid-Induced Constipation in Patients Being Treated for Noncancer Pain.

Nationally, the prescription of opioids for acute and chronic pain is increasing. As opioid use continues to expand and become of increased concern for health-care practitioners, so do the adverse effects and long-term management of those effects. Opioid-induced constipation (OIC) presents a unique challenge because tolerance does not develop to this particular adverse effect, making chronic pain management a delicate balance between relieving pain and preventing long-term adverse effects such as constipation and dependence. Several agents have been developed for the treatment of OIC in patients with chronic noncancer pain on the basis of short-term studies of 12 weeks or less. However, chronic pain management often extends beyond this 12-week boundary, resulting in health-care professionals questioning the safety and efficacy of continued treatment with OIC agents. This review evaluates available literature on long-term treatment of OIC in patients with chronic noncancer pain with lubiprostone, naloxegol, and methylnaltrexone as well as preliminary results of the recently completed naldemedine long-term trial, COMPOSE-3.