Delphi consensus on strategies in the management of opioid-induced constipation in cancer patients.

BACKGROUND: Opioid-induced constipation (OIC) is a frequent and bothersome adverse event related with opioid therapy in cancer patients. Despite the high prevalence, medical management of OIC is often uncertain. The current project aimed to investigate expert opinion on OIC management and provide practical recommendations to improve the clinical approach of OIC in cancer patient. METHODS: A modified Delphi method was conducted involving 46 different physicians experts in OIC. Using a structured questionnaire of 67 items this project intended to seek consensus on aspects related to diagnosis, treatment, and quality of life of cancer patients suffering with OIC. RESULTS: After two rounds, a consensus was reached in 91% of the items proposed, all in agreement. Agreement was obtained on OIC definition (95.7%). Objective and patient-reported outcomes included in that definition should be assessed routinely in clinical practice. Responsive to symptom changes and easy-to-use assessment tools were recommended (87.2%). Successful diagnosis of OIC requires increase clinicians awareness of OIC and proactivity to discuss symptoms with their patients (100%). Successful management of OIC requires individualization of the treatment (100%), regular revaluation once is established, and keeping it for the duration of opioid treatment (91.5%). Oral Peripherally Acting µ-Opioid Receptor Agonists (PAMORAs), were considered good alternatives for the treatment of OIC in cancer patients (97.9%). This drugs and laxatives can be co-prescribed if OIC coexist with functional constipation. CONCLUSIONS: The panelists, based on their expert clinical practice, presented a set of recommendations for the management of OIC in cancer patients.

Variation in Hospice Patient and Admission Characteristics by Referral Location.

BACKGROUND: Little is known regarding differences between patients referred to hospice from different care locations. OBJECTIVE: The objective this study was to describe the associations between hospice referral locations and hospice patient and admission characteristics. RESEARCH DESIGN: Cross-sectional analysis of hospice administrative data. SUBJECTS: Adult (age older than 18 y) decedents of a national, for-profit, hospice chain across 19 US states who died between January 1, 2012, and December 31, 2016. MEASURES: Patients' primary hospice diagnosis, hospice length stay, and hospice care site. We also determined the frequency of opioid prescriptions with and without a bowel regimen on hospice admission. RESULTS: Among 78,647 adult decedents, the mean age was 79.2 (SD=13.5) years, 56.4% were female, and 69.9% were a non-Hispanic White race. Most hospice referrals were from the hospital (51.9%), followed by the community (21.9%), nursing homes (17.4%), and assisted living (8.8%). Cancer (33.6%) was the most prevalent primary hospice diagnosis; however, this varied significantly between referral locations (P<0.001). Similarly, home hospice (32.8%) was the most prevalent site; however, this also varied significantly between referral locations (P<0.001). More hospital-referred patients (55.6%) had a hospice length of stay <7 days compared with patients referred from nursing homes (30.3%), the community (28.9%), or assisted living (18.7%), P<0.001. Hospital-referred patients also had the lowest frequency (58.4%) of coprescribed opioids and bowel regimen on hospice admission compared with other referral locations. CONCLUSION: We observed significant differences in hospice patient and admission characteristics by referral location.

Comparing the effectiveness of magnesium oxide and naldemedine in preventing opioid-induced constipation: a proof of concept, single institutional, two arm, open-label, phase II, randomized controlled trial: the MAGNET study.

BACKGROUND: Patients taking opioids are known to develop opioid-induced constipation (OIC), which reduces their quality of life. The aim of this study is to compare magnesium oxide with naldemedine and determine which is more effective in preventing OIC. METHODS: This proof-of-concept, prospective, randomized controlled trial commenced in Japan in March 2018. Initially, a questionnaire-based survey will be conducted targeting adult patients with cancer who concomitantly commenced opioid treatment and OIC prevention treatment. Patients will then be randomly allocated to a magnesium oxide group (500 mg thrice daily) or a naldemedine group (0.2 mg once daily). Each drug will be orally administered for 12 weeks. The primary endpoint is defined as any improvement in scores on the Japanese version of Patient Assessment of Constipation Quality of Life questionnaire (JPAC-QOL) from baseline to 2 weeks of treatment. DISCUSSION: The primary endpoint is change in JPAC-QOL score from baseline to 2 weeks of intervention. The key secondary endpoint will be change in spontaneous bowel movements at 2 and 12 weeks of intervention. This study will determine whether magnesium oxide or naldemedine is more effective for the prevention of OIC. TRIAL REGISTRATION: University Hospital Medical Information Network (UMIN) Clinical Trials Registry, UMIN000031891. Registered March 25, 2018.

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.

Prolonged-Release (PR) Oxycodone/Naloxone Improves Bowel Function Compared with Oxycodone PR and Provides Effective Analgesia in Chinese Patients with Non-malignant Pain: A Randomized, Double-Blind Trial.

INTRODUCTION: Prolonged-release oxycodone/naloxone (OXN PR), combining an opioid analgesic with selective blockade of enteric µ-opioid receptors, provided effective analgesia and improved bowel function in patients with moderate-to-severe pain and opioid-induced constipation in clinical trials predominantly conducted in Western countries. This double-blind randomized controlled trial investigated OXN PR (N = 116) versus prolonged-release oxycodone (OXY PR, N = 115) for 8 weeks at doses up to 50 mg/day in patients with moderate-to-severe, chronic, non-malignant musculoskeletal pain and opioid-induced constipation recruited in China. METHODS: A total of 234 patients at least 18 years of age with non-malignant musculoskeletal pain for more than 4 weeks that was moderate-to-severe in intensity and required round-the-clock opioid therapy were randomized (1:1) to OXN PR or OXY PR. The primary endpoint was bowel function using the Bowel Function Index (BFI). Secondary endpoints included safety, Brief Pain Inventory-Short Form (BPI-SF), use of analgesic and laxative rescue medication, and health-related quality of life (EQ-5D). RESULTS: While BFI scores were comparable at baseline, at week 8 improvements were greater with OXN PR vs OXY PR (least squares mean [LSM] difference (95% CI) - 9.1 (- 14.0, - 4.2); P < 0.001. From weeks 2 to 8, mean BFI scores were in the range of normal bowel function (≤ 28.8) with OXN PR but were in the range of constipation (> 28.8) at all timepoints with OXY PR. Analgesia with OXN PR was similar and non-inferior to OXY PR on the basis of modified BPI-SF average 24-h pain scores at week 8: LSM difference (95% CI) - 0.3 (- 0.5, - 0.1); P < 0.001. The most frequent treatment-related AEs were nausea (OXN PR 5% vs OXY PR 6%) and dizziness (4% vs 4%). CONCLUSION: OXN PR provided clinically meaningful improvements in bowel function and effective analgesia in Chinese patients with moderate-to-severe musculoskeletal pain and pre-existing opioid-induced constipation. TRIAL REGISTRATION: ClinicalTrials.gov, identifier NCT01918098.

Constipação induzida por opióides em cuidado paliativo: o estado da arte / Opioid-induced constipation in palliative care: state of the art / Presión de vientre induzida por opióides en cuidado paliativo: el estado del arte

Objetivo: Objetivou-se realizar o estado da arte de publicações que relatem estratégias de como minimizar a constipação induzida pelo uso de opioides, de pacientes em cuidado paliativo. Método: Trata-se de um estudo exploratório através de uma revisão integrativa em quatro bases de dados de artigos publicados entre os anos de 2013 a 2017. Resultados: Evidenciaram-se 117 publicações, as quais 17 apresentaram os critérios de inclusão da pesquisa. Conclusão: Apesar das drogas aliviarem a dor, as reações adversas geram desconforto e perda da qualidade de vida. Existem dados limitados referentes ao tratamento da constipação intestinal em cuidado paliativo. Observou-se que poucos autores mencionaram a dieta como auxiliador no quadro, enfatizando o uso de medicamentos. Mais estudos devem ser estimulados no intuito de encontrar o equilíbrio entre analgesia e redução de efeitos adversos causados pelos opioides

Objective: The study's purpose has been to address the state of the art in investigations such as clinical trials, systematic reviews with metaanalysis and case studies, which report how to minimize opioid-induced constipation in patients undergoing palliative care. Methods: This is an exploratory study through an integrative review of four databases addressing published articles from 2013 to 2017. Results: A total of 117 publications were presented, which 17 presented the inclusion criteria. The studies describe the prevalence of constipation rates induced by the use of opioids. Conclusion: Although these drugs alleviate pain, the adverse reactions may generate discomfort and loss of the patient's life quality. There are limited data on the treatment of constipation. It was observed that few authors mentioned diet as a helper on this situation, emphasizing the use of medications. Further studies should be encouraged aiming to find the balance between analgesia and reduction of adverse effects

Objetivo: Se objetivó realizar el estado del arte de publicaciones que relatan estrategias de cómo minimizar el constipación inducida por el uso de opioides, de pacientes en cuidado paliativo. Método: Se trata de un estudio exploratorio a través de una revisión integrativa en cuatro bases de datos de artículos publicados entre los años de 2013 a 2017. Resultados: Se evidenció 117 publicaciones, las cuales 17 presentaron los criterios de inclusión de la investigación. Conclusión: A pesar de las drogas aliviar el dolor, las reacciones adversas generan incomodidad y pérdida de la calidad de vida. Existen datos limitados referentes al tratamiento del estreñimiento intestinal en el cuidado paliativo. Se observó que pocos autores mencionaron la dieta como auxiliador en el cuadro, enfatizando el uso de medicamentos. Más estudios deben ser estimulados con el fin de encontrar el equilibrio entre analgesia y reducción de efectos adversos causados por los opioide

Opioid-Induced Constipation in Oncological Patients: New Strategies of Management.

OPINION STATEMENT: Cancer-associated pain has traditionally been treated with opioid analgesics, often in escalating doses. Opioid-induced constipation (OIC) is a common problem associated with chronic use of opioid analgesics. Typical treatment strategies to alleviate constipation are based on dietary changes, exercise, and laxatives. However, laxatives have a nonspecific action and do not target underlying mechanisms of OIC. This article will review prevalent, clinical presentation and recommendations for the treatment of OIC. An independent literature search was carried out by the authors. We reviewed the literature for randomized controlled trials that studied the efficacy of laxatives, naloxone, and naloxegol in treating OIC. Newer strategies addressing the causal pathophysiology of OIC are needed for a more effective assessment and management of OIC. Finally, traditional recommended therapies are appraised and compared with the latest pharmacological developments. Future research should address whether naloxegol is more efficacious by its comparison directly with first-line treatments, including laxatives.