Predictors for Diarrhea After Administration of Naldemedine: Analysis Focusing on the Administration Period of Opioid Analgesics Before the Start of Naldemedine

Hashizume, Junya; Ryu, Emi; Nose, Seiichi; Miyanaga, Kei; Reiko, Kishikawa; Nakamura, Tadahiro; Muro, Takahiro; Kodama, Yukinobu; Yamashita, Haruna; Ishii, Koji; Sasaki, Hidetada

doi:10.2512/jspm.15.101

Cited by 5 publications

(11 citation statements)

References 16 publications

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“…A previous study reported that the incidences of diarrhea in patients who started NAL treatment within 3 days and more than 3 days of opioid therapy were 4 and 22%, respectively [15]. Another study reported that the incidence of diarrhea (40%) significantly increased in patients who started NAL treatment after more than 7 days of opioid therapy [16]. As our results and previous study results indicate that prolonged duration of opioid therapy before NAL administration affects the incidence of NAL-induced diarrhea.…”

Section: Discussionsupporting

confidence: 78%

“…On the other hand, there is a difference in the cutoff value of duration of opioid therapy before NAL administration between studies. In previous studies [ 15 , 16 ], the cutoff values for duration of opioid therapy before NAL administration were not clearly mentioned. By contrast, we statistically calculated the cutoff value by ROC curve method.…”

Section: Discussionmentioning

confidence: 99%

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Opioid therapy duration before naldemedine treatment is a significant independent risk of diarrhea: a retrospective cohort study

Okamoto

Ikemura

Mizutani

et al. 2021

J Pharm Health Care Sci

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Background The most common adverse event (AE) associated with opioid analgesics is opioid-induced constipation (OIC). Naldemedine (NAL) is widely used for the treatment of OIC. However, diarrhea has been reported as the most common treatment-emergent AE of NAL, and little is known about the risk factors associated with the development of diarrhea during NAL administration. This study examined the risk factors for NAL-induced diarrhea via a retrospective chart review of hospitalized patients. Methods The data of 101 hospitalized adult patients who received NAL for the first time for the treatment of OIC at Mie University Hospital between June 2017 and December 2018 were extracted from electronic medical records. According to the inclusion and exclusion criteria, 70 of the 101 patients were enrolled in this study. Diarrhea was defined as “diarrhea” on the medical record within 2 weeks of NAL administration. Univariate and multivariate analyses were performed to identify risk factors for the development of diarrhea in patients receiving NAL. Results Twenty-two of the 70 patients enrolled (31%) developed diarrhea within 2 weeks of NAL administration. The median duration (range) of NAL treatment before diarrhea onset was 3 (1–12) days. Patients with diarrhea had a significantly longer duration of opioid therapy before NAL administration than patients without diarrhea (P=0.002). Multivariate logistic regression analysis indicated that the independent risk factors for the development of NAL-induced diarrhea were NAL administration after more than 17 days of opioid therapy (odds ratio [OR]=7.539; P=0.016) and pancreatic cancer (OR=6.217; P=0.025). In fact, the incidence of diarrhea in patients who were administered NAL within a day of opioid therapy was significantly lower than that in patients who were administered NAL after more than 17 days of opioid therapy (13% vs. 54%, P=0.030). Conclusions These results suggested that a prolonged duration of opioid therapy prior to NAL initiation is associated with increased incidence of diarrhea.

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Section: Discussionsupporting

confidence: 78%

Section: Discussionmentioning

confidence: 99%

Opioid therapy duration before naldemedine treatment is a significant independent risk of diarrhea: a retrospective cohort study

Okamoto

Ikemura

Mizutani

et al. 2021

J Pharm Health Care Sci

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“…We previously reported that NAL-induced diarrhea significantly increased when opioid analgesics were administered for more than 8 d prior to the initiation of NAL. 20) Similar results also have been reported by other groups. 21,22) On the other hand, NAL is mainly metabolized by CYP3A4.…”

Section: Introductionsupporting

confidence: 87%

“…On the other hand, 12.5% of patients administered opioid analgesics within 7 d developed NAL-induced diarrhea in the previous study. 20) The incidence of diarrhea was 7.1% (5/70) in patients who did not have any of the predictors. The three predictors identified in the present study help to prevent NAL-induced diarrhea.…”

Section: Discussionmentioning

confidence: 92%

“…In the previous study, we reported that the duration of opioid analgesics was the predictive factor of NAL-induced diarrhea. Then, we extended the study period to increase the number of patients in order to improve the reliability of the information compared to previous reports, 20) and conducted retrospective study including the presence or absence of concomitant use of CYP3A4 inhibitors. As a result, we have found for the first time that the combinations of CYP3A4 inhibitors or laxatives are predictive factors for NAL-induced diarrhea.…”

Section: Introductionmentioning

confidence: 99%

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Analysis of Predictive Factors for Diarrhea after the Administration of Naldemedine

Hashizume

Shiojiri

Ryu

et al. 2021

Biological & Pharmaceutical Bulletin

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Naldemedine (NAL), a peripherally acting μ-opioid receptor antagonist, is effective for opioid-induced constipation (OIC). However, diarrhea is the most common adverse event. We investigated the incidence of NAL-induced diarrhea in patients who started NAL at Nagasaki University Hospital between June 2017 and March 2019. Predictors of NAL-induced diarrhea were analyzed using a multivariate logistic regression model. Two hundred and forty-two patients were included in the present study, and NAL-induced diarrhea was observed in 17.8% (43 patients). The results of multiple logistic regression analyses identified the administration of opioid analgesics for 8 d or longer before the initiation of NAL (odds ratio (OR): 2.20, 95% confidence interval (95% CI): 1.04-4.64, p 0.039), the combination of a laxative (OR: 2.22, 95%CI: 1.03-4.81, p 0.042), and the combination of CYP3A4 inhibitors (strong/moderate) (OR: 2.80, 95%CI: 1.02-7.67, p 0.045) as risk factors. Therefore, the development of diarrhea needs to be considered in patients with these risk factors. Furthermore, diarrhea may be controlled by the initiation of NAL within 7 d of opioid analgesics and, where possible, the discontinuation of or change in the combination of moderate or strong CYP3A4 inhibitors.

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Survey of Prophylactic Administration of Naldemedine for Opioid-induced Constipation

et al. 2023

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Opioid-induced constipation (OIC), an adverse event that occurs due to opioid analgesics, reportedly causes poor quality of life and adherence to opioid analgesics in patients. Therefore, this issue must be addressed appropriately. Naldemedine (NAL), a peripherally-acting μ-opioid receptor antagonist, is currently recommended for treating OIC when other laxatives are ineffective, but there have been no clinical reports of NAL being used prophylactically for OIC. Therefore, we conducted a retrospective survey of hospitalized patients who received NAL as prophylaxis for OIC with strong opioid analgesics to clarify the reality of this situation and to consider points to be taken into account in its clinical implementation. In this study, 61.7% of the subjects had an Eastern Cooperative Oncology Group performance status score of 3 or higher. The rate of addition of new laxatives and increased laxatives during seven days of NAL prophylaxis was 46.8%, and the rate of diarrhea was 6.1%. This study suggests that patients initiated with strong opioid analgesics during hospitalization often presented with poor performance status, and it is important to pay attention to constipation even under NAL prophylaxis. However, the incidence of diarrhea was low, and the safety of NAL prophylaxis was considered to be good.

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Predictors for Diarrhea After Administration of Naldemedine: Analysis Focusing on the Administration Period of Opioid Analgesics Before the Start of Naldemedine

Cited by 5 publications

References 16 publications

Opioid therapy duration before naldemedine treatment is a significant independent risk of diarrhea: a retrospective cohort study

Opioid therapy duration before naldemedine treatment is a significant independent risk of diarrhea: a retrospective cohort study

Analysis of Predictive Factors for Diarrhea after the Administration of Naldemedine

Survey of Prophylactic Administration of Naldemedine for Opioid-induced Constipation

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