Itopride Increases The Effectiveness Of The Management Of Opioid-Induced Constipation In Palliative Care Patients: An Observational Non-Interventional StudyⅡ

Results 

The studied population 

The data of 130 patients were collected. Ninety-two patients met the inclusion criteria (female 54.3%) and were analyzed in four groups: OXN + ITP (N = 9), ITP (N = 11), OXN (N = 12), and CTRL (N = 61). The study flow is presented in Figure 1. The groups did not differ in terms of sex, age, diagnosis, and oral morphine equivalent of strong opioids on day 0 and day 7. The opioids used were as follows: morphine (oral or parenteral), oxycodone, fentanyl, buprenorphine, and tapentadol. The demographic details are presented in Table II.

Click on constipation treatment

The symptoms of constipation 

The laxative prevention or treatment aimed to achieve at least three bowel movements a  week and an acceptable intensity of abdominal symptoms, and this aim was achieved in all groups. There were no statistical differences found for the mean values among the groups in terms of particular symptoms of constipation (Table III). Eighty-two (89%) patients had been diagnosed with constipation, with insignificant differences among groups. However, the anti-constipation strategy appeared successful, on average, in all four groups. Overall, manual stool evacuation was performed in 4 patients receiving laxatives only, and not in other groups. Enemas were used in 16 patients, and 14 of them were in the control group.

The reduction of laxative use 

Although there were no statistical differences among groups regarding bowel symptoms or the frequency of bowel movements, the necessity of laxatives decreased in groups in which itopride was used (Kruskal-Wallis ANOVA p = 0.0027). In the ITP group, the necessity to use laxatives decreased by 0.64 (–0.64; 95% CI: –1.6–1.8) and in the OXN + ITP group by 0.67 (–0.67; 95% CI: –1.5– 1.7) in the 0–4 scale. These values might seem insignificant, but they were statistically different (Mann-Whitney U  test) from oxycodone/naloxone (ITP vs. OXN p = 0.009, OXN + ITP vs. OXN p = 0.017) and the control group (ITP vs. CTRL p = 0.010, OXN + ITP vs. CTRL p = 0.0.25). There was no decrease in laxative use in patients taking oxycodone/naloxone vs. the control group (p = 0.22) (Figure 2).

Adverse effects 

This study was a retrospective analysis of the structured history of patients, and none of the 130 patients reported any side effects. This does not mean that there were no adverse effects of treatment, but rather that they were typical and of mild or moderate intensity, so it was not necessary to report them in routine documentation. No patient stopped using itopride between day 0 and day 7. Although the cases in which itopride was used on day 0 were excluded from the analysis, none of the patients stopped itopride use in the next 7 days. Thus, it can be inferred that the medicine was well tolerated. The history after day 7 was not analyzed.

Discussion 

This was a  non-interventional study, with all the limitations that non-randomized clinical trials bear. However, its advantage is a gross effect in the real environment, when using itopride as an element of laxative prevention and treatment. This is probably the first clinical report aiming directly at the use of itopride in OIC. Physicians did not participate in the analysis and were only asked to provide structured data without specific study goals, to limit possible bias. 

They delivered the questionnaires regardless of their laxative therapy pattern and use of prokinetics. It also explains the over-representation of a  control group, because most patients received regular laxatives, and a minority were treated with oxycodone/naloxone or itopride. The number of collected cases was sufficient to achieve statistically justified conclusions. There were no statistical differences between the studied groups in terms of age, sex, primary diagnosis, performance status (ECOG), opioids used, or the intensity of symptoms of constipation among the groups. 

Following the aforementioned recommendations, every patient receiving opioid analgesics should also receive constipation prophylaxis through the use of laxatives or by using opioids in combination with antagonists (e.g. oxycodone/ naloxone) [2, 3]. The Polish guidelines suggest that adding prokinetics may increase the effectiveness of laxative therapy, but there was no direct clinical evidence for that [14]. According to these guidelines, verified in a  medium-sized cohort study [7], the prevention of OIC should be provided with an intensiveness that ensures bowel movements at least three times per week and good subjective control of bowel symptoms. 

This goal was achieved in all studied groups, which did not differ from each other in terms of the intensity of symptoms of constipation. In other words, all four strategies appeared equally effective in the prevention of OIC: (1) itopride added to laxatives, (2) oxycodone/naloxone used with laxatives, (3) oxycodone/naloxone and itopride added to laxatives, or (4) regular laxatives only. It was achieved by intensifying laxative use if necessary.

The main finding of this study is that adding itopride to laxative therapy decreased the necessity to use laxatives. On the other hand, using oxycodone/naloxone did not affect the use of laxatives. What is more, the combined use of oxycodone/ naloxone and itopride did not increase the effectiveness of the preventive management of OIC. The findings confirm the sparse clinical evidence available so far [31].

In conclusion, all strategies of OIC prevention seem equally effective in clinical practice. Itopride, but not naloxone, appeared effective in reducing the use of laxatives in OIC. However, using oxycodone/naloxone or itopride could be associated with decreasing the necessity of interventive and burdensome methods, such as manual stool evacuation or enemas. 

The conclusions should be taken with caution because it was not a  prospective blinded study. We should treat these results as preliminary. We suggest that an RCT would be valuable to confirm the value of itopride in the strategy of prevention and treatment of OIC.

Natural Herbal Medicine For Relieving Constipation-Cistanche 

Cistanche is a genus of parasitic plants that belongs to the family Orobanchaceae. These plants are known for their medicinal properties and have been used in Traditional Chinese Medicine (TCM) for centuries. Cistanche species are predominantly found in arid and desert regions of China, Mongolia, and other parts of Central Asia. Cistanche plants are characterized by their fleshy, yellowish stems and are highly valued for their potential health benefits. In TCM, Cistanche is believed to have tonic properties and is commonly used to nourish the kidney, enhance vitality, and support sexual function. It is also used to address issues related to aging, fatigue, and overall well-being. While Cistanche has a long history of use in traditional medicine, scientific research on its efficacy and safety is ongoing and limited. However, it is known to contain various bioactive compounds such as phenylethanoid glycosides, iridoids, lignans, and polysaccharides, which may contribute to its medicinal effects.

Wecistanche's cistanche powder, cistanche tablets, cistanche capsules, and other products are developed using desert cistanche as raw materials, all of which have a good effect on relieving constipation. The specific mechanism is as follows: Cistanche is believed to have potential benefits for relieving constipation based on its traditional use and certain compounds it contains. While scientific research specifically on Cistanche's effect on constipation is limited, it is thought to have multiple mechanisms that may contribute to its potential to relieve constipation. Laxative Effect: Cistanche has long been used in Traditional Chinese Medicine as a remedy for constipation. It is believed to have a mild laxative effect, which can help promote bowel movements and induce constipation. This effect may be attributed to various compounds found in Cistanche, such as phenylethanoid glycosides and polysaccharides. Moistening the Intestines: Based on traditional use, Cistanche is considered to have moisturizing properties, specifically targeting the Intestines. Promoting hydration and lubrication of the Intestines may help soften tools and facilitate easier passage, thereby relieving constipation. Anti-inflammatory Effect: Constipation can sometimes be associated with inflammation in the digestive tract. Cistanche contains certain compounds, including phenylethanoid glycosides and lignans, that are believed to have anti-inflammatory properties. By reducing inflammation in the intestines, it may help improve bowel movement regularity and relieve constipation.