What is more effective for treating diarrhea, racecadotril or loperamide?

From the Guidelines

Loperamide is the preferred treatment for diarrhea due to its faster symptomatic relief and widespread use, as recommended in the 2018 ESMO clinical practice guidelines 1. When considering the treatment of diarrhea, both racecadotril and loperamide are effective options, but they have different mechanisms of action and advantages.

• Loperamide works by slowing intestinal motility and reducing the frequency of bowel movements, with a typical adult dose of 4mg initially, followed by 2mg after each loose stool, not exceeding 16mg daily.
• Racecadotril, on the other hand, reduces intestinal hypersecretion without affecting motility, which may make it preferable for certain patients, particularly children, with an adult dose of 100mg three times daily. However, the 2018 ESMO guidelines suggest that loperamide can be started at an initial dose of 4 mg followed by 2 mg every 2–4 h or after every unformed stool, with a maximum daily dose of 16 mg 1. Additionally, the guidelines recommend oral rehydration therapy (ORT) and the use of oral rehydration solutions (ORS) for patients with mild to moderate diarrhea, and rapid fluid resuscitation for patients with severe hypovolaemia 1. It is also important to note that both medications should be used alongside appropriate rehydration therapy, and neither should be used in cases of bloody diarrhea or high fever, which may indicate invasive bacterial infection requiring antibiotics. In terms of side effects, racecadotril may cause fewer side effects like constipation or abdominal discomfort compared to loperamide, but loperamide provides faster symptomatic relief for many patients. Overall, while both medications are effective, loperamide is the preferred treatment for diarrhea due to its faster symptomatic relief and widespread use, as recommended in the 2018 ESMO clinical practice guidelines 1.

From the FDA Drug Label

INDICATIONS AND USAGE Loperamide hydrochloride capsules are indicated for the control and symptomatic relief of acute nonspecific diarrhea in patients 2 years of age and older and of chronic diarrhea in adults associated with inflammatory bowel disease. There is no information about racecadotril in the provided drug labels. The FDA drug label does not answer the question.

From the Research

Comparison of Racecadotril and Loperamide

• Both racecadotril and loperamide are used to treat diarrhea, but they work in different ways. Racecadotril is an enkephalinase inhibitor, which means it helps to reduce the amount of fluid secreted into the intestines, while loperamide works by slowing down the movement of the intestines to allow for more water and electrolyte absorption 2.
• Studies have shown that both drugs are effective in treating acute diarrhea in adults. A randomized, double-blind study found that racecadotril and loperamide had similar efficacy in reducing the duration of diarrhea and the number of stools passed, but loperamide was associated with a higher incidence of rebound constipation 3.
• Another study compared the efficacy, safety, and tolerability of racecadotril and loperamide in adults with acute diarrhea and found that both treatments were rapid and equally effective, but loperamide was associated with a higher incidence of treatment-related constipation 4.
• A systematic review and meta-analysis of studies on the use of racecadotril in children with acute diarrhea found that racecadotril was more effective than placebo in reducing the duration of symptoms and stool output, and was safe and well tolerated. However, the quality of the evidence was limited due to sparse data, heterogeneity, and risk of bias 5.
• In terms of adverse events, studies have found that loperamide is associated with a higher incidence of constipation, while racecadotril may be associated with a higher incidence of itching 4.
• Overall, the evidence suggests that both racecadotril and loperamide are effective treatments for acute diarrhea, but they have different side effect profiles and may be more or less suitable for different patients depending on their individual needs and medical histories 2, 3, 6, 4, 5.

Efficacy and Safety

• The efficacy of racecadotril and loperamide in treating acute diarrhea has been demonstrated in several studies, with both drugs showing rapid and significant reductions in the duration of symptoms and stool output 3, 4.
• However, the safety profiles of the two drugs differ, with loperamide associated with a higher incidence of constipation and racecadotril associated with a higher incidence of itching 4.
• The long-term effects of using racecadotril and loperamide to treat diarrhea are not well established, and further research is needed to fully understand their safety and efficacy in different patient populations 2.

Clinical Use

• Racecadotril and loperamide are both used to treat acute diarrhea in adults and children, but the choice of drug may depend on the individual patient's needs and medical history 3, 4.
• For example, patients who are prone to constipation may be better suited to treatment with racecadotril, while patients who require rapid relief from diarrhea may be better suited to treatment with loperamide 4.
• Further research is needed to fully establish the clinical utility of racecadotril and loperamide in different patient populations, and to determine the optimal dosing regimens and treatment durations for each drug 2, 5.