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Bisacodyl: comprehensive findings direct effective and safe use in constipation
Constipation is one of the most common gastrointestinal diseases, with an estimated global prevalence of 14% [1]. The most significant symptoms include an infrequent passage of hard stools, excessive straining during defecation and the feeling of incomplete bowel emptying. When constipation is an occasional event, it can usually be treated with self-medication. The available treatment options here include – in addition to the osmotic laxatives ¬– stimulant laxatives such as bisacodyl. Stimulant laxatives combine prokinetic and secretagogic (secretion-promoting) effects. The review by Corsetti et al. provides a detailed summary of statements concerning the drug bisacodyl, and thereby allows effective and safe advice to be given to patients with constipation [2].
Bisacodyl has only local effects
Once the gastroresistant and enteric coating of bisacodyl tablets has dissolved in the colon, the prodrug is converted into the active metabolite bis-(p-hydroxyphenyl)-pyridyl-2-methane (BHPM). This metabolite increases the motility and water content of the stool (Fig. 1). The active metabolite does not undergo systemic absorption.
Fig.1. Mode of action of the stimulant laxative bisacodyl. The increase in muscle tone is achieved through a direct myogenic effect involving L-type calcium channels. Two mechanisms are involved in BHPM-induced ion secretion: potassium secretion, when BHPM acts on the mucosa from the intestinal lumen, and neuronally-mediated chloride and hydrogen carbonate secretion after absorption into the intestinal wall.
Significant improvement in objective and subjective symptoms
In a large, randomised, double-blind and placebo-controlled study published in 2011 [3], patients were given 5–10 mg bisacodyl (n = 247) or placebo (n = 121) once daily for four weeks. The number of complete, spontaneous bowel movements (CSBM) per week – which was 1.1 at the beginning of the study – increased significantly (p < 0.0001) to 5.2 in the active treatment group, whereas there was only a minor increase to an average of 1.9 CSBM per week in the placebo group. Patients under bisacodyl treatment also benefitted from a marked improvement in quality of life. As yet unpublished data showed that subjective symptoms (e.g., bloating and discomfort) also improved under bisacodyl and patient satisfaction with their bowel habits increased (statistically significant increase compared with placebo).
Tolerability increases with dose adjustment and duration of use
Diarrhoea and abdominal pain are among the most common unwanted effects of treatment with stimulant laxatives such as bisacodyl. According to study data, these side effects markedly improved parallel to an adjustment of the individual dose and also as treatment progresses. Available data (guidelines, review articles, clinical studies, case reports) allow us to conclude that when used correctly, stimulant laxatives such as bisacodyl are also safe when taken in the long-term and their use is not associated with habituation [4].
First indications of a positive effect on the gut microbiome
The review by Corsetti et al. [1] described the first results of studies that examined the influence of bisacodyl on the gut microbiome [5]. Compared to healthy subjects, faecal samples of patients with chronic constipation showed a reduced concentration of bifidobacteria and lactobacilli as well as an increased concentration of potentially pathogenic bacteria and/or fungi. Four weeks of treatment with bisacodyl led to a normalisation of intestinal transit time and a decrease in potentially pathogenic micro-organisms, whilst the gut flora returned to normal, including an increase in Bifidobacterium and Bacteroides strains.
Fig. 2. Bisacodyl causes a decrease in potentially pathogenic microorganisms and a faster regeneration of obligate gut flora.
Summary
Bisacodyl has a dual mechanism of action: prokinetic and hydrating (anti-absorptive, secretory). Bisacodyl makes stools softer, shortens stool transit time, and eases defecation. Bisacodyl improves the quality of life of patients and its action is purely local. Results from studies also indicate positive effects on the gut microbiome. It appears advisable to start treatment with a low dose of bisacodyl (5 mg) and then increase wherever necessary. Tolerability generally improves when the dose is adjusted to patient needs and with increasing duration of treatment. Clinical experience, guidelines and review articles suggest that there are no concerns on a long-term use of bisacodyl. A combination with other laxatives may be considered for patients who do not respond to monotherapy.
Literature
- Suares NC, Ford AC. Prevalence of, and risk factors for, chronic idiopathic constipation in the community: systematic review and meta-analysis. Am J Gastroenterol. 2011;106:1582–91.
- Corsetti M, et al. Bisacodyl: A review of pharmacology and clinical evidence to guide use in clinical practice in patients with constipation. Neurogastroenterology & Motility. 2021;33:e14123. doi:10.1111/nmo.14123.
- Kamm MA, Mueller-Lissner S, Wald A, Richter E, Swallow R, Gessner U. Oral bisacodyl is effective and well-tolerated in patients with chronic constipation. Clin Gastroenterol Hepatol. 2011;9:577–83.
- Müller-Lissner S, Kamm MA, et al. Myths and misconceptions about chronic constipation. Am J Gastroenterol. 2005;100(1):232–42. doi: 10.1111/j.1572-0241.2005.40885.x.
- Khalif IL, Quigley EM, Konovitch EA, Maximova ID. Alterations in the colonic flora and intestinal permeability and evidence of immune activation in chronic constipation. Dig Liver Dis. 2005;37(11):838–49. doi: 10.1016/j.dld.2005.06.008.
Conflict of interest: S. Landes, M. Eberlin and R. Lange are employees of Sanofi-Aventis.
Disclosure: Medical writing and publication funded by Sanofi-Aventis Deutschland GmbH.
