Bisacodyl [4,4’-diacetoxy-diphenyl-(pyridyl-2)-methane], a diphenylmethane derivative stimulant laxative, has been available as a laxative since 1952.[1][2][3] It is an effective and well-tolerated treatment for patients with constipation. It improves bowel function, constipation-related symptoms, and disease-related quality of life (QOL).[1] It has been used as a first-line laxative for functional constipation management and, more recently, used to facilitate bowel preparation before investigational procedures (i.e., colonoscopy, sigmoidoscopy), surgery, or pharmacologic provocation during colon manometry.[2][3] Bisacodyl is effective when administered to patients with neuropathy.[3] Bisacodyl appears superior to the other drugs for changing the number of bowel movements per week.[4] Its effect occurs in the large intestine within 6 to 12 hours after ingestion by mouth and within 15 to 60 minutes after rectal administration.[1][5][6] Bisacodyl classifies as having level 4 evidence regarding its safety and efficacy for chronic constipation in a systematic review.[1] In 2005, The American College of Gastroenterology Chronic Constipation Task Force stated that there are insufficient data to make a recommendation about the efficacy of stimulant laxative for the management of chronic constipation.[7]

Bisacodyl’s target of action is the gastrointestinal tract.[2] Absorption from the GI tract is minimal because its formulation is a coated tablet, which is resistant to destruction in the stomach and small intestine and thus achieves transit to the colon in its intact form. It then dissolves in the colon and ensures a laxative effect after oral intake.[2][6][7] Intestinal deacetylase and bacterial enzymes hydrolyze bisacodyl to a deacetylated active metabolite, bis-(p-hydroxyphenyl)-pyridyl-2-methane (BHPM), which stimulates the intestinal mucosa, causing peristalsis, which is responsible for the laxative action.[5][6] BPHM has a dual activity in the colon, including an anti-absorptive-secretory effect and a direct prokinetic effect by stimulating parasympathetic nerve endings in the colonic mucosa.[6][8][9] It acts locally in the large bowel by stimulating the colon’s myoelectrical and motor activity and intestinal secretion, thus enhancing the colon’s motility, reducing overall colonic transit time, and increasing the water content of the stool.[10][2][11] Ratnaike et al. demonstrated that bisacodyl impairs fluid absorption by activating adenylate cyclase in the small intestinal enterocytes which increases the amount of cyclic AMP, and causes the active secretion of Cl- and HCO3-, passive efflux of Na+, K+ and water, and inhibition of Na+ and Cl- absorption into the enterocyte.[12] Bisacodyl may also exhibit its laxative effect by decreasing the expression of aquaporin 3 (AQP3) in the colon, therefore inhibiting water transfer from the intestinal tract to the vascular side of the cells.[13] Bassotti et al. investigated the effect of a 10 mg bisacodyl solution and found that about 90% of patients with slow transit constipation showed motor response characterized by one or more high amplitude propagated contractions (HAPCs).[14] Min et al. conducted a study showing that bisacodyl increases sigmoid colon longitudinal muscle tone through direct action on the smooth muscle, but not in the colonic circular muscle, and suggest that bisacodyl could be effectively administered to manage constipation in patients with neuropathy because bisacodyl improves the spatiotemporal-coordinated pattern of HAPCs.[3]

Bisacodyl administration can be via oral or rectal routes.[1][2][6] In adults, bisacodyl is given in doses of 5 to 10 mg tablet daily administered at night or bedtime, because it works within 6 to 12 hours following administration when taken orally so that the therapeutic effect will occur in the morning. It also can be given in 10 mg as an enema or suppository administered in the morning because bisacodyl will work within 15 to 60 minutes following rectal administration. Doses of 10 to 20 mg are given by mouth for complete bowel evacuation, followed by 10 mg as a suppository the next morning.[6] In children from 3 to 10 years old, bisacodyl oral or rectal is given in doses of 5 mg per day in one dose at night. Ten years old or older can be given in up to 10 mg per day in one dose a day at night. Continued use of bisacodyl may result in a decrease in its efficacy, which occurs because bisacodyl increases the production of PGE2, which decreases the expression of AQP3, and the effectiveness of compounds that decrease AQP3 expression in the colon can become reduced by continued use.[13]

The most common adverse effects seen in more than 5 percent of patients taking bisacodyl are diarrhea, abdominal pain (mostly in the upper abdomen), and headache.[1] Although it is unlikely that chronic use of bisacodyl is harmful to the colon, it could induce abdominal discomfort and cramping pain.[15] But, it is generally well-tolerated, safe, and effective for adults and children.[16] Joo JS et al. showed that 45 percent of patients using bisacodyl or other laxatives (phenolphthalein, senna, and casanthranol) more than three times per week for one year or longer (This is defined as chronic stimulant laxative use.) had subsequent radiographic changes of colonic redundancy and dilation of colon, with loss of haustral markings which did not occur in the control groups.[17] It may suggest that these agents cause a neuronal injury or damage to colonic longitudinal musculature.[17] Myenteric plexus or smooth muscle damage due to stimulant laxatives is rare, and it is unclear if this is due to constipation or laxative use.[18] The association between stimulant laxatives and colorectal neoplasm in humans remains inconclusive, and the data is lacking in human studies, but in vitro studies showed that bisacodyl was found to induce proliferative epithelial lesions, including a transitional-cell carcinoma, but only in the urinary bladder epithelium of rats.[15] Other side effects of bisacodyl include muscle weakness, nausea, vomiting, anorexia, and rectal irritation.[19] It also has correlations with salt overload, hypokalemia, and protein-losing entropy.[20] Ajani et al. reported a case that showed that bisacodyl correlates with colonic ischemia (CI), but the explanation for bisacodyl-induced CI is not clear.[21] Rectal administration of bisacodyl may cause rectal mucosa irritation and a sensation of burning and mild proctitis. Bisacodyl has some interactions with other drugs such as digoxin, antacids, and H2-receptor antagonist. Wang et al. conclude that bisacodyl interferences the absorption of digoxin, resulting in the reduction of the serum digoxin concentration.[22] Antacid and H2-receptor antagonists cause the enteric coating to dissolve too rapidly and may result in gastric or duodenal irritation when administered within one hour of bisacodyl tablets.

Bisacodyl's primary indicated use is for adults or children with constipation, especially chronic constipation. Bisacodyl is contraindicated in patients with acute gastrointestinal diseases such as appendicitis or diarrhea, with ileus or suspected bowel obstruction, bowel perforation, colitis, toxic megacolon, having severe dehydration, electrolyte imbalance (i.e., hypokalemia, hyponatremia, metabolic alkalosis or acidosis), or are allergic or hypersensitive to bisacodyl.[5][23] Rectal administration of bisacodyl suppositories is also a contraindication in the patient who has inflammation or an ulcer in the distal colon (ulcerative proctitis) and/or anal fissures.[16]