Continuing Education Activity

Constipation, a prevalent condition affecting both children and adults, poses significant challenges if left unmanaged, potentially leading to complications like fecal impaction. With constipation ranking high among outpatient gastrointestinal (GI) diagnoses clinicians must navigate a diverse array of pharmacologic options, including over-the-counter laxatives in various formulations such as bulking agents, stool softeners, stimulant laxatives like bisacodyl, and osmotic laxatives. To optimize patient outcomes and enhance their quality of life, clinicians should engage in thorough discussions with patients, coordinate closely with nurses or caregivers, and carefully weigh the risks and benefits of laxative use, particularly bisacodyl, which demands attention due to its potential adverse effects. 

This activity reviews the necessary education for best practice use of biscodyl, particularly in cases where laxative misuse is intertwined with complex psychiatric disorders like bulimia or anorexia nervosa, necessitating referral for specialized psychiatric care. Through collaborative efforts encompassing clinicians, pharmacists, gastroenterologists, and nurses, a multidisciplinary approach can effectively mitigate risks associated with bisacodyl and other laxatives when striving for optimal patient outcomes.

Objectives:

• Differentiate between the mechanisms of action of bisacodyl and other laxatives.

• Apply evidence-based guidelines in selecting bisacodyl for constipation management in clinical practice.

• Select alternative treatment options if bisacodyl is contraindicated or ineffective.

• Implement communication among interprofessional team members to improve outcomes and treatment efficacy for patients who might benefit from bisacodyl therapy.

Indications

Bisacodyl [4,4’-diacetoxy-diphenyl-(pyridyl-2)-methane], a diphenylmethane derivative stimulant laxative, has been indicated for constipation since the 1950s. Bisacodyl is an effective and well-tolerated treatment option for patients with constipation. It improves bowel function, constipation-related symptoms, and disease-related quality of life (QOL).[1][2][3]

FDA-Approved Indications

Bisacodyl has been used as a first-line laxative for transient relief of occasional constipation. The 2023 guidelines from the American College of Gastroenterology (ACG) and the American Gastroenterological Association (AGA) endorse the short-term use of bisacodyl as a therapeutic option for addressing chronic idiopathic constipation.[4] More recently, it has been used for bowel preparation before investigational procedures (ie, colonoscopy, sigmoidoscopy), surgery, or pharmacologic provocation during colonoscopy manometry. Bisacodyl appears superior to the other drugs for changing the number of bowel movements per week.[5] Its effect occurs in the large intestine within 6 to 12 hours following oral ingestion and 15 to 60 minutes after rectal administration.[6][7] In a systematic review, bisacodyl has level 4 evidence regarding its safety and efficacy for chronic constipation.

Off-Label Uses

Bisacodyl is effective when administered to patients with neuropathy.[3] The North American Society of Pediatric Gastroenterology, Hepatology, and Nutrition (2023 NASPGHAN guidelines) recommends bisacodyl as a stimulant laxative for postoperative Hirschsprung disease patients. In cases resistant to oral laxative therapy, a retrograde enema, including rectal therapies like suppositories bisacodyl, is advocated by the guidelines. Bisacodyl may also be used for opioid-induced constipation.[8] A study in children undergoing colonic manometry aimed to compare high-amplitude propagated contractions induced by A and Glycerin. The results of the study included 45 patients, showing that HAPCs following A had a longer duration, greater propagation, and more occurrences than Glycerin. However, no differences were observed in HAPC amplitude and onset of action between the 2 medications.[9]

Mechanism of Action

Bisacodyl's target of action is the gastrointestinal (GI) tract. Absorption from the GI tract is minimal because its formulation is a coated tablet resistant to destruction in the stomach and small intestine and thus achieves transit to the colon in its intact form. After oral intake, it dissolves in the colon, ensuring a laxative effect.[2][10] 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.[6][7] 

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.[7][11][12] The metabolite acts locally in the large bowel by stimulating the colon's myoelectrical and motor activity and intestinal secretion, enhancing the colon's motility, reducing overall colonic transit time, and increasing the water content of the stool.[13][14] 

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 HCO^3-, passive efflux of Na+, K+, and water, and inhibition of Na+ and Cl- absorption into the enterocyte.[15] Bisacodyl may also exhibit its laxative effect by decreasing the expression of aquaporin 3 (AQP3) in the colon, inhibiting water transfer from the intestinal tract to the vascular side of the cells.[16] 

Bassotti et al investigated the effect of a 10 mg bisacodyl solution. About 90% of patients with slow transit constipation showed motor response characterized by one or more high amplitude propagated contractions (HAPCs).[17] 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, suggesting that bisacodyl could be effectively used and administered to manage constipation in patients with neuropathy because bisacodyl improves the spatiotemporal-coordinated pattern of HAPCs.[3]

Pharmacokinetics

Absorption: Bisacodyl's absorption from the GI tract is minimal. No correlative relationship was found between the plasma concentrations of the metabolite and the laxative effect, suggesting that systemic absorption was not required for the laxative action, and the impact of bisacodyl was subject to local mediation.[2] 

Distribution: The volume of distribution is 181 L after a single dose of bisacodyl and 289 L at a steady state.[18]

Metabolism: Bisacodyl becomes deacetylated in the colon to its active metabolite. The metabolite conjugates to the mono-glucuronide in the wall of the intestine or liver.[19] Bisacodyl's absorption from the GI tract is minimal. Therefore, only a small amount of bisacodyl's absorbed metabolite gets excreted in the urine as the glucuronide.[7]

Excretion: The predominant route of bisacodyl elimination occurs through the feces, with 13% to 17% of the administered dose excreted in the urine as the active metabolite.

Administration

Available Dosage Forms and Strengths

Bisacodyl administration can be via oral or rectal routes.[1][2] 

Adult Dosage

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. The medication can also be administered in 10 mg as an enema or suppository in the morning because bisacodyl will work within 15 to 60 minutes following rectal administration. Dosages of 10 to 20 mg are given by mouth for complete bowel evacuation, followed by 10 mg as a suppository the next morning.[7] Continued use of bisacodyl may decrease its efficacy because bisacodyl increases the production of PGE2, which decreases the expression of AQP3. The effectiveness of compounds that decrease AQP3 expression in the colon can be reduced by continued use.[16]

Specific Patient Populations

Hepatic impairment: The manufacturer's labeling does not include any recommendations for dosage adjustments for bisacodyl. Bisacodyl is not linked to serum enzyme elevations or clinically apparent liver injury.[20]

Renal impairment: Considering the unique property of bisacodyl as a cAMP-mediated stimulant laxative, which has been suggested to increase fecal potassium secretion by stimulating cAMP-mediated upregulation of colonic big potassium channels and has been shown to decrease intradialytic hyperkalemia in patients on hemodialysis, bisacodyl might be a reasonable choice of laxative in terms of lowering elevated potassium levels in advanced chronic kidney disease.[21] However, it is important to use caution when prescribing and monitoring bisacodyl in patients with chronic kidney disease due to electrolyte imbalances.

Pregnancy considerations: Bisacodyl exhibits minimal absorption with poor bioavailability. The use of stimulant laxatives like bisacodyl may induce abdominal cramps, and prolonged usage raises theoretical concerns about the possible emergence of electrolyte imbalances.[22] Considering dietary modification and the inclusion of fiber supplements may be advisable.[23]

Breastfeeding considerations: Bisacodyl is minimally absorbed from the GI tract, and its undetectable active metabolite in breast milk allows its use during breastfeeding without special precautions. In a study with 16 postpartum non-breastfeeding women, both oral enteric-coated bisacodyl tablets (10 mg daily) and oral liquid sodium picosulfate (10 mg daily) showed undetectable levels of the active BHPM in all collected milk samples.[24]

Pediatric patients: For children aged 3 to 10 years, a daily dose of 5 mg of bisacodyl, administered orally or rectally, is recommended as a single nightly dose. Children aged 10 and older may receive up to 10 mg daily, administered in a single nightly dose.

Older patients: The potential adverse effects of long-term usage in older individuals suggest that stimulant laxatives, such as bisacodyl, should be used only after attempting fiber and osmotic laxatives.[25]

Adverse Effects

The most common adverse effects, seen in more than 5% of patients taking bisacodyl, are diarrhea, abdominal pain (mainly 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.[26][27] Joo JS et al summarized that 45% of patients using bisacodyl or other laxatives (phenolphthalein, senna, and casanthranol) more than 3 times per week for 1 year or longer had subsequent radiographic changes of colonic redundancy and dilation of the colon, with loss of haustral markings which did not occur in the control groups. These agents may cause a neuronal injury or damage colonic longitudinal musculature.[28] 

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.[29] 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.[26] Other side effects of bisacodyl include muscle weakness, nausea, vomiting, anorexia, and rectal irritation.[30] Bisacodyl also has correlations with salt overload, hypokalemia, and protein-losing entropy.[31] Ajani et al reported a case that showed that bisacodyl correlates with colonic ischemia, but the explanation for bisacodyl-induced CI is not clear.[32] Rectal administration of bisacodyl may cause rectal mucosa irritation, burning sensation, and mild proctitis.[33]

Drug-Drug Interactions

Bisacodyl interacts with drugs such as digoxin, antacids, and H2-receptor antagonists. Wang et al conclude that bisacodyl interferes with digoxin absorption, with a resultant reduction of the serum digoxin concentration.[34] Antacid and H2-receptor antagonists cause the enteric coating to dissolve too rapidly and may result in gastric or duodenal irritation when administered within 1 hour of bisacodyl tablets. Simultaneous oral sodium sulfate and bisacodyl use may increase the risk of ischemic colitis.[35]

Contraindications

The primary indicated use of bisacodyl is for adults or children with constipation, especially chronic constipation. Bisacodyl is contraindicated in patients with acute GI diseases such as appendicitis or diarrhea, with ileus or suspected bowel obstruction, bowel perforation, colitis, toxic megacolon, severe dehydration, electrolyte imbalance (ie, hypokalemia, hyponatremia, metabolic alkalosis or acidosis), or are allergic or hypersensitive to bisacodyl.[6][36] Rectal administration of bisacodyl suppositories is also a contraindication in patients with inflammation or an ulcer in the distal colon (ulcerative proctitis) and anal fissures.[27]

Warnings

According to the Institute for Safe Medication Practices, the brand name of bisacodyl may be confused with docusate. Check the prescription before dispensing.[37]

Monitoring

Monitoring bisacodyl's metabolite is possible in human urine, serum, and stool within 24 hours after ingestion. A serum electrolyte test is necessary when the patient is administered bisacodyl and shows acid/base disorder. Gas chromatography-mass spectrometry (GC-MS) and liquid chromatography analyze bisacodyl's metabolites. The concentrations of bisacodyl diphenol, a metabolite of bisacodyl, in the patient's urine and serum were determined using bisphenol A as the internal standard.[19] Monitor disease severity and response to therapy; underlying disorders such as hypothyroidism should be evaluated. Bisacodyl stands out as the predominant laxative subjected to misuse, particularly linked to patients contending with eating disorders.[38]

Toxicity

Signs and Symptoms of Overdose

Overdosing of bisacodyl can induce diarrhea, leading to electrolyte disturbances, including hypokalemia, hypocalcemia, metabolic acidosis, or alkalosis, which may also produce vomiting and muscle weakness. Short-term use (3 days) of the recommended dose does not affect serum electrolytes.[2] A case report of chronic abuse of bisacodyl in a female patient showed a frequent and repetitive formation of urinary calculi with rapid double J stent encrustation.[39]

Management of Overdose

The management of bisacodyl overdose is supportive, focusing on ensuring adequate hydration and correcting any electrolyte imbalances.

Recommendations

The treatment of laxative abuse is to cease the causative agent; this is challenging because constipation may occur again after stopping this drug, leading to patient distress.[40] Bisacodyl is not recommended for use for more than 4 weeks due to harmful long-term colonic effects and possible carcinogenic risk of stimulant laxatives. Epidemiological studies investigating its effects and safety over longer terms are warranted.[12]

Enhancing Healthcare Team Outcomes

Constipation is a common disease that affects children and adults, especially older patients. Unmanaged constipation can progress to fecal impaction, which further impairs patients' quality of life and increases healthcare costs. Constipation is one of the most prevalent outpatient diagnoses among GI disorders.[40] Many pharmacologic agents are available for constipation, including over-the-counter (OTC) laxative products, rectal suppositories, and enemas. Oral products can be classified as bulking agents, stool softeners, stimulant laxatives, and osmotic laxatives.[36] 

Clinicians should assess the risks and benefits of using bisacodyl and individualize treatment based on the patient's symptoms and pathophysiology. Pharmacists must counsel, make recommendations, and contact the treating clinician if necessary. Nurses must take a thorough medication history. Referral to a gastroenterologist may be necessary for refractory cases. This interprofessional team approach ensures optimal patient outcomes.

Laxatives are used to relieve symptoms, but some patients may misuse them. Such misuse of laxatives may indicate an underlying medical disorder. Determining what may promote the behavior is the first step in treating laxative misuse. The individual who misuses the laxatives has to stop the stimulant laxatives and replace them with osmotic supplements to establish regular bowel movements.

Education and further treatment are required to maintain a healthy bowel program. Referral for psychiatric treatment is essential in the case of eating disorders such as bulimia or anorexia nervosa to lessen the reliance on laxatives as a method to alter perceived weight and shape.[41] Interprofessional collaboration with open communication between clinicians (MDs, DOs, NPs, PAs), pharmacists, gastroenterologists, and nurses can minimize the risk associated with bisacodyl and achieve optimal patient outcomes.