Continuing Education Activity

Docusate is a medication utilized for managing and treating constipation. Belonging to the stool softener class of drugs, it reduces the surface tension of the oil and water interface within the stool, facilitating the passage of water and lipids into the stool mass. The goal is for the stool to become softer and move through the intestinal tract more easily. Docusate has no indications approved by the U.S. Food and Drug Administration (FDA). This activity aims to review the indications, mechanism of action, and contraindications of docusate in treating and managing constipation. This activity will highlight the adverse event profile and other crucial factors of docusate, including dosing, monitoring, and relevant interactions, pertinent to interprofessional team members involved in caring for patients with constipation and related conditions.

Objectives:

• Identify the appropriate indications for docusate usage in managing constipation and differentiate it from other laxative options.
• Screen patients for contraindications and potential drug interactions before prescribing docusate to ensure safe and effective use.
• Assess the efficacy of docusate in managing constipation and improving bowel movements for each patient and adjust treatment plans accordingly.
• Communicate effectively with patients about docusate therapy, involving them in shared decision-making while discussing its indications, risks, and benefits.

Indications

Constipation is a prevalent complaint encountered in clinical practice, affecting approximately 16% of all adults and 33% of adults 60 and older. There is no universally applicable definition of constipation. Most clinicians commonly define constipation as infrequent bowel movements, usually less than 3 per week. However, patients often describe constipation with a broader range of symptoms, including difficulty passing stool, firmer stool consistency, abdominal cramping, and a feeling of incomplete stool evacuation.[1]

The non-pharmacological management of chronic constipation begins with patient education and adjusting dietary and lifestyle habits. Clinicians must clarify to patients that not having a daily bowel movement is neither abnormal nor necessary. Moreover, increased physical activity has been linked to lower rates of constipation.[2] The dietary changes should promote increased consumption of fluid and fiber-rich foods. If these adjustments do not effectively address constipation, then the use of laxatives becomes necessary.

The different classes of commonly used laxatives for treating and managing constipation are listed below.

• Bulk-forming laxatives (methylcellulose and psyllium)
• Osmotic agents (polyethylene glycol, lactulose, and magnesium citrate)
• Stimulant laxatives (bisacodyl and senna)
• Surfactants or stool softeners (docusate and liquid paraffin)
• Lubricants (mineral oil)
• Prokinetic agents (tegaserod and cisapride)
• Newer agents include:
  • Linaclotide is a guanylate cyclase-C agonist that stimulates peristalsis through increased fluid secretion and reduced visceral hypersensitivity.[3]
  • Lubiprostone is a chloride channel activator that stimulates intestinal secretion and improves motility.[4]

Docusate, also known as dioctyl sulfosuccinate, is of 2 types that can be administered orally. They come in the form of either docusate sodium or docusate calcium salts. Docusate is classified as an over-the-counter (OTC) medication and has the marketing status of "OTC monograph not final," according to the U.S. National Library of Medicine, DailyMed resource. The U.S. Food and Drug Administration (FDA) has not determined the safety and efficacy of docusate for managing constipation in individuals. As a result, docusate is not featured on the FDA's rundown of authorized drugs, and there are no approved indications for its use.

According to the product monograph, docusate is indicated for use when peristaltic stimulants are contraindicated, aiming to alleviate difficult or painful defecation.

Docusate facilitates the passage of hard stools, which can benefit patients with painful anorectal conditions or cardiac comorbidities. Stool softening typically occurs within 12 to 72 hours after initiating therapy with docusate. Notably, several studies have demonstrated that docusate is ineffective for treating constipation in individuals.[5] 

A randomized, double-blind, placebo-controlled trial was conducted to assess the efficacy of docusate in managing constipation in hospice patients. A total of 74 hospice patients were included in the study and were assigned to receive either docusate and senna or placebo and senna for 10 days. The results indicated no significant differences between the docusate and placebo groups in the assessed outcomes. Consequently, the study concluded that the use of docusate in managing constipation in hospice patients should be evaluated individually.[6] 

Numerous systematic reviews examining the efficacy of docusate have yielded no significant evidence to support its use.[7][8][9][10] Nevertheless, docusate continues to be one of the most frequently prescribed laxatives.[11]

Furthermore, the summary of evidence by the Canadian Agency for Drugs and Technologies in Health involved a comprehensive search of 367 citations from the literature. Among these, 5 studies were included, comprising 2 systematic reviews, 1 randomized controlled trial, and 2 non-randomized trials. For patients who are on opioid medications, docusate (either calcium or sodium) has not shown to be more effective than a placebo or sennosides alone in increasing the frequency of bowel movements, softening stool consistency, making it easier to pass stools, achieving complete evacuation, or alleviating other symptoms associated with opioid-induced bowel dysfunction, such as abdominal cramps or delayed stomach emptying.[12]

A study with cancer patients found that the sennosides-only protocol resulted in more frequent bowel movements than a stepwise approach that included both sennosides and docusate sodium. A sub-analysis of symptom control or supportive care revealed that patients who adhered to the sennosides-only protocol had significantly more bowel movements, occurring more than 50% of the time, in contrast to those who followed the docusate and sennosides protocol (62.5% versus 31.6%, respectively).[13]

The study conducted by Tarumi et al did not observe any statistical significance in reported interventions when comparing the docusate plus sennosides group to the sennosides-only group in hospice patients (68.6% versus 74.4%, respectively). In contrast, Hawley and Byeon reported that 57% of cancer patients in the docusate plus sennosides protocol required additional interventions such as lactulose, suppositories, or enemas. In contrast, only 40% of cancer patients following the sennosides-only protocol needed such interventions in their symptom control or supportive care sub-analysis.[6][14][13][15]

A recent comprehensive review by McRorie et al in 2021 published in the American Journal of Gastroenterology included 7 randomized placebo-controlled clinical studies between 1956 and 2021 to evaluate the efficacy of docusate for softening stool in constipated patients. No significant difference was observed between docusate (100 to 400 mg per day) and placebo. During the eighth study, the effectiveness of docusate sodium and psyllium in treating patients with chronic idiopathic constipation was compared. The study found that docusate did not have a significant impact on the water content of stool. Therefore, the article concluded that docusate is not an effective stool-softening therapy and does not show any difference from the placebo.[16]

Docusate sodium is sometimes used as a cerumenolytic agent, even though it is not officially approved.[17] According to the American Academy of Otolaryngology guidelines, docusate can be utilized to visualize the tympanic membranes obscured by cerumen. The application of docusate sodium is followed by irrigation if necessary.[18]

Mechanism of Action

Docusate is classified as an emollient stool softener, belonging to the class of surfactant laxatives. Docusate functions by reducing the surface tension of the oil and water interface of the stool, thereby facilitating the passage of water and lipids into the stool mass. As a result, the stool softens and moves more easily through the intestinal tract.[19]

Docusate sodium is a water-based agent that helps hydrate and break down earwax, making cerumen removal easier and more effective.[20]

Administration

As discussed above, the efficacy of docusate is not well established. Docusate is a medication that can either be taken orally as tablets, capsules, liquids, or syrups or rectally through suppositories or enemas and even as ear drops.[21] 

• Oral docusate sodium is usually administered to patients once daily or in divided dosages. The typical dosing of docusate sodium is 100 mg twice daily.[22] On the other hand, docusate calcium is administered at a dosage of 240 mg once daily.
• Rectal enemas should be administered to patients 1 to 3 times a day through a disposable syringe as per the prescribed dosage of 283 mg per 5 mL. According to the guidelines provided by the North American Society of Pediatric Gastroenterology, Hepatology, and Nutrition, the use of low-volume OTC docusate enemas may not be feasible in Hirschsprung disease due to a significant compromise of the anal sphincter complex. As patients may have difficulty retaining the enema, limiting its maximum effect, alternative techniques should be employed.[23]
• Although docusate is used for opioid-induced constipation (OIC), its effectiveness is doubtful. A review of primary studies, guidelines, and consensus suggestions revealed weak evidence supporting its use. Therefore, institutions and healthcare providers should assess OIC protocols to ensure evidence-based therapy, minimize unnecessary drug use and costs, and consider the possibility of removing docusate when appropriate.[24]
• As a cerumenolytic agent, the liquid docusate is administered intra-aurally using a syringe, which may necessitate irrigation with lukewarm saline.[17][18]

Specific Patient Population

Patients with renal impairment: The manufacturer's labeling does not include dosage recommendations or adjustments for docusate in cases of renal impairment.

Patients with hepatic impairment: The manufacturer's labeling does not offer dosage recommendations or adjustments for docusate in cases of hepatic impairment.

Pregnancy considerations: Clinical data concerning the use of docusate during pregnancy is limited. However, no evidence suggests that docusate use is associated with adverse outcomes in pregnancy.[25] However, there is 1 reported case of a newborn developing symptomatic hypomagnesemia due to chronic maternal use of docusate during pregnancy.[26]

Breastfeeding considerations: According to the Academy of Breastfeeding Medicine, docusate is minimally absorbed from the gastrointestinal tract and is considered safe for breastfeeding mothers.[27] Due to negligible absorption, docusate is unlikely to be present in breast milk.[28]

Pediatric patients: The safety and efficacy of docusate have not been established in patients younger than 2. For patients between the ages of 2 and 12, docusate may be administered at 50 to 150 mg in single or divided doses.

Geriatric patients: Docusate is commonly used for treating constipation in older adults, despite limited evidence supporting its effectiveness. Docusate may help alleviate straining in certain patients, such as those who have recently undergone rectal surgery or experienced a myocardial infarction.[29][30]

Adverse Effects

The adverse effects of docusate are generally mild. Anorexia, diarrhea, and vomiting are usually associated with excess doses of docusate medication. Some people may experience abdominal cramping or, rarely, develop a rash as adverse reactions to docusate.[19] 

As syrup and liquid formulations of docusate can cause throat irritation and a bitter taste, it is recommended to administer them with adequate amounts of water. Mixing docusate with milk or fruit juice may alleviate throat irritation. A significant drawback is that medical professionals may only resort to proven constipation treatments after docusate has failed, potentially leading to lower patient satisfaction are extended hospital stays, thereby contributing to increased healthcare costs. Patients may also decline essential medications due to the excessive number of prescribed drugs.[31] 

Drug-Drug Interactions

Use docusate with caution when administering it with mineral oil, as there might be increased absorption of the mineral oil, potentially leading to systemic lipid granulomas.[32]

Contraindications

Contraindications and precautions related to docusate include:

• Hypersensitivity reaction to any of the docusate ingredients. 
• Nausea or vomiting due to the requirement of consuming a significant amount of fluid when using docusate.
• Intestinal obstruction, symptoms of appendicitis, acute abdominal pain, and fecal impaction, especially in children. Docusate use may mask the underlying problem.
• Dependency due to excessive medication use after self-medicating for more than 7 days.[21]
• Gasping syndrome in neonates due to the presence of benzyl alcohol in some docusate formulations.[33]

Monitoring

Excessive use of docusate may lead to dependence on bowel function. Patients with anorexia nervosa or bulimia and older patients who use laxatives for constipation are at risk of developing dependency and potential misuse. Alternating diarrhea with constipation can be a presentation of laxative abuse. Inducing excessive bowel movements through laxative use can result in fluid and electrolyte losses via the gastrointestinal tract. This condition can manifest with hypokalemia, hypomagnesemia, and non-anion gap metabolic acidosis. Hypovolemia can lead to acute kidney injury. The treatment of laxative abuse is to stop the offending agent. Rebound signs and symptoms, such as constipation, weight gain, and edema, may occur after discontinuing a laxative. Diuretics can be used cautiously in such cases to manage edema.[19][34][35][36]

An outbreak of Burkholderia cepacia infections was associated with exposure to specific liquid docusate formulations. The Centers for Disease Control and Prevention (CDC) collaborated with the FDA and other healthcare facilities to investigate the outbreak. Consequently, the FDA issued a voluntary recall of certain brands of liquid docusate formulations due to contaminated water to address the risk of product contamination with Burkholderia cepacia and the potential for human infection.[37] The healthcare team or patients are advised to promptly report any suspected adverse events to the FDA MedWatch program.[38]

Toxicity

Docusate has a well-documented safety and tolerability profile and has been in use in the United States since the 1950s. Animal studies have demonstrated that docusate sodium ear drops can cause significant ototoxicity. Therefore, docusate ear drops should be avoided in patients with tympanic membrane perforation.[20] 

Although propylene glycol (PG) present in some docusate products is considered safe, it can cause toxicity in children when used in high doses or for extended periods. PG may cause various health problems, including central nervous system toxicity, hyperosmolarity, hemolysis, cardiac arrhythmia, and lactic acidosis.[39]

Docusate is metabolized in the liver, where it undergoes significant first-pass metabolism, forming both active and inactive metabolites. Although docusate undergoes hepatic metabolism and has high plasma protein binding, there have been no reports of clinically apparent hepatoxicity.[40]

Enhancing Healthcare Team Outcomes

For effective constipation management, it is crucial to identify and treat the underlying etiology. Constipation can result from various disease states, such as chronic kidney disease, hypothyroidism, irritable bowel syndrome, diabetes, dementia, depression, colorectal cancer, autonomic neuropathy, hemorrhoids, hypercalcemia, hypokalemia, multiple sclerosis, Parkinson disease, and stroke. Mitigating the underlying cause can ameliorate constipation symptoms and enhance the overall quality of life. Furthermore, certain medications, including opioids, anticholinergics, iron supplements, and calcium channel blockers, may instigate constipation. 

For patients already using docusate, assessing their constipation status and communicating with the prescribing healthcare provider about discontinuing docusate when appropriate is recommended. Laxative therapy should be advised when suitable for those patients who require medication to manage their condition. This activity emphasizes that healthcare teams should collaborate to review and exclude docusate from the prescribing order if it appears in pre-printed forms or order sets. These measures can prevent unnecessary docusate prescribing and promote the adoption of evidence-based alternatives for constipation management.

According to an article from the Choosing Wisely initiative in the Journal of Hospital Medicine, it is recommended to discontinue prescribing docusate for patients already taking the drug before being admitted to the hospital. The article also suggests removing the medication from the hospital formulary. Despite limited evidence supporting its efficacy, the recommendation stems from the everyday use of docusate for constipation treatment and prevention. Instead, the article suggests opting for more effective therapies such as polyethylene glycol, lactulose, psyllium, or sennosides to manage constipation.[31] 

An observational study revealed that despite its ineffectiveness, docusate is frequently prescribed to medical inpatients, including those at high risk of constipation. Furthermore, there is a notable rate of new prescriptions on discharge, which can potentially exacerbate polypharmacy. Surprisingly, among patients already receiving docusate, 80% of them are still prescribed the medication when they are discharged, which indicates that there are missed opportunities for deprescribing.[41] 

A team consisting of internal medicine resident physicians and pharmacists initiated a quality improvement project to tackle the concern of docusate use in hospitalized patients. The team devised and implemented 2 interventions, encompassing education for residents and pharmacists and introducing an additional process-related barrier. As a result of this strategy, there was a substantial decrease in docusate orders without any adverse impact on the length of hospital stay for patients. The successful collaboration among the interprofessional team highlights the efficacy of this approach in promoting evidence-based medicine.[42]

Although a primary care physician or advanced practice practitioner typically manages most cases of constipation initially, referral to a subspecialist may be necessary depending on the underlying cause, as mentioned earlier. In some cases, the involvement of a surgeon, gastroenterologist, neurologist, psychiatrist, or endocrinologist may also be necessary for providing better care for patients dealing with constipation issues. A radiologist can provide valuable information through imaging studies about bowel pathology by collaborating with a physician or surgeon. A dietician is critical in modifying dietary risk factors. A pharmacist will verify that the patient is not taking any medications that could worsen constipation and recommend suitable alternatives if necessary. An otorhinolaryngologist can use docusate for cerumen impaction treatment. Nurses play a crucial role in the interprofessional team, providing direct patient care, education, and counseling in both outpatient and hospital settings. Their effective communication skills enable them to raise concerns and contribute significantly to patient care by alerting other clinicians. Ensuring patient education on the effectiveness of docusate is of utmost importance.

Adopting an interprofessional approach with effective communication and shared decision-making among prescribing physicians, advanced practice practitioners, nurses, pharmacists, specialists, and dieticians is crucial for enhancing patient experience and optimizing outcomes.