Constipation Part 2: Implications for Palliative Care

Evidence About the Pharmacological Management of CONSTIPATION PART 2: IMPLICATIONS FOR PALLIATIVE CARE

Constipation remains a challenging problem for patients and caregivers in home healthcare. Part 1 of this two-part series discussed the scope, physiology, and evidence-based practice for nonpharmacological interventions for constipation. This second article will focus on evidence-based pharmacological prevention and management of constipation, medication cost, and implications for palliative care.

Matthew Pitlick, PharmD, BCPS, and Deborah Fritz, PhD, RN

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Copyright © 2013 Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited. While eliminating causative factors and increasing fluid/fiber intake should be attempted when possible, these are often inappropriate or unreasonable options in palliative care. Many medications are available and differ in efficacy, safety, adverse effect profile, overall tolerability, and cost.

Case Study Introduction focuses on pharmacologic treatment of constipa- Mr. M. is a 66-year-old African American man who tion and implications for palliative care patients. was diagnosed with multiple myeloma 3 months ago after complaints of bone pain and fatigue. His Pharmacological Therapy problem list includes anemia, hypercalcemia, Bulk-Forming Laxatives and well-controlled diabetes mellitus on oral These agents’ bulk-forming laxatives, including medications. He is receiving lenalidomide, dexa- methylcellulose, polycarbophil, and psyllium, bulk methasone, and melphalan to treat his cancer. He stool contents, increase retention of water, and in- is not eligible for an autologous stem cell trans- crease the rate of stool transit through the intes- plantation. Ms. M. states that her husband has tine (Powell & Fleming, 2011). These actions result less energy to do the activities he has enjoyed in increased stool frequency. Bulk-forming laxa- since retirement. Although his bone pain is now tives may take 3 to 5 days for effect but can take well controlled, she is concerned that his chronic longer. Adequate fluid intake (1.5–2 L) is required constipation is affecting his quality of life. for use. Abdominal distention and flatulence are Mr. M.’s current medications are: common adverse effects but can resolve with contin- ued use. In general, these laxatives should not be • lenalidomide orally 25 mg daily, used in palliative care situations, as they can cause • dexamethasone orally 40 mg in the morning, obstructions of the esophagus, stomach, small intes- • melphalan orally 6 mg daily, tine, and colon, especially with inadequate fluid • zoledronic acid 4 mg IV every 4 weeks, intake (Powell & Fleming, 2011; Spinzi et al., 2009). • metformin orally 1,000 mg twice daily (BID), Psyllium has been associated with anaphylactic • morphine sulfate ER orally 30 mg BID, reactions, as well (Ho et al., 2008). The palliative • morphine sulfate IR orally 10 mg every 2 to 3 care patient, generally, cannot tolerate or intake hours as needed for breakthrough pain, and the amount of fluid needed for bulk-forming laxa- • docusate sodium orally 200 mg BID. tives to work properly and safely.

Background Emollients The goal of patient management for home health- Commonly known as stool softeners, these agents care providers, in particular for palliative care work by increased wetting and softening fecal patients, is the improvement of quality of life mass, which allows for easier passage of stool. issues that affect the physical and psychological Softening of stools generally occurs in 1 to 3 days well-being of their patients. These issues may in- (Powell & Fleming, 2011). Docusate is the most clude pain, fatigue, reduced mobility, and, com- commonly used stool softener and should be used monly, constipation. Constipation continues to to prevent painful defecation and straining in situ- challenge home healthcare providers, especially ations when this should be avoided such as se- in palliative care. For a detailed definition of con- vere hypertension, cardiovascular disease, and stipation, please refer to Part 1 of this article recent surgery or myocardial infarction. Docusate (Fritz & Pitlick, 2012). In an effort to improve may increase fecal soiling, otherwise there are symptoms of constipation, pharmacologic mea- very few side effects associated with these agents sures may be necessary. This second part article (Powell & Fleming, 2011). Stool softeners are

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Copyright © 2013 Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited. ineffective in treating constipation and should not an abundance of evidence showing efficacy and be used as monotherapy for treatment of constipa- safety with PEG over placebo (Locke, et al., 2000; tion (Gallegos-Orozco et al., 2012). However, they Powell & Fleming, 2011; Ramkumar & Rao, 2005; work well when combined with stimulant laxa- Weitzel & Goode, 2012). Unlike other laxatives, tives and lead to a softer, easier stool to pass as PEG has been shown safe when used up to 6 to the stimulant causes laxation (Locke et al., 2000; 12 months (Powell & Fleming, 2011; Singh & Rao, Powell & Fleming, 2011; Weitzel & Goode, 2012). 2010). PEG has been shown superior to lactulose as well (Ramkumar & Rao, 2005). Lubricant Lactulose and sorbitol are hyperosmotic laxa- Mineral oil can soften stool and prevent strain- tives that work in a similar way. In addition to ing, similar to emollients. It typically works in 2 altering fluid activity, these agents decrease pH in to 3 days. However, safety concerns severely the colon, which increases colonic peristalsis. limit its use. Lipid pneumonia can result from This increases stool frequency and consistency. aspiration, especially in the very ill and elderly. Adverse effects include flatulence, nausea, In addition, absorption of Vitamins A, D, E, and K abdominal discomfort or bloating, diarrhea, and can be disrupted. Other adverse effects such as electrolyte imbalances. Lactulose has been shown pruritus and soiling can occur as well (Leung et to be superior to placebo for chronic constipa- al., 2011; Powell & Fleming, 2011). Given these tion and effective in opioid-induced constipation issues, mineral oil should not be recommended in (Liu, 2011). Sorbitol is similar to lactulose, is more palliative care situations (Locke et al., 2000; cost-effective, and causes less nausea. However, Powell & Fleming, 2011; Weitzel & Goode, 2012). hyperglycemia may occur with sorbitol, so it is important to monitor patients with diabetes. Osmotic Laxatives Lactulose and sorbitol could be useful in palliative These agents include glycerin, polyethylene glycol care situations; however, there are not enough stud- (PEG, brand name: Miralax), lactulose, sorbitol, ies in this patient population and more frequent use and saline laxatives such as magnesium hydrox- of the laxative is needed. See Box 1 for evidence- ide, citrate, phosphate, and sodium phosphate. based practice regarding lactulose and PEG. These agents draw water into the colon through Saline laxatives include magnesium hydrox- osmosis, leading to a softer stool, and induce a ide, citrate, sulfate, phosphate, and sodium phos- bowel movement. Adverse effects are common phates. These agents act primarily by osmosis in among these laxatives (except glycerin and PEG) the small and large intestines (oral) or colon and elderly patients tend to be more susceptible. (rectal). They increase the intraluminal pressure Glycerin is a very safe and effective laxative for acute evacuation. It is available in suppository form and induces bowel movement in 30 minutes. Box 1. Evidence-Based Practice: Adverse effects are rare but may include mild Lactulose Versus Polyethylene Glycol rectal irritation. Lactulose versus polyethylene glycol for chronic PEG is an osmotic laxative with adequate effi- constipation (Lee-Robichaud et al., 2010). cacy and a favorable adverse effect profile. PEG Research Problem: To determine if lactulose possesses fewer adverse effects than other os- or polyethylene glycol is more effective to treat motic laxatives because it is not absorbed sys- chronic constipation. temically or metabolized by colonic bacteria. For Methods: Comprehensive literature review with constipation during palliative care, PEG is an ex- meta-analysis of randomized controlled trials cellent choice because of its wetting and stimula- comparing lactulose to polyethylene glycol. tion effects with low incidence of adverse effects. Results: Ten randomized controlled trials were in- Possible adverse effects include abdominal pain, cluded. Polyethylene glycol was found to be better than lactulose in outcomes of stool frequency and electrolyte disturbances, and dehydration; how- form of stool. ever, incidence is lower than that for other laxa- Implications for home healthcare practice: tives (Clemens & Klaschik, 2008). Additionally, Polyethylene glycol should be considered over PEG must be dissolved in a glass of water (8 oz), lactulose for treatment of chronic constipation. which can be an issue if the patient is fluid re- SORT LEVEL: B stricted or cannot tolerate excess fluids. There is

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Copyright © 2013 Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited. less effective drug (Locke et al., 2000; Powell & A very common Fleming, 2011; Weitzel & Goode, 2012). In the past, clinicians have hesitated using stimulant ccause of laxatives due to the theoretical potential of cconstipation in harming the colon with chronic use. It was ppalliative care thought that stimulant laxative use leads to “cathartic colon,” damaging the enteric nervous ppatients is opioids. system and leading to physical dependence of OOpioids decrease laxatives (Leung et al., 2011). However, little ggastric motility, evidence exists that this occurs when given in appropriate doses (Leung et al., 2011). Bisacodyl leleading to harder has been shown to be significantly better than sstools and no placebo in treatment of acute constipation, ttolerance develops improving stool frequency and consistency (Kienzle-Horn et al., 2006). There is also evidence to constipation as it does with other showing the superiority of bisacodyl over pla- opioid-related adverse effects. cebo in chronic constipation; however, there is little evidence in regard to use of senna and little is known about the risks of long-term use of stimulant laxatives (Leung et al., 2011). Clinically, and intestinal motility. These laxatives should be bisacodyl and senna are considered equally used for occasional, acute evacuation only, as they effective with similar risks. See Box 1 for evidence- can result in fluid loss and electrolyte imbalances. based practice regarding bisacodyl. Special consideration (i.e., renal impairment, chronic heart failure, or sodium-restricted diets) Chloride Channel Activator for patients with risk of hypermagnesemia, hy- This is a new drug class that includes lubipros- pernatremia, and hyperphosphatemia need to be tone (brand name: Amitiza). This agent increases taken into account (Locke et al., 2000; Powell & intraluminal fluid secretion that helps to soften Fleming, 2011; Weitzel & Goode, 2012). Bowel stool and accelerate GI transit time. Currently, movement typically occurs in a few hours after lubiprostone is approved only for chronic oral dose or within 1 hour after rectal administra- idiopathic constipation in adults. Evidence tion (Powell & Fleming, 2011). There is an overall shows lubiprostone improves straining, stool lack of efficacy data with saline laxatives (Ho et consistency, and overall constipation severity al., 2008; Leung et al., 2011; Liu, 2011), especially (Johanson & Ueno, 2007). Bowel movements in chronic constipation (Brandt et al., 2005). generally occur in 1 to 2 days. Common adverse effects include headache, diarrhea, and nausea Stimulant Laxatives with less common adverse effects being abdomi- These laxatives, including senna and bisacodyl, nal distention, pain, and flatulence. In addition, exhibit effects in the colon to increase intestinal this medication should be taken with food. One motility by local irritation of the mucosa or on advantage of this laxative over older laxatives is nerves and smooth muscle (Singh & Rao, 2010). that it does not cause electrolyte disturbances. Stimulant laxatives are often used in combination Because of the high cost and lack of long-term with stool softeners and are used frequently in pal- studies, lubiprostone should be reserved for liative care. These laxatives are commonly used those whom other laxatives fail and is not to be to treat opioid-induced constipation. Common used for occasional constipation (Liu, 2011; adverse effects include abdominal pain/cramping Powell & Fleming, 2011; Singh & Rao, 2010). and fluid/electrolyte imbalance. In addition, senna can turn urine a pink or red color. Antacids, Opioid Receptor Antagonists proton pump inhibitors, and histamine-2 recep- Currently, there are two opioid receptor available: tor antagonists should be avoided with bisacodyl alvimopan (brand name: Enterg) and methylnal- as these medications can cause the breakdown trexone (brand name: Relistor). These agents of enteric coating of bisacodyl, resulting in a do not affect the analgesic effects of opioids

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Copyright © 2013 Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited. because they do not cross the blood–brain barrier. Alvimopan is an oral gastrointestinal (GI)-specific Box 2. Evidence-Based Practice: mu-receptor antagonist approved for short-term Laxatives Versus Methynaltrexone use in hospitalized patients after bowel surgery. (MNTX) It is only available through a special program Laxatives versus MNTX for the management of (EASE), and the hospital must be registered be- constipation in palliative care patients (Candy et fore the drug is administered (Singh & Rao, al., 2011). 2010). Adverse effects include nausea and vom- Research Problem: Is Relistor (MNTX) helpful for iting. Alvimopan is contraindicated in patients managing constipation in palliative care patients? receiving therapeutic opioid doses for greater Methods: Comprehensive literature review of than 7 days before surgery as these patients may randomized controlled trials comparing laxatives or MNTX with either active treatment or placebo. be more sensitive to the drug’s effects. However, Results: There is insufficient evidence to recom- it is unlikely that palliative care patients will use mend one laxative over another for patients on this medication given the contraindications. Cost- palliative care. Methynaltrexone may increase the effective analysis shows it reduces mean hospital frequency of bowel movements but also increases stay by 1 day resulting in cost savings of $879– the risk of dizziness and gas. 977 per patient. Implications for home healthcare practice: Methylnaltrexone (MNTX) is a peripheral Choice of a laxative may be influenced by potential side effects. mu-receptor antagonist for opioid-induced constipation in patients with advanced disease receiv- SORT LEVEL: B ing palliative care or when response to traditional laxative therapy has been insufficient. Dosing is weight-based, usually given every other day via in 30 min. Soapsuds enemas are no longer rec- subcutaneous injection. No more than one dose ommended because they may cause infections should be administered in a 24-hour period. of the prostate and colitis issues (Powell & MNTX is contraindicated in the presence of or Fleming, 2011). suspected GI obstructions (Powell & Fleming, 2011). Adverse effects include abdominal pain, Probiotics flatulence, nausea, diarrhea, and dizziness (Ho It is reported that low levels of normal flora, et al., 2008). Long-term use of MNTX has not been specifically lactobacillus and bifidobacterium, evaluated (Singh & Rao, 2010). A 2008 study for exist in patients with chronic constipation. Pro- MNTX use in advanced illness, whose constipation biotics can improve stool frequency and con- was opioid-induced, and unresponsive to tradi- sistency (Liu, 2011). Evidence does exist for tional laxatives, showed significantly more patients use of lactobacillus in improving constipation had a bowel movement within the first 4 hours of for nursing home patients (Leung et al., 2011). MNTX dose compared to placebo. This same However, there is no evidence to recommend group also required significantly less rescue probiotics as prophylaxis for constipation or laxative use as well (Thomas et al., 2008). Al- treatment over conventional laxatives (Gallegos- though the evidence shows MNTX is an effective Orozco et al., 2012). laxative, cost is its major limitation at $55 per injection (Micromedex 2012). See Box 2 for Herbal Medications evidence-based practice for methynaltrexone. Herbal medications such as aloe vera, cascara sagrada bark, feverfiew, licorice, flaxseed, and Castor Oil senna leaves have all been marketed to improve This laxative should not be used in palliative care or regulate bowel function. Flaxseed and senna due to strong purgative action and associated are the only herbal medications recommended by adverse effects (Powell & Fleming, 2011). the Food and Drug Administration for use in constipation (Ho et al., 2008). Tap-Water/Soapsuds Enema This treatment can be used for acute evacuation Opioid-Induced Constipation for relief of constipation. Dose includes 200 ml of A very common cause of constipation in pallia- tap water and often results in a bowel movement tive care patients is opioids. Opioids decrease

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Copyright © 2013 Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited. unreasonable options in palliative care (Liu, ChronicC 2011). Many medications are available and differ in efficacy, safety, adverse effect profile, overall cconstipation is a tolerability, and cost. See Table 1 for a quick vvery significant reference guide. aand costly Special consideration needs to be used when choosing a laxative for constipation management pproblem in in palliative care (Table 2). Certain medical condi- ppalliative care tions (i.e., renal disease, heart failure), drug inter- ppatients. actions, and patient characteristics may preclude the use of certain laxatives. In addition, many of these patients are elderly and age-related concerns need to be taken into account including changing absorption, distribution, metabolism, and elimination of medications (Ho et al., 2008). gastric motility, leading to harder stools, and no Several laxatives should not be recommended tolerance develops to constipation as it does for treatment of constipation in the palliative with other opioid-related adverse effects. Oral care patient for various reasons (Table 2). Those opioids are more likely to cause constipation, include bulk-forming, mineral oil, castor oil, pro- probably due to increased contact time in the GI biotics, and herbal supplements. Bulk-forming tract. Transdermal fentanyl has been shown to laxatives generally cannot be tolerated due to the be associated with less constipation (Wolf et al., amount of fluid needed to work properly and 2012). It is extremely important that a patient be safely (Kyle, 2007). Mineral oil should not be rec- given a bowel regimen, either osmotic laxative ommended due to severe adverse effects includ- (i.e., PEG or lactulose) or combination stimulant ing aspiration causing pneumonia and vitamin laxative/stool softener when beginning an opioid deficiencies (Locke et al., 2000; Powell & Fleming, medication. Using stimulant laxatives alone could 2011; Weitzel & Goode, 2012). Stool softeners, cause severe straining and hard stools. A large such as docusate, should not be used as mono- study of 348 patients compared PEG, sodium therapy for treatment of constipations because picosulfate, and lactulose for opioid-induced they are ineffective in causing stool to pass constipation and recommended PEG or SPS (Gallegos-Orozco et al., 2012). However, they may rather than lactulose due to more effective re- be used effectively when combined with stimu- sults (Wirz et al., 2012). If the osmotic laxative or lant laxatives that lead to a softer and easier combination stimulant laxative/stool softener is stool to pass as the stimulant causes laxation ineffective or intolerable, MNTX should be con- (Locke et al., 2000; Powell & Fleming, 2011; sidered. This medication has been shown to be Weitzel & Goode, 2012). Saline laxatives such as effective and tolerable; however, it should be magnesium hydroxide or magnesium citrate should considered lastly due to its high cost over other be used only for acute evacuation. Chronic use of laxatives. Saline laxatives should only be used for these laxatives can cause electrolyte disorders, acute evacuation, if needed. Bulk-forming laxa- especially in patients with renal impairment. tives are not a good choice for opioid-induced Management of constipation generally consists constipation as these agents do not induce of either treatment for acute evacuation or chronic movement of stool. treatment, both of which impact palliative care patients. Both require different treatment modali- Nursing Management of Constipation ties, and medications can differ in their effective- in Palliative Care ness for acute or chronic issues. Constipation managed without medications is the Generally, acute evacuation works best with an best-case scenario for treatment; however, this is enema or suppository. Tap-water enema and glyc- unlikely in the majority of palliative care situa- erin suppository are good choices due to a high tions. While eliminating causative factors and in- success rate of evacuation and lack of side creasing fluid/fiber intake should be attempted effects. If these treatments are not effective, PEG, when possible, these are often inappropriate or oral sorbitol, or lactulose, and low-dose stimulant

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Drug Class Dosage Forms Dose Onset Adverse Drug Cost (Trade Name) Reactions

Psyllium Bulk forming Tablets 4–6 g/day 2–3 days Flatulence, bloating, $0.10–0.88 abdominal pain, per dose Polycarbophil Capsules obstruction (rare) Methylcellulose Powders Fiber chews Wafers Gummies

Docusate Emollient Capsule 100–300 mg Will not Cramping $0.14–0.80 sodium/calcium BID induce per dose laxation

Glycerin Osmotic Suppository 1 suppository 15–60 Local irritation $0.18 per minutes dose

Polyethylene Osmotic Powder for 17 g BID 1–3 days Abdominal pain, $0.10–$1.50 glycol solution nausea, diarrhea per dose (Miralax)

Lactulose Osmotic Liquid 15–60 ml BID 1–2 days Flatulence, cramps, $0.50–1.00 abdominal discomfort, per dose nausea Sweet taste

Sorbitol Osmotic Solution 30–150 ml 1–2 days Flatulence, cramps, $0.05–0.50 abdominal discomfort per dose

Magnesium Osmotic Suspension 30–45 ml 1–6 Abdominal pain, $0.01 per hydroxide (milk daily susp hours cramping, electrolyte dose of magnesia) disturbances

Magnesium Solution 240–300 ml $1–2 per citrate solution course

Senna Stimulant Tablet 8.6 mg 8–12 Watery diarrhea, $0.02–0.10 per pill Liquid 1–2 tabs hours abdominal pain, nausea $0.05–0.13 Fluid/electrolyte per liquid disorders dose

Bisacodyl Stimulant Tablet 5–10 mg daily 6–12 Watery diarrhea, ab $0.22–0.40 hours pain, nausea per pill

Suppository Fluid/electrolyte $3 per sup- disorders pository

Lubiprostone Chloride channel Oral pill 24 mcg BID 12–24 Nausea, diarrhea, $5 per pill activator hours headache

Alvimopan Opioid receptor Oral capusle 6–12 mg BID 1 day Nausea, vomiting $1,200 per antagonists for 7 days course

MNTX Opioid receptor Subcutaneous 8–12 mg every 30–60 Abdominal cramping, $55 per antagonists injection other day minutes flatulence, nausea injection

Note: BID = twice daily; MNTX = methynaltrexone. Sources: Data from Micromedex and Facts and Comparisons eAnswers drug databases, accessed November 2012.

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Copyright © 2013 Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited. laxative should be considered (Powell & Fleming, effects, and ease of use. PEG is an excellent 2011). If those modalities fail, magnesium hydrox- choice because of its softening and stimulating ide or magnesium citrate can be considered if the effects. A recent Cochrane review investigated patient does not have underlying renal dysfunction. the use of lactulose versus PEG for chronic con- Overall, limited evidence is available for use stipation. The review found that PEG was more of medications in chronic constipation with ad- efficacious than lactulose in terms of improved vanced illness, especially recommending one stool frequency, stool form, abdominal pain, and over another (Larkin et al., 2008; Librach et al., need for rescue laxation (Box 1). However, the 2010). Chronic constipation is a very significant subjects included in the review were all ambula- and costly problem in palliative care patients. tory, and 6 of the 10 studies only included chil- More potent laxatives are often needed, such dren or adolescents as patients. Therefore, this as osmotic and stimulant laxatives (Powell & review may not be completely applicable to the Fleming, 2011). PEG, bisacodyl, MNTX, and lubi- palliative care patient (Lee-Robichaud et al., prostone have all been shown to be more effec- 2010). If an osmotic agent cannot be used, it is tive than placebo (Ford & Suares, 2011). Data are unsuccessful, or cost is an issue, a combination limited for lactulose use (Ford & Suares, 2011). of stimulant laxative (senna or bisacodyl) and The 2010 Cochrane review on laxatives con- emollient (docusate sodium) should be used cluded that insufficient evidence is available to (Locke et al., 2000; Powell & Fleming, 2011; recommend one laxative over another based on Weitzel & Goode, 2012). If constipation is opioid- seven studies that investigated different laxa- induced, the combination can be used first line. tives (including MNTX) (Candy et al., 2011). A combination should always be used as emol- MNTX has shown to be effective over placebo; lients do not provide adequate motility of stool but however, no comparison studies have been do provide enhanced wetting and easy bowel done with other laxatives. In these studies, use of movements that stimulant laxatives do not. Use of conventional laxatives was not always reported stimulant laxatives should be regularly moni- but was used. MNTX effect when compared to tored, as they can cause severe abdominal placebo long-term safety has not been evaluated. cramping and possible fluid loss with resulting Osmotic laxatives are a good first choice be- electrolyte imbalance. A randomized, double- cause of their fast onset, low number of adverse blind, placebo-controlled, parallel-group trial in- vestigating 4-week bisacodyl 10 mg once daily Table 2. Medication Recommendations use, found increased bowel movements per week, for Chronic Constipation in Palliative decreased constipation-related symptoms, and Care improved quality of life over placebo. Adverse Recommendation Treatment effects were significantly more with bisacodyl and decreased after initial treatment (Box 3) First line Polyethylene glycol (Kamm et al., 2011). One study found senna to be Stimulant laxative (bisacodyl no different clinically from lactulose in the treat- or senna) + stool softener (docusate sodium) ment of opioid-induced constipation in terminal cancer patients (Agra et al., 1998). However, Second line Lactulose senna is the least expensive choice of the stimu- Sorbitol lant laxatives and much less expensive than PEG. Due to the high cost and lack of long-term stud- Third line Lubiprostone ies, lubiprostone should be reserved for those MNTX (opioid-induced only) who fail other laxatives and is not to be used for Not recommended Bulk-forming laxatives occasional constipation (Liu, 2010; Powell & Mineral oil Fleming, 2011; Singh & Rao, 2010). Castor oil Constipation treatment during palliative care is a complex and costly problem. Constipation Probiotics can severely affect quality of life and, although Herbal medications rare, possible complications, such as fecal Stool softener monotherapy impaction, rectal tearing/fissure, bowel obstruc- Note: MNTX = methynaltrexone. tion, hemorrhoids, and intestinal perforation, can

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Copyright © 2013 Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited. the newer laxatives such as lubiprostone and Box 3. Evidence-Based Practice: MNTX (if opioid-induced) should be reserved for Bisacodyl those patients who have failed or cannot tolerate Oral bisacodyl is effective and well-tolerated in pa- other laxatives due to the exorbitant cost with tients with chronic constipation (Kamm et al., 2011). these medications. In difficult cases, always Research Problem: To determine the safety and consult your pharmacist team members for efficacy of oral bisacodyl in patients with chronic medication-related questions. constipation. In the case study presented, Mr. M.’s bone Methods: In this double-blind, placebo-controlled, pain is well controlled with morphine sulfate that parallel-group study, 368 patients with history is contributing to his daily constipation. He is of constipation were assigned to bisacodyl or placebo once daily for 4 weeks. Stool dairy was currently on ducosate only (monotherapy), recorded daily electronically. which has been effective in softening his stool, Results: Bisacodyl was found to improve stool but does not allow for laxation or evacuation. consistency and frequency and was safe for chronic Miralax (PEG) was added to his daily regimen—17 g constipation. Bisacodyl produced no clinically initially once daily and was increased to twice significant adverse effects, was effective, did not cause electrolyte imbalance, and improved disease- daily after 1 week. He is now having daily soft related quality of life. bowel movements, without abdominal cramping Implications for home healthcare practice: or bloating, and his wife states his quality of life Bisacodyl while over-the-counter should be consid- has significantly improved. ered as first line for chronic constipation.

SORT LEVEL: B Matthew Pitlick, PharmD, BCPS, is an Assistant Professor of Pharmacy Practice, St. Louis College of Pharmacy, Ambulatory Care Clinical Pharmacist, arise (Larkin et al., 2008). A cost analysis of treat- John Cochran VA Medical Center, St. Louis, Missouri. ing constipation in a long-term care facility costs Deborah Fritz, PhD, RN, is a Family Nurse $2,253 per resident/per year (drug and nursing Practitioner, Primary Care Service Line, John costs) (Larkin et al., 2008). Another analysis in- Cochran VA Medical Center, St. Louis, Missouri. vestigating costs of constipation in a specialized The authors and planners have disclosed that they palliative care unit found that mean cost of treat- have no financial relationships related to this article. ment was $48.74 per admission with 85% of those Address for correspondence: Deborah Fritz, costs coming from staff time. If cost of caring for PhD, RN, 915 N. Grand, St. Louis, MO 63106 the patient after bowel clearance and discussion ([email protected]). of bowel care at handoff meetings were included, the cost increased dramatically to $258.33 per DOI:10.1097/NHH.0b013e3182885dd8 admission. A considerable amount of time was spent adding laxatives and changing doses to op- REFERENCES Agra, Y., Sacristán, A., González, M., Ferrari, M., Portugués, timize therapy; however, only 13% of the cost per A., & Calvo, M. J. (1998). Efficacy of senna versus admission was related to drug expenditure (Wee lactulose in terminal cancer patients treated with et al., 2010). This number is likely to increase with opioids. Journal of Pain and Symptom Management, the use of newer and more expensive laxatives. 15(1), 1-7. Brandt, L. J. , Prather, C. M. , Quigley, E. M., Schiller, L. Case Study Conclusion R., Schoenfeld, P., & Talley, N. J. (2005). Systematic One of the most important pieces is to individual- review on the management of chronic constipation ize each patient’s care and base choice of laxative in North America. American Journal of Gastroenter- on patient’s symptoms, performance, and prefer- ology, 100(Suppl. 1), S5-S21. ence (Larkin et al., 2008). Although evidence is Candy, B., Jones, L., Goodman, M. L., Drake, R., & Tookman, lacking in recommending one laxative over an- A. (2011). Laxatives or methylnaltrexone for the management of constipation in palliative care other, chronic constipation should first be treated patients. Cochrane Database of Systematic Reviews with PEG, combination stimulant laxative/stool (1), CD003448. softener, or both. Lactulose and sorbitol can be Clemens, K. E., & Klaschik, E. (2008). Management of considered if the patient has failed or not toler- constipation in palliative care patients. Current ated previous treatments. Although efficacious, Opinion in Supportive and Palliative Care, 2(1), 22-27.

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