Evidence About the Pharmacological Management of 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 vol. 31 no. 4 April 2013 Home Healthcare Nurse 207

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 Mr. M. is a 66-year-old African American man who was diagnosed with multiple myeloma 3 months ago after complaints of bone pain and fatigue. His problem list includes anemia, hypercalcemia, and well-controlled diabetes mellitus on oral medications. He is receiving lenalidomide, dexamethasone, and melphalan to treat his cancer. He is not eligible for an autologous stem cell transplantation. Ms. M. states that her husband has less energy to do the activities he has enjoyed since retirement. Although his bone pain is now well controlled, she is concerned that his chronic constipation is affecting his quality of life. Mr. M. s current medications are: lenalidomide orally 25 mg daily, dexamethasone orally 40 mg in the morning, melphalan orally 6 mg daily, zoledronic acid 4 mg IV every 4 weeks, metformin orally 1,000 mg twice daily (BID), morphine sulfate ER orally 30 mg BID, morphine sulfate IR orally 10 mg every 2 to 3 hours as needed for breakthrough pain, and docusate sodium orally 200 mg BID. Background The goal of patient management for home healthcare providers, in particular for palliative care patients, is the improvement of quality of life issues that affect the physical and psychological well-being of their patients. These issues may include pain, fatigue, reduced mobility, and, commonly, constipation. Constipation continues to challenge home healthcare providers, especially in palliative care. For a detailed definition of constipation, please refer to Part 1 of this article (Fritz & Pitlick, 2012). In an effort to improve symptoms of constipation, pharmacologic measures may be necessary. This second part article focuses on pharmacologic treatment of constipation and implications for palliative care patients. Pharmacological Therapy Bulk-Forming Laxatives These agents bulk-forming laxatives, including methylcellulose, polycarbophil, and psyllium, bulk stool contents, increase retention of water, and increase the rate of stool transit through the intestine (Powell & Fleming, 2011). These actions result in increased stool frequency. Bulk-forming laxatives may take 3 to 5 days for effect but can take longer. Adequate fluid intake (1.5 2 L) is required for use. Abdominal distention and flatulence are common adverse effects but can resolve with continued use. In general, these laxatives should not be used in palliative care situations, as they can cause obstructions of the esophagus, stomach, small intestine, and colon, especially with inadequate fluid intake (Powell & Fleming, 2011; Spinzi et al., 2009). Psyllium has been associated with anaphylactic reactions, as well (Ho et al., 2008). The palliative care patient, generally, cannot tolerate or intake the amount of fluid needed for bulk-forming laxatives to work properly and safely. Emollients Commonly known as stool softeners, these agents work by increased wetting and softening fecal mass, which allows for easier passage of stool. Softening of stools generally occurs in 1 to 3 days (Powell & Fleming, 2011). Docusate is the most commonly used stool softener and should be used to prevent painful defecation and straining in situations when this should be avoided such as severe hypertension, cardiovascular disease, and recent surgery or myocardial infarction. Docusate may increase fecal soiling, otherwise there are very few side effects associated with these agents (Powell & Fleming, 2011). Stool softeners are 208 Home Healthcare Nurse www.homehealthcarenurseonline.com

ineffective in treating constipation and should not be used as monotherapy for treatment of constipation (Gallegos-Orozco et al., 2012). However, they work well when combined with stimulant laxatives and lead to a softer, easier stool to pass as the stimulant causes laxation (Locke et al., 2000; Powell & Fleming, 2011; Weitzel & Goode, 2012). Lubricant Mineral oil can soften stool and prevent straining, similar to emollients. It typically works in 2 to 3 days. However, safety concerns severely limit its use. Lipid pneumonia can result from aspiration, especially in the very ill and elderly. In addition, absorption of Vitamins A, D, E, and K can be disrupted. Other adverse effects such as pruritus and soiling can occur as well (Leung et al., 2011; Powell & Fleming, 2011). Given these issues, mineral oil should not be recommended in palliative care situations (Locke et al., 2000; Powell & Fleming, 2011; Weitzel & Goode, 2012). Osmotic Laxatives These agents include glycerin, polyethylene glycol (PEG, brand name: Miralax), lactulose, sorbitol, and saline laxatives such as magnesium hydroxide, citrate, phosphate, and sodium phosphate. These agents draw water into the colon through osmosis, leading to a softer stool, and induce a bowel movement. Adverse effects are common among these laxatives (except glycerin and PEG) and elderly patients tend to be more susceptible. Glycerin is a very safe and effective laxative for acute evacuation. It is available in suppository form and induces bowel movement in 30 minutes. Adverse effects are rare but may include mild rectal irritation. PEG is an osmotic laxative with adequate efficacy and a favorable adverse effect profile. PEG possesses fewer adverse effects than other osmotic laxatives because it is not absorbed systemically or metabolized by colonic bacteria. For constipation during palliative care, PEG is an excellent choice because of its wetting and stimulation effects with low incidence of adverse effects. Possible adverse effects include abdominal pain, electrolyte disturbances, and dehydration; however, incidence is lower than that for other laxatives (Clemens & Klaschik, 2008). Additionally, PEG must be dissolved in a glass of water (8 oz), which can be an issue if the patient is fluid restricted or cannot tolerate excess fluids. There is an abundance of evidence showing efficacy and safety with PEG over placebo (Locke, et al., 2000; Powell & Fleming, 2011; Ramkumar & Rao, 2005; Weitzel & Goode, 2012). Unlike other laxatives, PEG has been shown safe when used up to 6 to 12 months (Powell & Fleming, 2011; Singh & Rao, 2010). PEG has been shown superior to lactulose as well (Ramkumar & Rao, 2005). Lactulose and sorbitol are hyperosmotic laxatives that work in a similar way. In addition to altering fluid activity, these agents decrease ph in the colon, which increases colonic peristalsis. This increases stool frequency and consistency. Adverse effects include flatulence, nausea, abdominal discomfort or bloating, diarrhea, and electrolyte imbalances. Lactulose has been shown to be superior to placebo for chronic constipation and effective in opioid-induced constipation (Liu, 2011). Sorbitol is similar to lactulose, is more cost-effective, and causes less nausea. However, hyperglycemia may occur with sorbitol, so it is important to monitor patients with diabetes. Lactulose and sorbitol could be useful in palliative care situations; however, there are not enough studies in this patient population and more frequent use of the laxative is needed. See Box 1 for evidencebased practice regarding lactulose and PEG. Saline laxatives include magnesium hydroxide, citrate, sulfate, phosphate, and sodium phosphates. These agents act primarily by osmosis in the small and large intestines (oral) or colon (rectal). They increase the intraluminal pressure Box 1. Evidence-Based Practice: Lactulose Versus Polyethylene Glycol Lactulose versus polyethylene glycol for chronic constipation (Lee-Robichaud et al., 2010). Research Problem: To determine if lactulose or polyethylene glycol is more effective to treat chronic constipation. Methods: Comprehensive literature review with meta-analysis of randomized controlled trials comparing lactulose to polyethylene glycol. Results: Ten randomized controlled trials were included. Polyethylene glycol was found to be better than lactulose in outcomes of stool frequency and form of stool. Implications for home healthcare practice: Polyethylene glycol should be considered over lactulose for treatment of chronic constipation. SORT LEVEL: B vol. 31 no. 4 April 2013 Home Healthcare Nurse 209

A very common cause of constipation in palliative care patients is opioids. Opioids decrease gastric motility, leading to harder stools and no tolerance develops to constipation as it does with other opioid-related adverse effects. and intestinal motility. These laxatives should be used for occasional, acute evacuation only, as they can result in fluid loss and electrolyte imbalances. Special consideration (i.e., renal impairment, chronic heart failure, or sodium-restricted diets) for patients with risk of hypermagnesemia, hypernatremia, and hyperphosphatemia need to be taken into account (Locke et al., 2000; Powell & Fleming, 2011; Weitzel & Goode, 2012). Bowel movement typically occurs in a few hours after oral dose or within 1 hour after rectal administration (Powell & Fleming, 2011). There is an overall lack of efficacy data with saline laxatives (Ho et al., 2008; Leung et al., 2011; Liu, 2011), especially in chronic constipation (Brandt et al., 2005). Stimulant Laxatives These laxatives, including senna and bisacodyl, exhibit effects in the colon to increase intestinal motility by local irritation of the mucosa or on nerves and smooth muscle (Singh & Rao, 2010). Stimulant laxatives are often used in combination with stool softeners and are used frequently in palliative care. These laxatives are commonly used to treat opioid-induced constipation. Common adverse effects include abdominal pain/cramping and fluid/electrolyte imbalance. In addition, senna can turn urine a pink or red color. Antacids, proton pump inhibitors, and histamine-2 receptor antagonists should be avoided with bisacodyl as these medications can cause the breakdown of enteric coating of bisacodyl, resulting in a less effective drug (Locke et al., 2000; Powell & Fleming, 2011; Weitzel & Goode, 2012). In the past, clinicians have hesitated using stimulant laxatives due to the theoretical potential of harming the colon with chronic use. It was thought that stimulant laxative use leads to cathartic colon, damaging the enteric nervous system and leading to physical dependence of laxatives (Leung et al., 2011). However, little evidence exists that this occurs when given in appropriate doses (Leung et al., 2011). Bisacodyl has been shown to be significantly better than placebo in treatment of acute constipation, improving stool frequency and consistency (Kienzle-Horn et al., 2006). There is also evidence showing the superiority of bisacodyl over placebo 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, bisacodyl and senna are considered equally effective with similar risks. See Box 1 for evidencebased practice regarding bisacodyl. Chloride Channel Activator This is a new drug class that includes lubiprostone (brand name: Amitiza). This agent increases intraluminal fluid secretion that helps to soften stool and accelerate GI transit time. Currently, lubiprostone is approved only for chronic idiopathic constipation in adults. Evidence shows lubiprostone improves straining, stool consistency, and overall constipation severity (Johanson & Ueno, 2007). Bowel movements generally occur in 1 to 2 days. Common adverse effects include headache, diarrhea, and nausea with less common adverse effects being abdominal distention, pain, and flatulence. In addition, this medication should be taken with food. One advantage of this laxative over older laxatives is that it does not cause electrolyte disturbances. Because of the high cost and lack of long-term studies, lubiprostone should be reserved for those whom other laxatives fail and is not to be used for occasional constipation (Liu, 2011; Powell & Fleming, 2011; Singh & Rao, 2010). Opioid Receptor Antagonists Currently, there are two opioid receptor available: alvimopan (brand name: Enterg) and methylnaltrexone (brand name: Relistor). These agents do not affect the analgesic effects of opioids 210 Home Healthcare Nurse www.homehealthcarenurseonline.com

because they do not cross the blood brain barrier. Alvimopan is an oral gastrointestinal (GI)-specific mu-receptor antagonist approved for short-term use in hospitalized patients after bowel surgery. It is only available through a special program (EASE), and the hospital must be registered before the drug is administered (Singh & Rao, 2010). Adverse effects include nausea and vomiting. Alvimopan is contraindicated in patients receiving therapeutic opioid doses for greater than 7 days before surgery as these patients may be more sensitive to the drug s effects. However, it is unlikely that palliative care patients will use this medication given the contraindications. Costeffective analysis shows it reduces mean hospital stay by 1 day resulting in cost savings of $879 977 per patient. Methylnaltrexone (MNTX) is a peripheral mu-receptor antagonist for opioid-induced constipation in patients with advanced disease receiving palliative care or when response to traditional laxative therapy has been insufficient. Dosing is weight-based, usually given every other day via subcutaneous injection. No more than one dose should be administered in a 24-hour period. MNTX is contraindicated in the presence of or suspected GI obstructions (Powell & Fleming, 2011). Adverse effects include abdominal pain, flatulence, nausea, diarrhea, and dizziness (Ho et al., 2008). Long-term use of MNTX has not been evaluated (Singh & Rao, 2010). A 2008 study for MNTX use in advanced illness, whose constipation was opioid-induced, and unresponsive to traditional laxatives, showed significantly more patients had a bowel movement within the first 4 hours of MNTX dose compared to placebo. This same group also required significantly less rescue laxative use as well (Thomas et al., 2008). Although the evidence shows MNTX is an effective laxative, cost is its major limitation at $55 per injection (Micromedex 2012). See Box 2 for evidence-based practice for methynaltrexone. Castor Oil This laxative should not be used in palliative care due to strong purgative action and associated adverse effects (Powell & Fleming, 2011). Tap-Water/Soapsuds Enema This treatment can be used for acute evacuation for relief of constipation. Dose includes 200 ml of tap water and often results in a bowel movement Box 2. Evidence-Based Practice: Laxatives Versus Methynaltrexone (MNTX) Laxatives versus MNTX for the management of constipation in palliative care patients (Candy et al., 2011). Research Problem: Is Relistor (MNTX) helpful for managing constipation in palliative care patients? Methods: Comprehensive literature review of randomized controlled trials comparing laxatives or MNTX with either active treatment or placebo. Results: There is insufficient evidence to recommend one laxative over another for patients on palliative care. Methynaltrexone may increase the frequency of bowel movements but also increases the risk of dizziness and gas. Implications for home healthcare practice: Choice of a laxative may be influenced by potential side effects. SORT LEVEL: B in 30 min. Soapsuds enemas are no longer recommended because they may cause infections of the prostate and colitis issues (Powell & Fleming, 2011). Probiotics It is reported that low levels of normal flora, specifically lactobacillus and bifidobacterium, exist in patients with chronic constipation. Probiotics can improve stool frequency and consistency (Liu, 2011). Evidence does exist for use of lactobacillus in improving constipation for nursing home patients (Leung et al., 2011). However, there is no evidence to recommend probiotics as prophylaxis for constipation or treatment over conventional laxatives (Gallegos- Orozco et al., 2012). Herbal Medications Herbal medications such as aloe vera, cascara sagrada bark, feverfiew, licorice, flaxseed, and senna leaves have all been marketed to improve or regulate bowel function. Flaxseed and senna are the only herbal medications recommended by the Food and Drug Administration for use in constipation (Ho et al., 2008). Opioid-Induced Constipation A very common cause of constipation in palliative care patients is opioids. Opioids decrease vol. 31 no. 4 April 2013 Home Healthcare Nurse 211

Chronic constipation is a very significant and costly problem in palliative care patients. gastric motility, leading to harder stools, and no tolerance develops to constipation as it does with other opioid-related adverse effects. Oral opioids are more likely to cause constipation, probably due to increased contact time in the GI tract. Transdermal fentanyl has been shown to be associated with less constipation (Wolf et al., 2012). It is extremely important that a patient be given a bowel regimen, either osmotic laxative (i.e., PEG or lactulose) or combination stimulant laxative/stool softener when beginning an opioid medication. Using stimulant laxatives alone could cause severe straining and hard stools. A large study of 348 patients compared PEG, sodium picosulfate, and lactulose for opioid-induced constipation and recommended PEG or SPS rather than lactulose due to more effective results (Wirz et al., 2012). If the osmotic laxative or combination stimulant laxative/stool softener is ineffective or intolerable, MNTX should be considered. This medication has been shown to be effective and tolerable; however, it should be considered lastly due to its high cost over other laxatives. Saline laxatives should only be used for acute evacuation, if needed. Bulk-forming laxatives are not a good choice for opioid-induced constipation as these agents do not induce movement of stool. Nursing Management of Constipation in Palliative Care Constipation managed without medications is the best-case scenario for treatment; however, this is unlikely in the majority of palliative care situations. While eliminating causative factors and increasing fluid/fiber intake should be attempted when possible, these are often inappropriate or unreasonable options in palliative care (Liu, 2011). Many medications are available and differ in efficacy, safety, adverse effect profile, overall tolerability, and cost. See Table 1 for a quick reference guide. Special consideration needs to be used when choosing a laxative for constipation management in palliative care (Table 2). Certain medical conditions (i.e., renal disease, heart failure), drug interactions, 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). Several laxatives should not be recommended for treatment of constipation in the palliative care patient for various reasons (Table 2). Those include bulk-forming, mineral oil, castor oil, probiotics, and herbal supplements. Bulk-forming laxatives generally cannot be tolerated due to the amount of fluid needed to work properly and safely (Kyle, 2007). Mineral oil should not be recommended due to severe adverse effects including aspiration causing pneumonia and vitamin deficiencies (Locke et al., 2000; Powell & Fleming, 2011; Weitzel & Goode, 2012). Stool softeners, such as docusate, should not be used as monotherapy for treatment of constipations because they are ineffective in causing stool to pass (Gallegos-Orozco et al., 2012). However, they may be used effectively when combined with stimulant laxatives that lead to a softer and easier stool to pass as the stimulant causes laxation (Locke et al., 2000; Powell & Fleming, 2011; Weitzel & Goode, 2012). Saline laxatives such as magnesium hydroxide or magnesium citrate should be used only for acute evacuation. Chronic use of these laxatives can cause electrolyte disorders, especially in patients with renal impairment. Management of constipation generally consists of either treatment for acute evacuation or chronic treatment, both of which impact palliative care patients. Both require different treatment modalities, and medications can differ in their effectiveness for acute or chronic issues. Generally, acute evacuation works best with an enema or suppository. Tap-water enema and glycerin suppository are good choices due to a high success rate of evacuation and lack of side effects. If these treatments are not effective, PEG, oral sorbitol, or lactulose, and low-dose stimulant 212 Home Healthcare Nurse www.homehealthcarenurseonline.com

Table 1. Quick Reference for Medications and Associated Cost Drug (Trade Name) Class Dosage Forms Dose Onset Adverse Drug Reactions Cost Psyllium Polycarbophil Methylcellulose Bulk forming Tablets Capsules Powders 4 6 g/day 2 3 days Flatulence, bloating, abdominal pain, obstruction (rare) $0.10 0.88 per dose Fiber chews Wafers Gummies Docusate sodium/calcium Emollient Capsule 100 300 mg BID Will not induce laxation Cramping $0.14 0.80 per dose Glycerin Osmotic Suppository 1 suppository 15 60 minutes Local irritation $0.18 per dose Polyethylene glycol (Miralax) Osmotic Powder for solution 17 g BID 1 3 days Abdominal pain, nausea, diarrhea $0.10 $1.50 per dose Lactulose Osmotic Liquid 15 60 ml BID 1 2 days Flatulence, cramps, abdominal discomfort, nausea Sweet taste Sorbitol Osmotic Solution 30 150 ml 1 2 days Flatulence, cramps, abdominal discomfort $0.50 1.00 per dose $0.05 0.50 per dose Magnesium hydroxide (milk of magnesia) Osmotic Suspension 30 45 ml daily susp 1 6 hours Abdominal pain, cramping, electrolyte disturbances $0.01 per dose Magnesium citrate Solution 240 300 ml solution $1 2 per course Senna Stimulant Tablet Liquid 8.6 mg 1 2 tabs 8 12 hours Watery diarrhea, abdominal pain, nausea Fluid/electrolyte disorders $0.02 0.10 per pill $0.05 0.13 per liquid dose Bisacodyl Stimulant Tablet 5 10 mg daily 6 12 hours Watery diarrhea, ab pain, nausea $0.22 0.40 per pill Suppository Fluid/electrolyte disorders $3 per suppository Lubiprostone Chloride channel activator Oral pill 24 mcg BID 12 24 hours Nausea, diarrhea, headache $5 per pill Alvimopan Opioid receptor antagonists Oral capusle 6 12 mg BID for 7 days 1 day Nausea, vomiting $1,200 per course MNTX Opioid receptor antagonists Subcutaneous injection 8 12 mg every other day 30 60 minutes Abdominal cramping, flatulence, nausea $55 per injection Note: BID = twice daily; MNTX = methynaltrexone. Sources: Data from Micromedex and Facts and Comparisons eanswers drug databases, accessed November 2012. vol. 31 no. 4 April 2013 Home Healthcare Nurse 213

laxative should be considered (Powell & Fleming, 2011). If those modalities fail, magnesium hydroxide or magnesium citrate can be considered if the patient does not have underlying renal dysfunction. Overall, limited evidence is available for use of medications in chronic constipation with advanced illness, especially recommending one over another (Larkin et al., 2008; Librach et al., 2010). Chronic constipation is a very significant and costly problem in palliative care patients. More potent laxatives are often needed, such as osmotic and stimulant laxatives (Powell & Fleming, 2011). PEG, bisacodyl, MNTX, and lubiprostone have all been shown to be more effective than placebo (Ford & Suares, 2011). Data are limited for lactulose use (Ford & Suares, 2011). The 2010 Cochrane review on laxatives concluded that insufficient evidence is available to recommend one laxative over another based on seven studies that investigated different laxatives (including MNTX) (Candy et al., 2011). MNTX has shown to be effective over placebo; however, no comparison studies have been done with other laxatives. In these studies, use of conventional laxatives was not always reported but was used. MNTX effect when compared to placebo long-term safety has not been evaluated. Osmotic laxatives are a good first choice because of their fast onset, low number of adverse Table 2. Medication Recommendations for Chronic Constipation in Palliative Care Recommendation First line Second line Third line Not recommended Treatment Polyethylene glycol Stimulant laxative (bisacodyl or senna) + stool softener (docusate sodium) Lactulose Sorbitol Note: MNTX = methynaltrexone. Lubiprostone MNTX (opioid-induced only) Bulk-forming laxatives Mineral oil Castor oil Probiotics Herbal medications Stool softener monotherapy effects, and ease of use. PEG is an excellent choice because of its softening and stimulating effects. A recent Cochrane review investigated the use of lactulose versus PEG for chronic constipation. The review found that PEG was more efficacious than lactulose in terms of improved stool frequency, stool form, abdominal pain, and need for rescue laxation (Box 1). However, the subjects included in the review were all ambulatory, and 6 of the 10 studies only included children or adolescents as patients. Therefore, this review may not be completely applicable to the palliative care patient (Lee-Robichaud et al., 2010). If an osmotic agent cannot be used, it is unsuccessful, or cost is an issue, a combination of stimulant laxative (senna or bisacodyl) and emollient (docusate sodium) should be used (Locke et al., 2000; Powell & Fleming, 2011; Weitzel & Goode, 2012). If constipation is opioidinduced, the combination can be used first line. A combination should always be used as emollients do not provide adequate motility of stool but do provide enhanced wetting and easy bowel movements that stimulant laxatives do not. Use of stimulant laxatives should be regularly monitored, as they can cause severe abdominal cramping and possible fluid loss with resulting electrolyte imbalance. A randomized, doubleblind, placebo-controlled, parallel-group trial investigating 4-week bisacodyl 10 mg once daily use, found increased bowel movements per week, decreased constipation-related symptoms, and improved quality of life over placebo. Adverse effects were significantly more with bisacodyl and decreased after initial treatment (Box 3) (Kamm et al., 2011). One study found senna to be no different clinically from lactulose in the treatment of opioid-induced constipation in terminal cancer patients (Agra et al., 1998). However, senna is the least expensive choice of the stimulant laxatives and much less expensive than PEG. Due to the high cost and lack of long-term studies, lubiprostone should be reserved for those who fail other laxatives and is not to be used for occasional constipation (Liu, 2010; Powell & Fleming, 2011; Singh & Rao, 2010). Constipation treatment during palliative care is a complex and costly problem. Constipation can severely affect quality of life and, although rare, possible complications, such as fecal impaction, rectal tearing/fissure, bowel obstruction, hemorrhoids, and intestinal perforation, can 214 Home Healthcare Nurse www.homehealthcarenurseonline.com

Box 3. Evidence-Based Practice: Bisacodyl Oral bisacodyl is effective and well-tolerated in patients with chronic constipation (Kamm et al., 2011). Research Problem: To determine the safety and efficacy of oral bisacodyl in patients with chronic constipation. Methods: In this double-blind, placebo-controlled, parallel-group study, 368 patients with history of constipation were assigned to bisacodyl or placebo once daily for 4 weeks. Stool dairy was recorded daily electronically. Results: Bisacodyl was found to improve stool consistency and frequency and was safe for chronic constipation. Bisacodyl produced no clinically significant adverse effects, was effective, did not cause electrolyte imbalance, and improved diseaserelated quality of life. Implications for home healthcare practice: Bisacodyl while over-the-counter should be considered as first line for chronic constipation. SORT LEVEL: B arise (Larkin et al., 2008). A cost analysis of treating constipation in a long-term care facility costs $2,253 per resident/per year (drug and nursing costs) (Larkin et al., 2008). Another analysis investigating costs of constipation in a specialized palliative care unit found that mean cost of treatment was $48.74 per admission with 85% of those costs coming from staff time. If cost of caring for the patient after bowel clearance and discussion of bowel care at handoff meetings were included, the cost increased dramatically to $258.33 per admission. A considerable amount of time was spent adding laxatives and changing doses to optimize therapy; however, only 13% of the cost per admission was related to drug expenditure (Wee et al., 2010). This number is likely to increase with the use of newer and more expensive laxatives. Case Study Conclusion One of the most important pieces is to individualize each patient s care and base choice of laxative on patient s symptoms, performance, and preference (Larkin et al., 2008). Although evidence is lacking in recommending one laxative over another, chronic constipation should first be treated with PEG, combination stimulant laxative/stool softener, or both. Lactulose and sorbitol can be considered if the patient has failed or not tolerated previous treatments. Although efficacious, the newer laxatives such as lubiprostone and MNTX (if opioid-induced) should be reserved for those patients who have failed or cannot tolerate other laxatives due to the exorbitant cost with these medications. In difficult cases, always consult your pharmacist team members for medication-related questions. In the case study presented, Mr. M. s bone pain is well controlled with morphine sulfate that is contributing to his daily constipation. He is currently on ducosate only (monotherapy), which has been effective in softening his stool, but does not allow for laxation or evacuation. Miralax (PEG) was added to his daily regimen 17 g initially once daily and was increased to twice daily after 1 week. He is now having daily soft bowel movements, without abdominal cramping or bloating, and his wife states his quality of life has significantly improved. Matthew Pitlick, PharmD, BCPS, is an Assistant Professor of Pharmacy Practice, St. Louis College of Pharmacy, Ambulatory Care Clinical Pharmacist, John Cochran VA Medical Center, St. Louis, Missouri. Deborah Fritz, PhD, RN, is a Family Nurse Practitioner, Primary Care Service Line, John Cochran VA Medical Center, St. Louis, Missouri. The authors and planners have disclosed that they have no financial relationships related to this article. Address for correspondence: Deborah Fritz, PhD, RN, 915 N. Grand, St. Louis, MO 63106 (deborah.fritz@va.gov). DOI:10.1097/NHH.0b013e3182885dd8 REFERENCES Agra, Y., Sacristán, A., González, M., Ferrari, M., Portugués, A., & Calvo, M. J. (1998). Efficacy of senna versus lactulose in terminal cancer patients treated with opioids. Journal of Pain and Symptom Management, 15(1), 1-7. Brandt, L. J., Prather, C. M., Quigley, E. M., Schiller, L. R., Schoenfeld, P., & Talley, N. J. (2005). Systematic review on the management of chronic constipation in North America. American Journal of Gastroenterology, 100(Suppl. 1), S5-S21. Candy, B., Jones, L., Goodman, M. L., Drake, R., & Tookman, A. (2011). Laxatives or methylnaltrexone for the management of constipation in palliative care patients. Cochrane Database of Systematic Reviews (1), CD003448. Clemens, K. E., & Klaschik, E. (2008). Management of constipation in palliative care patients. Current Opinion in Supportive and Palliative Care, 2(1), 22-27. vol. 31 no. 4 April 2013 Home Healthcare Nurse 215

Ford, A. C., & Suares, N. C. (2011). Effect of laxatives and pharmacological therapies in chronic idiopathic constipation: Systematic review and meta-analysis. Gut, 60(2), 209-218. Fritz, D., & Pitlick, M. (2012). Evidence about the prevention and management of constipation: Implications for comfort, Part 1. Home Healthcare Nurse, 30(9), 533-540. Gallegos-Orozco, J. F., Foxx-Orenstein, A. E., Sterler, S. M., & Stoa, J. M. (2012). Chronic constipation in the elderly. American Journal of Gastroenterology, 107(1), 18-25. Ho, J., Kuhn, R. J., & Smith, K. M. (2008). Update on treatment options for constipation. Orthopedics, 31(6), 570-574. Johanson, J., & Ueno, R. (2007). Lubiprostone, a locally acting chloride channel activator, in adult patients with chronic constipation: A double-blind, placebocontrolled, dose-ranging study to evaluate efficacy and safety. Alimentary Pharmacology & Therapeutics, 25(11), 1351-1361. Kamm, M. A., Mueller-Lissner, S., Wald, A., Richter, E., Swallow, R., & Gessner, U. (2011). Oral bisacodyl is effective and well-tolerated in patients with chronic constipation. Clinical Gastroenterology and Hepatology, 9(7), 577-583. Kienzle-Horn, S., Vix, J. M., Schuijt, C., Peil, H., Jordan, C., & Kamm, M. A. (2006). Efficacy and safety of bisacodyl in the acute treatment of constipation: A doubleblind, randomized, placebo-controlled study. Alimentary Pharmacology & Therapeutics, 23(10), 1479-1488. Kyle, G. (2007). Constipation and palliative care: Where are we now? International Journal of Palliative Nursing, 13(1), 6-16. Larkin, P. J., Sykes, N. P., Centeno, C., Ellershaw, J. E., Elsner, F., Eugene, B.,..., European Consensus Group on Constipation in Palliative Care. (2008). The management of constipation in palliative care: Clinical practice recommendations. Palliative Medicine, 22(7), 796-807. Lee-Robichaud, H., Thomas, K., Morgan, J., & Nelson, R. L. (2010). Lactulose versus polyethylene glycol for chronic constipation. Cochrane Database of Systematic Reviews (7), CD007570. Leung, L., Riutta, T., Kotecha, J., & Rosser, W. (2011). Chronic constipation: An evidence-based review. Journal of the American Board of Family Medicine, 24(4), 436-451. Librach, S. L., Bouvette, M., De Angelis, C., Farley, J., Oneschuk, D., Pereira, J. L.,..., Canadian Consensus Development Group for Constipation in Patients with Advanced Progressive Illness. (2010). Consensus recommendations for the management of constipation in patients with advanced, progressive illness. Journal of Pain and Symptom Management, 40(5), 761-773. Liu, L. W. (2011) Chronic constipation: Current treatment options. Canadian Journal of Gastroenterology, 25(Suppl. B), 22B-28B. Locke, G. R., 3rd, Pemberton, J. H., & Phillips, S. F. (2000). American Gastroenterological Association Medical Position Statement: Guidelines on constipation. Gastroenterology, 119(6), 1761-1766. Powell, P., & Fleming, V. (2011). Chapter 43. Diarrhea, constipation, and irritable bowel syndrome. In R. L. Talbert, J. T. DiPiro, G. R. Matzke, L. M. Posey, B. G. Wells, & G. C. Yee (Eds.), Pharmacotherapy: A pathophysiologic approach (8th ed.). Retrieved from http:// www.accesspharmacy.com/content.aspx?aid=7978775 Ramkumar, D., & Rao, S. S. (2005). Efficacy and safety of traditional medical therapies for chronic constipation: Systematic review. American Journal of Gastroenterology, 100(4), 936-971. Singh, S., & Rao, S. S. (2010). Pharmacologic management of chronic constipation. Gastroenterology Clinics of North America, 39(3), 509-527. Spinzi, G., Amato, A., Imperiali, G., Lenoci, N., Mandelli, G., Paggi, S.,..., Terruzzi, V. (2009). Constipation in the elderly: Management strategies. Drug & Aging, 26(6), 469-474. Thomas, J., Karver, S., Cooney, G. A., Chamberlain, B. H., Watt, C. K., Slatkin, N. E.,..., Israel, J. K. (2008). Methylnaltrexone for opioid-induced constipation in advanced illness. New England Journal of Medicine, 358(22), 2332-2343. Wee, B., Adams, A., Thompson, K., Percival, F., Burslem, K., & Jobanputra, M. (2010). How much does it cost a specialist palliative care unit to manage constipation in patients receiving opioid therapy. Journal of Pain and Symptom Management, 39(4), 644-654. Weitzel, K., & Goode, J. (2012). Chapter 15. Constipation. In D. Krinsky, R. Berardi, S. Ferreri, A. Hume, G. Newton, C. Rollins, K. Tietze (Eds.), Handbook of nonprescription drugs: An interactive approach to selfcare (17th ed.). American Pharmacists Association. Wirz, S., Nadstawek, J., Elsen, C., Junker, U., & Wartenberg, H. C. (2012). Laxative management in ambulatory cancer patients on opioid therapy: A prospective, open-label investigation of polyethylene glycol, sodium picosulphate and lactulose. European Journal for Cancer Care, 21(1), 131-140. Wolf, R. F., Aune, D., Truyers, C., Hernandez, A. V., Misso, K., Riemsma, R., & Kleijnen, J. (2012). Systematic review of efficacy and safety of buprenorphine versus fentanyl or morphine in patients with chronic moderate to severe pain. Current Medical Research and Opinion, 28(5), 833-845. For 37 additional continuing nursing education articles on gastrointestinal topics and 44 on hospice and palliative care topics, go to http://nursingcenter.com/ce. 216 Home Healthcare Nurse www.homehealthcarenurseonline.com