Long-Term Care Updates

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Long-Term Care Updates August 2017 By Alyson Lozicki, PharmD As the prevalence of obesity continues to rise, and with now over one-third (36.5%) of American adults considered obese, the number of weight loss surgeries performed has also seen a steady increase. 1 Bariatric surgery has been shown to be an effective treatment option for morbidly obese patients, resulting in substantial weight loss and improving outcomes for some of the comorbid conditions perpetuated by obesity. The goal of surgery is to reduce the size of the stomach and ultimately limit food intake. There are several types of bariatric procedures, but laparoscopic operations are most commonly performed and the safest option. 2 While bariatric surgery is an effective treatment for weight loss, it is not without risks. Complications can occur in the immediate postoperative period and in the months following surgery. The risk and severity of these complications varies depending on the type of procedure, but malnutrition and marginal ulcer development are inherent complications of all bariatric surgeries. Alterations to gastrointestinal physiology, the presence of a foreign body, reduced intake of nutrients, and the use of inappropriate medications and dosage forms can increase a patient s risk for complications. 3-4 Pharmacists can play a key role in reducing these risks and improving outcomes through pre- and postoperative medication reviews and patient education. The American Society for Metabolic and Bariatric Surgery (ASMBS) clinical practice guidelines provide recommendations for the postoperative management of bariatric patients, and were updated in 2017. The update addresses the increasing need for nutritional management of bariatric patients, as the prevalence of malnutrition is rising and the screening for deficiencies in follow-up care is declining, and focuses solely on the prevention and treatment of micronutrient deficiencies. 5 The following newsletter will provide guideline updates and recommendations from ASMBS and other relevant organizations which will assist pharmacists in managing the dietary and medication needs of post-bariatric surgery patients.

The 2017 guideline update from the ASMBS outlines recommendations on screening for micronutrient deficiencies before and after surgery, and provides dosing recommendations for specific micronutrients during the postoperative period. Bariatric surgery patients should receive a daily multivitamin that will provide vitamin B1, vitamin A, vitamin E, vitamin K, iron, folate, zinc, and copper supplementation at or above the recommended daily allowance. Additional vitamin B12, iron, calcium, and vitamin D3 supplements are also recommended. The dosing and route of administration vary depending on the health status of the patient, the type of surgery that was performed, and whether the goal is preventative or therapeutic. A summary of the guideline dosing recommendations can be found in Table 1. In general, a liquid or chewable tablet dosage form is recommended for all patients, unless otherwise indicated. 5-6 Development of marginal ulcers is a well-known complication of bariatric surgery, particularly with Roux-en Y gastric bypass (RYGB), that can develop immediately after surgery or in the months following. Ulcers occur near the site of anastomosis, and can result from poor tissue perfusion, excess acid exposure, non-steroidal anti-inflammatory drugs (NSAID) use, infection, and smoking. 7 Guidelines for postoperative management of these patients recommend the use of proton pump inhibitors (PPIs) for treatment of ulceration, but it is also common practice to use acid-suppressing agents prophylactically. Since this is not directly addressed by the guidelines, several recent studies have investigated the effectiveness of short-term PPI use postoperatively. 3,7-11 A 2016 systematic review and meta-analysis evaluated the benefit of marginal ulcer prophylaxis in RYGB patients, and included studies from 2006 to 2010. The choice of PPI in each study was largely unspecified, and the duration of therapy ranged from 1 month to 3 months. However, the prophylactic use of PPIs was shown to be significantly beneficial in reducing the occurrence of marginal ulceration. The greatest effect was seen in patients who tested positive for preoperatively, regardless of whether they had been treated appropriately. 9 The results of this study do support the prophylactic use of PPIs, but further prospective studies are needed to provide specific recommendations for dosing and duration of therapy in RYGB patients, and to evaluate the benefit in other types of bariatric surgery. There is ample evidence to support the recommendation that NSAIDs should be avoided in patients following bariatric surgery, particularly for Roux-en Y gastric bypass, due to the increased risk of marginal ulcer development. Acetaminophen is the preferred analgesic/anti-inflammatory agent. 3,6 Additionally, corticosteroids should be used with caution when necessary due to the risk of marginal ulceration and poor healing. The use of aspirin following surgery is not addressed by the guidelines, but a few review articles also advise against its use unless the patient has a vascular or coronary stent, or has had a previous cerebrovascular accident. 4,6,12 These medications should be avoided in all patients for all types of surgery.

Table 1. Supplements and dosing recommendations for the prevention of micronutrient deficiencies 5-6 Multivitamin Recommendations Supplement Procedure/Patients Preventative Dose Iron (Diminished absorption with iron sulfate; Consider alternative salt form) Vitamin B1 Low risk patients (i.e. males and patients with no history of anemia) RYGB, SG,, or menstruating females 18mg daily 45-60mg daily elemental iron (multivitamin + additional supplementation), in divided doses 12mg daily; in cases of deficiency, up to 100mg daily may be necessary Fat Soluble Vitamins LABG, RYGB, SG Vitamin E: 15mg daily Vitamin A: 5000-10000IU daily Vitamin K: 90-120mcg daily Vitamin A: 10000IU daily Vitamin K: 300mcg daily Folate 400-800mcg daily 16-22mg daily Zinc RYGB 8-22mg daily SG/LAGB 8-11mg daily Copper (Copper gluconate or sulfate recommended) or RYGB SG or LAGB 2mg daily 1mg daily Adjunctive Supplements Vitamin B12 Calcium (From all sources) Vitamin D3 LAGB, SG, RYGB ODT, SL, or liquid: 350-500mcg daily Parenteral: 1000mcg monthly Nasal spray: as directed by manufacturer 1800-2400mg daily in divided doses 1200-1500mg daily in divided doses Preventative dose should be based on serum levels; 3000IU daily until serum level > 30ng/mL Abbreviations: ODT = orally disintegrating tablet; SL = sublingual; = biliopancreatic diversion/duodenal switch; LAGB = laparoscopic adjust gastric band; SG = sleeve gastrectomy; RYGB = Roux-en Y gastric bypass

The release of medication and absorption of some long-acting, extended-release, and enteric coated oral formulations may be affected by bariatric surgery. It is recommended that all post-operative patients use immediate release oral formulations or an alternative route of administration to avoid the potential for decreased absorption and efficacy. In the case that these dosage forms cannot be avoided, patient response should be monitored. Gastric binding procedures are restrictive and have a lower potential to cause pharmacokinetic changes, and these patients may achieve a therapeutic response using long-acting medications with appropriate monitoring and dose adjustments. Following RYGB and biliopancreatic diversion/duodenal switch () procedures, however, patients should continue to use immediate release (or an alternative) formulations long-term. These procedures involve rerouting the gastrointestinal tract, which allows for a greater potential for erratic absorption due to the structural alterations and resulting changes in gastric ph. 3,6 Caution should be used with medications that require food or gastric acid for absorption and bioavailability (e.g. carbamazepine and selegiline). It is recommended to monitor patients taking any of these medications for changes in therapeutic effect, and consider alternatives if necessary. 6 Table 2. Medications Which Should Be Avoided in Patients Following Bariatric Surgery 3,4,6,12 Risk of Serious Adverse Events Decreased Absorption and Effectiveness NSAIDs Corticosteroids Aspirin Extended-release formulations Long-acting agents Enteric-coated products Following bariatric surgery, patients are at an increased risk of micronutrient deficiencies and the development of marginal ulcers. Current guidelines provide specific recommendations for dietary supplementation in preventing nutrient deficiencies. Most patients should receive supplementation in the form of a daily multivitamin, in addition to vitamin B12, iron, calcium, and vitamin D supplements to prevent micronutrient deficiencies. To reduce the risk of marginal ulceration following surgery, prophylactic initiation of a PPI may be beneficial. NSAIDs should be avoided. Corticosteroids should also be avoided when possible, and used with caution if necessary. Additionally, long-acting, extended release, and enteric coated medications should be used with caution due to the potential for variable absorption and effectiveness.

1. Adult Obesity Facts. Centers for Disease Control and Prevention website. Available at https://www.cdc.gov/obesity/data/adult.html. September 1, 2016. Accessed July 25, 2017. 2. Estimates of Bariatric Surgery Numbers, 2011-2015. American Society for Metabolic and Bariatric Surgery website. Available at https://asmbs.org/resources/estimate-of-bariatric-surgery-numbers. July 2016. Accessed July 25, 2017. 3. Mechanick JI, Youdim A, Jones DB, et al. Clinical Practice Guidelines for the Perioperative Nutritional, Metabolic, and Nonsurgical Support of the Bariatric Surgery Patient-2013 Update: Cosponsored by American Association of Clinical Endocrinologists, The Obesity Society, and American Society for Metabolic & Bariatric Surgery.. 2013;9:159-91. 4. Ellsmere JC. Late complications of bariatric surgical operations. UpToDate website. Available at https://www.uptodate.com/contents/late-complications-of-bariatric-surgical-operations. June 2017. Accessed July 25, 2017. 5. Parrot J, Frank L, Rabena R, et al. American Society for Metabolic and Bariatric Surgery (ASMBS) Integrated Health Nutritional Guidelines for the Surgical Weight Loss Patient 2016, Update: Micronutrients.. 2017;13(5):727-741. 6. PL Detail-Document, Bariatric Surgery and Medication Use.. http://pharmacistsletter.therapeuticresearch.com/pl/articledd.aspx?nidchk=1&cs=cepda&s=pl&pt=2&fpt=31&dd=291203&pb =PL&searchid=61485082&segment=6363&AspxAutoDetectCookieSupport=1. December 2013. Accessed July 13, 2017. 7. Steinemann D, Schiesser M, et al. Laparoscopic gastric pouch and remnant resection: a novel approach to refractory anastomotic ulcers after Roux-en-Y Gastric Bypass: Case report.. 2011;11:33. https://bmcsurg.biomedcentral.com/track/pdf/10.1186/1471-2482-11-33?site=bmcsurg.biomedcentral.com. 8. Coblijn UK, Lagarde SM, de Castro SM, et al. The influence of prophylactic proton pump inhibitor treatment on the development of symptomatic marginal ulceration in Roux-en-Y gastric bypass patients: a historic cohort study.. 2016;12(2):246-52. 9. Ying VW, Kim SH, Khan KJ, et al. Prophylactic PPI help reduce marginal ulcers after gastric bypass surgery: a systematic review and meta-analysis of cohort studies.. 2015;29(5):1018-23. doi: 10.1007/s00464-014-3794-1. 10. Wilson JA, Romagnuolo J, Byrne TK, et al. Predictors of endoscopic findings after Roux-en-Y gastric bypass.. 2006;101(10):2194-9. 11. Carr WR, Mahawar KK, Balupuri S, and Small PK. An evidence-based algorithm for the management of marginal ulcers following Rouxen-Y gastric bypass.. 2014;24(9):1520-7. 12. Hamand G. Bariatric surgery: Postoperative and long-term management of the uncomplicated patient. UpToDate website. Available at https://www.uptodate.com/contents/bariatric-surgery-postoperative-and-long-term-management-of-the-uncomplicatedpatient?source=search_result&search=bariatric%20surgery%20management&selectedtitle=1~150. August 2016. Accessed July 25, 2017. http://creighton.edu/pharmerica