HEALTHLINE May 2006 NEW DRUGS/INDICATIONS LEVEMIR (Insulin detemir [rDNA origin]) A long-acting insulin indicated for Type 1 diabetes (in adults and children) and type 2 diabetes (in adults) when long-acting insulin is needed. Insulin detemir is a basal (long-acting) insulin analogue with duration of action ranging from 5.7 hours at the lowest dose to 23.3 hours at the highest dose. After SC injection, the serum concentrations for insulin detemir indicate a slower, more prolonged absorption over 24 hours in comparison to NPH human insulin. Maximum serum concentration is reached between 6–8 hours after administration with a terminal half-life of 5–7 hours depending on dose. In general, patients treated with insulin detemir achieved levels of glycemic control similar to those treated with NPH human insulin or insulin glargine, as measured by glycosylated hemoglobin (HbA1C). In trials of up to 6 months duration in patients with type 1 and type 2 diabetes, insulin detemir was associated with somewhat less weight gain than NPH. Detemir should not be mixed or diluted with other insulins. Detemir effects may be potentiated by oral antidiabetic drugs, ACE inhibitors, disopyramide, fibrates, fluoxetine, MAOIs, propoxyphene, salicylates, somatostatin analogue, and sulfonamide antibiotics. Detemir activity may be antagonized by corticosteroids, danazol, diuretics, sympathomimetics, isoniazid, phenothiazines, and somatropin. Variable effects have been associated with β-blockers, clonidine, lithium salts, alcohol. Adverse reactions may include hypoglycemia, local or systemic allergy, lipodystrophy, and edema. DP WARNINGS AND ADVERSE EFFECTS Advair and Serevent Updated Label Warning Product labels for Advair Diskus (fluticasone propionate/salmeterol xinafoate) and Serevent Diskus (salmeterol xinafoate) have been updated to include a strict new warning that advises physicians to limit their prescribing of the drugs to specific patient populations. According to the FDA, long-acting beta 2-agonists (LABAs) such as these can decrease the occurrence of asthma episodes, but make them more severe if they occur. A recent study showed that salmeterol can increase the risk of death during a severe episode. The new label suggests that physicians evaluate whether a patient's asthma can be adequately controlled by using other controller drugs, such as inhaled corticosteroids (ICS), before prescribing a LABA. The label also recommends that physicians consider whether the severity of a patient's disease warrants initial treatment with an ICS and a LABA. SK REGULATORY UPDATE CMS Releases New Surveyor Guidance On March 10, 2006, CMS published advanced copies of the State Operations Manual (SOM) Survey Guidance on Psychosocial Outcomes, Activities, and Quality Assurance and Assessment. All three documents discussed below have been provided as advanced copies however CMS does not anticipate any changes. The following website can be used to access a copy of the new guidance to surveyors: http://www.cms.hhs.gov/SurveyCertificationGenInfo/PMSR/list.asp#TopOfPage> After going to the website, the information will be listed beginning with the year 2001. Scroll all the way to the bottom to get to the documents under 2006. Copyright 2006 All Rights Reserved Published by Omnicare, Inc. distributed by PBM Plus, Inc. Page - 1 HEALTHLINE May 2006 Revised Activities Guidance (Tags F248 and 249) New surveyor guidance for surveying activities requirements in long term care facilities will become effective June 1, 2006. At that time, a final copy of the guidance will be available at http://www.cms.hhs.gov/Transmittals/. This guidance will be incorporated into Appendix PP of the State Operations Manual. The interpretive guidelines clarify areas such as assessment, care planning, interventions and activity approaches for residents with behavior symptoms. Included as a part of this document are interpretive guidelines, and an investigative protocol along with guidelines for determination of compliance. New Psychosocial Outcomes Severity Guide New surveyor guidance for using the psychosocial outcome severity guide for surveying long term care facilities will become effective June 1, 2006. At that time, a final copy of this new guidance will be available at http://www.cms.hhs.gov/Transmittals/. This information will be incorporated into Appendix P of the State Operations Manual. The guide clarifies when to apply the “reasonable person concept” and included in this information are instructions and clarification of terms along with the severity guide. The severity guide provides criteria for the determination of the correct levels of negative psychosocial outcomes that developed, continued, or worsened because of the facility’s non-compliance. Revised Surveyor Guidance for Quality Assessment and Assurance (QAA) (Tags F520 and F521) [I found this article difficult to read and certainly not at the reading level for nurses. See if my edits will help in your opinion] The revised surveyor guidance for surveying QAA requirements in long term care facilities will become effective June 1, 2006. At that time, a final copy of the guidance will be available at http://www.cms.hhs.gov/Transmittals/. This information will be incorporated into Appendix PP of the State Operations Manual. The revised guidance provides categories of deficiencies and how to investigate and interpret deficiencies. The guidance outlines the QAA committee composition and frequency of meetings. As well advice is provided on how to identify quality deficiencies, develop and implement action plans and correct identified quality deficiencies. The protocol explains what the surveyors will need for their investigation. The deficiency categories provide guidance for the determining the correct level of severity of outcome to residents from deficiencies identified at Tag F520. Compliance Statement for the Installation of Emergency Lighting and the Replacement of Existing Roller Latches in Corridor Doors A memorandum was sent to state survey agencies from CMS dated March 10, 2006 which concerns several fire safety requirements related to the adoption of the 2000 edition of the Life Safety Code. The regulation gave facilities until March 13, 2006 to comply with two changes to the requirements. Those requirements included: 1) Replacing batteries used in emergency lighting, where required, to provide illumination for a minimum of 90 minutes; and 2) Replacing roller latches commonly found in corridor doors with a positive latching device. Beginning with surveys completed after March 13, 2006, deficiencies concerning installation of the 90 minute duration batteries used in emergency lighting shall be cited at Tag K46 which deals with emergency lighting requirements. Deficiencies in the replacement of roller latches with the Copyright 2006 All Rights Reserved Published by Omnicare, Inc. distributed by PBM Plus, Inc. Page - 2 HEALTHLINE May 2006 positive latching device will be cited at Tag K18 which includes requirements for corridor doors and latching requirements. To access a copy of the survey and certification letter concerning these requirements, please go the following website: http://www.cms.hhs.gov/SurveyCertificationGenInfo/downloads/SCLetter06-08.pdf Medicare Provider Education Articles The Medicare learning Network has renamed the provider education articles which were previously known as “MedLearn Matters” articles, as “MLN Matters”. The MLN stands for Medicare Learning Network. The articles can now be accessed from http://www.cms.hhs.gov/MLNMattersArticles. In addition, the URLs for the Medicare Learning Network have changed and they can be reached from the cms.hhs.gov main page by clicking on “Outreach and Education” KM PATIENT CARE Focus on Hyperphosphatemia Associated with Chronic Kidney Disease (CKD) There are over 300,000 stage 5 CKD dialysis patients in the United States. These patients have limited or no kidney function and depend on dialysis, along with dietary restrictions and phosphate binders to minimize serum phosphorus. Hyperphosphatemia, or high phosphate blood concentration, has been shown to significantly increase patient mortality and morbidity and can occur in any patient with CKD. Phosphorus control is critical to the quality of care for CKD patients. Hyperphosphatemia and disorders of mineral metabolism are associated with progression of CKD. This leads to an increased risk of soft tissue, vascular and organ calcification, cardiovascular events and mortality. There are many factors affecting serum phosphorus concentrations in CKD. These include dietary intake of phosphate, ingestion of phosphate binders, degree of secondary hyperparathyroidism, magnitude of vitamin D deficiency and treatment with vitamin D, dialysis (frequency, duration, and adequacy), and high intake of calcium supplements. In renal disease, tubular failure causes phosphate excretion to be inhibited because of the nonresponsiveness of the tubules to parathyroid hormone. Therefore, phosphate concentrations rise while calcium concentrations fall. In addition, active vitamin D production is reduced, lowering absorbed calcium. The goals of therapy have become more aggressive over the past several years, because of the high morbidity and mortality associated with altered phosphorus, calcium and parathyroid (PTH) metabolism. It is now recommended to normalize serum calcium, phosphorus, and calciumphosphorus product in patients with CKD. The goal of therapy for serum phosphorus is to maintain the concentration in the range of 2.5 mg/dl to 5.5 mg/dl. Patients with known or suspected CKD should be evaluated to determine if phosphorus, calcium or PTH levels are elevated. Hyperphosphatemia is managed through dialysis, diet modification and utilization of phosphate binders to inhibit absorption of dietary phosphorus. Due to the limitations of dialysis and the Copyright 2006 All Rights Reserved Published by Omnicare, Inc. distributed by PBM Plus, Inc. Page - 3 HEALTHLINE May 2006 challenges of dietary phosphorus restriction, almost all dialysis patients rely on a phosphate binder to reduce phosphorus absorption and prevent hyperphosphatemia. If phosphorus or intact PTH concentrations cannot be controlled within the target range despite dietary phosphorus restriction, phosphate binders should be prescribed. Phosphate binders bind dietary phosphorus in the gastrointestinal tract. Calcium-containing phosphate binders are the most common class of phosphate binders prescribed to patients with CKD. They have the advantage in that they treat both hyperphosphatemia and hypocalcemia. Calcium-containing phosphate binders are relatively inexpensive. The primary disadvantage of this class of agents is that they may cause hypercalcemia, especially when used in conjunction with Vitamin D. As many as 50% of patients with Stage 5 CKD treated with calcium-containing phosphate binders may develop hypercalcemia. The total dose of elemental calcium provided by the calcium-based phosphate binders should not exceed 1,500 mg/day, and the total intake of elemental calcium (including dietary calcium) should not exceed 2,000 mg/day. Calcium-based phosphate binders should not be used in dialysis patients who are hypercalcemic (corrected serum calcium of >10.2 mg/dL), or whose plasma PTH concentrations are <150 pg/mL on 2 consecutive measurements. Noncalcium-containing phosphate binders are preferred in dialysis patients with severe vascular and/or other soft tissue calcifications. All are similarly effective (Table 1). Calcium-based products are often used as first line due to their ease of administration, and limited risk of toxicity. However, non-calcium based products are a safer alternative in patients who experience hypercalcemic symptoms or have an elevated calcium-phosphate product (>55 mg2/dL2). Table 1. Phosphate Binders Compound (Brand name) Calcium carbonate (Tums, Oscal, etc) Estimate of % Calcium absorbed Approximately 20-30% is absorbed Potential side effects Hypercalcemia, extraskeletal calcification, GI side effects, constipation Calcium Acetate (Phos- With meals: ~21% Lo) Between meals: ~40% Hypercalcemia, extraskeletal calcification, GI side effects Sevelamer (Renagel) None (noncalcium) GI side effects Lanthanum (Fosrenol) None (noncalcium) GI side effects Renagel (sevelamer) is a non-calcium containing phosphate binder indicated for hyperphosphatemia in patients with ESRD. Short-term clinical studies in patients with ESRD have established that sevelamer is as efficacious as calcium carbonate or acetate at lowering serum phosphorus, and is well-tolerated. Furthermore, short-term control of hyperparathyroidism has proved to be adequate, with maintenance of normal serum calcium concentrations, and in addition, short-term favorable effects on the lipid profile have been observed, with a 20-30% Copyright 2006 All Rights Reserved Published by Omnicare, Inc. distributed by PBM Plus, Inc. Page - 4 HEALTHLINE May 2006 decrease in low density lipoprotein (LDL) cholesterol, and a 5-15% increase in high density lipoprotein (HDL) cholesterol concentrations, presumably related to the binding of bile acids by the compound. This dual action is clinically significant since atherosclerosis and CVD are major causes of morbidity and mortality in this population. Non-calcium phosphate binders, such as sevelamer, prevent calcification of coronary arteries seen in patients with CKD that receive calcium-based binders. There are many complications associated with treating hyperphosphatemia. It is difficult for patients to adhere to a low phosphate diet. Dosage titration of phosphate binders is complex often requiring multiple tablets or capsules each day. The use of calcium-based phosphate binders is associated with the development of hyperphosphatemia. Continued monitoring and dosage adjustment of phosphorus binders is necessary to maintain appropriate phosphorus concentration and to increase the likelihood of positive outcomes for the patient. Please contact your Consultant Pharmacist for more information. KH K/DOQI Clinical Practice Guidelines for Bone Metabolism and Disease in Chronic Kidney Disease. 2004. _________________________________________________________________________ Contributing Authors for This Issue: Kelly Hollenack, PharmD, CGP, FASCP National Director Health Management Susan Klem, BS Pharm, CGP, FASCP Regional Clinical Director Great Lakes and Great Plains Regions Kelli Marsh, RHIA, RAC-C Vice President of Support Services Omnicare Pharmacies of Northern and Central Ohio David Pregizer, RPh Area Clinical Manager NeighborCare Allentown Editorial Board Karen Burton, R. Ph., GCP, FASCP Mark Coggins, Pharm. D., GCP, FASCP Kelly Hollenack, Pharm. D. CGP Philip King, Pharm. D., GCP, FASCP Susan Kleim, B.S., Pharm., GCP, FASCP Terry O’Shea, Pharm. D., GCP, FASCP Elmer Schmidt, Pharm. D., GCP, FASCP Barbara J. Zarowitz, Pharm. D., GCP, FASCP Copyright 2006 All Rights Reserved Published by Omnicare, Inc. distributed by PBM Plus, Inc. Page - 5