1. Phosphate Binders … Not Just for Breakfast Anymore by Aimee Henry, DTR Sodexo Dietetic Intern

2. Objectives To list some of the complications associated with high phosphorous levels To gain a better understanding of the challenges to patients when it comes to binders To learn about the various types of phosphate binders, including a new-to-market binder

3. Complications of High Phosphorous Symptoms you may see in your patients... Red eyes Complains of painful joints Itchy skin Chronic hyperphosphatema can contribute to… Vascular Calcification (found in 90% of ESRD population) Renal Osteodystrophy And possibly… Photos compliments of Google Images

4. Calciphylaxis The Facts: -Highly morbid condition of vascular calcification and skin necrosis affecting 1-4% of ESRD population -Poorly understood, systemic calcification -Chronic inflammatory process, 60-80% mortality -Affects more women than men, 3:1 ratio -Mean Age 48 ± 16 years -Increased probability with younger patients on dialysis for a long time -Increased incidence over last ten years

5. Calciphylaxis Comorbid Factors/Events: Chronic renal failure Obesity DM Hypercalcemia Hyperphosphatemia Secondary hyperparathyroidism Elevated calcium-phosphate product Perhaps a variety of hypercoagulable states Although these complications are common in ESRD patients….this syndrome is RARE Compliments of Google Images

6. Source: The Lancet 2014; 383:1067 (DOI:10.1016/S0140-6736(14)60235-X)The Lancet 2014; 383:1067 Terms and Conditions Calciphylaxis

7. Early Stages of Calciphylaxis All photos compliments of Google Images

8. Patient Challenges Why don’t they just take their binders? Potential Side Effects Common GI Issues: -N/V/D -Dyspepsia -Abdominal Pain -Flatulence -Constipation In Rare Cases: -Fecal Impaction -Ileus -Bowel Obstruction -Bowel Perforation Compliments of Google Images

9. Discontinuation of Binders- New Research Journal of Renal Nutrition- March 2014 Wang S, Anum EA, et al looked at nonadherence to phosphate binder regimes Retrospective, Observational Analysis over two years Looked at EMRs of 30,933 Medicare in-center HD patients age ≥ 18 yrs Compliments of Google Images

10. Understanding Barriers to Adherence Reasons for Phosphate Binder Discontinuation CategorynPercentage Discontinued, no reason cited15,48950.1 Lab Results8,46927.4 Patient not tolerating*3,33910.8 Expense, insurance2,4988.1 Other patient circumstance1,1383.7 Total30,933100

11. Understanding Barriers to Adherence Reasons for Phosphate Binder Discontinuation, Subcategories within “Patient Not Tolerating” SubcategorynWithin-Category Percentage Gastrointestinal upset1,59647.8 Patient not tolerating, no reason cited96028.8 Patient refuses, no reason cited46213.8 Patient can’t chew/swallow pill2537.6 Allergic reaction682.0 Subtotal3,339100

12. Pick a Binder, Any Binder Determining the Right Binder for the Right Patient Considerations include: Lab Values Health Status/Metabolic Disturbances Patient Feedback/Intolerances Predicted Compliance/Track Record Side Effects Meals/Meal Patterns Chewing/Swallowing Issues Pill Burden Cost Insurance Coverage/Assistance

13. Commonly Prescribed Binders Calcium-based binders: PhosLo®, Phoslyra® (calcium acetate), Tums® (calcium carbonate) May also serve as calcium supplements, concerns about absorbing too much calcium, may ultimately cause deposits in small blood vessels. Monitor calcium levels.

14. Commonly Prescribed Binders, cont. Aluminum-based binders: Alu-Cap® (aluminum hydroxide) Now rarely prescribed as they have been shown to have toxic side effects that cause bone disease, dementia and damage to the nervous system. May be prescribed for short-term use when PO4 is high and other binders are not effective. Aluminum-free, calcium-free binders: Renvela® (sevelamer carbonate) tablets or powder, Fosrenol® (lanthanum carbonate) a chewable wafer. These mix with phosphorous in the GI tract and do not cause problems with excesses of aluminum or calcium load. Magnesium-based binders: MagnaBind® An alternative to calcium-based binders, when lower calcium intake is necessary. May be appropriate for PD patients, who tend to have lower magnesium levels. Monitor magnesium.

15. Coming Soon…to a Pharmacy Near You The first iron-based, non-calcium, chewable tablet Recommended Starting Dose: 3 (500 mg) tablets (1500mg/day), 1 tablet with each meal Maximum dose: 6 chewable tablets/day Berry flavored Chewed or crushed, not swallowed whole

16. Velphoro® Results Dose Tritation Study 1,054 HD/PD Patients 2-4 week binder washout period Randomized -Velphoro starting dose 1,000 (may inc up to 3,000 mg) -Sevelamer carbonate (active control) Given for 24 weeks

17. Velphoro® Advantages Decreased pill burden Easy to take Iron absorption is low/Risk of systemic iron toxicity is negligible Studies indicate greater changes from baseline serum phosphorous achieved after week 16 compared to sevelamer carbonate Disadvantages Discolored Feces (12%) Diarrhea (6%) Often mild and transient, resolving with continued tx As with any Rx- potential drug interactions Not to be taken with oral Vit D analogs Not tested on patients with iron-related diseases/disorders Possible taste aversion

18. Questions for Review List 3 side effects or complications of high phosphorous levels List 3 reasons why a patient doesn’t take their binders Name one of the main benefits of the new binder, Velphoro®

19. References 1. Calciphylaxis by Julia R Nunley, MD http://emedicine.medscape.com/article/1095481- overview#a0199 Copyright © 1994-2014 by WebMD LLC.http://emedicine.medscape.com/article/1095481- overview#a0199 2. Kettler M and Biggar PH, Review Article: Getting the balance right: Assessing causes and extent of vascular calcification in chronic kidney disease, Nephrology 2009; 14, 389-394. http://onlinelibrary.wiley.com/doi/10.1111/j.1440-1797.2009.01149.x/pdf 3. Velphoro Prescribing Information 12/2013 4. Phosphorous Binders and the Dialysis Diet http://www.davita.com/kidney-disease/diet-and-nutrition/diet-basics/phosphorus-binders- (phosphate-binders)-and-the-dialysis-diet/e/5307 5. Hyperphosphatemia in End Stage Renal Disease http://nurse-practitioners-and-physician- assistants.advanceweb.com/Article/Hyperphosphatemia-in-End-Stage-Renal-Disease.aspx 6. Wang MS, Anum EA, Ramakrishnan K, et al. Reasons for Phosphate Binder Discontinuation Vary by Binder Type, Journal of Renal Nutrition, Vol 24, No 2 (March), 2014: pp 105-109