Phosphate Binders…Not Just for Breakfast Anymore

by

Aimee Henry, DTR

Sodexo Dietetic Intern

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

Complications of High PhosphorousSymptoms 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

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

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

Source: The Lancet 2014; 383:1067 (DOI:10.1016/S0140-6736(14)60235-X)

Terms and Conditions

Calciphylaxis

Early Stages of Calciphylaxis

All photos compliments of Google Images

Patient ChallengesWhy 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

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

Understanding Barriers to Adherence

Reasons for Phosphate Binder Discontinuation

Category n Percentage

Discontinued, no reason cited 15,489 50.1Lab Results 8,469 27.4Patient not tolerating* 3,339 10.8Expense, insurance 2,498 8.1Other patient circumstance 1,138 3.7

Total 30,933 100

Understanding Barriers to Adherence

Reasons for Phosphate Binder Discontinuation, Subcategories within “Patient Not Tolerating”

Subcategory n Within-Category Percentage

Gastrointestinal upset 1,596 47.8Patient not tolerating, no reason cited 960 28.8Patient refuses, no reason cited 462 13.8Patient can’t chew/swallow pill 253 7.6Allergic reaction 68 2.0

Subtotal 3,339 100

Pick a Binder, Any BinderDetermining 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

Commonly Prescribed BindersCalcium-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.

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.

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

Velphoro® ResultsDose 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

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

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®

References1. Calciphylaxis by Julia R Nunley, MD http://emedicine.medscape.com/article/1095481-overview#a0199 Copyright © 1994-2014 by WebMD LLC.

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