Update on phosphate binders: the old and the new.
After reading this article, the reader should be able to:
1. Describe the prevalence of hyperphosphatemia in the hemodialysis population.
2. Explain the pathophysiology and identify important long-term consequences of hyperphosphatemia in patients receiving maintenance hemodialysis.
3. Differentiate between the types of oral phosphate binders used and be able to outline their respective roles in therapy.
4. Discuss newer phosphate binders available, such as iron-based phosphate binder therapies.
Hyperphosphatemia is a common complication of end-stage renal disease (ESRD), and is a known risk factor for cardiovascular morbidity and mortality (Kuhlmann, 2006). In addition to its negative effects on the cardiovascular system, hyperphosphatemia can also lead to abnormalities in bone metabolism. These derangements of the bone are commonly referred to as Chronic Kidney Disease-Mineral Bone Disorder (CKD-MBD), a syndrome that is relatively asymptomatic, but can increase the risk of fractures (Tomasello, 2007). Furthermore, it has also been shown that hyperphosphatemia can increase the risk for hospitalizations (Vaiciuniene, Kuzminskis, Ziginskiene, Skarupskiene, & Bumblyte, 2011).
Treatment of hyperphosphatemia in ESRD patients generally involves removing phosphate via hemodialysis, restricting dietary intake of phosphate, and use of oral phosphate binders. Dietary restriction alone, however, is not sufficient in controlling serum phosphate levels in patients with advanced kidney disease, and can result in malnutrition. For this reason, prescription of a phosphate binder is often used to adjunctively manage hyperphosphatemia (Malberti, 2013). This review will focus on the use of phosphate binders for patients on hemodialysis (HD).
PATHOPHYSIOLOGY OF HYPERPHOSPHATEMIA IN CHRONIC KIDNEY DISEASE
Phosphate is one of the most abundant elements in the human body. The majority of phosphate is found in the bones and teeth, with only around 1% existing extracellularly in the plasma (Bellasi, Kooienga, & Block, 2006). The normal plasma phosphate concentration in healthy adults ranges from 0.80 to 1.45 mmol/L, and is the result of a balance between dietary intake, intestinal absorption, and urinary phosphate excretion (Bellasi et al., 2006).
The kidneys play a large role in regulating the excretion of phosphate from the body. Chronic damage to the kidneys impairs the body's ability to maintain phosphate balance, and dysregulation of phosphate homeostasis occurs (Hruska, Mathew, Lund, Qiu, & Pratt, 2008).
Hyperphosphatemia is common in the late stages of CKD, and often disrupts the regulation of other inter-related processes such as the regulation of parathyroid hormone (PTH) by the parathyroid gland. High phosphate levels stimulate the parathyroid gland to produce and release PTH in an attempt to decrease the reabsorption of phosphate via the kidneys and promote excretion in the urine (Tomasello, 2007). Phosphate has a high affinity for calcium and, thus, high serum concentrations of phosphorus increases the risk of calcium and phosphorus binding and precipitating in the blood (Tomasello, 2007). This can lead to vascular calcification, which is highly correlated with morbidity and mortality related to adverse cardiovascular events (Zhu, Mackenzie, Farquharson, & Macrae, 2012).
Hypocalcemia is another consequence related to the precipitation of the calcium-phosphate product, and results in further production and secretion of PTH by the parathyroid gland. Furthermore, both the decrease in kidney function and hyperphosphatemia lead to decreased activation of vitamin D3. This leads to further decreases in serum calcium concentrations and once again stimulates the parathyroid gland to produce and secrete PTH (Tomasello, 2007). Therefore, chronically high levels of serum phosphate lead to a series of changes with respect to bone metabolism and can ultimately lead to CKD-mineral bone disorder (Figure 1).
MANAGEMENT OF HYPERPHOSPHATEMIA
A multi-faceted approach is generally used to manage hyperphosphatemia, and generally includes dietary restriction of phosphate, hemodialysis (for ESRD patients), and with oral phosphate binders. Although dietary measures and hemodialysis are important in controlling serum phosphate, this review will focus on phosphate binders.
Over the past several decades, many different types of phosphate binders have been developed for the treatment of hyperphosphatemia. These agents are often categorized into calcium-based (calcium acetate, calcium carbonate, and calcium citrate) and calcium-free binders (aluminum hydroxide, sevelamer hydrochloride, sevelamer carbonate, lanthanum carbonate, nicotinamide, and magnesium carbonate), all of which are effective in lowering serum phosphate (Malberti, 2013). Given the comparable efficacy of all these agents, selection is often based on other important considerations such as patient tolerability and cost (Malberti, 2013). It should be noted that phosphate binders must be taken with food in order to be effective, ideally at the start of the meal (i.e., with the first bite). The prescribed dose is based on the total phosphate content (phosphate "load") of the meal. For example, one 1,250 mg tablet of calcium carbonate (contains 500 mg of elemental calcium) can bind approximately 50 mg of phosphate (National Kidney Foundation [NKF], 2003). Therefore, dietitians are key to assessing the patient's diet and helping with the dosing of phosphate binders. A comparison of the available phosphate binders can be found in Table 1.
Aluminum-based binders. Introduced in the 1970s, the first phosphate binders included aluminum salts. Despite the excellent efficacy of these agents in reducing serum phosphate levels, their use was later restricted due to concerns of central nervous system (CNS), hematological, and bone toxicities related to accumulation of the aluminum (Yagil et al., 2015). Patients with end-stage renal disease (ESRD) are particularly susceptible to adverse effects related to cumulative ingestion of aluminum-containing compounds, as the removal of large amounts of aluminum by dialysis is not possible due to plasma protein binding (Salusky, 2006).
Although extremely effective, aluminum-based binders currently have a very limited role in therapy, and are generally reserved as a last resort for short-term use in patients with excessively high serum phosphate levels (DiPiro et al., 2014). When used short-term, aluminum-based binders' adverse effects are generally limited to gastrointestinal (GI) side effects such as constipation, nausea, and stomach cramps (DiPiro et al., 2014). In terms of cost, they are relatively inexpensive and widely available as an over-the-counter product in Canadian pharmacies.
Calcium-based phosphate binders. Calcium-containing binders have long been the most commonly prescribed phosphate binders due to their wide availability and relatively low cost. They also have an agreeable safety profile, with the most common side effects being gastrointestinal-related, mainly constipation and GI upset (NKF, 2003). They first rose to popularity after aluminum-based binders were found to have toxic central nervous system effects (Bellasi et al., 2006). Despite being safer than aluminum, calcium binders do not have as high an affinity for phosphate as aluminum and, thus, require higher doses to achieve the same level of serum phosphate control (Bellasi et al., 2006). Furthermore, calcium-based agents do not come without risk. The additional calcium intake can increase the total body calcium load and can lead to hypercalcemia (Salusky, 2006). The concerns of calcium loading led the NKF Kidney Disease Outcomes Quality Initiative (NKF KDOQI) group to recommend limiting the total calcium intake from all sources to 2 g/day, including calcium supplemented from binders (Taksande & Worcester, 2014). The problem is that many patients may require up to 6.5 g of calcium carbonate (contains 2.6 g of elemental calcium) to control phosphate levels, based on a 1,000 mg/ day phosphate diet (Taksande & Worcester, 2014). There is also growing evidence to suggest there is increased risk of both cardiovascular and soft tissue calcification with prolonged use of these agents (Salusky, 2006). More data are needed to adequately assess the risk for adverse cardiovascular outcomes.
In addition to side effects, there are some clinically significant drug interactions with calcium-based phosphate binders that should be noted. Antimicrobial agents are implicated, including fluoroquinolones (e.g., ciprofloxacin, levofloxacin) and tetracyclines (e.g., tetracycline, doxycycline). These antibiotics should be administered at least one hour prior to taking calcium products or three hours after (Tomasello, 2007). Other medications such as levothyroxine and oral iron supplements should also be separated in the same fashion in order to allow adequate absorption of these agents (Tomasello, 2007).
There are several calcium-based phosphate binder products on the market, such as calcium acetate, calcium carbonate, and calcium citrate, which come in a variety of formulations. Calcium acetate is no longer available in Canada; calcium citrate is quite expensive and rarely used. Calcium carbonate, for example, contains 40% elemental calcium and can be purchased as a single ingredient formulation or as part of various antacid products (e.g., TUMS[R], TUMS Ultra[R]). In order to maximize efficacy, calcium-based phosphate binders should be taken with food at the start of the meal. Higher doses of binders may be required for meals containing a larger phosphate load.
Sevelamer hydrochloride and sevelamer carbonate.
Sevelamer hydrochloride is a non-absorbable polymer that contains neither aluminum, lanthanum, or calcium. It is the first of its kind and was first marketed in 1999 as Renagel[R] for the treatment of hyperphosphatemia in hemodialysis patients (Cozzolino, Rizzo, Stucchi, Cusi, & Gallieni, 2012). Sevelamer is a hydrogel that contains amines, which can bind phosphate and make sevelamer effective in controlling serum phosphate levels (Cozzolino et al., 2012). It does not contain calcium, making it a favourable choice for patients with high serum calcium levels (Cozzolino et al., 2012). Given the cost of sevelamer relative to calcium-based phosphate binders, its use in clinical practice is often limited to the treatment of hyperphosphatemia in patients at risk for hypercalcemia. Its access is further limited due to the fact that it is not covered by most provincial drug plans in Canada, unless both calcium and phosphate levels are elevated for a documented period of time (as set by the provincial drug plan provider in each province). For instance, Ontario's Exceptional Access Program (EAP) requires documentation of two instances of elevated serum phosphate (greater than 1.8 mmol/L) and calcium (greater than 2.65 mmol/L) at least one month apart.
Another caveat of sevelamer is that often a large number of tablets are required to adequately control phosphate levels. This can be a significant burden on a patient's everyday life, and may result in lower adherence rates (Gray, Krishnasamy, Vardesh, Hollett, & Anstey, 2011). Adverse effects of sevelamer are primarily gastrointestinal-related, and include nausea, bloating, and constipation (Tomasello, 2007). It is important that sevelamer tablets and capsules be swallowed whole, and not crushed or chewed, as sevelamer is insoluble in water. This limits its use to patients with intact swallowing capabilities and makes the drug unavailable by other routes of administration such as nasogastric and entero-gastric feeding tubes (Tomasello, 2007). Relevant drug interactions for sevelamer are similar to those for calcium-based binders, and include ciprofloxacin, levothyroxine, and tetracycline antibiotics (Sanofi-Aventis Canada Inc., 2014). These agents should be administered separately from sevelamer, either one hour prior or two hours after the binder.
Sevelamer carbonate (Renvela[R]) is a similar compound, and is derived from sevelamer hydrochloride. It exists as a buffered form of the original drug, and studies suggest that it may be better tolerated than sevelamer hydrochloride, although this finding is not consistent (Cozzolino et al., 2012). The main advantage of the carbonate form is that it can be crushed, but both sevelamer compounds have similar phosphate-binding capabilities (Biggar & Ketteler, 2010).
Lanthanum carbonate. Lanthanum carbonate (Fosrenol[R]) is a non-aluminum, non-calcium phosphate binder that first gained approval from Health Canada in 2006 for the treatment of hyperphosphatemia in dialysis patients (Health Canada, 2007). Like aluminum, it is a trivalent heavy metal and is an effective phosphate binder. However, lanthanum has a better overall safety profile. It is not believed to cross the blood-brain barrier, alleviating concerns of adverse neurological effects related to CNS toxicity (Bellasi et al., 2006).
Lanthanum has been shown to have similar efficacy to calcium-based phosphate binders in terms of controlling serum phosphate, with fewer incidences of hypercalcemia (Salusky, 2006). Furthermore, lanthanum tablets with higher dosage strengths allow for a reduction in pill burden, which may improve adherence to therapy (Malberti, 2013). It is generally supplied only as a chewable tablet, as it must be sufficiently pulverized in order to exert its phosphate-binding effect (Okamoto et al., 2014). This essentially limits lanthanum phosphate binder therapy to those with sufficient ability to masticate and swallow the pulverized tablet.
Although lanthanum is a calcium-free alternative and is effective in achieving control of phosphate levels in the plasma, there is some concern with regards to accumulation of lanthanum. This is a reasonable concern, given the toxicity found with the cumulative ingestion of aluminum-based binders. Results from a recent systematic review, however, suggest that accumulation of lanthanum in both the serum and bone is minimal and is well below toxic levels (Zhang, Wen, Li & Fan, 2013). Despite the fact that side effects related to lanthanum therapy are generally limited to gastrointestinal adverse effects, its use as a phosphate binder has not been shown to have any benefit in terms of mortality, as compared to the previously mentioned phosphate binders (Zhang et al., 2013). Moreover, lanthanum is expensive and is not covered under most provincial plans without sufficient documentation of elevated serum calcium and phosphate. The criteria for coverage are similar to that of sevelamer hydrochloride (Renagel[R]). Relevant drug interactions with lanthanum are similar to the aforementioned phosphate binders (i.e., fluoroquinolone antibiotics, levothyroxine, tetracycline antibiotics), all of which should be separated from lanthanum by two hours when administered.
Magnesium salts. Magnesium-based phosphate binders were first introduced in the mid 1980s, as a replacement for aluminum-containing binders (Malberti, 2013). Available as magnesium carbonate and magnesium hydroxide, both agents are effective in binding phosphorus. Despite their efficacy, use of magnesium salts in current clinical practice is limited given that diarrhea and hypermagnesemia are common adverse effects at doses above 2 g per day (Malberti, 2013).
Niacin (nicotinamide). Niacin, or nicotinic acid, is a form of the water-soluble vitamin B3. Nicotinamide is the amide form of niacin and can be used as a phosphate binder. Its use in practice, however, has largely been abandoned due to side effects such as facial flushing and concerns over disproportionate increases in phosphate absorption when doses are skipped or are too low (Ketteler & Biggar, 2013).
Iron-containing phosphate binders. Recent studies have evaluated the use of novel, iron-containing phosphate binders for the treatment of hyperphosphatemia. Several compounds, such as ferric citrate, iron-magnesium hydroxycarbonate, and sucroferric oxyhydroxide, have undergone clinical trials for evaluation of efficacy and safety (Negri & Torres, 2014).
Ferric citrate has been used in Japan for the treatment of anemia in ESRD patients, and has recently been approved by the U.S. Food and Drug Administration (FDA) as an oral treatment for hyperphosphatemia in chronic kidney disease (Negri & Torres, 2014). After administration, ferric citrate dissociates into two components. One of these components, a ferric ion (Fe3+), can then bind to multiple phosphate (PO4-) ions and form a precipitate that allows the iron-phosphate complex to be eliminated in the stool.
In addition to their ability to reduce phosphate levels, there is evidence to suggest that iron-containing phosphate binders may also provide benefit to anemic patients by repleting iron stores needed for hemoglobin production (Rodby et al., 2015). In a 2014 phase III study, ferric citrate was found to be non-inferior to sevelamer in terms of serum phosphate reduction, and was also shown to increase both transferrin saturation and ferritin levels. The clinical relevance of this, however, cannot yet be established (Negri & Torres, 2014). This could, in theory, result in cost-savings to health care systems by reducing the need for administration of intravenous iron in practice (Rodby et al., 2015). The ferric ion (Fe3+), however, must be converted to the ferrous ion (Fe2+) in the intestinal lumen in order to be absorbed. Because of this, the extent to which iron absorption occurs is not known, but it is expected to be limited compared to other commercially available oral iron preparations (Pennoyer & Bridgeman, 2015).
The most common side effects of ferric citrate found in clinical studies were stool discolouration and constipation (Negri & Torres, 2014). This is not surprising given the side effect profile of already available iron salts that have long been used for supplementation in patients with iron deficiencies. Relevant drug interactions for ferric citrate are similar to those of previously mentioned phosphate binding agents with the addition of bisphosphonates, levodopa, and methyldopa, all of which should be administered at least two hours apart from ferric citrate (Negri & Torres, 2014). In terms of dosing, the manufacturer recommends two tablets administered orally, three times daily with food (Keryx Biopharmaceuticals, Inc., 2014). It should be noted that iron-containing phosphate binders are not yet available in Canada.
Many phosphate binders exist on the market for the treatment of hyperphosphatemia in dialysis patients, all of which are effective in reducing serum phosphate levels. Given that many of the most common agents have similar efficacy and safety profiles, choice of phosphate binders for dialysis patients should be focused on cost, convenience, and patient-specific comorbidities. There are newer phosphate binders, notably iron-based salts, yet more clinical studies are needed before any distinct advantages or disadvantages can be elucidated.
Bellasi, A., Kooienga, L., & Block, G.A. (2006). Phosphate binders: New products and challenges. Hemodialysis International, 10(3), 225-234. doi:10.1111/j.1542-4758.2006.00100.x
Bigger, P, & Ketteler, M. (2010). Sevelamer carbonate for the treatment of hyperphosphatemia in patients with kidney failure (CKD III-V). Expert Opinion Pharmacotherapy, 11, 2739-2750.
Cozzolino, M., Rizzo, M. A., Stucchi, A., Cusi, D., & Gallieni, M. (2012). Sevelamer for hyperphosphataemia in kidney failure: Controversy and perspective. Therapeutic Advances in Chronic Disease, 3(2), 59-68. doi:10.1177/2040622311433771
DiPiro, J.T., Talbert, R.L., Yee, G.C., Matzke, G.R., Wells, B.G., & Posey, L.M. (2014). Pharmacotherapy: A pathophysiologic approach (9th ed.). New York: McGraw Hill Medical.
Gray, N.A., Krishnasamy, R., Vardesh, D.L., Hollett, PR., & Anstey, C.M. (2011). Impact of non-traditional phosphate binders and cinacalcet on haemodialysis patient biochemistry, pill burden and cost. Nephrology, 16(8), 688-696. doi:10.1111/j.1440-1797.2011.01482.x
Health Canada (2007). Summary basis of decision (SBD): Fosrenol[R]. Heath Products and Food Branch, issued on November 5, 2007.
Hruska, K.A., Mathew, S., Lund, R., Qiu, P, & Pratt, R. (2008). Hyperphosphatemia of chronic kidney disease. Kidney International, 74(2), 148-157. doi:10.1038/ki.2008.130
Keryx Biopharmaceuticals, Inc. (2014). Auryxia (ferric citrate) prescribing information. New York, New York.
Ketteler, M., & Biggar, P H. (2013). Use of phosphate binders in chronic kidney disease. Current Opinion in Nephrology and Hypertension, 22(4), 413-420. doi:10.1097/ mnh.0b013e32836214d4
Kuhlmann, M.K. (2006). Management of hyperphosphatemia. Hemodialysis International, 10(4), 338-345. doi:10.1111/j.1542-4758.2006.00126.x
Malberti, F. (2013). Hyperphosphataemia: Treatment options. Drugs, 73(7), 673-688. doi:10.1007/s40265-013-0054-y
National Kidney Foundation (2003). NKF KDOQI guidelines: KDOQI clinical practice guidelines for bone metabolism and disease in chronic kidney disease. American Journal of Kidney Disease, 42(4), Suppl 3. Retrieved from http://www2.kidney. org/professionals/kdoqi/guidelines_bone/background.htm
Negri, A.L., & Torres, PA. (2014). Iron-based phosphate binders: Do they offer advantages over currently available phosphate binders? Clinical Kidney Journal, 8(2), 161-167. doi:10.1093/ ckj/sfu139
Okamoto, H., Haruhara, K., Kamejima, S., Mafune, H., Manabe, M., Kanzaki, G., ... Yokoo, T. (2014). Is granular formulation of lanthanum carbonate more effective than chewable tablets? Therapeutic Apheresis and Dialysis, 18, 23-27. doi:10.1111/1744-9987.12207
Pennoyer, A., & Bridgeman, M.B. (2015). Ferric citrate (Auryxia) for the treatment of hyperphosphatemia. Pharmacy and Therapeutics, 40(5), 329-339.
Rodby, R.A., Umanath, K., Niecestro, R., Bond, T.C., Sika, M., Lewis, J., & Dwyer, J.P (2015). Ferric citrate, an iron-based phosphate binder, reduces health care costs in patients on dialysis based on randomized clinical trial data. Drugs in R&D, 15(3), 271-279. doi:10.1007/s40268-015-0103-y
Salusky, I.B. (2006). A new era in phosphate binder therapy: What are the options? Kidney International, 70, S10-S15. doi:10.1038/sj.ki.5001997
Sanofi-Aventis Canada Inc. (2014). Renagel product monograph. Retrieved from http://products.sanofi.ca/en/renagel.pdf
Taksande, S.R., & Worcester, E.M. (2014). Calcium supplementation in chronic kidney disease. Expert Opinion on Drug Safety, 13(9), 1175-1185. doi:10.1517/14740338.2014.937421
Tomasello, S.R. (2007). Bone metabolism and disease in chronic kidney disease. Pharmacotherapy Self-Assessment Program (PSAP), 6th Edition, Book 2, Nephrology II (pp. 55-67). Lenexa, KS: American College of Clinical Pharmacy.
Vaiciuniene, R., Kuzminskis, V., Ziginskiene, E., Skarupskiene, I., & Bumblyte, I.A. (2011). Adherence to treatment and hospitalization risk in hemodialysis patients. Journal of Nephrology, 25(5), 672-678. doi:10.5301/jn.5000038
Yagil, Y., Fadem, S. Z., Kant, K.S., Bhatt, U., Sika, M., Lewis, J.B., & Negoi, D. (2015). Managing hyperphosphatemia in patients with chronic kidney disease on dialysis with ferric citrate: Latest evidence and clinical usefulness. Therapeutic Advances in Chronic Disease, 6(5), 252-263. doi:10.1177/2040622315589934
Zhang, C., Wen, J., Li, Z., & Fan, J. (2013). Efficacy and safety of lanthanum carbonate on chronic kidney disease-mineral and bone disorder in dialysis patients: A systematic review. BMC Nephrology, 14(1), 226. doi:10.1186/1471-2369-14-226 Zhu, D., Mackenzie, N.C., Farquharson, C., & Macrae, V.E. (2012). Mechanisms and clinical consequences of vascular calcification. Frontiers in Endocrinology, 3(95), 1-12. doi:10.3389/ fendo.2012.00095
1. Sustained high serum phosphate levels can cause which of the following?
a) increased cardiovascular morbidity and mortality
d) mineral bone disease
e) all of the above
2. Which of the following is an advantage of sevelamer hydrochloride (Renagel[R])?
a) decreased pill burden
b) relatively low cost
c) low risk for hypercalcemia
d) higher affinity for phosphorous
e) all of the above
3. Angus is a 60-year-old man without private drug plan coverage who worked his entire life as a grocery store clerk. His doctor recently diagnosed him with CKD and he does not like taking a lot of pills at once. What do you recommend Angus takes to lower his phosphate levels?
a) calcium carbonate (TUMS[R] Ultra)
b) aluminum hydroxide (Amphogel[R])
c) lanthanum carbonate (Fosrenol[R])
d) sevelamer hydrochloride (Renagel[R])
4. Which of the following is true with respect to aluminum hydroxide (Amphogel[R])?
a) it is a first-line agent for the treatment of hyperphosphatemia in CKD patients
b) aluminum accumulation is a concern for CNS toxicity, worsening anemia, and constipation
c) it requires less monitoring and is safe for long-term use
d) it reverses bone demineralization, preventing osteomalacia
5. One of your patients, Mrs. Johnson, takes calcium carbonate 1,250 mg with each meal to help control her phosphate levels, but her serum phosphate levels have still been consistently high over the past few months. Upon further questioning, you discover she is taking it incorrectly and tell her that she should:
a) swallow the tablet whole at the end of every meal
b) chew the tablet once in the morning and once before bed
c) swallow the tablet whole on an empty stomach 30 minutes before eating
d) chew or swallow the tablet with the first bite of every meal
6. Which of the following about aluminum-based phosphate binders is true?
a) aluminum is largely removed by dialysis, and thus higher doses are necessary to control serum phosphate levels
b) they are safe for short-term use to control high phosphate levels
c) they are first-line agents for treating hyperphosphatemia in dialysis patients, and are widely available in many different dosage forms
d) chronic use may increase risk for hypercalcemia
7. Which of the following about hyperphosphatemia is true?
a) hyperphosphatemia is a common finding in the early stages of CKD
b) serum phosphate levels can often be controlled with dietary modifications alone
c) phosphate is largely removed by hemodialysis, but dietary modifications and phosphate binders are often required to achieve sufficient serum phosphate control
d) phosphate is not removed by hemodialysis and, thus, phosphate binders are needed to control serum phosphate levels
8. Which of the following medications should be administered separately (i.e., either one hour before, or two hours after) from sevelamer?
d) both a and c
e) all of the above
9. Which of the following is true regarding phosphate binders?
a) calcium carbonate contains 20% elemental calcium
b) lanthanum carbonate must be swallowed whole, as it is insoluble in water
c) constipation and hypermagnesemia are common dose-limiting side effects of magnesium-based phosphate binders, and so they are not commonly used
d) the most common side effects of ferric citrate are discoloured stools and constipation
10. Which of the following about sevelamer hydrochloride (Renagel[R]) is false?
a) the tablets must be chewed in order to exert their phosphate-binding effect
b) patients may need to take several tablets with each meal to control phosphate levels, resulting in a high pill burden
c) the most common side effects of sevelamer hydrochloride are gastrointestinal-related, and include bloating and constipation
d) sevelamer is an option for patients at high risk for recurrent episodes of hypercalcemia
* Select the best answer and circle the appropriate letter on the answer grid below.
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POST-TEST ANSWER GRID
Please circle your answer choice:
1. a b c d e
2. a b c d e
3. a b c d e
4. a b c d e
5. a b c d e
6. a b c d e
7. a b c d e
8. a b c d e
9. a b c d e
10. a b c d e
Jacob Cashin, BScPhm, PharmD Student, Department of Pharmacy, University Health Network, Toronto, Ontario.
Marisa Battistella, BScPhm, PharmD, ACPR, Clinician Scientist, Assistant Professor, Leslie Dan Faculty of Pharmacy, University of Toronto, Clinical Pharmacist--Nephrology, University Health Network, Toronto, Ontario.
Table 1: Comparison of Common Phosphate Binders Available in Canada Binder Dosage Trade Names Dose (Mineral Forms Content) Aluminum Tablets Amphojel[R] 600 mg (208 mg hydroxide (a) elemental) Liquid Almagel Plus[R] 200 mg/5 mL (69.3 mg/5 mL elemental) Calcium Tablets TUMS[R] 500 mg (200 mg carbonate (b,c) elemental) TUMS[R] Extra 750 mg (300 mg Strength elemental) TUMS[R] Ultra 1000 mg (400 mg elemental) Webber Naturals[R] 1250 mg (500 mg Calcium elemental) Carbonate Lanthanum Tablets Fosrenol[R] 250 mg, 500 mg, carbonate 750 mg, 1000 mg Sevelamer Tablets Renagel[R] 800 mg hydrochloride Sevelamer Tablets Renvela[R] 800 mg carbonate Binder Potential Advantages Potential Disadvantages Aluminum Relatively inexpensive, Constipation is hydroxide (a) wide variety of common, chalky products taste, aluminum toxicity with Calcium-free long-term use Highly effective phosphate binder Calcium Inexpensive, wide Constipation, carbonate (b,c) variety of products belching, and Effective phosphate flatulence are binder common side effects. Can also cause hypercalcemia. Lanthanum Available as chewable Nausea, diarrhea, carbonate tablets and abdominal pain common. Expensive, Effective phosphate not covered by most binder provincial drug plans * Sevelamer Non-calcium, Nausea, diarrhea, hydrochloride non-aluminum and abdominal pain Effective phosphate common. Large pill binder burden Expensive Cannot crush or chew Sevelamer Same as Renagel[R] Same as Renagel[R], carbonate except tablets can be crushed (a,b) Many formulations exist; not all trade names and preparations are listed. (c) Contains 40% elemental calcium. * Specific criteria for coverage exist in each province. ([dagger]) This is not a comprehensive list. Some formulations not listed as they are no longer available in Canada.
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|Title Annotation:||CONTINUING EDUCATION SERIES: CONTACT HOUR: 2.0 HRS|
|Author:||Cashin, Jacob; Battistella, Marisa|
|Date:||Jan 1, 2016|
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