Phosphate-binder therapy for hyperphosphataemia is key to the treatment of patients with chronic kidney disease (CKD)-mineral and bone disorder (MBD). Calcium-free phosphate binders are increasingly favoured since calcium-based agents potentially cause harmful calcium overload and vascular calcification that confound the benefits of reducing serum phosphorus. Several calcium-free phosphate binders are available, including the non-absorbed agent sevelamer and the absorbed agents, e.g. lanthanum and magnesium salts. Randomised controlled studies consistently show that sevelamer and lanthanum carbonate offer equivalent lowering of serum phosphorus and often effectively achieve phosphorus targets versus calcium salts, with sevelamer having a positive effect on bone disease, vascular calcification, and patient-level outcomes in dialysis patients in several trials. There is also evidence that lanthanum carbonate can improve bone health, but data are limited to its effects to vascular calcification or patient-level outcomes. Magnesium salts have also been shown to reduce serum phosphorus levels, but clear evidence is lacking on bone, vascular, or clinical outcomes. It also remains to be established whether long-term systemic accumulation of lanthanum and magnesium, in tissues including bone, has clinically relevant toxic effects. This review summarises the evidence of efficacy and safety for newer calcium-free phosphate binders in CKD-MBD management.

1.
Spasovski GB: Bone health and vascular calcification relationships in chronic kidney disease. Int Urol Nephrol 2007;39:1209–1216.
2.
Slatopolsky E, Brown A, Dusso A: Role of phosphorus in the pathogenesis of secondary hyperparathyroidism. Am J Kidney Dis 2001;37(suppl 2):S54–S57.
3.
Prie D, Urena Torres P, Friedlander G: Latest findings in phosphate homeostasis. Kidney Int 2009;75:882–889.
4.
Mathew S, Tustison KS, Sugatani T, Chaudhary LR, Rifas L, Hruska KA: The mechanism of phosphorus as a cardiovascular risk factor in CKD. J Am Soc Nephrol 2008;19:1092–1105.
5.
Kestenbaum B, Sampson JN, Rudser KD, Patterson DJ, Seliger SL, Young B, Sherrard DJ, Andress DL: Serum phosphate levels and mortality risk among people with chronic kidney disease. J Am Soc Nephrol 2005;16:520–528.
6.
Voormolen N, Noordzij M, Grootendorst DC, Beetz I, Sijpkens YW, van Manen JG, Boeschoten EW, Huisman RM, Krediet RT, Dekker FW: High plasma phosphate as a risk factor for decline in renal function and mortality in pre-dialysis patients. Nephrol Dial Transplant 2007;22:2909–2916.
7.
Isakova T, Gutierrez OM, Chang Y, Shah A, Tamez H, Smith K, Thadhani R, Wolf M: Phosphorus binders and survival on hemodialysis. J Am Soc Nephrol 2009;20:388–396.
8.
Kidney Disease: Improving Global Outcomes (KDIGO) CKD-MBD Work Group: KDIGO clinical practice guideline for the diagnosis, evaluation, prevention, and treatment of chronic kidney disease-mineral and bone disorder (CKD-MBD). Kidney Int Suppl 2009;76(suppl 113):S1–S130.
9.
Martin KJ, Gonzalez EA: Prevention and control of phosphate retention/hyperphosphatemia in CKD-MBD: what is normal, when to start, and how to treat? Clin J Am Soc Nephrol 2011;6:440–446.
10.
Molony DA, Stephens BW: Derangements in phosphate metabolism in chronic kidney diseases/end-stage renal disease: therapeutic considerations. Adv Chronic Kidney Dis 2011;18:120–131.
11.
National Kidney Foundation: KDOQI Clinical Practice Guidelines for Bone Metabolism and Disease in Chronic Kidney Disease. Am J Kidney Dis 2003;42(suppl 3):S1–S201.
12.
Takeda E, Yamamoto H, Nishida Y, Sato T, Sawada N, Taketani Y: Phosphate restriction in diet therapy. Contrib Nephrol. Basel, Karger, 2007, vol 155, pp 113–124.
13.
Benini O, D’Alessandro C, Gianfaldoni D, Cupisti A: Extra-phosphate load from food additives in commonly eaten foods: a real and insidious danger for renal patients. J Ren Nutr 2011;21:303–308.
14.
Shinaberger CS, Greenland S, Kopple JD, Van Wyck D, Mehrotra R, Kovesdy CP, Kalantar-Zadeh K: Is controlling phosphorus by decreasing dietary protein intake beneficial or harmful in persons with chronic kidney disease? Am J Clin Nutr 2008;88:1511–1518.
15.
Pohlmeier R, Vienken J: Phosphate removal and hemodialysis conditions. Kidney Int Suppl 2001;78:S190–S194.
16.
Mudge DW, Johnson DW, Hawley CM, Campbell SB, Isbel NM, van Eps CL, Petrie JJ: Does aluminium continue to have a role as a phosphate binder in contemporary practice? BMC Nephrol 2011;12:20.
17.
Slatopolsky E, Weerts C, Norwood K, Giles K, Fryer P, Finch J, Windus D, Delmez J: Long-term effects of calcium carbonate and 2.5 mEq/liter calcium dialysate on mineral metabolism. Kidney Int 1989;36:897–903.
18.
Emmett M, Sirmon MD, Kirkpatrick WG, Nolan CR, Schmitt GW, Cleveland MB: Calcium acetate control of serum phosphorus in hemodialysis patients. Am J Kidney Dis 1991;17:544–550.
19.
Bushinsky DA: Contribution of intestine, bone, kidney, and dialysis to extracellular fluid calcium content. Clin J Am Soc Nephrol 2010;5(suppl 1):S12–S22.
20.
Renagel tablets (sevelamer hydrochloride) (prescribing information). Cambridge/Mass, Genzyme Corp, 2007.
21.
Renvela (sevelamer carbonate) tablets or for oral suspension (prescribing information). Cambridge/Mass, Genzyme Corp, 2009.
22.
Slatopolsky EA, Burke SK, Dillon MA: Renagel, a nonabsorbed calcium- and aluminum-free phosphate binder, lowers serum phosphorus and parathyroid hormone. The RenaGel Study Group. Kidney Int 1999;55:299–307.
23.
Chertow GM, Dillon M, Burke SK, Steg M, Bleyer AJ, Garrett BN, Domoto DT, Wilkes BM, Wombolt DG, Slatopolsky EA: A randomized trial of sevelamer hydrochloride (renagel) with and without supplemental calcium. Strategies for the control of hyperphosphatemia and hyperparathyroidism in hemodialysis patients. Clin Nephrol 1999;51:18–26.
24.
Braun J, Asmus HG, Holzer H, Brunkhorst R, Krause R, Schulz W, Neumayer HH, Raggi P, Bommer J: Long-term comparison of a calcium-free phosphate binder and calcium carbonate-phosphorus metabolism and cardiovascular calcification. Clin Nephrol 2004;62:104–115.
25.
Block GA, Raggi P, Bellasi A, Kooienga L, Spiegel DM: Mortality effect of coronary calcification and phosphate binder choice in incident hemodialysis patients. Kidney Int 2007;71:438–41.
26.
Barreto DV, Barreto Fde C, de Carvalho AB, Cuppari L, Draibe SA, Dalboni MA, Moyses RM, Neves KR, Jorgetti V, Miname M, Santos RD, Canziani ME: Phosphate binder impact on bone remodeling and coronary calcification – results from the BRiC study. Nephron Clin Pract 2008;110:c273–c283.
27.
Navaneethan SD, Palmer SC, Craig JC, Elder GJ, Strippoli GF: Benefits and harms of phosphate binders in CKD: a systematic review of randomized controlled trials. Am J Kidney Dis 2009;54:619–637.
28.
De Francisco AL, Leidig M, Covic AC, Ketteler M, Benedyk-Lorens E, Mircescu GM, Scholz C, Ponce P, Passlick-Deetjen J: Evaluation of calcium acetate/magnesium carbonate as a phosphate binder compared with sevelamer hydrochloride in haemodialysis patients: a controlled randomized study (CALMAG study) assessing efficacy and tolerability. Nephrol Dial Transplant 2010;25:3707–3717.
29.
Spasovski G, Vanholder R: Is combined calcium/magnesium phosphate binder really noninferior to sevelamer hydrochloride? Nephrol Dial Transplant 2011;26:1442–1444.
30.
Fan S, Ross C, Mitra S, Kalra P, Heaton J, Hunter J, Plone M, Pritchard N: A randomized, crossover design study of sevelamer carbonate powder and sevelamer hydrochloride tablets in chronic kidney disease patients on haemodialysis. Nephrol Dial Transplant 2009;24:3794–3799.
31.
Fishbane S, Delmez J, Suki WN, Hariachar SK, Heaton J, Chasan-Taber S, Plone MA, Moe S: A randomized, parallel, open-label study to compare once-daily sevelamer carbonate powder dosing with thrice-daily sevelamer hydrochloride tablet dosing in CKD patients on hemodialysis. Am J Kidney Dis 2010;55:307–15.
32.
Evenepoel P, Selgas R, Caputo F, Foggensteiner L, Heaf JG, Ortiz A, Kelly A, Chasan-Taber S, Duggal A, Fan S: Efficacy and safety of sevelamer hydrochloride and calcium acetate in patients on peritoneal dialysis. Nephrol Dial Transplant 2009;24:278–285.
33.
Ketteler M, Rix M, Fan S, Pritchard N, Oestergaard O, Chasan-Taber S, Heaton J, Duggal A, Kalra PA: Efficacy and tolerability of sevelamer carbonate in hyperphosphatemic patients who have chronic kidney disease and are not on dialysis. Clin J Am Soc Nephrol 2008;3:1125–1130.
34.
Russo D, Miranda I, Ruocco C, Battaglia Y, Buonanno E, Manzi S, Russo L, Scafarto A, Andreucci VE: The progression of coronary artery calcification in predialysis patients on calcium carbonate or sevelamer. Kidney Int 2007;72:1255–1261.
35.
Delmez J, Block G, Robertson J, Chasan-Taber S, Blair A, Dillon M, Bleyer AJ: A randomized, double-blind, crossover design study of sevelamer hydrochloride and sevelamer carbonate in patients on hemodialysis. Clin Nephrol 2007;68:386–391.
36.
Al-Baaj F, Speake M, Hutchison AJ: Control of serum phosphate by oral lanthanum carbonate in patients undergoing haemodialysis and continuous ambulatory peritoneal dialysis in a short-term, placebo-controlled study. Nephrol Dial Transplant 2005;20:775–782.
37.
Hutchison AJ, Laville M: Switching to lanthanum carbonate monotherapy provides effective phosphate control with a low tablet burden. Nephrol Dial Transplant 2008;23:3677–3684.
38.
Mehrotra R, Martin KJ, Fishbane S, Sprague SM, Zeig S, Anger M: Higher strength lanthanum carbonate provides serum phosphorus control with a low tablet burden and is preferred by patients and physicians: a multicenter study. Clin J Am Soc Nephrol 2008;3:1437–1445.
39.
Sprague SM, Abboud H, Qiu P, Dauphin M, Zhang P, Finn W: Lanthanum carbonate reduces phosphorus burden in patients with CKD stages 3 and 4: a randomized trial. Clin J Am Soc Nephrol 2009;4:178–185.
40.
Hutchison AJ, Maes B, Vanwalleghem J, Asmus G, Mohamed E, Schmieder R, Backs W, Jamar R, Vosskuhler A: Long-term efficacy and tolerability of lanthanum carbonate: results from a 3-year study. Nephron Clin Pract 2006;102:c61–c71.
41.
Sprague SM, Ross EA, Nath SD, Zhang P, Pratt RD, Krause R: Lanthanum carbonate vs. sevelamer hydrochloride for the reduction of serum phosphorus in hemodialysis patients: a crossover study. Clin Nephrol 2009;72:252–258.
42.
Spiegel DM: Magnesium in chronic kidney disease: unanswered questions. Blood Purif 2011;31:172–176.
43.
Oe PL, Lips P, van der Meulen J, de Vries PM, van Bronswijk H, Donker AJ: Long-term use of magnesium hydroxide as a phosphate binder in patients on hemodialysis. Clin Nephrol 1987;28:180–185.
44.
Moriniere P, Vinatier I, Westeel PF, Cohemsolal M, Belbrik S, Abdulmassih Z, Hocine C, Marie A, Leflon P, Roche D, et al: Magnesium hydroxide as a complementary aluminium-free phosphate binder to moderate doses of oral calcium in uraemic patients on chronic haemodialysis: lack of deleterious effect on bone mineralisation. Nephrol Dial Transplant 1988;3:651–656.
45.
Parsons V, Baldwin D, Moniz C, Marsden J, Ball E, Rifkin I: Successful control of hyperparathyroidism in patients on continuous ambulatory peritoneal dialysis using magnesium carbonate and calcium carbonate as phosphate binders. Nephron 1993;63:379–383.
46.
Delmez JA, Kelber J, Norword KY, Giles KS, Slatopolsky E: Magnesium carbonate as a phosphorus binder: a prospective, controlled, crossover study. Kidney Int 1996;49:163–167.
47.
Tzanakis IP, Papadaki AN, Wei M, Kagia S, Spadidakis VV, Kallivretakis NE, Oreopoulos DG: Magnesium carbonate for phosphate control in patients on hemodialysis. A randomized controlled trial. Int Urol Nephrol 2008;40:193–201.
48.
Deuber HJ: Long-term efficacy and safety of an oral phosphate binder containing both calcium acetate and magnesium carbonate in hemodialysis patients. Nieren Hochdruck 2004;33:403–408.
49.
Spiegel DM, Farmer B, Smits G, Chonchol M: Magnesium carbonate is an effective phosphate binder for chronic hemodialysis patients: a pilot study. J Ren Nutr 2007;17:416–422.
50.
Osvaren (calcium acetate 435 mg/magnesium carbonate 235 mg) film-coated tablets. Summary of product characteristics. Fresenius Medical Care Nephrologica Bad Homburg, Germany.
51.
McIntyre CW, Pai P, Warwick G, Wilkie M, Toft AJ, Hutchison AJ: Iron-magnesium hydroxycarbonate (Fermagate): a novel non-calcium-containing phosphate binder for the treatment of hyperphosphatemia in chronic hemodialysis patients. Clin J Am Soc Nephrol 2009;4:401–409.
52.
Tzanakis IP, Oreopoulos DG: Beneficial effects of magnesium in chronic renal failure: a foe no longer. Int Urol Nephrol 2009;41:363–371.
53.
Chertow GM, Burke SK, Raggi P: Sevelamer attenuates the progression of coronary and aortic calcification in hemodialysis patients. Kidney Int 2002;62:245–252.
54.
Block GA, Spiegel DM, Ehrlich J, Mehta R, Lindbergh J, Dreisbach A, Raggi P: Effects of sevelamer and calcium on coronary artery calcification in patients new to hemodialysis. Kidney Int 2005;68:1815–1824.
55.
Qunibi W, Moustafa M, Muenz LR, He DY, Kessler PD, Diaz-Buxo JA, Budoff M: A 1-year randomized trial of calcium acetate versus sevelamer on progression of coronary artery calcification in hemodialysis patients with comparable lipid control: the Calcium Acetate Renagel Evaluation-2 (CARE-2) study. Am J Kidney Dis 2008;51:952–965.
56.
Borzecki AM, Lee A, Wang SW, Brenner L, Kazis LE: Survival in end stage renal disease: calcium carbonate vs. sevelamer. J Clin Pharm Ther 2007;32:617–624.
57.
Igarashi P, Aronson PS: Late-breaking clinical trials at renal week. Clin J Am Soc Nephrol 2008;3:RB01–RB04.
58.
Floege J: Calcium-containing phosphate binders in dialysis patients with cardiovascular calcifications: should we CARE-2 avoid them? Nephrol Dial Transplant 2008;23:3050–3052.
59.
Jager KJ, Stel VS, Zoccali C, Wanner C, Dekker FW: The issue of studying the effect of interventions in renal replacement therapy – to what extent may we be deceived by selection and competing risk? Nephrol Dial Transplant 2010;25:3836–3839.
60.
Mendoza FJ, Lopez I, Montes de Oca A, Perez J, Rodriguez M, Aguilera-Tejero E: Metabolic acidosis inhibits soft tissue calcification in uremic rats. Kidney Int 2008; 73:407–414.
61.
Salusky IB, Goodman WG, Sahney S, Gales B, Perilloux A, Wang HJ, Elashoff RM, Juppner H: Sevelamer controls parathyroid hormone-induced bone disease as efficiently as calcium carbonate without increasing serum calcium levels during therapy with active vitamin D sterols. J Am Soc Nephrol 2005;16:2501–2508.
62.
Ferreira A, Frazao JM, Monier-Faugere MC, Gil C, Galvao J, Oliveira C, Baldaia J, Rodrigues I, Santos C, Ribeiro S, Hoenger RM, Duggal A, et al: Effects of sevelamer hydrochloride and calcium carbonate on renal osteodystrophy in hemodialysis patients. J Am Soc Nephrol 2008;19:405–412.
63.
Raggi P, James G, Burke SK, Bommer J, Chasan-Taber S, Holzer H, Braun J, Chertow GM: Decrease in thoracic vertebral bone attenuation with calcium-based phosphate binders in hemodialysis. J Bone Miner Res 2005;20:764–772.
64.
Asmus HG, Braun J, Krause R, Brunkhorst R, Holzer H, Schulz W, Neumayer HH, Raggi P, Bommer J: Two-year comparison of sevelamer and calcium carbonate effects on cardiovascular calcification and bone density. Nephrol Dial Transplant 2005;20:1653–1661.
65.
Suki WN, Zabaneh R, Cangiano JL, Reed J, Fischer D, Garrett L, Ling BN, Chasan-Taber S, Dillon MA, Blair AT, Burke SK: Effects of sevelamer and calcium-based phosphate binders on mortality in hemodialysis patients. Kidney Int 2007;72:1130–1137.
66.
Shantouf R, Budoff MJ, Ahmadi N, Tiano J, Flores F, Kalantar-Zadeh K: Effects of sevelamer and calcium-based phosphate binders on lipid and inflammatory markers in hemodialysis patients. Am J Nephrol 2008;28:275–279.
67.
Caglar K, Yilmaz MI, Saglam M, Cakir E, Acikel C, Eyileten T, Yenicesu M, Oguz Y, Vural A, Carrero JJ, Axelsson J, Lindholm B, et al: Short-term treatment with sevelamer increases serum fetuin-A concentration and improves endothelial dysfunction in chronic kidney disease stage 4 patients. Clin J Am Soc Nephrol 2008;3:61–68.
68.
Oliveira RB, Cancela AL, Graciolli FG, Dos Reis LM, Draibe SA, Cuppari L, Carvalho AB, Jorgetti V, Canziani ME, Moysés RM: Early control of PTH and FGF-23 in normophosphatemic CKD patients: a new target in CKD-MBD therapy? Clin J Am Soc Nephrol 2010;5:286–291.
69.
Striker GE: Beyond phosphate binding: the effect of binder therapy on novel biomarkers may have clinical implications for the management of chronic kidney disease patients. Kidney Int 2009;76(suppl 114):S1–S2.
70.
Jamal SA, Fitchett D, Lok CE, Mendelssohn DC, Tsuyuki RT: The effects of calcium-based versus non-calcium-based phosphate binders on mortality among patients with chronic kidney disease: a meta-analysis. Nephrol Dial Transplant 2009;24:3168–3174.
71.
Toussaint ND, Lau KK, Polkinghorne KR, Kerr PG: Attenuation of aortic calcification with lanthanum carbonate versus calcium-based phosphate binders in haemodialysis: a pilot randomized controlled trial. Nephrology (Carlton) 2011;16:290–298.
72.
D’Haese PC, Spasovski GB, Sikole A, Hutchison A, Freemont TJ, Sulkova S, Swanepoel C, Pejanovic S, Djukanovic L, Balducci A, Coen G, Sulowicz W, et al: A multicenter study on the effects of lanthanum carbonate (Fosrenol) and calcium carbonate on renal bone disease in dialysis patients. Kidney Int Suppl 2003;S73–S78.
73.
Malluche HH, Siami GA, Swanepoel C, Wang GH, Mawad H, Confer S, Smith M, Pratt RD, Monier-Faugere MC: Improvements in renal osteodystrophy in patients treated with lanthanum carbonate for two years. Clin Nephrol 2008;70:284–295.
74.
Wilson R, Zhang P, Smyth M, Pratt R: Assessment of survival in a 2-year comparative study of lanthanum carbonate versus standard therapy. Curr Med Res Opin 2009;25:3021–3028.
75.
Navarro-Gonzalez JF, Mora-Fernandez C, Garcia-Perez J: Clinical implications of disordered magnesium homeostasis in chronic renal failure and dialysis. Semin Dial 2009;22:37–44.
76.
Spiegel DM, Farmer B: Long-term effects of magnesium carbonate on coronary artery calcification and bone mineral density in hemodialysis patients: a pilot study. Hemodial Int 2009;13:453–459.
77.
Turgut F, Kanbay M, Metin MR, Uz E, Akcay A, Covic A: Magnesium supplementation helps to improve carotid intima media thickness in patients on hemodialysis. Int Urol Nephrol 2008;40:1075–1082.
78.
Suki WN: Effects of sevelamer and calcium-based phosphate binders on mortality in hemodialysis patients: results of a randomized clinical trial. J Ren Nutr 2008;18:91–98.
79.
Slatopolsky E, Liapis H, Finch J: Progressive accumulation of lanthanum in the liver of normal and uremic rats. Kidney Int 2005;68:2809–2813.
80.
Nikolov IG, Joki N, Vicca S, Patey N, Auchere D, Flinois JP, Beaune P, Drueke T, Lacour B. Effects of long-term lanthanum carbonate administration on tissue La content and liver function in rats with chronic renal failure. ASN Renal Week, San Francisco 2007.
81.
Gonella M, Ballanti P, Della Rocca C, Calabrese G, Pratesi G, Vagelli G, Mazzotta A, Bonucci E: Improved bone morphology by normalizing serum magnesium in chronically hemodialyzed patients. Miner Electrolyte Metab 1988;14:240–245.
82.
Spasovski GB, Sikole A, Gelev S, Masin-Spasovska J, Freemont T, Webster I, Gill M, Jones C, De Broe ME, D’Haese PC: Evolution of bone and plasma concentration of lanthanum in dialysis patients before, during 1 year of treatment with lanthanum carbonate and after 2 years of follow-up. Nephrol Dial Transplant 2006;21:2217–2224.
83.
Fosrenol tablets (lanthanum carbonate) (prescribing information). Wayne/Pa, Shire US Inc, Oct 2004.
84.
Altmann P, Barnett ME, Finn WF: Cognitive function in stage 5 chronic kidney disease patients on hemodialysis: no adverse effects of lanthanum carbonate compared with standard phosphate-binder therapy. Kidney Int 2007;71:252–259.
85.
Finn WF, Joy MS: A long-term, open-label extension study on the safety of treatment with lanthanum carbonate, a new phosphate binder, in patients receiving hemodialysis. Curr Med Res Opin 2005;21:657–664.
86.
Finn WF: Lanthanum carbonate versus standard therapy for the treatment of hyperphosphatemia: safety and efficacy in chronic maintenance hemodialysis patients. Clin Nephrol 2006;65:191–202.
87.
Hutchison AJ, Barnett ME, Krause R, Kwan JT, Siami GA: Long-term efficacy and safety profile of lanthanum carbonate: results for up to 6 years of treatment. Nephron Clin Pract 2008;110:c15–c23.
88.
Hutchison AJ, Barnett ME, Krause R, Siami GA: Lanthanum carbonate treatment, for up to 6 years, is not associated with adverse effects on the liver in patients with chronic kidney disease stage 5 receiving hemodialysis. Clin Nephrol 2009;71:286–295.
89.
Alfrey AC, Miller NL: Bone magnesium pools in uremia. J Clin Invest 1973;52:3019–3027.
90.
Braun J: Extraosseous calcification in patients with chronic renal failure – no escape? Nephrol Dial Transplant 2005;20:2054–2059.
91.
Tonelli M, Pannu N, Manns B: Oral phosphate binders in patients with kidney failure. N Engl J Med 2010;362:1312–1324.
92.
Hutchison AJ, Maes B, Vanwalleghem J, Asmus G, Mohamed E, Schmieder R, Backs W, Jamar R, Vosskuhler A: Efficacy, tolerability, and safety of lanthanum carbonate in hyperphosphatemia: a 6-month, randomized, comparative trial versus calcium carbonate. Nephron Clin Pract 2005;100:c8–c19.
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.