Efficacy and side-effect profile of sevelamer hydrochloride used in combination with conventional phosphate binders.
BACKGROUND
Poor phosphate control is common among patients with end-stage renal disease. Sevelamer hydrochloride has been demonstrated to be a safe and effective phosphate binder when used as a monotherapy. However, cost limits its usefulness in many countries. Data assessing its effectiveness and safety in combination with conventional phosphate binders are lacking.


METHODS
Dialysis patients meeting the following inclusion criteria participated in this study: (i) hyperphosphataemia >1.8 mmol/L (5.6 mg/dL); and (ii) an inability to tolerate currently available binders. The trial was conducted in three phases each lasting 3 months: (i) an observation phase (patients continued on their regular phosphate binders); (ii) a titration phase (sevelamer was added at a dose of 403 mg three times daily with meals, titrated to a maximum of 1209 mg three times daily); and (iii) a maintenance phase.


RESULTS
Twenty-five patients were recruited into the study. Eighteen patients completed all three trial phases. Mean serum phosphate dropped from 2.11 +/- 0.06 mmol/L (6.6 +/- 0.2 mg/dL) during the observation period to 1.91 +/- 0.01 mmol/L (5.9 +/- 0.003 mg/dL) during the maintenance phase (P=0.02). Calcium x phosphate product fell from 5.49 +/- 0.17 mmol2/L2 (68.64 +/- 2.11 mg2 dL2) to 4.89 +/- 0.27 mmol2/L2 (61.36 +/- 3.35 mg2 dL2) (P=0.02). There was no significant change in serum calcium or parathyroid hormone. Total serum cholesterol fell from 3.8 mmol/L (3.4-4.37) 147 mg/dL (131-169) to 3.55 mmol/L (2.97-4.2) 137 mg/dL (115-162) (P=0.02). Serum low-density lipoprotein cholesterol also fell significantly from 1.67 +/- 0.10 mmol/L (65 +/- 4 mg/dL) to 1.52 +/- 0.11 mmol/L (59 +/- 4 mg/dL) (P=0.04). The average prescribed dose of sevelamer was 2.4 g/day. Elemental calcium dropped from 3.4 g/day (1.4 to 4.6) to 1.2 g/day (0.6-2.4) (P=0.04). Seventy-two per cent of patients reported mild flatulence, nausea and indigestion. Three patients discontinued treatment because of adverse effects.


CONCLUSIONS
Sevelamer in combination with conventional phosphate binders is effective in lowering serum phosphate and calcium-phosphate product in patients with refractory hyperphosphataemia. Beneficial effects on lipid profile were also observed. Mild gastrointestinal upset is common.
Sturtevant
Joanna M
JM
Department of Nephrology, Princess Alexandra Hospital, Brisbane, Queensland, Australia. jo_sturtevant@health.qld.gov.au
Hawley
Carmel M
CM
Reiger
Kylie
K
Johnson
David W
DW
Campbell
Scott B
SB
Burke
John R
JR
Bofinger
Andrew
A
Isbel
Nicole M
NM
D000536:Aluminum Hydroxide / Q000008:administration & dosage*; D002118:Calcium / Q000097:blood; D002119:Calcium Carbonate / Q000008:administration & dosage; D004359:Drug Therapy, Combination; D004852:Epoxy Compounds / Q000008:administration & dosage* / Q000009:adverse effects; D005260:Female; D006801:Humans; D007676:Kidney Failure, Chronic / Q000097:blood / Q000150:complications*; D008055:Lipids / Q000097:blood; D017633:Magnesium Silicates; D008297:Male; D008875:Middle Aged; D010281:Parathyroid Hormone / Q000097:blood; D010710:Phosphates / Q000097:blood*; D010760:Phosphorus Metabolism Disorders / Q000097:blood / Q000188:drug therapy* / Q000209:etiology; D011073:Polyamines; D011095:Polyethylenes / Q000008:administration & dosage* / Q000009:adverse effects; D006435:Renal Dialysis; D000069603:Sevelamer
D004852:Epoxy Compounds; D008055:Lipids; D017633:Magnesium Silicates; D010281:Parathyroid Hormone; D010710:Phosphates; D011073:Polyamines; D011095:Polyethylenes; D000536:Aluminum Hydroxide; D000069603:Sevelamer; C001671:magnesium trisilicate; D002119:Calcium Carbonate; D002118:Calcium