Dose Of Sevelamer Research Articles

The progression of coronary artery calcification in predialysis patients on calcium carbonate or sevelamer

Coronary artery calcification is more prevalent in dialysis patients than in patients without kidney disease and this is associated with high serum phosphorus. In this study, we evaluate the effect of calcium carbonate or sevelamer treatments on the progression of calcification in 90 predialysis patients. Inclusion criteria were stable serum calcium, phosphorus, parathyroid hormone, and a similar baseline total calcium score (TCS). These patients were not treated by phosphate binder, vitamin D, or statin. They were given low-phosphorus diets without or with daily calcium carbonate or sevelamer throughout the study that averaged 2 years. Baseline demographic or clinical characteristics along with biochemical parameters were not different among the three groups. The TCS significantly increased in patients on the low-phosphorus diet alone, to a lesser extent in calcium carbonate-treated patients, and not at all in sevelamer-treated patients. The progression of coronary calcification paralleled that of the calcium score. Our study shows that sevelamer treatment should not be restricted to dialysis patients; however, a larger study should be undertaken to confirm these results.

Implementation of 'K/DOQI Clinical Practice Guidelines for Bone Metabolism and Disease in Chronic Kidney Disease' after the introduction of cinacalcet in a population of patients on chronic haemodialysis

The purpose of the present study was to evaluate the impact of cinacalcet administration on the attainment of Kidney Disease Outcomes Quality Initiative of the National Kidney Foundation (NFK-K/DOQI) targets, in a group of dialysis patients with secondary hyperparathyroidism that were not controlled with vitamin D metabolites due to inadequate elevations in serum calcium and/or phosphorus. Twenty-eight patients undergoing haemodialysis that presented secondary hyperparathyroidism (PTH > 300 pg/ml) with difficulty to use vitamin D either because of hypercalcaemia (>10.2 mg/dl) and/or hyperphosphoraemia (>5.5 mg/dl) were included in this study. The follow-up period was 9 months before and after the introduction of cinacalcet. We started by adding 30 mg of cinacalcet orally once daily to their previous vitamin D metabolite treatment. The following variables were calculated and recorded: the mean of all measurements of serum Ca, P and parathyroid hormones (PTH), and Ca x P in each patient; calcium in dialysate (mEq/l); doses of vitamin D administered; doses of cinacalcet used, and the average prescription of calcium-based phosphate binders, sevelamer hydrochloride and aluminum binders, corresponding to two periods according to the introduction of cinacalcet. The proportions of patients with different serum Ca levels as well as serum P levels; serum PTH levels and CaxP at the beginning and at the end of the nine month period of treatment with cinacalcet were calculated. Serum PTH (826.9 +/- 325 vs 248.1 +/- 77.3, P < 0.001), serum calcium (9.9 +/- 0.6 vs 8.6 +/- 0.4, P < 0.001) and the Ca x P product (94.7 +/- 7.3 vs 43.6 +/- 8.5; P < 0.001) diminished significantly whereas serum phosphorus remained unchanged (4.8 +/- 1.5 vs 4.3 +/- 1.1; P = NS). Before cinacalcet, 23 patients had severe hyperparathyroidism (serum PTH > 500) and 15 patients hypercalcaemia (serum calcium >10.2 mg/dl). After 9 months of treatment, all 28 patients showed serum PTH < 500 pg/ml and serum calcium <10.2 mg/dl; 64.7% of the patients achieved Ca, P, Ca x P and PTH objectives simultaneously. While the mean dose of cinacalcet increased along the 9 months of treatment (P < 0.001), there were no significant changes in vitamin D metabolites (P = 0.5), neither in the mean doses of calcium-containing agents, nor in the mean prescribed doses of sevelamer (P < 0.01), and aluminium-containing agents diminished significantly (P < 0.05). In summary, the combination of cinacalcet and low doses of vitamin D improved significantly the control of PTH and Ca x P in patients with severe secondary hyperparathyroidism on chronic haemodialysis, without adverse effects and with lower doses of phosphate binders.

Results of a Randomized Crossover Study Comparing Once-Daily and Thrice-Daily Sevelamer Dosing

Patients with renal failure require complex regimens of renal replacement therapies and medications, including ingestion of phosphate-binding agents 3 times daily. Previous studies suggested that sevelamer may provide extended phosphate binding and be effective with once-daily dosing, thus simplifying the phosphate-binder regimen. Twenty-four patients were enrolled in this study, 21 of whom were randomly assigned to sevelamer administration at their previously prescribed dose, either once daily with the largest meal or thrice daily with meals, with crossover to the other regimen after 4 weeks. Eighteen patients completed both treatment periods. The primary efficacy measure for which the study was powered is comparison of the effect of once-daily versus standard thrice-daily sevelamer dosing on serum phosphorus level control, determined by using equivalence testing. Secondary efficacy measures are the effects of the 2 regimens on serum calcium level corrected for albumin level; calcium x phosphorus product; albumin; intact parathyroid hormone; total, low-density lipoprotein, high-density lipoprotein, and non-high-density lipoprotein cholesterol; and triglyceride levels. Once-daily sevelamer was as effective as thrice-daily dosing of sevelamer in controlling serum phosphorus, calcium, calcium x phosphorus product, serum albumin, and serum lipid levels. Bioequivalence was not shown for intact parathyroid hormone, likely because of high variability. Mean serum phosphorus levels were 4.6 +/- 0.3 mg/dL (1.49 +/- 0.10 mmol/L) during thrice-daily dosing and 5.0 +/- 0.3 mg/dL (1.61 +/- 0.10 mmol/L) during once-daily dosing. The average prescribed dose of sevelamer during both treatment regimens was 6.7 +/- 2.4 g. Routine laboratory measures were similar in the 2 groups. Both regimens were well-tolerated. Despite concerted patient-directed educational efforts, phosphorus level control in patients with renal failure is suboptimal and contributes to increased mortality risk. Once-daily sevelamer could simplify these regimens and encourage medication compliance, perhaps improving hyperphosphatemia management.

Sevelamer Treatment Strategy in Peritoneal Dialysis Patients: Conventional Dose Does Not Make Best Use of Resources

BACKGROUND The significant incremental expense in the use of conventional sevelamer dose prompted us to evaluate the role of prescribing a lower dose of sevelamer. METHODS To determine the optimum strategy for prescribing sevelamer in peritoneal dialysis patients, we conducted an open-label randomized study comparing the treat-to-goal strategy (4.0-g daily sevelamer dose) with lower sevelamer dose (1.2-g daily dose). RESULTS Twenty-seven peritoneal dialysis patients with serum calcium x phosphorus product above 55 mg2/dL2 were recruited. Eighteen were randomized to the low-dose treatment group (1.2 g daily), and 9 to the treat-to-goal (4.0 g daily) group. Overall, significantly lower calcium x phosphorus product and serum phosphorus levels at 6 months were achieved by the treat-to-goal treatment. The proportions of patients who attained the Kidney Disease Outcomes Quality Initiative (K/DOQI) treatment target, however, did not differ significantly between the treat-to-goal and low-dose treatment groups (66.7% +/- 30.8% vs. 33.3% +/- 21.8%, p=0.10). The numbers needed to treat to benefit 1 patient who attains the K/DOQI recommendation are 1.5 patients (95% confidence interval [95% CI], 1.0-2.8) in the 4.0-g daily dose and 3 patients (95% CI, 1.8-8.7) in the 1.2-g daily dose group. Therefore, an extra 66.7% of subjects would be able to attain the treatment recommendation within the same budget if the daily dose of sevelamer used was 1.2 g instead of the usual 4.0 g. Compared with a 1.2-g daily dose of sevelamer, the 4.0-g daily dose had an incremental cost-effectiveness ratio (ICER) of US $2,353 per additional patient achieving the K/DOQI target. Multivariate analysis showed that only the calcium x phosphorus product after 1 month of sevelamer treatment was predictive of treatment response. CONCLUSIONS Low-dose sevelamer treatment might be a cost-effective approach, which is good for many rather than best for a few.

Gastric pH, sevelamer hydrochloride and omeprazole

Sevelamer hydrochloride is a polymer containing multiple amines (40% amine hydrochloride) separated by one carbon from the polymer backbone, and it is not absorbed by the intestine. These amines are partially protonated and interact with phosphate molecules through ionic and hydrogen bonding, therefore reducing phosphate absorption and lowering serum phosphate concentration. Alterations of gastric pH, in particular excessive alkalinization, could interfere with sevelamer phosphate binding capacity. A 30-year-old dialysis patient affected by secondary hyperparathyroidism started sevelamer treatment, 4.8 g/day, with a basal serum phosphate of 6.9 mg/dl. The patient was also treated with omeprazole (20 mg/day) because of chronic gastritis. Phosphate levels normalized (4.2 mg/dl), but after four months of follow-up serum phosphate unexpectedly increased to 7.2 mg/dl. We found out that in the same period she had autonomously increased the dosage of omeprazole to 80 mg/day, due to worsening of dyspepsia. Gastric pH measurement showed a median level of 4.1, rather than the normal values of 1 - 2, indicating excessive pharmacological alkalinization. When omeprazole was reduced to the correct dose of 20 mg/day, we observed a rapid decrease of phosphate levels. This case report highlights the influence of gastric pH on sevelamer phosphate binding capacity. The high dose of omeprazole and the consequent excessive increase in gastric pH was probably responsible for a decreased phosphate binding capacity of sevelamer. When patients taking appropriate doses of sevelamer do not respond to treatment, a potential interaction with drugs determining an increase of gastric pH should be considered.

The Effect of Sevelamer on Tacrolimus Target Levels

Herein we report on a 55-year-old male patient who received his second kidney transplant because of recurrent IgA nephropathy in 1999. The graft function had been stable during the first years following the transplantation, with the immunosuppressive therapy consisting of tacrolimus, mycophenolate mofetil, and low-dose steroid. In July 2004, cardiac surgery was performed because of severe coronary artery disease and aortic stenosis. The patient was dependent on dialysis perioperatively. Mycophenolate mofetil was discontinued because of a persistently low creatinine clearance. However, the patient refused to return on a chronic hemodialysis program and was therefore kept on low doses of tacrolimus and steroid. Intermittent dialysis treatments were performed. In August 2004, sevelamer (Renagel, 800 mg tablets by Genzyme) was started because of a high calcium-phosphate product. The oral medication was otherwise retained unchanged. Subsequently, a progressive decline in tacrolimus blood levels was observed. In spite of an increased tacrolimus dosage, target levels were measurable only temporarily in the context of further deteriorations of kidney function (Fig. 1). Significant reductions in the peak level of tacrolimus (Cmax) and the area under the curve (AUC) following one oral dose of 1.5 mg tacrolimus were found when compared to tacrolimus kinetics in the same patient three days after discontinuation of sevelamer, with Cmax 9.9 vs. 13.1 ng/ml and AUC7 4.02 vs. 9.69 ng×h/ml (Fig. 2). For performance of the pharmacokinetic study, tacrolimus levels were measured immediately before and 1, 2, 5, and 7 hr after intake of the drug by immunoassay (EMIT by Dade Behring), the calculation of the AUC was performed by the trapezoidal rule. Informed consent was obtained from the patient.FIGURE 1.: Time course of serum creatinine, tacrolimus blood levels (with the detection limit of the assay being 2.5 ng/ml), and daily tacrolimus dosage.FIGURE 2.: Tacrolimus blood levels in ng/ml (assay detection limit 2.5 ng/ml) following one dose of tacrolimus 1.5 mg p.o., with and without sevelamer 3×800 mg p.o.Sevelamer hydrochloride is a nonabsorbable, polymeric phosphate binder that does not contribute to calcium load, aluminium toxicity, or changes in acid-base status. Within the intestinal lumen, the cationic sevelamer binds phosphate through ion exchange. Sevelamer is known to reduce absorption of vitamin D, E, K, and folic acid. More importantly, decreases in the peak concentration and AUC of mycophenolate mofetil have been described (1). There are conflicting data regarding the interaction of sevelamer with cyclosporine; a marked decrease in trough levels was described in a patient on hemodialysis, whereas the pharmacokinetic profile of cyclosporine in patients with a stable graft function after renal transplantation was not significantly affected by sevelamer (1,2). Although no other drug interactions have been substantiated so far, it is recommended to take any accompanying medication at least one hour before or three hours after a dose of sevelamer when changes in absorption of oral medications may have significant clinical consequences. This is the first time a decrease in tacrolimus blood levels with concomitant intake of sevelamer is reported. A direct binding of lipophilic substances by sevelamer as discussed for cyclosporine seems to be the most likely mechanism of interaction (3).

Effect of Sevelamer on Dyslipidemia and Chronic Inflammation in Maintenance Hemodialysis Patients

Hemodialysis (HD) patients often experience cardiovascular events, that might be related to altered calcium-phosphate metabolism, dyslipidemia, and chronic inflammation in addition to hypertension. Sevelamer, a non-calcium-containing phosphate binder, may improve the lipid profile of HD patients. However, the influence of sevelamer on chronic inflammation has not been clarified. We enrolled 36 maintenance HD patients with a serum calcium (Ca) or phosphate (P) level constantly greater than 9.5 mg/dL and 5.5 mg/dL, respectively. The dose of sevelamer was titrated to achieve a serum Ca and P in the target ranges. The study period was 24 weeks. Patients underwent the following measurements: bone mineral markers, lipids, and a high-sensitivity C-reactive protein (hs-CRP). In the 28 patients who completed the study, sevelamer significantly reduced the mean non-high-density lipoprotein cholesterol (non-HDL-C) level by 15% and 20% (p < 0.0001) after 12 and 24 weeks, respectively, in addition to reducing the serum P level and Ca x P product. Similarly, there was a significant reduction of the serum hs-CRP level after 12 and 24 weeks [median at baseline: 1.03 mg/dL (interquartile range 0.26-3.98 mg/dL) versus 0.57 (0.17-1.47) and 0.38 (0.16-1.03), respectively, p = 0.0259]. The reduction rate of hs-CRP was significantly correlated with those of non-HDL-C (r = 0.451, p < 0.0401) and P (r = 0.453, p < 0.0008) Hs-CRP levels were reduced by sevelamer administration, as well as non-HDL-C, P, and the Ca x P product. Sevelamer may have an anti-inflammatory effect, in addition to lowering phosphate and lipid levels in HD patients.

Treatment of hyperphosphatemia in patients with chronic kidney disease on maintenance hemodialysis

Treatment of hyperphosphatemia in patients with chronic kidney disease on maintenance hemodialysis. Hyperphosphatemia in patients with ESRD leads to secondary hyperparathyroidism, renal osteodystrophy, and is independently associated with mortality risk. The exact mechanism by which hyperphosphatemia increases mortality risk is unknown, but it may relate to enhanced cardiovascular calcification. National Kidney Foundation K/DOQI bone metabolism and disease guidelines recommend maintenance of serum phosphorus (P) below 5.5 mg/dL, and Ca x P product less than 55 mg(2)/dL(2). Although calcium-based phosphate binders (CBPB) are cost effective, long-term safety concerns relate to their postulated role in progression of cardiovascular calcification. Sevelamer hydrochloride has been recommended as an alternative noncalcium phosphate binder. Results from the Calcium Acetate Renagel Evaluation (CARE study) indicate that calcium acetate is more effective than sevelamer in controlling serum phosphorous and Ca x P product in hemodialysis patients. In the Treat-to-Goal study, dialysis patients treated with sevelamer had slower progression of coronary and aortic calcification than patients treated with CBPB. The mechanism underlying the beneficial effect of sevelamer is unknown, but may relate to decreased calcium loading or to dramatic reductions in LDL cholesterol in sevelamer-treated patients. At present, evidence incriminating CBPB in the progression of cardiovascular calcification in ESRD remains largely circumstantial. As calcium acetate is more efficacious and cost effective than sevelamer, it remains an accepted first-line phosphate binder. In this review, we will examine these issues and provide rational guidelines for the use of calcium-based phosphate binders in patients on maintenance hemodialysis.

Combination Therapy with Sevelamer Hydrochloride and Calcium Carbonate in Japanese Patients with Long‐Term Hemodialysis: Alternative Approach for Optimal Mineral Management

Calcium (Ca) overload by Ca-containing phosphorus (P) binder has been suggested to be implicated in the pathogenesis of soft tissue and vascular calcification, which contribute to increased morbidity and mortality of cardiovascular disease in patients undergoing dialysis. Recently, a noncalcium P binder, sevelamer hydrochloride (sevelamer), has become available in Japan. However, Japanese patients undergoing dialysis might be less tolerant of sevelamer treatment, and it is likely to cause hypocalcemia because their dietary Ca intake is less than that in European and American patients. We evaluated the effects of combination therapy with sevelamer and calcium carbonate (CC) on mineral metabolism in Japanese hemodialysis patients, as an alternative form of P management. A total of 210 hemodialysis patients were enrolled, and were given a small dose of sevelamer (0.75-1.5 g/day) on CC treatment. Sevelamer dose was gradually increased, while CC decreased during 24 weeks. Five patients discontinued sevelamer treatment because of severe constipation, anorexia, and parathyroidectomy for severe secondary hyperparathyroidism. After 24 weeks, the dose of sevelamer was significantly increased to 3.29 g/day (initial dose: 1.47 g/day), while CC was decreased by 54%. Adjusted serum Ca significantly decreased (9.63 +/- 0.57-9.45 +/- 0.67 mg/dL; P = 0.0012), although serum P increased (5.89 +/- 1.32-6.25 +/- 1.32 mg/dL; P = 0.017). Serum intact PTH (iPTH) significantly increased in patients with a low or normal iPTH level (< or =300 pg/mL), while it did not change in patients with secondary hyperparathyroidism (>300 pg/mL). The results suggest that the therapeutic regimen is more tolerant and reduces Ca load in Japanese hemodialysis patients while avoiding hypocalcemia. In addition, the mitigated Ca overload could improve PTH hyposecretion in patients with adynamic bone disease, which is associated with soft tissue calcification and higher mortality in uremia.

Effect of Sevelamer on Dyslipidemia and Chronic Inflammation in Maintenance Hemodialysis Patients

Background: Hemodialysis (HD) patients often experience cardiovascular events, that might be related to altered calcium–phosphate metabolism, dyslipidemia, and chronic inflammation in addition to hypertension. Sevelamer, a non-calcium-containing phosphate binder, may improve the lipid profile of HD patients. However, the influence of sevelamer on chronic inflammation has not been clarified. Methods: We enrolled 36 maintenance HD patients with a serum calcium (Ca) or phosphate (P) level constantly greater than 9.5 mg/dL and 5.5 mg/dL, respectively. The dose of sevelamer was titrated to achieve a serum Ca and P in the target ranges. The study period was 24 weeks. Patients underwent the following measurements: bone mineral markers, lipids, and a high-sensitivity C-reactive protein (hs-CRP). Results: In the 28 patients who completed the study, sevelamer significantly reduced the mean non-high-density lipoprotein cholesterol (non-HDL-C) level by 15% and 20% (p < 0.0001) after 12 and 24 weeks, respectively, in addition to reducing the serum P level and Ca × P product. Similarly, there was a significant reduction of the serum hs-CRP level after 12 and 24 weeks [median at baseline: 1.03 mg/dL (interquartile range 0.26–3.98 mg/dL) versus 0.57 (0.17–1.47) and 0.38 (0.16–1.03), respectively, p = 0.0259]. The reduction rate of hs-CRP was significantly correlated with those of non-HDL-C (r = 0.451, p < 0.0401) and P (r = 0.453, p < 0.0008) Conclusion: Hs-CRP levels were reduced by sevelamer administration, as well as non-HDL-C, P, and the Ca × P product. Sevelamer may have an anti-inflammatory effect, in addition to lowering phosphate and lipid levels in HD patients.

Efficacy and side‐effect profile of sevelamer hydrochloride used in combination with conventional phosphate binders

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. 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. 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. 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.

Safety and Efficacy of Sevelamer in the Treatment of Uncontrolled Hyperphosphataemia of Haemodialysis Patients

Background/Aim: The treatment of hyperphosphataemia is of major importance in the management of patients on dialysis. Traditional phosphate binders can be associated with undesirable effects. Recently, a new non-absorbable phosphate-binding polymer, sevelamer hydrochloride, has been available. Clinical information is scarce, and its cost could be a limiting factor for its wider use. No studies have evaluated its usefulness in uncontrolled hyperphosphataemic patients. Methods: We identified 34 patients with a maintained serum phosphorus concentration >6.5 mg/dl and/or toxicity related to standard phosphorus-binding treatment (aluminium or calcium based). Sevelamer was added and titrated up fortnightly to achieve phosphorus control. Previous phosphate binders were decreased, whenever possible. The period of the study was 6 months. Results: Thirteen patients (38%) dropped out because of side effects, mainly related to the gastro-intestinal tract. The efficacy analysis disclosed that the phosphorus concentration decreased from 2.39 ± 0.48 to 1.84 ± 0.48 mmol/l (p < 0.001). The mean dose of sevelamer was stabilised at 3.4 ± 1.8 g/day. The amount of calcium- and aluminium-based phosphate binders could be decreased from 5.1 ± 3.5 to 3.1 ± 2.7 g/day (38% decrease) and from 2.4 ± 1.5 to 1.5 ± 1.7 g/day (36% decrease), respectively. The Ca × P product was significantly decreased from 5.83 ± 1.19 to 4.36 ± 1.12 mmol/l² (p < 0.001). The total cholesterol concentration decreased from 4.34 ± 0.9 to 3.98 ± 0.9 mmol/l (p < 0.01) and the low-density lipoprotein cholesterol level from 2.61 ± 0.98 to 2.20 ± 0.77 mmol/l (p < 0.03). Conclusions: Sevelamer is an effective phosphate binder that allows a better serum phosphorus control, while allowing a decrease in the dose of calcium- and aluminium-based phosphate binders in these difficult patients. The drawbacks are the high intolerance rate and the price of the product.

Dietary phosphorus reduction by pretreatment of human breast milk with sevelamer.

Hyperphosphatemia leading to hyperparathyroidism and ultimately renal osteodystrophy is a well-known complication of chronic renal failure. A new hydrogel binder, sevelamer, has recently become available for use in hyperphosphatemic patients with renal failure. We had previously mixed the capsule with pumped breast milk and formula, but discovered that the hydrogel formed a viscous solution that infants were unable or unwilling to swallow. We therefore evaluated the phosphorus content of fresh and frozen breast milk before and after treating with different doses of sevelamer at different temperatures and for varying lengths of time. The hydrogel bound promptly to phosphorus, reducing the phosphorus content 78% within 5 min. The viscous hydrogel settled to the bottom of the container within 10 min allowing the supernatant to be easily decanted. We also evaluated the breast milk for changes in other electrolytes, osmolality, pH, and macronutrient content. These results show that fresh or frozen breast milk can be safely pretreated with sevelamer without significantly changing its macronutrient or ionic content, with the exception of calcium and protein. The supernatant can be fed to infants or instilled through a gastrostomy tube without difficulty since the viscous hydrogel settles rapidly to the bottom of the container.

A prospective study of combination therapy for hyperphosphataemia with calcium-containing phosphate binders and sevelamer in hypercalcaemic haemodialysis patients.

Hyperphosphataemia is predictive of death, in haemodialysis (HD) patients. Sevelamer is a mineral-free phosphate binder not limited by the hypercalcaemia often encountered when utilizing calcium-containing phosphate binders. Highly positive calcium balance is associated with ectopic calcification and potentially accelerated vascular disease. Unfortunately, exclusive use of sevelamer entails a large cost differential, limiting its use in many centres. We report on a strategy of partial replacement of calcium with sevelamer for the management of hyperphosphataemia in hypercalcaemic chronic HD patients. We identified 23 HD patients with serum calcium >2.6 mmol/l. Dietary phosphate and calcium intake were assessed and baseline serum calcium, phosphate and 1alpha calcidol and elemental calcium dose recorded. Fifty per cent of this initial calcium dose was exchanged for sevelamer. Vitamin D doses were left unchanged. If serum calcium was still >2.6 mmol/l after 4 weeks a further 50% of calcium was exchanged. If serum phosphate was >2 mmol/l the sevelamer dose was increased by 25%. The patients were followed up for a further 4 weeks. Seven patients complained of gastrointestinal intolerance of sevelamer. Serum calcium fell from a mean value of 2.8+/-0.04 (2.64-3.54) mmol/l to 2.56+/-0.03 (2.4-2.9) mmol/l, P<0.0005. The hypercalcaemic percentage of patients fell from 100 to 26%. Mean serum phosphate was not significantly changed, 1.59+/-0.1 (0.57-2.6) mmol/l to 1.63+/-0.11 (0.55-2.68) mmol/l, 17-22% of patients having serum phosphate >2 mmol/l. Serum intact parathyroid hormone increased from 166+/-47 (12-933) ng/l to 276+/-104 (20-1013) ng/l, P=0.02. Mean sevelamer dose was 2.77+/-0.36 (0-5.6) g per day. Elemental calcium dose fell from 2.05+/-0.23 (0.5-4.5) g to 1.03+/-0.1 (0.5-2.5) g, P<0.0001. A regimen based on the combination of sevelamer and calcium is capable of effectively managing hyperphosphataemia, without hypercalcaemia, in the majority of hypercalcaemic HD patients. Such a minimally calcaemic approach might reduce the financial burden of sevelamer therapy, and enable a wider range of patients to be treated.

Sevelamer Hydrochloride (Renagel®), a Nonabsorbed Phosphate‐Binding Polymer, Does Not Interfere with Digoxin or Warfarin Pharmacokinetics

Sevelamer hydrochloride (Renagel) is a nonabsorbed phosphate-binding polymer marketed for the treatment of hyperphosphatemia in adult patients receiving hemodialysis. Sevelamer also exhibits bile acid-binding properties resulting in LDL cholesterol lowering. Potential drug interactions between digoxin and warfarin and sevelamer were studied. These two drugs were chosen because they are known to bind to the bile acid-binding polymers, cholestyramine and colestipol. Studies were single dose, crossover, with or without six 2.4 g doses of sevelamer. Plasma concentrations were determined using validated analytical methods. The pharmacokinetic profiles of digoxin and warfarin were not altered by the simultaneous and continued administration of sevelamer. Values for the ratio of ln[AUC(0-infinity)], ln[AUC(0-t)], and ln[Cmax] with and without sevelamer were close to 100%, and the 90% confidence intervals for these ratios were within the 80% to 125% range. It was concluded that sevelamer does not interfere with the absorption or excretion of digoxin or warfarin.