Sevelamer

Pronunciation

Class: Phosphate-removing Agents
VA Class: GU900
Chemical Name: 2-Propen-1-amine polymer with (chloromethyl)oxirane, carbonate
Molecular Formula: (C3H7N)m (C3H5ClO)n•H2CO3(C3H7N)m (C3H5ClO)n•HCl
CAS Number: 845273-93-0
Brands: Renagel, Renvela

Introduction

Phosphate binder used to reduce the intestinal absorption of phosphates;1 2 3 4 5 6 7 8 22 23 allylamine polymer (cross-linked with epichlorohydrin).1 2 3 4 5 6 7 8 22

Uses for Sevelamer

Hyperphosphatemia

Reduction of serum phosphorus in patients with chronic kidney disease (CKD) who are undergoing dialysis.1 2 3 4 6 23

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Risk of hypercalcemia is less than with calcium salts.2

Safety and efficacy not established in patients with CKD who are not undergoing dialysis.1 23

Sevelamer Dosage and Administration

Administration

Oral Administration

Administer orally 3 times daily with meals.1 23

Dosage

Available as sevelamer carbonate and sevelamer hydrochloride; dosage expressed in terms of the salts.1 23 Sevelamer carbonate dosage expected to be similar to that of sevelamer hydrochloride because of rapid disintegration of sevelamer carbonate tablets in gastric hydrochloric acid.23

Adults

Hyperphosphatemia in CKD Patients Undergoing Dialysis
Sevelamer Carbonate

Initial dosage in patients not currently receiving a phosphate binder (e.g., calcium acetate) depends on serum phosphorus concentrations.23

Initial Sevelamer Carbonate Dosage in Patients not Currently Receiving a Phosphate Binder

Serum Phosphorus Concentration (mg/dL)

Initial Sevelamer Carbonate Dosage

Number of Tablets per Dose

>5.5 and <7.5

800 mg 3 times daily23

One 800-mg tablet23

≥7.5 and <9

1.6 g 3 times daily23

Two 800-mg tablets23

≥9

1.6 g 3 times daily 23

Two 800-mg tablets23

Initial dosage in patients being transferred to sevelamer from calcium acetate therapy depends on current calcium acetate dosage.23

Initial Sevelamer Carbonate Dosage in Patients Being Transferred from Calcium Acetate Therapy

Calcium Acetate Dosage

Initial Sevelamer Carbonate Dosage

Number of Tablets per Dose

667 mg 3 times daily

800 mg 3 times daily23

One 800-mg tablet23

1.334 g 3 times daily

1.6 g 3 times daily23

Two 800-mg tablets23

2.001 g 3 times daily

2.4 g 3 times daily23

Three 800-mg tablets23

For the treatment of hyperphosphatemia in patients currently receiving sevelamer hydrochloride therapy, the recommended initial dosage of sevelamer carbonate is equivalent to the patient's current sevelamer hydrochloride dosage on a gram per gram basis.23

Adjust dosage of sevelamer carbonate for all patients according to the patient’s serum phosphorus concentrations with the goal of controlling serum phosphorus concentrations within the target range of 3.5–5.5 mg/dL.23 Increase or decrease dosage in increments of 1 tablet (800 mg) per meal at 2-week intervals as needed.23

Average dosage of sevelamer carbonate in one study was 6 g daily; maximum dosage studied was 14 g daily.23

Sevelamer Hydrochloride

Initial dosage in patients not currently receiving a phosphate binder (e.g., calcium acetate) depends on serum phosphorus concentrations.1

Initial Sevelamer Hydrochloride Dosage in Patients not Currently Receiving a Phosphate Binder

Serum Phosphorus Concentration (mg/dL)

Initial Sevelamer Hydrochloride Dosage

Number of Tablets per Dose

>5.5 and <7.5

800 mg 3 times daily1

Two 400-mg tablets or one 800-mg tablet1

≥7.5 and <9

1.2 or 1.6 g 3 times daily1

1.2-g dose: three 400-mg tablets1

1.6-g dose: two 800-mg tablets1

≥9

1.6 g 3 times daily 1

Four 400-mg tablets or two 800-mg tablets1

Initial dosage in patients being transferred to sevelamer from calcium acetate therapy depends on current calcium acetate dosage.1

Initial Sevelamer Hydrochloride Dosage in Patients Being Transferred from Calcium Acetate Therapy

Calcium Acetate Dosage

Initial Sevelamer Hydrochloride Dosage

Number of Tablets per Dose

667 mg 3 times daily

800 mg 3 times daily1

Two 400-mg tablets or one 800-mg tablet1

1.334 g 3 times daily

1.2 or 1.6 g 3 times daily1

1.2-g dose: three 400-mg tablets1

1.6-g dose: two 800-mg tablets1

2.001 g 3 times daily

2 or 2.4 g 3 times daily1

2-g dose: five 400-mg tablets1

2.4-g dose: three 800-mg tablets1

Adjust dosage of sevelamer hydrochloride for all patients according to serum phosphorus concentrations with the goal of reducing concentrations to ≤5.5 mg/dL.1 Increase or decrease dosage in increments of 1 tablet (400 or 800 mg) per meal at 2-week intervals as needed.1 7 22

Dosage Titration of Sevelamer Hydrochloride for All CKD Patients Undergoing Dialysis

Serum Phosphorus Concentration (mg/dL)

Dosage Adjustment

<3.5

Decrease dosage by 1 tablet (400 or 800 mg) per meal 1 22

3.5–5.5

Maintain current dosage1

> 5.5

Increase dosage by 1 tablet (400 or 800 mg) per meal 1 22

Average dosage of sevelamer hydrochloride in one study was 2.4 g per meal (7.2 g daily); maximum average dosage studied was 13 g daily.1

Special Populations

Geriatric Patients

Select dosage cautiously, usually initiating therapy at the low end of the dosage range.1 23

Cautions for Sevelamer

Contraindications

  • Hypophosphatemia.1 23

  • Bowel obstruction.1 23

Warnings/Precautions

General Precautions

GI Disease or Surgery

Use with caution in patients with swallowing or severe GI motility disorders (including severe constipation), dysphagia, or major GI tract surgery.1 23 Provide appropriate treatment to patients who develop constipation or experience worsening of existing constipation to avoid the development of severe complications (e.g., fecal impaction, ileus, intestinal obstruction, intestinal perforation).1 23

Monitor patients on peritoneal dialysis for proper use of aseptic technique and for signs and symptoms of peritonitis.1 23

Effects on Vitamins

Sevelamer hydrochloride has decreased plasma concentrations of vitamins D, E, and K and folic acid in animals when given at doses 6–10 times the recommended human dosage.1 No evidence of decreased vitamin concentrations in some short-term studies of patients receiving sevelamer hydrochloride;1 2 5 23 however, a decrease in serum 25-hydroxy vitamin D3 concentrations from 39 to 34 mcg/mL (normal range: 10–55 mcg/mL) was reported in one 1-year study.1 Most patients (75%) in clinical studies of sevelamer hydrochloride have received vitamin supplements.1 23 Monitor for reduced serum concentrations of vitamin D, E, K (clotting factors) and folic acid.1

Adequate Patient Monitoring

Monitor serum chloride and bicarbonate concentrations.1 22 23

Specific Populations

Pregnancy

Category C.1 23

Requirements for vitamins and other nutrients are increased during pregnancy; the effect of sevelamer on vitamin and other nutrient absorption has not been studied in pregnant women.1 23

Lactation

Caution is advised if used in nursing women.22

Pediatric Use

Safety and efficacy not established in children <18 years of age.1 2 3 4 22 23

Geriatric Use

Insufficient experience in patients ≥65 years of age to determine whether geriatric patients respond differently than younger adults; select dosage with caution.1 23 (See Geriatric Patients under Dosage and Administration.)

Common Adverse Effects

Abdominal pain,1 23 constipation,1 23 diarrhea,1 2 3 4 23 dyspepsia,1 3 4 5 23 flatulence,1 23 nausea,1 2 3 4 23 peritonitis (in patients on peritoneal dialysis),1 23 vomiting.1 2 3 23

Interactions for Sevelamer

Effects on GI Absorption of Drugs

Possible decreased bioavailability of orally administered drugs given concomitantly; when reduced bioavailability would have a clinically important effect on the drug's safety or efficacy, administer the drug ≥1 hour before or 3 hours after sevelamer administration or consider monitoring blood concentrations.1 23

Specific Drugs

No drug interaction studies have been performed with sevelamer carbonate.23 Drug interactions studies have been performed with sevelamer hydrochloride in humans.23

Drug

Interaction

Comments

Antiarrhythmic agents

Possible decreased antiarrhythmic bioavailability with concomitant oral administration1 23

Use concomitantly with caution; administer antiarrhythmics orally ≥1 hour before or 3 hours after sevelamer, or consider monitoring antiarrhythmic concentrations1 23

Anticonvulsants

Possible decreased anticonvulsant bioavailability with concomitant oral administration1 23

Use concomitantly with caution; administer anticonvulsants orally ≥1 hour before or 3 hours after sevelamer, or consider monitoring anticonvulsant concentrations1 23

Ciprofloxacin

50% decrease in ciprofloxacin bioavailability reported with concomitant oral administration1 23

Use concomitantly with caution; administer ciprofloxacin orally ≥1 hour before or 3 hours after sevelamer1 23

Digoxin

Pharmacokinetic interaction unlikely1 19 20 21 23

Enalapril

Pharmacokinetic interaction unlikely1 19 20 21 23

Iron preparations (ferrous sulfate)

Pharmacokinetic interaction unlikely1 19 20 21 23

Levothyroxine

Possible increase in TSH concentrations1 23

Monitor TSH concentrations more closely1 23

Metoprolol

Pharmacokinetic interaction unlikely1 19 20 21 23

Warfarin

Pharmacokinetic interaction unlikely1 19 20 21 23

Sevelamer Pharmacokinetics

Absorption

Not systemically absorbed following oral administration in healthy individuals;1 3 4 5 6 7 8 23 no absorption studies to date in patients with renal disease.1 23

Elimination

Elimination Route

Excreted in the feces as unabsorbed drug bound to phosphate ions2 3 4 5 8 and to bile acids.2 22

Stability

Storage

Oral

Tablets

25°C (may be exposed to 15–30°C).1 23 Protect from moisture.1 23

Actions

  • Following oral administration, binds phosphate ions through ionic and hydrogen bonding.1 2 3 4 5 23

  • Reduced phosphate absorption decreases serum and urinary phosphorus concentrations1 8 22 23 and increases fecal excretion of phosphorus.8

  • No substantial changes in serum calcium concentrations reported.2 3 4 5 6

  • Binds bile acids in the intestine,1 2 23 forming a nonabsorbable complex.22

  • May interfere with normal fat absorption, possibly reducing absorption of fat-soluble vitamins (e.g., vitamin A, D, K).1 23

  • Decreases serum total and LDL-cholesterol concentrations;1 2 3 4 5 6 7 8 23 does not appear to alter serum HDL-cholesterol1 5 23 or triglyceride1 3 6 23 concentrations.

  • Does not alter serum chloride,3 bicarbonate,3 or albumin concentrations.1 23

  • Does not contain aluminum or other metals; does not produce aluminum toxicity.4 5

Advice to Patients

  • Importance of adherence to instructions about diet.1 10 23

  • Importance of taking sevelamer with meals.1 23

  • Importance of advising patients to take certain other drugs (e.g., antiarrhythmic agents, anticonvulsants, ciprofloxacin) ≥1 hour before or 3 hours after taking sevelamer.1 23

  • Importance of advising patients of risk of severe complications from untreated constipation; importance of patients promptly reporting new onset or worsening of existing constipation to clinician.1 23

  • Importance of women informing their clinician if they are or plan to become pregnant or plan to breast-feed.1 23

  • Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs.1 23

  • Importance of informing patients of other important precautionary information. (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Sevelamer Carbonate

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Tablets, film-coated

800 mg

Renvela

Genzyme

Sevelamer Hydrochloride

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Tablets, film-coated

400 mg

Renagel

Genzyme

800 mg

Renagel

Genzyme

Comparative Pricing

This pricing information is subject to change at the sole discretion of DS Pharmacy. This pricing information was updated 02/2014. Actual costs to patients will vary depending on the use of specific retail or mail-order locations and health insurance copays.

Renagel 400MG Tablets (GENZYME): 180/$308.88 or 540/$892.09

Renagel 800MG Tablets (GENZYME): 30/$101.99 or 90/$295.97

Renvela 800MG Tablets (GENZYME): 30/$83.99 or 90/$242.97

AHFS DI Essentials. © Copyright, 2004-2014, Selected Revisions January 1, 2009. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

References

1. Genzyme. Renagel (sevelamer hydrochloride) tablets prescribing information. Cambridge, MA; 2007 Nov.

2. Bleyer AJ, Burke SK, Dillon M et al. A comparison of the calcium-free phosphate binder sevelamer hydrochloride with calcium acetate in the treatment of hyperphosphatemia in hemodialysis patients. Am J Kidney Dis. 1999; 33:694-701. [IDIS 426185] [PubMed 10196011]

3. Chertow GM, Dillon M, Burke SK et al. 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. [IDIS 424158] [PubMed 9988142]

4. Chertow GM, Burke SK, Lazarus JM et al. Poly[allylamine hydrochloride] (RenaGel): a noncalcemic phosphate binder for the treatment of hyperphosphatemia in chronic renal failure. Am J Kidney Dis. 1997; 29:66-71. [IDIS 378868] [PubMed 9002531]

5. Wilkes BM, Reiner D, Kern M et al. Simultaneous lowering of serum phosphate and LDL-cholesterol by sevelamer hydrochloride (RenaGel) in dialysis patients. Clin Nephrol. 1998; 50:381-6. [IDIS 420525] [PubMed 9877112]

6. Slatopolsky EA, Burke SK, Dillon MA and the RenaGel Study Group. RenaGel, a nonadsorbed calcium- and aluminum-free phosphate binder, lowers serum phosphorus and parathyroid hormone. Kidney Int. 1999; 55:299-307. [PubMed 9893140]

7. Goldberg DI, Dillon MA, Slatopolsky EA et al. Effect of RenaGel, a non-absorbed, calcium- and aluminum-free phosphate binder, on serum phosphorus, calcium, and intact parathyroid hormone in end-stage renal disease patients. Nephrol Dial Transplant. 1998; 13:2303-10. [PubMed 9761513]

8. Burke SK, Slatopolsky EA, Goldberg DI. RenaGel, a novel calcium- and aluminum-free phosphate binder, inhibits phosphate absorption in normal volunteers. Nephrol Dial Transplant. 1997; 12:1640-4. [PubMed 9269642]

9. Sakhaee, K Gonzalez GB. Update on Renal Osteodystrophy: Pathogenesis and clinical management. Am J Med Sci. 1999; 317:251-60. [IDIS 427313] [PubMed 10210362]

10. Genzyme. Renagel (sevelamer hydrochloride hydrochloride) information for dialysis patients. Cambridge, MA. Undated.

11. National Institutes of Health Consensus Development Conference Panel. Morbidity and mortolity of renal dialysis: an NIH consensus conference statement. Ann Intern Med. 1994; 121:62-70. [PubMed 8198352]

12. Braintree Laboratories. PhosLo (calcium acetate) tablets prescribing information (dated May 1992). In: Physicians’ desk reference. 52nd ed. Montvale, NJ; 1998:733-4.

13. Tan AU Jr, Levine BS, Mazess RB et al. Effective suppression of parathyroid hormone by 1 alpha-hydroxy-vitamin D2a in hemodialysis patients with moderate to severe secondary hyperparathyroidism. Kidney Int. 1997; 51:317-23. [PubMed 8995749]

14. Bone Care International. Hectorol (doxercalciferol) capsules prescribing information. Madison, WI; 1999 Jun 9.

15. Chertow GM, Burke SK, Dillon MA et al. Long-term effects of sevelamer hydrochloride on the calcium x phosphate product and lipid profile of haemodialysis patients. Nephrol Dial Transplant. 1999; 14:2907-14. [PubMed 10570096]

16. Chertow GM, Dillon MA, Amin N et al. Sevelamer is more effective at controlling disorders of mineral metabolism than calcium-based phosphate binders in hemodialysis patients. J Am Soc Nephrol. 2001; 12:195-6A.

17. Raggi P, Burke SK, Dillon MA et al. Sevelamer attenuates the progression of coronary and aortic calcification compared with calcium-based phosphate binders. J Am Soc Nephrol. 2001; 12:239A.

18. Burke S, Dillon MA, Goldberg DI. Control of P1 with Renagel, a calcium and aluminum free phosphate binder, combined with vitamin D stabilizes iPTH in ESRD independent of Ca++. Nephrology. 1997; (Suppl 1):S183.

19. Burke S, Amin N, Incerti C et al. Sevelamer hydrochloride (Renagel), a nonabsorbed phosphate-binding polymer, does not interfere with digoxin or warfarin pharmacokinetics. J Clin Pharmacol. 2001; 41:193-8. [IDIS 459592] [PubMed 11210401]

20. Burke SK, Amin NS, Incerti C et al. Sevelamer hydrochloride (Renagel), a phosphate-binding polymer, does not alter the pharmacokinetics of two commonly used antihypertensives in healthy volunteers. J Clin Pharmacol. 2001; 41:199-205. [IDIS 459593] [PubMed 11210402]

21. Pruchnicki MC, Coyle JD, Bay WH. Effect of phosphate binders on supplemental iron absorption in healthy subjects. J Am Soc Nephrol. 2001; 12:407.

22. Genzyme, Boston, MA: Personal communication..

23. Genzyme. Renvela (sevelamer carbonate) tablets prescribing information. Cambridge, MA; 2007 Nov.

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