Identification

Name
Sevelamer
Accession Number
DB00658  (APRD01226)
Type
Small Molecule
Groups
Approved
Description

Sevelamer is a phosphate binding drug used to prevent hyperphosphataemia in patients with chronic renal failure. When taken with meals, sevelamer binds to dietary phosphate and prevents its absorption. It is marketed by Genzyme under the trade name Renagel.

Structure
Thumb
Synonyms
  • Sevelamer
  • Sévélamer
  • Sevelamero
  • Sevelamerum
External IDs
GT 16026 A / GT 335-012
Product Ingredients
IngredientUNIICASInChI Key
Sevelamer carbonate9YCX42I8IU845273-93-0Not applicable
Sevelamer hydrochlorideGLS2PGI8QG152751-57-0Not applicable
Product Images
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
RenagelTablet800 mg/1OralAphena Pharma Solutions Tennessee, Inc.2008-06-06Not applicableUs
RenagelTablet800 mg/1OralAtlantic Biologicals Corps.2008-06-06Not applicableUs
RenagelTablet400 mgOralSanofi Genzyme, a Division of Sanofi Aventis Canada Inc2001-11-212005-08-08Canada
RenagelTablet400 mg/1OralCardinal Health2008-06-06Not applicableUs
RenagelTablet800 mgOralSanofi Aventis2001-11-21Not applicableCanada
RenagelTablet800 mg/1OralGenzyme Corporation2008-06-06Not applicableUs
RenagelCapsule403 mgOralSanofi Genzyme, a Division of Sanofi Aventis Canada Inc2000-08-142004-07-23Canada
RenagelTablet800 mg/1OralRemedy Repack2013-05-152016-04-05Us
RenagelTablet400 mg/1OralGenzyme Corporation2008-06-06Not applicableUs
RenagelTablet800 mg/1OralDoh Central Pharmacy2009-07-01Not applicableUs
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Accel-sevelamerTablet800 mgOralAccel Pharma Inc2017-11-08Not applicableCanada
Sevelamer CarbonatePowder, for suspension800 mg/1OralAurobindo Pharma2017-06-13Not applicableUs
Sevelamer CarbonateTablet, film coated800 mg/1OralRemedy Repack2017-10-09Not applicableUs
Sevelamer CarbonateTablet, film coated800 mg/1OralAurobindo Pharma2017-07-17Not applicableUs
Sevelamer carbonateTablet, film coated800 mg/1OralRemedy Repack2017-12-14Not applicableUs
Sevelamer CarbonateTablet, film coated800 mg/1OralGolden State Medical Supply2017-10-20Not applicableUs
Sevelamer CarbonateTablet, film coated800 mg/1OralDr Reddy's Laboratories2017-09-29Not applicableUs
Sevelamer CarbonatePowder, for suspension2.4 g/1OralWinthrop U.S.2018-01-01Not applicableUs
Sevelamer CarbonateTablet, film coated800 mg/1OralKaiser Foundations Hospitals2017-12-18Not applicableUs
Sevelamer CarbonatePowder, for suspension2400 mg/1OralAurobindo Pharma2017-06-13Not applicableUs
Unapproved/Other Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Sevelamer carbonateTablet, film coated800 mg/1OralInva Gen Pharmaceuticals Inc.2017-10-26Not applicableUs
Sevelamer carbonateTablet, film coated800 mg/1OralExelan Pharmaceuticals, Inc.2017-11-08Not applicableUs
Sevelamer CarbonateTablet, film coated800 mg/1OralAmneal Pharmaceuticals2017-11-28Not applicableUs
Sevelamer carbonateTablet, film coated800 mg/1OralCipla Limited2017-10-26Not applicableUs
Sevelamer CarbonateTablet, film coated800 mg/1OralAv Kare, Inc.2017-11-10Not applicableUs
International/Other Brands
Phosblock (Kyowa Hakko Kirin)
Categories
UNII
941N5DUU5C
CAS number
52757-95-6
Weight
Average: 149.619
Monoisotopic: 149.060741718
Chemical Formula
C6H12ClNO
InChI Key
ZNSIZMQNQCNRBW-UHFFFAOYSA-N
InChI
InChI=1S/C3H5ClO.C3H7N/c4-1-3-2-5-3;1-2-3-4/h3H,1-2H2;2H,1,3-4H2
IUPAC Name
2-(chloromethyl)oxirane; prop-2-en-1-amine
SMILES
NCC=C.ClCC1CO1

Pharmacology

Indication

For the control of serum phosphorus in patients with Chronic Kidney Disease (CKD) on hemodialysis.

Structured Indications
Pharmacodynamics

Patients with end-stage renal disease (ESRD) retain phosphorus and can develop hyperphosphatemia. High serum phosphorus can precipitate serum calcium resulting in ectopic calcification. When the product of serum calcium and phosphorus concentrations (Ca x P) exceeds 55 mg2/dL2, there is an increased risk that ectopic calcification will occur. Hyperphosphatemia plays a role in the development of secondary hyperparathyroidism in renal insufficiency. An increase in parathyroid hormone (PTH) levels is characteristic of patients with chronic renal failure. Increased levels of PTH can lead to osteitis fibrosa, a bone disease. A decrease in serum phosphorus may decrease serum PTH levels. Treatment of hyperphosphatemia includes reduction in dietary intake of phosphate, inhibition of intestinal phosphate absorption with phosphate binders, and removal of phosphate with dialysis. Sevelamer taken with meals has been shown to decrease serum phosphorus concentrations in patients with ESRD who are on hemodialysis. In vitro studies have shown that the capsule and tablet formulations bind phosphate to a similar extent. Sevelamer treatment also results in a lowering of low-density lipoprotein (LDL) and total serum cholesterol levels.

Mechanism of action

Sevelamer prevents hyperphosphatemia by binding to dietary phosphate in the gut, preventing its absorption and thus decreasing serum parathyroid hormone levels.

TargetActionsOrganism
APhosphate
binder
Human
Absorption

Not absorbed following oral administration, however no absorption studies have been performed in patients with renal disease.

Volume of distribution
Not Available
Protein binding
Not Available
Metabolism
Not Available
Route of elimination
Not Available
Half life
Not Available
Clearance
Not Available
Toxicity

Sevelamer has been given to normal healthy volunteers in doses of up to 14 grams per day for eight days with no adverse effects. Sevelamer has been given in average doses up to 13 grams per day to hemodialysis patients. There are no reported overdosages of sevelamer in patients. Since sevelamer is not absorbed, the risk of systemic toxicity is low.

Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteractionDrug group
CalcitriolThe serum concentration of Calcitriol can be decreased when it is combined with Sevelamer.Approved, Nutraceutical
Cholic AcidSevelamer can cause a decrease in the absorption of Cholic Acid resulting in a reduced serum concentration and potentially a decrease in efficacy.Approved
CinoxacinSevelamer can cause a decrease in the absorption of Cinoxacin resulting in a reduced serum concentration and potentially a decrease in efficacy.Approved, Investigational, Withdrawn
CyclosporineThe serum concentration of Cyclosporine can be decreased when it is combined with Sevelamer.Approved, Investigational, Vet Approved
EnoxacinSevelamer can cause a decrease in the absorption of Enoxacin resulting in a reduced serum concentration and potentially a decrease in efficacy.Approved, Investigational
FleroxacinSevelamer can cause a decrease in the absorption of Fleroxacin resulting in a reduced serum concentration and potentially a decrease in efficacy.Approved
FlumequineSevelamer can cause a decrease in the absorption of Flumequine resulting in a reduced serum concentration and potentially a decrease in efficacy.Withdrawn
GarenoxacinSevelamer can cause a decrease in the absorption of Garenoxacin resulting in a reduced serum concentration and potentially a decrease in efficacy.Investigational
GatifloxacinSevelamer can cause a decrease in the absorption of Gatifloxacin resulting in a reduced serum concentration and potentially a decrease in efficacy.Approved, Investigational
GemifloxacinSevelamer can cause a decrease in the absorption of Gemifloxacin resulting in a reduced serum concentration and potentially a decrease in efficacy.Approved, Investigational
GrepafloxacinSevelamer can cause a decrease in the absorption of Grepafloxacin resulting in a reduced serum concentration and potentially a decrease in efficacy.Investigational, Withdrawn
LevofloxacinSevelamer can cause a decrease in the absorption of Levofloxacin resulting in a reduced serum concentration and potentially a decrease in efficacy.Approved, Investigational
LevothyroxineThe serum concentration of Levothyroxine can be decreased when it is combined with Sevelamer.Approved
Mycophenolic acidThe serum concentration of Mycophenolic acid can be decreased when it is combined with Sevelamer.Approved
Nalidixic AcidSevelamer can cause a decrease in the absorption of Nalidixic Acid resulting in a reduced serum concentration and potentially a decrease in efficacy.Approved, Investigational
NemonoxacinSevelamer can cause a decrease in the absorption of Nemonoxacin resulting in a reduced serum concentration and potentially a decrease in efficacy.Investigational
NorfloxacinSevelamer can cause a decrease in the absorption of Norfloxacin resulting in a reduced serum concentration and potentially a decrease in efficacy.Approved
Oxolinic acidSevelamer can cause a decrease in the absorption of Oxolinic acid resulting in a reduced serum concentration and potentially a decrease in efficacy.Experimental
PazufloxacinSevelamer can cause a decrease in the absorption of Pazufloxacin resulting in a reduced serum concentration and potentially a decrease in efficacy.Investigational
PefloxacinSevelamer can cause a decrease in the absorption of Pefloxacin resulting in a reduced serum concentration and potentially a decrease in efficacy.Approved
Pipemidic acidSevelamer can cause a decrease in the absorption of Pipemidic acid resulting in a reduced serum concentration and potentially a decrease in efficacy.Experimental
Piromidic acidSevelamer can cause a decrease in the absorption of Piromidic acid resulting in a reduced serum concentration and potentially a decrease in efficacy.Experimental
PrulifloxacinSevelamer can cause a decrease in the absorption of Prulifloxacin resulting in a reduced serum concentration and potentially a decrease in efficacy.Investigational
RosoxacinSevelamer can cause a decrease in the absorption of Rosoxacin resulting in a reduced serum concentration and potentially a decrease in efficacy.Approved, Investigational
RufloxacinSevelamer can cause a decrease in the absorption of Rufloxacin resulting in a reduced serum concentration and potentially a decrease in efficacy.Experimental
SitafloxacinSevelamer can cause a decrease in the absorption of Sitafloxacin resulting in a reduced serum concentration and potentially a decrease in efficacy.Experimental, Investigational
SparfloxacinSevelamer can cause a decrease in the absorption of Sparfloxacin resulting in a reduced serum concentration and potentially a decrease in efficacy.Approved, Investigational
TacrolimusThe serum concentration of Tacrolimus can be decreased when it is combined with Sevelamer.Approved, Investigational
Technetium Tc-99m oxidronateSevelamer can cause a decrease in the absorption of Technetium Tc-99m oxidronate resulting in a reduced serum concentration and potentially a decrease in efficacy.Approved
TemafloxacinSevelamer can cause a decrease in the absorption of Temafloxacin resulting in a reduced serum concentration and potentially a decrease in efficacy.Withdrawn
TrovafloxacinSevelamer can cause a decrease in the absorption of Trovafloxacin resulting in a reduced serum concentration and potentially a decrease in efficacy.Approved, Investigational, Withdrawn
Food Interactions
Not Available

References

Synthesis Reference

Deepak Anant Hedge, Varsha Shashank Choudhary, Venkatasubramanian Radhakrjshnan Tarur, Dhananjay Govind Sathe, Harish Kashinath Mondkar, Samadhan Daulat Patil, Sasikumar Mohan Thoovara, Yogesh Sharad Bhide, "Process for the Preparation of Sevelamer Hydrochloride and Formulation Thereof." U.S. Patent US20090280178, issued November 12, 2009.

US20090280178
General References
Not Available
External Links
Human Metabolome Database
HMDB14796
KEGG Drug
D01983
PubChem Compound
3085017
PubChem Substance
46505951
ChemSpider
2341997
ChEMBL
CHEMBL1201798
PharmGKB
PA164781197
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Sevelamer
ATC Codes
V03AE02 — Sevelamer
AHFS Codes
  • 40:18.19 — Phosphate-removing Agents
FDA label
Download (36.4 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedNot AvailableHealthy Volunteers1
1CompletedBasic ScienceKidney Failure,Chronic1
1CompletedTreatmentDiabetic Nephropathies1
1CompletedTreatmentHealthy Volunteers2
1RecruitingTreatmentHyperphosphataemia2
2CompletedPreventionCardiovascular Disease (CVD) / Kidney Failure,Chronic1
2CompletedTreatmentChronic Kidney Disease (CKD)4
2CompletedTreatmentChronic Kidney Disease (CKD) / Hyperphosphataemia2
2CompletedTreatmentChronic Kidney Failure1
2CompletedTreatmentDiabetic Nephropathies1
2CompletedTreatmentHyperparathyroidism, Secondary / Renal Osteodystrophy1
2CompletedTreatmentHyperphosphatemia Patients With Chronic Kidney Disease on 3x/Week Replacement Therapy1
2CompletedTreatmentInfection, Human Immunodeficiency Virus I1
2CompletedTreatmentKidney Failure,Chronic1
2CompletedTreatmentRenal Failure1
2RecruitingTreatmentInsulin Sensitivity2
3CompletedPreventionHyperphosphataemia / Renal Failure1
3CompletedTreatmentChronic Kidney Disease (CKD) / Chronic Kidney Disease on Hemodialysis1
3CompletedTreatmentChronic Kidney Disease (CKD) / Dialysis therapy / Hyperphosphataemia1
3CompletedTreatmentChronic Kidney Disease (CKD) / Hyperparathyroidism1
3CompletedTreatmentChronic Kidney Disease (CKD) / Hyperphosphataemia2
3CompletedTreatmentChronic Kidney Disease (CKD) / Impaired Renal Function / Renal Dialysis1
3CompletedTreatmentChronic Kidney Disease (CKD) / Peritoneal dialysis therapy1
3CompletedTreatmentChronic Kidney Disease Requiring Chronic Dialysis2
3CompletedTreatmentChronic Kidney Disease, Stage 51
3CompletedTreatmentChronic Renal Failure (CRF)1
3CompletedTreatmentChronic Renal Insufficiency / End-Stage Renal Disease (ESRD) / Kidney Diseases1
3CompletedTreatmentHemodialysis-dependent patients / Hyperphosphataemia1
3CompletedTreatmentRenal Failure Chronic1
3Not Yet RecruitingTreatmentHyperphosphataemia1
3RecruitingTreatmentHyperphosphataemia1
3TerminatedTreatmentChronic Kidney Disease (CKD) / Hyperphosphataemia1
3TerminatedTreatmentChronic Kidney Failure1
3TerminatedTreatmentChronic Renal Failure (CRF) / Hemodialysis-dependent patients1
3Unknown StatusTreatmentChronic Kidney Disease Stages 3-51
4CompletedPreventionWe Investigated the Relationship Between Plasma FGF23 Levels and Endothelial Dysfunction in a Sizable Series of Incident Stage 3-4 CKD Patients1
4CompletedTreatmentArteriosclerosis / Calcinosis / Hyperparathyroidism, Secondary1
4CompletedTreatmentCardiovascular Events / Hemodialysis-dependent patients / Hyperphosphataemia1
4CompletedTreatmentChronic Kidney Disease (CKD)2
4TerminatedPreventionChronic Kidney Disease (CKD)1
Not AvailableActive Not RecruitingNot AvailableHyperphosphataemia / Hypophosphatemia, Familial / Hypovitaminosis D1
Not AvailableCompletedNot AvailableChronic Kidney Disease (CKD) / Hyperphosphataemia1
Not AvailableCompletedBasic ScienceType 2 Diabetes Mellitus1
Not AvailableCompletedPreventionChronic Kidney Disease (CKD)1
Not AvailableCompletedPreventionHyperparathyroidism, Secondary1
Not AvailableCompletedPreventionRenal Failure1
Not AvailableCompletedTreatmentCardiovascular Mortality1
Not AvailableCompletedTreatmentEnd Stage Renal Disease (ESRD) / Hemodialysis-dependent patients / Intimal Media Thickness1
Not AvailableCompletedTreatmentEndstage Renal Disease1
Not AvailableRecruitingTreatmentAtherosclerosis / Cardiovascular Disease (CVD) / Dialysis therapy / Hyperphosphataemia / Inflammatory Reaction1
Not AvailableUnknown StatusNot AvailableChronic Kidney Disease (CKD)1
Not AvailableWithdrawnTreatmentEnd-Stage Renal Disease (ESRD) / Hyperphosphataemia / Insulin Resistance / Kidney Failure,Chronic1
Not AvailableWithdrawnTreatmentHaemodialyzed Patients / Hyperphosphataemia1

Pharmacoeconomics

Manufacturers
  • Genzyme corp
  • Genzyme Corporation
Packagers
Dosage forms
FormRouteStrength
CapsuleOral403 mg
TabletOral400 mg
TabletOral400 mg/1
TabletOral800 mg
TabletOral800 mg/1
Powder, for suspensionOral1.6 g
Powder, for suspensionOral2.4 g
Powder, for suspensionOral2400 mg/1
Powder, for suspensionOral800 mg/1
Tablet, film coatedOral800 mg
Powder, for suspensionOral.8 g/1
Powder, for suspensionOral2.4 g/1
Tablet, film coatedOral800 mg/1
Prices
Unit descriptionCostUnit
Renagel 800 mg tablet2.41USD tablet
Renvela 800 mg tablet2.17USD tablet
Renagel 400 mg tablet1.66USD tablet
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US5496545No1993-08-112013-08-11Us
CA2310960No2003-05-272014-08-10Canada
CA2169356No2000-07-042014-08-10Canada
US7985418No2005-10-272025-10-27Us
US6733780No2000-10-182020-10-18Us
US9095509No2010-12-062030-12-06Us

Properties

State
Solid
Experimental Properties
PropertyValueSource
water solubilityInsolubleNot Available
logP0.559Not Available
Predicted Properties
PropertyValueSource
logP0.68ChemAxon
pKa (Strongest Basic)-4.2ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count1ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area12.53 Å2ChemAxon
Rotatable Bond Count2ChemAxon
Refractivity20.06 m3·mol-1ChemAxon
Polarizability8.38 Å3ChemAxon
Number of Rings1ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterNoChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9908
Blood Brain Barrier+0.9723
Caco-2 permeable+0.5783
P-glycoprotein substrateNon-substrate0.7654
P-glycoprotein inhibitor INon-inhibitor0.921
P-glycoprotein inhibitor IINon-inhibitor0.9399
Renal organic cation transporterNon-inhibitor0.7531
CYP450 2C9 substrateNon-substrate0.8823
CYP450 2D6 substrateNon-substrate0.8029
CYP450 3A4 substrateNon-substrate0.7617
CYP450 1A2 substrateNon-inhibitor0.5084
CYP450 2C9 inhibitorNon-inhibitor0.7543
CYP450 2D6 inhibitorNon-inhibitor0.839
CYP450 2C19 inhibitorNon-inhibitor0.5583
CYP450 3A4 inhibitorNon-inhibitor0.8711
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.6708
Ames testAMES toxic0.9498
CarcinogenicityCarcinogens 0.5468
BiodegradationNot ready biodegradable0.889
Rat acute toxicity2.9282 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.7403
hERG inhibition (predictor II)Non-inhibitor0.8883
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Taxonomy

Description
This compound belongs to the class of organic compounds known as epoxides. These are compounds containing a cyclic ether with three ring atoms(one oxygen and two carbon atoms).
Kingdom
Organic compounds
Super Class
Organoheterocyclic compounds
Class
Epoxides
Sub Class
Not Available
Direct Parent
Epoxides
Alternative Parents
Oxacyclic compounds / Dialkyl ethers / Organopnictogen compounds / Organochlorides / Monoalkylamines / Hydrocarbon derivatives / Alkyl chlorides
Substituents
Dialkyl ether / Oxirane / Ether / Oxacycle / Amine / Primary amine / Organooxygen compound / Organonitrogen compound / Organochloride / Organohalogen compound
Molecular Framework
Not Available
External Descriptors
Not Available

Targets

Kind
Small molecule
Organism
Human
Pharmacological action
Yes
Actions
Binder
References
  1. Cannata-Andia JB, Rodriguez-Garcia M, Roman-Garcia P, Tunon-le Poultel D, Lopez-Hernandez F, Rodriguez-Puyol D: New therapies: calcimimetics, phosphate binders and vitamin D receptor activators. Pediatr Nephrol. 2010 Apr;25(4):609-16. doi: 10.1007/s00467-010-1462-9. Epub 2010 Feb 12. [PubMed:20151157]
  2. Novak JE, Szczech LA: Phosphate binders in chronic kidney disease and end-stage renal disease: a patient-centered approach. Semin Dial. 2009 Jan-Feb;22(1):56-63. doi: 10.1111/j.1525-139X.2008.00514.x. Epub 2008 Oct 16. [PubMed:19000107]
  3. Salusky IB: A new era in phosphate binder therapy: what are the options? Kidney Int Suppl. 2006 Dec;(105):S10-5. [PubMed:17136110]
  4. Schucker JJ, Ward KE: Hyperphosphatemia and phosphate binders. Am J Health Syst Pharm. 2005 Nov 15;62(22):2355-61. [PubMed:16278327]

Drug created on June 13, 2005 07:24 / Updated on January 14, 2018 10:04