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Identification
NameSevelamer
Accession NumberDB00658  (APRD01226)
TypeSmall Molecule
GroupsApproved
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 Identifiers
  • GT 16026 A
  • GT 335-012
Approved Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Renageltablet800 mg/1oralGenzyme Corporation2008-06-06Not applicableUs
Renagelcapsule403 mgoralGenzyme Canada A Division Of Sanofi Aventis Canada Inc2000-08-142004-07-23Canada
Renageltablet800 mgoralSanofi Aventis Canada Inc2001-11-21Not applicableCanada
Renageltablet400 mg/1oralGenzyme Corporation2008-06-06Not applicableUs
Renageltablet800 mg/1oralCardinal Health2008-06-06Not applicableUs
Renageltablet800 mg/1oralAphena Pharma Solutions Tennessee, Llc2008-06-06Not applicableUs
Renageltablet400 mg/1oralCardinal Health2008-06-06Not applicableUs
Renageltablet800 mg/1oralREMEDYREPACK INC.2013-05-152016-04-05Us
Renageltablet800 mg/1oralAtlantic Biologicals Corps2008-06-06Not applicableUs
Renageltablet400 mgoralGenzyme Canada A Division Of Sanofi Aventis Canada Inc2001-11-212005-08-08Canada
Renvelatablet800 mgoralSanofi Aventis Canada Inc2010-11-25Not applicableCanada
Renvelatablet, film coated800 mg/1oralAvera Mc Kennan Hospital2015-03-01Not applicableUs
Renvelatablet, film coated800 mg/1oralCardinal Health2009-08-12Not applicableUs
Renvelatablet, film coated800 mg/1oralCarilion Materials Management2009-08-12Not applicableUs
Renvelapowder, for suspension800 mg/1oralGenzyme Corporation2009-08-12Not applicableUs
Renvelapowder, for suspension2400 mg/1oralGenzyme Corporation2009-08-12Not applicableUs
Renvelatablet, film coated800 mg/1oralGenzyme Corporation2009-08-12Not applicableUs
Renvelatablet, film coated800 mg/1oralKAISER FOUNDATION HOSPITALS2010-02-12Not applicableUs
Sevelamer Carbonatetablet, film coated800 mg/1oralGlobal Pharmaceuticals Division of IMPAX Laboratories, Inc.2014-04-16Not applicableUs
Approved Generic Prescription ProductsNot Available
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International Brands
NameCompany
PhosblockKyowa Hakko Kirin
Brand mixturesNot Available
Salts
Name/CASStructureProperties
Sevelamer carbonate
ThumbNot applicableDBSALT001006
Sevelamer hydrochloride
152751-57-0
ThumbNot applicableDBSALT001005
Categories
UNII941N5DUU5C
CAS number52757-95-6
WeightAverage: 149.619
Monoisotopic: 149.060741718
Chemical FormulaC6H12ClNO
InChI KeyInChIKey=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
Taxonomy
DescriptionThis 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).
KingdomOrganic compounds
Super ClassOrganoheterocyclic compounds
ClassEpoxides
Sub ClassNot Available
Direct ParentEpoxides
Alternative Parents
Substituents
  • Oxacycle
  • Ether
  • Oxirane
  • Dialkyl ether
  • Hydrocarbon derivative
  • Primary amine
  • Organooxygen compound
  • Organonitrogen compound
  • Organochloride
  • Organohalogen compound
  • Primary aliphatic amine
  • Amine
  • Alkyl halide
  • Alkyl chloride
  • Aliphatic heteromonocyclic compound
  • Aliphatic acyclic compound
Molecular FrameworkNot Available
External DescriptorsNot Available
Pharmacology
IndicationFor the control of serum phosphorus in patients with Chronic Kidney Disease (CKD) on hemodialysis.
PharmacodynamicsPatients 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 actionSevelamer prevents hyperphosphatemia by binding to dietary phosphate in the gut, preventing its absorption and thus decreasing serum parathyroid hormone levels.
Related Articles
AbsorptionNot absorbed following oral administration, however no absorption studies have been performed in patients with renal disease.
Volume of distributionNot Available
Protein bindingNot Available
MetabolismNot Available
Route of eliminationNot Available
Half lifeNot Available
ClearanceNot Available
ToxicitySevelamer 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
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
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 )
Pharmacoeconomics
Manufacturers
  • Genzyme corp
  • Genzyme Corporation
Packagers
Dosage forms
FormRouteStrength
Capsuleoral403 mg
Tabletoral400 mg
Tabletoral400 mg/1
Tabletoral800 mg
Tabletoral800 mg/1
Powder, for suspensionoral2400 mg/1
Powder, for suspensionoral800 mg/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)
CA2169356 No2000-07-042014-08-10Canada
CA2310960 No2003-05-272014-08-10Canada
US5496545 No1993-08-112013-08-11Us
US6733780 No2000-10-182020-10-18Us
US7985418 No2005-10-272025-10-27Us
US9095509 No2010-12-062030-12-06Us
Properties
StateSolid
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 FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Not Available
SpectraNot 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 ReferencesNot Available
External Links
ATC CodesV03AE02
AHFS Codes
  • 92:00.00
PDB EntriesNot Available
FDA labelDownload (36.4 KB)
MSDSNot Available
Interactions
Drug Interactions
Drug
CalcitriolThe serum concentration of Calcitriol can be decreased when it is combined with Sevelamer.
Cholic AcidSevelamer can cause a decrease in the absorption of Cholic Acid resulting in a reduced serum concentration and potentially a decrease in efficacy.
CiprofloxacinSevelamer can cause a decrease in the absorption of Ciprofloxacin resulting in a reduced serum concentration and potentially a decrease in efficacy.
CyclosporineThe serum concentration of Cyclosporine can be decreased when it is combined with Sevelamer.
GemifloxacinSevelamer can cause a decrease in the absorption of Gemifloxacin resulting in a reduced serum concentration and potentially a decrease in efficacy.
LevofloxacinSevelamer can cause a decrease in the absorption of Levofloxacin resulting in a reduced serum concentration and potentially a decrease in efficacy.
LevothyroxineThe serum concentration of Levothyroxine can be decreased when it is combined with Sevelamer.
MoxifloxacinSevelamer can cause a decrease in the absorption of Moxifloxacin resulting in a reduced serum concentration and potentially a decrease in efficacy.
Mycophenolate mofetilThe serum concentration of Mycophenolate mofetil can be decreased when it is combined with Sevelamer.
Mycophenolic acidThe serum concentration of Mycophenolic acid can be decreased when it is combined with Sevelamer.
NorfloxacinSevelamer can cause a decrease in the absorption of Norfloxacin resulting in a reduced serum concentration and potentially a decrease in efficacy.
OfloxacinSevelamer can cause a decrease in the absorption of Ofloxacin resulting in a reduced serum concentration and potentially a decrease in efficacy.
SparfloxacinSevelamer can cause a decrease in the absorption of Sparfloxacin resulting in a reduced serum concentration and potentially a decrease in efficacy.
TacrolimusThe serum concentration of Tacrolimus can be decreased when it is combined with Sevelamer.
Food InteractionsNot 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 ]
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Drug created on June 13, 2005 07:24 / Updated on June 25, 2016 01:51