Identification

Name
Amifostine
Accession Number
DB01143  (APRD00021)
Type
Small Molecule
Groups
Approved, Investigational
Description

A phosphorothioate proposed as a radiation-protective agent. It causes splenic vasodilation and may block autonomic ganglia. [PubChem]

Structure
Thumb
Synonyms
  • Amifostina
  • Amifostinum
  • Aminopropylaminoethyl thiophosphate
External IDs
WR-2721 / YM-08310
Product Ingredients
IngredientUNIICASInChI Key
Amifostine trihydrateM487QF2F4V112901-68-5TXQPXJKRNHJWAX-UHFFFAOYSA-N
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
AmifostineInjection, powder, lyophilized, for solution500 mg/10mLIntravenousBedford Pharmaceuticals2008-04-02Not applicableUs
EthyolInjection, powder, lyophilized, for solution500 mg/10mLIntravenousCumberland Pharmaceuticals2016-08-01Not applicableUs
Ethyol - Pws IV 500mg/vialPowder, for solution500 mgIntravenousMedimmune Oncology, Inc.1996-12-312008-01-01Canada
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
AmifostineInjection, powder, lyophilized, for solution50 mg/mLIntravenousSun Pharma Global FZE2008-03-142017-02-03Us
AmifostineInjection, powder, lyophilized, for solution50 mg/mLIntravenousSun Pharmaceutical Industries Limited2008-03-14Not applicableUs
International/Other Brands
Ethyol
Categories
UNII
ILA426L95O
CAS number
20537-88-6
Weight
Average: 214.223
Monoisotopic: 214.054099558
Chemical Formula
C5H15N2O3PS
InChI Key
JKOQGQFVAUAYPM-UHFFFAOYSA-N
InChI
InChI=1S/C5H15N2O3PS/c6-2-1-3-7-4-5-12-11(8,9)10/h7H,1-6H2,(H2,8,9,10)
IUPAC Name
({2-[(3-aminopropyl)amino]ethyl}sulfanyl)phosphonic acid
SMILES
NCCCNCCSP(O)(O)=O

Pharmacology

Indication

For reduction in the cumulative renal toxicity in patients with ovarian cancer (using cisplatin) and moderate to severe xerostomia in patients undergoing post-operative radiation treatment for head and neck cancer.

Structured Indications
Pharmacodynamics

Amifostine is an organic thiophosphate cytoprotective agent indicated to reduce the cumulative renal toxicity associated with repeated administration of cisplatin in patients with advanced ovarian cancer or non-small cell lung cancer and also to reduce the incidence of moderate to severe xerostomia in patients undergoing post-operative radiation treatment for head and neck cancer. Amifostine is a prodrug that is dephosphorylated by alkaline phosphatase in tissues to a pharmacologically active free thiol metabolite, believed to be responsible for the reduction of the cumulative renal toxicity of cisplatin and for the reduction of the toxic effects of radiation on normal oral tissues. Healthy cells are preferentially protected because amifostine and metabolites are present in healthy cells at 100-fold greater concentrations than in tumour cells.

Mechanism of action

The thiol metabolite is responsible for most of the cytoprotective and radioprotective properties of amifostine. It is readily taken up by cells where it binds to and detoxifies reactive metabolites of platinum and alkylating agents as well as scavenges free radicals. Other possible effects include inhibition of apoptosis, alteration of gene expression and modification of enzyme activity.

TargetActionsOrganism
UEctonucleotide pyrophosphatase/phosphodiesterase family member 1
inducer
Human
AAlkaline phosphatase, placental-like
inducer
Human
Absorption
Not Available
Volume of distribution
Not Available
Protein binding
Not Available
Metabolism

Amifostine is rapidly dephosphorylated by alkaline phosphatase in tissues primarily to the active free thiol metabolite and, subsequently, to a less active disulfide metabolite.

Route of elimination

After a 10-second bolus dose of 150 mg/m2 of ETHYOL, renal excretion of the parent drug and its two metabolites was low during the hour following drug administration, averaging 0.69%, 2.64% and 2.22% of the administered dose for the parent, thiol and disulfide, respectively.

Half life

8 minutes

Clearance
Not Available
Toxicity

Rat LD50: 826 mg/kg

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

Interactions

Drug Interactions
DrugInteractionDrug group
AcebutololAcebutolol may increase the hypotensive activities of Amifostine.Approved
AldesleukinThe risk or severity of adverse effects can be increased when Amifostine is combined with Aldesleukin.Approved
AliskirenAliskiren may increase the hypotensive activities of Amifostine.Approved, Investigational
AlprenololAlprenolol may increase the hypotensive activities of Amifostine.Approved, Withdrawn
AmbrisentanAmbrisentan may increase the hypotensive activities of Amifostine.Approved, Investigational
AmilorideThe risk or severity of adverse effects can be increased when Amifostine is combined with Amiloride.Approved
AmiodaroneThe risk or severity of adverse effects can be increased when Amifostine is combined with Amiodarone.Approved, Investigational
AmlodipineAmlodipine may increase the hypotensive activities of Amifostine.Approved
AmobarbitalAmobarbital may increase the hypotensive activities of Amifostine.Approved, Illicit
Amphotericin BThe risk or severity of adverse effects can be increased when Amifostine is combined with Amphotericin B.Approved, Investigational
Amyl NitriteThe risk or severity of adverse effects can be increased when Amifostine is combined with Amyl Nitrite.Approved
ApomorphineThe risk or severity of adverse effects can be increased when Amifostine is combined with Apomorphine.Approved, Investigational
ApraclonidineThe risk or severity of adverse effects can be increased when Amifostine is combined with Apraclonidine.Approved
AripiprazoleAripiprazole may increase the hypotensive activities of Amifostine.Approved, Investigational
ArotinololThe risk or severity of adverse effects can be increased when Amifostine is combined with Arotinolol.Approved, Investigational
Arsenic trioxideThe risk or severity of adverse effects can be increased when Amifostine is combined with Arsenic trioxide.Approved, Investigational
AtenololAtenolol may increase the hypotensive activities of Amifostine.Approved
Azilsartan medoxomilThe risk or severity of adverse effects can be increased when Amifostine is combined with Azilsartan medoxomil.Approved
BarbexacloneBarbexaclone may increase the hypotensive activities of Amifostine.Experimental
BarbitalBarbital may increase the hypotensive activities of Amifostine.Illicit
BarnidipineThe risk or severity of adverse effects can be increased when Amifostine is combined with Barnidipine.Approved
BenazeprilBenazepril may increase the hypotensive activities of Amifostine.Approved, Investigational
BendroflumethiazideBendroflumethiazide may increase the hypotensive activities of Amifostine.Approved
BepridilBepridil may increase the hypotensive activities of Amifostine.Approved, Withdrawn
BetaxololBetaxolol may increase the hypotensive activities of Amifostine.Approved
BethanidineBethanidine may increase the hypotensive activities of Amifostine.Approved
BietaserpineBietaserpine may increase the hypotensive activities of Amifostine.Experimental
BimatoprostBimatoprost may increase the hypotensive activities of Amifostine.Approved, Investigational
BisoprololBisoprolol may increase the hypotensive activities of Amifostine.Approved
BortezomibThe risk or severity of adverse effects can be increased when Amifostine is combined with Bortezomib.Approved, Investigational
BosentanBosentan may increase the hypotensive activities of Amifostine.Approved, Investigational
BQ-123BQ-123 may increase the hypotensive activities of Amifostine.Investigational
BretyliumBretylium may increase the hypotensive activities of Amifostine.Approved
BrimonidineBrimonidine may increase the hypotensive activities of Amifostine.Approved
BromocriptineThe risk or severity of adverse effects can be increased when Amifostine is combined with Bromocriptine.Approved, Investigational
BumetanideThe risk or severity of adverse effects can be increased when Amifostine is combined with Bumetanide.Approved
BupivacaineThe risk or severity of adverse effects can be increased when Amifostine is combined with Bupivacaine.Approved, Investigational
BupranololBupranolol may increase the hypotensive activities of Amifostine.Approved
CadralazineCadralazine may increase the hypotensive activities of Amifostine.Experimental
CafedrineCafedrine may increase the hypotensive activities of Amifostine.Investigational
CanagliflozinThe risk or severity of adverse effects can be increased when Amifostine is combined with Canagliflozin.Approved
CandesartanCandesartan may increase the hypotensive activities of Amifostine.Experimental
Candesartan cilexetilCandesartan cilexetil may increase the hypotensive activities of Amifostine.Approved
CandoxatrilCandoxatril may increase the hypotensive activities of Amifostine.Experimental
CaptoprilCaptopril may increase the hypotensive activities of Amifostine.Approved
CarbetocinThe risk or severity of adverse effects can be increased when Amifostine is combined with Carbetocin.Approved
CarteololCarteolol may increase the hypotensive activities of Amifostine.Approved
CarvedilolCarvedilol may increase the hypotensive activities of Amifostine.Approved, Investigational
CeliprololCeliprolol may increase the hypotensive activities of Amifostine.Approved, Investigational
ChlorothiazideChlorothiazide may increase the hypotensive activities of Amifostine.Approved, Vet Approved
ChlorpromazineThe risk or severity of adverse effects can be increased when Amifostine is combined with Chlorpromazine.Approved, Vet Approved
ChlorthalidoneChlorthalidone may increase the hypotensive activities of Amifostine.Approved
CicletanineCicletanine may increase the hypotensive activities of Amifostine.Investigational
CilazaprilCilazapril may increase the hypotensive activities of Amifostine.Approved
CilnidipineThe risk or severity of adverse effects can be increased when Amifostine is combined with Cilnidipine.Approved, Investigational
ClevidipineThe risk or severity of adverse effects can be increased when Amifostine is combined with Clevidipine.Approved
ClofarabineThe risk or severity of adverse effects can be increased when Amifostine is combined with Clofarabine.Approved, Investigational
ClomipramineThe risk or severity of adverse effects can be increased when Amifostine is combined with Clomipramine.Approved, Vet Approved
ClonidineClonidine may increase the hypotensive activities of Amifostine.Approved
CloranololCloranolol may increase the hypotensive activities of Amifostine.Experimental
ClozapineThe risk or severity of adverse effects can be increased when Amifostine is combined with Clozapine.Approved
ConivaptanThe risk or severity of adverse effects can be increased when Amifostine is combined with Conivaptan.Approved, Investigational
CryptenamineCryptenamine may increase the hypotensive activities of Amifostine.Approved
CyclopenthiazideCyclopenthiazide may increase the hypotensive activities of Amifostine.Experimental
CyclothiazideCyclothiazide may increase the hypotensive activities of Amifostine.Approved
DapagliflozinThe risk or severity of adverse effects can be increased when Amifostine is combined with Dapagliflozin.Approved
DebrisoquinDebrisoquin may increase the hypotensive activities of Amifostine.Approved, Investigational
DelaprilDelapril may increase the hypotensive activities of Amifostine.Experimental
DeserpidineDeserpidine may increase the hypotensive activities of Amifostine.Approved
DesfluraneThe risk or severity of adverse effects can be increased when Amifostine is combined with Desflurane.Approved
DexmedetomidineThe risk or severity of adverse effects can be increased when Amifostine is combined with Dexmedetomidine.Approved, Vet Approved
DiazoxideDiazoxide may increase the hypotensive activities of Amifostine.Approved
DiclofenamideThe risk or severity of adverse effects can be increased when Amifostine is combined with Diclofenamide.Approved
diethylnorsperminediethylnorspermine may increase the hypotensive activities of Amifostine.Investigational
DihydralazineDihydralazine may increase the hypotensive activities of Amifostine.Investigational
DiltiazemDiltiazem may increase the hypotensive activities of Amifostine.Approved
DinutuximabThe risk or severity of adverse effects can be increased when Amifostine is combined with Dinutuximab.Approved
DipyridamoleThe risk or severity of adverse effects can be increased when Amifostine is combined with Dipyridamole.Approved
DorzolamideDorzolamide may increase the hypotensive activities of Amifostine.Approved
DoxazosinDoxazosin may increase the hypotensive activities of Amifostine.Approved
DuloxetineAmifostine may increase the orthostatic hypotensive activities of Duloxetine.Approved
EfonidipineEfonidipine may increase the hypotensive activities of Amifostine.Approved, Investigational
EmpagliflozinThe risk or severity of adverse effects can be increased when Amifostine is combined with Empagliflozin.Approved
EnalaprilEnalapril may increase the hypotensive activities of Amifostine.Approved, Vet Approved
EnalaprilatEnalaprilat may increase the hypotensive activities of Amifostine.Approved
EndralazineEndralazine may increase the hypotensive activities of Amifostine.Experimental
EpanololEpanolol may increase the hypotensive activities of Amifostine.Experimental
EplerenoneThe risk or severity of adverse effects can be increased when Amifostine is combined with Eplerenone.Approved
EpoprostenolEpoprostenol may increase the hypotensive activities of Amifostine.Approved
EprosartanEprosartan may increase the hypotensive activities of Amifostine.Approved
EsmololThe risk or severity of adverse effects can be increased when Amifostine is combined with Esmolol.Approved
Etacrynic acidThe risk or severity of adverse effects can be increased when Amifostine is combined with Etacrynic acid.Approved
FelodipineFelodipine may increase the hypotensive activities of Amifostine.Approved, Investigational
FenoldopamFenoldopam may increase the hypotensive activities of Amifostine.Approved
Ferulic acidFerulic acid may increase the hypotensive activities of Amifostine.Experimental
FimasartanThe risk or severity of adverse effects can be increased when Amifostine is combined with Fimasartan.Approved, Investigational
FosinoprilFosinopril may increase the hypotensive activities of Amifostine.Approved
FurosemideThe risk or severity of adverse effects can be increased when Amifostine is combined with Furosemide.Approved, Vet Approved
GuanabenzGuanabenz may increase the hypotensive activities of Amifostine.Approved, Investigational
GuanadrelGuanadrel may increase the hypotensive activities of Amifostine.Approved
GuanazodineGuanazodine may increase the hypotensive activities of Amifostine.Experimental
GuanethidineGuanethidine may increase the hypotensive activities of Amifostine.Approved
GuanfacineGuanfacine may increase the hypotensive activities of Amifostine.Approved, Investigational
GuanoclorGuanoclor may increase the hypotensive activities of Amifostine.Experimental
GuanoxabenzGuanoxabenz may increase the hypotensive activities of Amifostine.Experimental
GuanoxanGuanoxan may increase the hypotensive activities of Amifostine.Experimental
HalothaneThe risk or severity of adverse effects can be increased when Amifostine is combined with Halothane.Approved, Vet Approved
HexamethoniumHexamethonium may increase the hypotensive activities of Amifostine.Experimental
HexobarbitalHexobarbital may increase the hypotensive activities of Amifostine.Approved
HydralazineHydralazine may increase the hypotensive activities of Amifostine.Approved
HydrochlorothiazideHydrochlorothiazide may increase the hypotensive activities of Amifostine.Approved, Vet Approved
HydroflumethiazideHydroflumethiazide may increase the hypotensive activities of Amifostine.Approved, Investigational
IloprostThe risk or severity of adverse effects can be increased when Amifostine is combined with Iloprost.Approved, Investigational
ImidaprilImidapril may increase the hypotensive activities of Amifostine.Investigational
ImipramineThe risk or severity of adverse effects can be increased when Amifostine is combined with Imipramine.Approved
IndapamideIndapamide may increase the hypotensive activities of Amifostine.Approved
IndenololIndenolol may increase the hypotensive activities of Amifostine.Withdrawn
IndoraminIndoramin may increase the hypotensive activities of Amifostine.Withdrawn
IrbesartanIrbesartan may increase the hypotensive activities of Amifostine.Approved, Investigational
IsocarboxazidThe risk or severity of adverse effects can be increased when Amifostine is combined with Isocarboxazid.Approved
IsofluraneThe risk or severity of adverse effects can be increased when Amifostine is combined with Isoflurane.Approved, Vet Approved
Isosorbide DinitrateThe risk or severity of adverse effects can be increased when Amifostine is combined with Isosorbide Dinitrate.Approved
Isosorbide MononitrateThe risk or severity of adverse effects can be increased when Amifostine is combined with Isosorbide Mononitrate.Approved
IsoxsuprineThe risk or severity of adverse effects can be increased when Amifostine is combined with Isoxsuprine.Approved, Withdrawn
IsradipineIsradipine may increase the hypotensive activities of Amifostine.Approved
KetanserinKetanserin may increase the hypotensive activities of Amifostine.Investigational
LabetalolLabetalol may increase the hypotensive activities of Amifostine.Approved
LacidipineLacidipine may increase the hypotensive activities of Amifostine.Approved, Investigational
LatanoprostLatanoprost may increase the hypotensive activities of Amifostine.Approved, Investigational
LercanidipineLercanidipine may increase the hypotensive activities of Amifostine.Approved, Investigational
LevobunololThe risk or severity of adverse effects can be increased when Amifostine is combined with Levobunolol.Approved
LevobupivacaineThe risk or severity of adverse effects can be increased when Amifostine is combined with Levobupivacaine.Approved, Investigational
LevodopaAmifostine may increase the orthostatic hypotensive activities of Levodopa.Approved
LevosimendanThe risk or severity of adverse effects can be increased when Amifostine is combined with Levosimendan.Approved, Investigational
LinsidomineLinsidomine may increase the hypotensive activities of Amifostine.Experimental
LisinoprilLisinopril may increase the hypotensive activities of Amifostine.Approved, Investigational
LofexidineLofexidine may increase the hypotensive activities of Amifostine.Approved, Investigational
LosartanLosartan may increase the hypotensive activities of Amifostine.Approved
MacitentanMacitentan may increase the hypotensive activities of Amifostine.Approved
ManidipineManidipine may increase the hypotensive activities of Amifostine.Approved, Investigational
MannitolThe risk or severity of adverse effects can be increased when Amifostine is combined with Mannitol.Approved, Investigational
MecamylamineMecamylamine may increase the hypotensive activities of Amifostine.Approved
MethazolamideThe risk or severity of adverse effects can be increased when Amifostine is combined with Methazolamide.Approved
MethohexitalMethohexital may increase the hypotensive activities of Amifostine.Approved
MethoserpidineMethoserpidine may increase the hypotensive activities of Amifostine.Experimental
MethyclothiazideThe risk or severity of adverse effects can be increased when Amifostine is combined with Methyclothiazide.Approved
MethyldopaMethyldopa may increase the hypotensive activities of Amifostine.Approved
MethylphenobarbitalMethylphenobarbital may increase the hypotensive activities of Amifostine.Approved
MetipranololMetipranolol may increase the hypotensive activities of Amifostine.Approved
MetolazoneMetolazone may increase the hypotensive activities of Amifostine.Approved
MetoprololMetoprolol may increase the hypotensive activities of Amifostine.Approved, Investigational
MetyrosineMetyrosine may increase the hypotensive activities of Amifostine.Approved
MibefradilMibefradil may increase the hypotensive activities of Amifostine.Investigational, Withdrawn
MinoxidilMinoxidil may increase the hypotensive activities of Amifostine.Approved
MoexiprilMoexipril may increase the hypotensive activities of Amifostine.Approved
MorphineThe risk or severity of adverse effects can be increased when Amifostine is combined with Morphine.Approved, Investigational
MoxonidineMoxonidine may increase the hypotensive activities of Amifostine.Approved, Investigational
MuzolimineMuzolimine may increase the hypotensive activities of Amifostine.Experimental
NabiloneThe risk or severity of adverse effects can be increased when Amifostine is combined with Nabilone.Approved, Investigational
NadololNadolol may increase the hypotensive activities of Amifostine.Approved
NaftopidilNaftopidil may increase the hypotensive activities of Amifostine.Investigational
NebivololNebivolol may increase the hypotensive activities of Amifostine.Approved, Investigational
NesiritideThe risk or severity of adverse effects can be increased when Amifostine is combined with Nesiritide.Approved, Investigational
NicardipineNicardipine may increase the hypotensive activities of Amifostine.Approved
NicorandilNicorandil may increase the hypotensive activities of Amifostine.Approved, Investigational
NifedipineThe risk or severity of adverse effects can be increased when Amifostine is combined with Nifedipine.Approved
NiguldipineNiguldipine may increase the hypotensive activities of Amifostine.Experimental
NilvadipineNilvadipine may increase the hypotensive activities of Amifostine.Approved, Investigational
NimodipineNimodipine may increase the hypotensive activities of Amifostine.Approved
NisoldipineNisoldipine may increase the hypotensive activities of Amifostine.Approved
NitrendipineNitrendipine may increase the hypotensive activities of Amifostine.Approved, Investigational
Nitric OxideThe risk or severity of adverse effects can be increased when Amifostine is combined with Nitric Oxide.Approved
NitroglycerinThe risk or severity of adverse effects can be increased when Amifostine is combined with Nitroglycerin.Approved, Investigational
NitroprussideNitroprusside may increase the hypotensive activities of Amifostine.Approved
ObinutuzumabThe risk or severity of adverse effects can be increased when Amifostine is combined with Obinutuzumab.Approved
OlmesartanOlmesartan may increase the hypotensive activities of Amifostine.Approved, Investigational
OmapatrilatOmapatrilat may increase the hypotensive activities of Amifostine.Investigational
OxprenololOxprenolol may increase the hypotensive activities of Amifostine.Approved
PaclitaxelThe risk or severity of adverse effects can be increased when Amifostine is combined with Paclitaxel.Approved, Vet Approved
PapaverineThe risk or severity of adverse effects can be increased when Amifostine is combined with Papaverine.Approved
PargylinePargyline may increase the hypotensive activities of Amifostine.Approved
PenbutololPenbutolol may increase the hypotensive activities of Amifostine.Approved, Investigational
PentobarbitalPentobarbital may increase the hypotensive activities of Amifostine.Approved, Vet Approved
PentoliniumPentolinium may increase the hypotensive activities of Amifostine.Approved
PerindoprilPerindopril may increase the hypotensive activities of Amifostine.Approved
PhenelzineThe risk or severity of adverse effects can be increased when Amifostine is combined with Phenelzine.Approved
PhenobarbitalPhenobarbital may increase the hypotensive activities of Amifostine.Approved
PhenoxybenzaminePhenoxybenzamine may increase the hypotensive activities of Amifostine.Approved
PhentolaminePhentolamine may increase the hypotensive activities of Amifostine.Approved
PinacidilPinacidil may increase the hypotensive activities of Amifostine.Withdrawn
PindololPindolol may increase the hypotensive activities of Amifostine.Approved
PipamperoneThe risk or severity of adverse effects can be increased when Amifostine is combined with Pipamperone.Approved, Investigational
Platelet Activating FactorPlatelet Activating Factor may increase the hypotensive activities of Amifostine.Experimental
PolythiazidePolythiazide may increase the hypotensive activities of Amifostine.Approved
PramipexoleThe risk or severity of adverse effects can be increased when Amifostine is combined with Pramipexole.Approved, Investigational
PrazosinPrazosin may increase the hypotensive activities of Amifostine.Approved
PrimidonePrimidone may increase the hypotensive activities of Amifostine.Approved, Vet Approved
PropofolThe risk or severity of adverse effects can be increased when Amifostine is combined with Propofol.Approved, Investigational, Vet Approved
PropranololPropranolol may increase the hypotensive activities of Amifostine.Approved, Investigational
QuetiapineThe risk or severity of adverse effects can be increased when Amifostine is combined with Quetiapine.Approved
QuinaprilQuinapril may increase the hypotensive activities of Amifostine.Approved, Investigational
RamiprilRamipril may increase the hypotensive activities of Amifostine.Approved
RasagilineThe risk or severity of adverse effects can be increased when Amifostine is combined with Rasagiline.Approved
RemifentanilThe risk or severity of adverse effects can be increased when Amifostine is combined with Remifentanil.Approved
RemikirenRemikiren may increase the hypotensive activities of Amifostine.Approved
RescinnamineRescinnamine may increase the hypotensive activities of Amifostine.Approved
ReserpineReserpine may increase the hypotensive activities of Amifostine.Approved, Investigational
RilmenidineRilmenidine may increase the hypotensive activities of Amifostine.Investigational
RiociguatRiociguat may increase the hypotensive activities of Amifostine.Approved
RisperidoneAmifostine may increase the hypotensive activities of Risperidone.Approved, Investigational
RopiniroleThe risk or severity of adverse effects can be increased when Amifostine is combined with Ropinirole.Approved, Investigational
RopivacaineThe risk or severity of adverse effects can be increased when Amifostine is combined with Ropivacaine.Approved
RotigotineThe risk or severity of adverse effects can be increased when Amifostine is combined with Rotigotine.Approved
SacubitrilThe risk or severity of adverse effects can be increased when Amifostine is combined with Sacubitril.Approved
SaprisartanSaprisartan may increase the hypotensive activities of Amifostine.Experimental
SecobarbitalSecobarbital may increase the hypotensive activities of Amifostine.Approved, Vet Approved
SelegilineThe risk or severity of adverse effects can be increased when Amifostine is combined with Selegiline.Approved, Investigational, Vet Approved
SelexipagSelexipag may increase the hypotensive activities of Amifostine.Approved
SevofluraneThe risk or severity of adverse effects can be increased when Amifostine is combined with Sevoflurane.Approved, Vet Approved
SitaxentanSitaxentan may increase the hypotensive activities of Amifostine.Approved, Investigational, Withdrawn
Sodium NitriteThe risk or severity of adverse effects can be increased when Amifostine is combined with Sodium Nitrite.Approved
SotalolThe risk or severity of adverse effects can be increased when Amifostine is combined with Sotalol.Approved
SpiraprilSpirapril may increase the hypotensive activities of Amifostine.Approved
SpironolactoneThe risk or severity of adverse effects can be increased when Amifostine is combined with Spironolactone.Approved
StreptokinaseThe risk or severity of adverse effects can be increased when Amifostine is combined with Streptokinase.Approved, Investigational
SufentanilThe risk or severity of adverse effects can be increased when Amifostine is combined with Sufentanil.Approved, Investigational
TalinololTalinolol may increase the hypotensive activities of Amifostine.Investigational
TamsulosinThe risk or severity of adverse effects can be increased when Amifostine is combined with Tamsulosin.Approved, Investigational
TelmisartanTelmisartan may increase the hypotensive activities of Amifostine.Approved, Investigational
TemocaprilTemocapril may increase the hypotensive activities of Amifostine.Experimental, Investigational
TerazosinThe risk or severity of adverse effects can be increased when Amifostine is combined with Terazosin.Approved
TerlipressinTerlipressin may increase the hypotensive activities of Amifostine.Approved, Investigational
TetrahydropalmatineTetrahydropalmatine may increase the hypotensive activities of Amifostine.Investigational
ThalidomideThe risk or severity of adverse effects can be increased when Amifostine is combined with Thalidomide.Approved, Investigational, Withdrawn
TheodrenalineTheodrenaline may increase the hypotensive activities of Amifostine.Investigational
ThiamylalThiamylal may increase the hypotensive activities of Amifostine.Approved, Vet Approved
ThiopentalThiopental may increase the hypotensive activities of Amifostine.Approved, Vet Approved
ThioridazineThe risk or severity of adverse effects can be increased when Amifostine is combined with Thioridazine.Approved, Withdrawn
TiboloneTibolone may increase the hypotensive activities of Amifostine.Approved, Investigational
TicrynafenTicrynafen may increase the hypotensive activities of Amifostine.Withdrawn
TimololTimolol may increase the hypotensive activities of Amifostine.Approved
TizanidineThe risk or severity of adverse effects can be increased when Amifostine is combined with Tizanidine.Approved
TolazolineTolazoline may increase the hypotensive activities of Amifostine.Approved, Vet Approved
TolcaponeThe risk or severity of adverse effects can be increased when Amifostine is combined with Tolcapone.Approved, Withdrawn
TolonidineTolonidine may increase the hypotensive activities of Amifostine.Experimental
TorasemideTorasemide may increase the hypotensive activities of Amifostine.Approved
TrandolaprilTrandolapril may increase the hypotensive activities of Amifostine.Approved
TranylcypromineThe risk or severity of adverse effects can be increased when Amifostine is combined with Tranylcypromine.Approved
TravoprostTravoprost may increase the hypotensive activities of Amifostine.Approved
TreprostinilTreprostinil may increase the hypotensive activities of Amifostine.Approved, Investigational
TretinoinThe risk or severity of adverse effects can be increased when Amifostine is combined with Tretinoin.Approved, Investigational, Nutraceutical
TriamtereneThe risk or severity of adverse effects can be increased when Amifostine is combined with Triamterene.Approved
TrichlormethiazideTrichlormethiazide may increase the hypotensive activities of Amifostine.Approved, Vet Approved
TrimazosinTrimazosin may increase the hypotensive activities of Amifostine.Experimental
TrimethaphanTrimethaphan may increase the hypotensive activities of Amifostine.Approved, Investigational
UnoprostoneUnoprostone may increase the hypotensive activities of Amifostine.Approved
UrapidilUrapidil may increase the hypotensive activities of Amifostine.Investigational
ValsartanValsartan may increase the hypotensive activities of Amifostine.Approved, Investigational
VerapamilThe risk or severity of adverse effects can be increased when Amifostine is combined with Verapamil.Approved
VincamineVincamine may increase the hypotensive activities of Amifostine.Experimental
VinpocetineVinpocetine may increase the hypotensive activities of Amifostine.Investigational
XipamideXipamide may increase the hypotensive activities of Amifostine.Experimental
XylometazolineXylometazoline may increase the hypotensive activities of Amifostine.Approved
ZofenoprilZofenopril may increase the hypotensive activities of Amifostine.Experimental
Food Interactions
Not Available

References

Synthesis Reference

Paul E. Kennedy, Roger A. Rajewski, John M. Baldoni, "Crystalline amifostine compositions and methods of the preparation and use of same." U.S. Patent US5424471, issued April, 1979.

US5424471
General References
  1. Santini V, Giles FJ: The potential of amifostine: from cytoprotectant to therapeutic agent. Haematologica. 1999 Nov;84(11):1035-42. [PubMed:10553165]
External Links
Human Metabolome Database
HMDB15274
KEGG Compound
C06819
PubChem Compound
2141
PubChem Substance
46505305
ChemSpider
2056
ChEBI
2636
ChEMBL
CHEMBL1006
PharmGKB
PA448365
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Amifostine
ATC Codes
V03AF05 — Amifostine
FDA label
Download (45.6 KB)
MSDS
Download (36.1 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1Active Not RecruitingTreatmentLung Cancers1
1CompletedSupportive CareDrug/Agent Toxicity by Tissue/Organ / Unspecified Adult Solid Tumor, Protocol Specific1
1CompletedSupportive CareUnspecified Adult Solid Tumor, Protocol Specific1
1CompletedTreatmentDrug/Agent Toxicity by Tissue/Organ / Leukemias1
1CompletedTreatmentLeukemias / Malignant Lymphomas / Unspecified Adult Solid Tumor, Protocol Specific1
1CompletedTreatmentMalignant Pleural Mesothelioma (MPM)1
1CompletedTreatmentRecurrent Melanoma / Recurrent Renal Cell Cancer / Stage III Melanoma / Stage IV Melanoma / Stage IV Renal Cell Cancer1
1CompletedTreatmentUnspecified Childhood Solid Tumor, Protocol Specific1
1TerminatedSupportive CareBrain and Central Nervous System Tumors / Cancer, Ovarian / Childhood Germ Cell Tumor / Chordomas / Liver Cancer / Neuroblastomas / Renal Cancers / Retinoblastoma / Sarcomas1
1TerminatedTreatmentDrug/Agent Toxicity by Tissue/Organ / Multiple Myeloma and Plasma Cell Neoplasm1
1Unknown StatusSupportive CareChronic Myeloproliferative Disorders / Drug/Agent Toxicity by Tissue/Organ / Leukemias / Malignant Lymphomas / Multiple Myeloma and Plasma Cell Neoplasm / Myelodysplastic Syndromes / Precancerous Conditions / Unspecified Adult Solid Tumor, Protocol Specific1
1Unknown StatusTreatmentCongenital Hypoplastic Anemia1
1WithdrawnTreatmentCervical Cancers1
1, 2CompletedTreatmentCancer of Head and Neck / Head and Neck Carcinoma / Head Cancer / Neck Cancer / Neoplasms, Neck1
1, 2CompletedTreatmentCancer, Breast / Cancer, Ovarian / Leukemias / Malignant Lymphomas / Neuroblastomas / Sarcomas / Unspecified Adult Solid Tumor, Protocol Specific1
1, 2CompletedTreatmentCancer, Ovarian / Primary Peritoneal Cavity Cancer1
1, 2CompletedTreatmentCarcinoma of Unknown Primary / Head and Neck Carcinoma1
1, 2CompletedTreatmentCervical Cancers / Radiation Toxicity1
1, 2CompletedTreatmentColorectal Cancers1
1, 2CompletedTreatmentDrug/Agent Toxicity by Tissue/Organ / Lung Cancers / Radiation Toxicity1
1, 2CompletedTreatmentHead and Neck Carcinoma / Oral Complications1
1, 2CompletedTreatmentLeukemia Acute Myeloid Leukemia (AML) / Leukemias1
1, 2CompletedTreatmentLeukemias / Myelodysplastic Syndromes1
1, 2Unknown StatusSupportive CareDrug/Agent Toxicity by Tissue/Organ / Head and Neck Carcinoma / Radiation Toxicity1
1, 2Unknown StatusTreatmentDrug/Agent Toxicity by Tissue/Organ / Lung Cancers1
2CompletedPreventionEsophagitis / Non-Small Cell Lung Carcinoma (NSCLC) / Pneumonitis1
2CompletedSupportive CareBrain and Central Nervous System Tumors1
2CompletedSupportive CareCancer, Breast / Cancer, Ovarian / Drug/Agent Toxicity by Tissue/Organ / Lung Cancers / Malignant Lymphomas / Unspecified Adult Solid Tumor, Protocol Specific1
2CompletedSupportive CareCancer, Breast / Cancer, Ovarian / Lung Cancers / Neurotoxicity / Prostate Cancer / Unspecified Adult Solid Tumor, Protocol Specific1
2CompletedSupportive CareCancer, Ovarian / Lung Cancers / Neurotoxicity1
2CompletedSupportive CareDrug/Agent Toxicity by Tissue/Organ / Head and Neck Carcinoma / Oral Complications / Radiation Toxicity1
2CompletedSupportive CareMalignant Lymphomas1
2CompletedSupportive CareMyelodysplastic Syndromes1
2CompletedSupportive CareProstatic Neoplasms1
2CompletedTreatmentBladder Cancers / Brain and Central Nervous System Tumors / Cancer, Ovarian / Carcinoma of Unknown Primary / Extragonadal Germ Cell Tumor / Head and Neck Carcinoma / Lung Cancers / Renal Cancers / Sarcomas / Testicular germ cell tumour / Unspecified Adult Solid Tumor, Protocol Specific1
2CompletedTreatmentBladder Cancers / Drug/Agent Toxicity by Tissue/Organ1
2CompletedTreatmentCancer, Breast / Drug/Agent Toxicity by Tissue/Organ1
2CompletedTreatmentCancer, Ovarian / Childhood Germ Cell Tumor / Drug/Agent Toxicity by Tissue/Organ / Extragonadal Germ Cell Tumor1
2CompletedTreatmentChemotherapeutic Agent Toxicity / Head and Neck Carcinoma / Mucositis / Radiation Toxicity / Xerostomia1
2CompletedTreatmentDrug/Agent Toxicity by Tissue/Organ / Lung Cancers1
2CompletedTreatmentDrug/Agent Toxicity by Tissue/Organ / Lung Cancers / Radiation Toxicity1
2CompletedTreatmentEndometrial Cancers1
2CompletedTreatmentHead and Neck Carcinoma2
2CompletedTreatmentHodgkins Disease (HD) / Malignant Lymphomas / Non-Hodgkin's Lymphoma (NHL)1
2CompletedTreatmentMyelodysplastic Syndromes1
2CompletedTreatmentMyelodysplastic Syndromes / Myelodysplastic/Myeloproliferative Neoplasms1
2CompletedTreatmentNeutropenias / Sarcomas1
2CompletedTreatmentProstate Cancer / Radiation Toxicity1
2TerminatedSupportive CareCancer, Ovarian / Cervical Cancers / Endometrial Cancers / Fallopian Tube Cancer / Neurotoxicity / Primary Peritoneal Cavity Cancer / Sarcomas1
2TerminatedSupportive CareHead and Neck Carcinoma / Mucositis / Swallowing Disorders / Xerostomia1
2TerminatedTreatmentColorectal Cancers1
2TerminatedTreatmentDrug/Agent Toxicity by Tissue/Organ / Head and Neck Carcinoma / Oral Complications / Radiation Toxicity1
2TerminatedTreatmentHead and Neck Carcinoma1
2Unknown StatusPreventionRectal Carcinoma1
2Unknown StatusSupportive CareDrug/Agent Toxicity by Tissue/Organ / Leukemias / Myelodysplastic Syndromes / Neutropenias1
2Unknown StatusSupportive CareDrug/Agent Toxicity by Tissue/Organ / Lung Cancers / Radiation Toxicity1
2Unknown StatusTreatmentAnemias / Myelodysplastic Syndromes1
2Unknown StatusTreatmentHead and Neck Carcinoma1
2Unknown StatusTreatmentLeukemias1
2Unknown StatusTreatmentLeukemias / Myelodysplastic Syndromes1
2Unknown StatusTreatmentMyelodysplastic Syndromes1
3Active Not RecruitingTreatmentStage I Lymphoepithelioma of the Nasopharynx / Stage I Squamous Cell Carcinoma of the Nasopharynx / Stage II Lymphoepithelioma of the Nasopharynx / Stage II Squamous Cell Carcinoma of the Nasopharynx / Stage III Lymphoepithelioma of the Nasopharynx / Stage III Squamous Cell Carcinoma of the Nasopharynx / Stage IV Lymphoepithelioma of the Nasopharynx / Stage IV Squamous Cell Carcinoma of the Nasopharynx1
3CompletedSupportive CareCancer, Ovarian / Quality of Life1
3CompletedSupportive CareDrug/Agent Toxicity by Tissue/Organ / Lung Cancers / Oral Complications / Radiation Toxicity1
3CompletedSupportive CareGestational Trophoblastic Disease / Neurotoxicity / Peripheral Neuropathy / Unspecified Adult Solid Tumor, Protocol Specific1
3CompletedTreatmentChildhood Hepatoblastoma / Recurrent Childhood Liver Cancer / Stage I Childhood Liver Cancer1
3CompletedTreatmentHead and Neck Carcinoma1
3CompletedTreatmentRefractory Multiple Myeloma / Stage II Multiple Myeloma / Stage III Multiple Myeloma1
3Unknown StatusTreatmentTrigeminal Neuralgia (TN)1
4CompletedSupportive CareDrug/Agent Toxicity by Tissue/Organ / Unspecified Adult Solid Tumor, Protocol Specific1
4SuspendedSupportive CareOral Mucositis / Vesicular Stomatitis1
Not AvailableActive Not RecruitingTreatmentCancer, Breast1
Not AvailableCompletedTreatmentHead and Neck Carcinoma / Lung Cancers1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Dosage forms
FormRouteStrength
Injection, powder, lyophilized, for solutionIntravenous50 mg/mL
Injection, powder, lyophilized, for solutionIntravenous500 mg/10mL
Powder, for solutionIntravenous500 mg
Prices
Unit descriptionCostUnit
Ethyol 500 mg vial605.88USD vial
Amifostine 500 mg vial600.0USD vial
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US5424471No1995-07-312012-07-31Us
CA2120133No1998-06-092013-07-30Canada
US5994409No1997-12-082017-12-08Us

Properties

State
Solid
Experimental Properties
PropertyValueSource
water solubility1000 mg/mLNot Available
logP-1.9Not Available
Predicted Properties
PropertyValueSource
Water Solubility18.7 mg/mLALOGPS
logP-1.4ALOGPS
logP-3.7ChemAxon
logS-1.1ALOGPS
pKa (Strongest Acidic)2.06ChemAxon
pKa (Strongest Basic)11.01ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count5ChemAxon
Hydrogen Donor Count4ChemAxon
Polar Surface Area95.58 Å2ChemAxon
Rotatable Bond Count7ChemAxon
Refractivity51.28 m3·mol-1ChemAxon
Polarizability21.01 Å3ChemAxon
Number of Rings0ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption-0.5944
Blood Brain Barrier-0.8229
Caco-2 permeable-0.6167
P-glycoprotein substrateNon-substrate0.5585
P-glycoprotein inhibitor INon-inhibitor0.9054
P-glycoprotein inhibitor IINon-inhibitor0.9537
Renal organic cation transporterNon-inhibitor0.8451
CYP450 2C9 substrateNon-substrate0.7683
CYP450 2D6 substrateNon-substrate0.7738
CYP450 3A4 substrateNon-substrate0.7689
CYP450 1A2 substrateNon-inhibitor0.9045
CYP450 2C9 inhibitorNon-inhibitor0.9071
CYP450 2D6 inhibitorNon-inhibitor0.9231
CYP450 2C19 inhibitorNon-inhibitor0.9026
CYP450 3A4 inhibitorNon-inhibitor0.8429
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.9592
Ames testNon AMES toxic0.5933
CarcinogenicityNon-carcinogens0.717
BiodegradationReady biodegradable0.6316
Rat acute toxicity2.3829 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.7047
hERG inhibition (predictor II)Non-inhibitor0.7772
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 GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
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
LC-MS/MS Spectrum - LC-ESI-QQ , positiveLC-MS/MSsplash10-0002-0900000000-5350b8c906608c1eb7e4
LC-MS/MS Spectrum - LC-ESI-QQ , positiveLC-MS/MSsplash10-0002-0900000000-bcddc871edb434e577ae
LC-MS/MS Spectrum - LC-ESI-QQ , positiveLC-MS/MSsplash10-0002-2900000000-58ff84f991edcac36e7d
LC-MS/MS Spectrum - LC-ESI-QQ , positiveLC-MS/MSsplash10-05nb-9200000000-ef847b9b156a08e7fa17
LC-MS/MS Spectrum - LC-ESI-QQ , positiveLC-MS/MSsplash10-0a4l-9000000000-c58215f6bca055f13ab7

Taxonomy

Description
This compound belongs to the class of organic compounds known as organothiophosphorus compounds. These are organic derivatives of thiophosphonic acid, thiophosphoric acid, dithiophosphoric acid, or phosphorotrithioic acid, or derivatives thereof. Thiophosphonic acid, dithiophosphoric acid, thiophosphoric acid, and phosphorotrithioic acid are thiophosphorus compounds with the formula OP(O)(=S), OP(S)(=S)O, OP(O)(=S)O, and OP(=S)(S)S, respectively.
Kingdom
Organic compounds
Super Class
Organophosphorus compounds
Class
Organothiophosphorus compounds
Sub Class
Not Available
Direct Parent
Organothiophosphorus compounds
Alternative Parents
Sulfenyl compounds / Dialkylamines / Organopnictogen compounds / Organic oxides / Monoalkylamines / Hydrocarbon derivatives
Substituents
Sulfenyl compound / Secondary amine / Organothiophosphorus compound / Secondary aliphatic amine / Organic nitrogen compound / Organic oxygen compound / Organopnictogen compound / Organic oxide / Hydrocarbon derivative / Primary amine
Molecular Framework
Aliphatic acyclic compounds
External Descriptors
organic thiophosphate, diamine (CHEBI:2636)

Targets

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inducer
General Function
Zinc ion binding
Specific Function
By generating PPi, plays a role in regulating pyrophosphate levels, and functions in bone mineralization and soft tissue calcification. PPi inhibits mineralization by binding to nascent hydroxyapat...
Gene Name
ENPP1
Uniprot ID
P22413
Uniprot Name
Ectonucleotide pyrophosphatase/phosphodiesterase family member 1
Molecular Weight
104923.58 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed:17016423]
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Inducer
General Function
Metal ion binding
Specific Function
Not Available
Gene Name
ALPPL2
Uniprot ID
P10696
Uniprot Name
Alkaline phosphatase, placental-like
Molecular Weight
57376.515 Da
References
  1. Capizzi RL: The preclinical basis for broad-spectrum selective cytoprotection of normal tissues from cytotoxic therapies by amifostine. Semin Oncol. 1999 Apr;26(2 Suppl 7):3-21. [PubMed:10348255]
  2. Orditura M, De Vita F, Roscigno A, Infusino S, Auriemma A, Iodice P, Ciaramella F, Abbate G, Catalano G: Amifostine: A selective cytoprotective agent of normal tissues from chemo-radiotherapy induced toxicity (Review). Oncol Rep. 1999 Nov-Dec;6(6):1357-62. [PubMed:10523712]
  3. Santini V, Giles FJ: The potential of amifostine: from cytoprotectant to therapeutic agent. Haematologica. 1999 Nov;84(11):1035-42. [PubMed:10553165]
  4. Plasswilm L, Hanjalic A, Hoeper J, Cordes N, Tannapfel A: Microvessel density and endothelial cell proliferation after amifostine (Ethyol) administration in vivo. Anticancer Res. 1999 Sep-Oct;19(5B):4241-5. [PubMed:10628381]
  5. Buschini A, Anceschi E, Carlo-Stella C, Regazzi E, Rizzoli V, Poli P, Rossi C: Amifostine (WR-2721) selective protection against melphalan genotoxicity. Leukemia. 2000 Sep;14(9):1642-51. [PubMed:10995012]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Pyrophosphatase activity
Specific Function
This isozyme may play a role in skeletal mineralization.
Gene Name
ALPL
Uniprot ID
P05186
Uniprot Name
Alkaline phosphatase, tissue-nonspecific isozyme
Molecular Weight
57304.435 Da
References
  1. Shaw LM, Bonner H, Lieberman R: Pharmacokinetic profile of amifostine. Semin Oncol. 1996 Aug;23(4 Suppl 8):18-22. [PubMed:8783662]

Drug created on June 13, 2005 07:24 / Updated on November 09, 2017 02:56