Identification

Name
Avanafil
Accession Number
DB06237
Type
Small Molecule
Groups
Approved
Description

Avanafil is a new phosphodiesterase-5 inhibitor that is faster acting and more selective than other drugs belonging to the same class. Chemically, it is a derivative of pyrimidine and is only available as the S-enantiomer. FDA approved on April 27, 2012.

Structure
Thumb
Synonyms
  • (S)-4-(3-Chloro-4-methoxybenzylamino)-2-(2-hydroxymethylpyrrolidin-1-yl)-N-pyrimidin-2-ylmethyl-5-pyrimidinecarboxamide
External IDs
TA-1790
Product Images
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
SpedraTablet200 mgOralMenarini International Operations Luxembourg S.A.2013-06-21Not applicableEu
SpedraTablet50 mgOralMenarini International Operations Luxembourg S.A.2013-06-21Not applicableEu
SpedraTablet100 mgOralMenarini International Operations Luxembourg S.A.2013-06-21Not applicableEu
SpedraTablet50 mgOralMenarini International Operations Luxembourg S.A.2013-06-21Not applicableEu
SpedraTablet200 mgOralMenarini International Operations Luxembourg S.A.2013-06-21Not applicableEu
SpedraTablet200 mgOralMenarini International Operations Luxembourg S.A.2013-06-21Not applicableEu
SpedraTablet100 mgOralMenarini International Operations Luxembourg S.A.2013-06-21Not applicableEu
SpedraTablet50 mgOralMenarini International Operations Luxembourg S.A.2013-06-21Not applicableEu
SpedraTablet200 mgOralMenarini International Operations Luxembourg S.A.2013-06-21Not applicableEu
SpedraTablet100 mgOralMenarini International Operations Luxembourg S.A.2013-06-21Not applicableEu
International/Other Brands
Stendra
Categories
UNII
DR5S136IVO
CAS number
330784-47-9
Weight
Average: 483.951
Monoisotopic: 483.17856544
Chemical Formula
C23H26ClN7O3
InChI Key
WEAJZXNPAWBCOA-INIZCTEOSA-N
InChI
InChI=1S/C23H26ClN7O3/c1-34-19-6-5-15(10-18(19)24)11-27-21-17(22(33)28-13-20-25-7-3-8-26-20)12-29-23(30-21)31-9-2-4-16(31)14-32/h3,5-8,10,12,16,32H,2,4,9,11,13-14H2,1H3,(H,28,33)(H,27,29,30)/t16-/m0/s1
IUPAC Name
4-{[(3-chloro-4-methoxyphenyl)methyl]amino}-2-[(2S)-2-(hydroxymethyl)pyrrolidin-1-yl]-N-(pyrimidin-2-ylmethyl)pyrimidine-5-carboxamide
SMILES
COC1=C(Cl)C=C(CNC2=C(C=NC(=N2)N2CCC[[email protected]]2CO)C(=O)NCC2=NC=CC=N2)C=C1

Pharmacology

Indication

Treatment of erectile dysfunction in males.

Structured Indications
Pharmacodynamics

Avanafil is a strong, competitive inhibitor of PDE5. It is also 100-times more potent for PDE5 than PDE6. The IC50 of avanafil is 5.2 nM. Compared to other PDE5 inhibitor like sildenafil and vardenafil, it is 16- and 21-fold more selective for PDE5 respectively. Avanafil does not bind to PDE6 and PDE11 to a considerable degree. The impact of this finding is that avanafil is less likely to cause side effects such as visual disturbances and myalgia. These are side effects that patients on sildenafil or tadalafil are more likely to experience. Furthermore, single oral doses of avanafil (200 mg) administered to healthy male volunteers resulted in mean changes from baseline in systolic/diastolic blood pressure of -5.3/-3.7 mmHg at 1 hour after dosing. Avanafil does not causes changes in QTc interval or ventricular repolarization.

Mechanism of action

Avanafil is a selective phosphodiesterase 5 (PDE5) enzyme inhibitor used for the treatment of erectile dysfunction caused by diabetes, age induced oxidative stress or other complications. Avanafil inhibits the cGMP specific phosphodiesterase type 5 (PDE5) which is responsible for degradation of cGMP in the corpus cavernosum located around the penis. Penile erection during sexual stimulation is caused by increased penile blood flow resulting from the relaxation of penile arteries and corpus cavernosal smooth muscle. This response is mediated by the release of nitric oxide (NO) from nerve terminals and endothelial cells, which stimulates the synthesis of cGMP in smooth muscle cells. Cyclic GMP causes smooth muscle relaxation and increased blood flow into the corpus cavernosum. The inhibition of phosphodiesterase type 5 (PDE5) by avanafil enhances erectile function by increasing the amount of cGMP.

TargetActionsOrganism
AcGMP-specific 3',5'-cyclic phosphodiesterase
inhibitor
Human
Absorption

Avanafil is rapidly absorbed and does not accumulate following multiple doses. Tmax = 30 - 45 minutes; Time to peak response = 10 minutes (20 minutes shorter than sildenafil)

Volume of distribution
Not Available
Protein binding

99% bound to plasma protein. Protein binding is independent of total drug concentrations, age, renal and hepatic function.

Metabolism

Avanafil is hepatically metabolized primarily by the enzyme, CYP3A4. Two major metabolites are formed, M4 and M16. M4 has 4% of the pharmacologic activity of avanafil. M16 is an inactive metabolite.

Route of elimination

After oral administration, avanafil is excreted as metabolites predominantly in the feces (approximately 62% of administered oral dose) and to a lesser extent in the urine (approximately 21% of the administered oral dose).

Half life

Mean elimination half-life = 5.36 - 10.66 hours

Clearance
Not Available
Toxicity

Avanafil is generally well tolerated. The most commonly reported adverse event are headache and facial flushing.

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

Interactions

Drug Interactions
DrugInteractionDrug group
AcebutololAvanafil may increase the antihypertensive activities of Acebutolol.Approved
AlfuzosinAvanafil may increase the hypotensive activities of Alfuzosin.Approved, Investigational
AliskirenAvanafil may increase the antihypertensive activities of Aliskiren.Approved, Investigational
AlprenololAvanafil may increase the antihypertensive activities of Alprenolol.Approved, Withdrawn
AlprostadilThe risk or severity of adverse effects can be increased when Avanafil is combined with Alprostadil.Approved, Investigational
AmbrisentanAvanafil may increase the antihypertensive activities of Ambrisentan.Approved, Investigational
AmiodaroneThe serum concentration of Avanafil can be increased when it is combined with Amiodarone.Approved, Investigational
AmlodipineAvanafil may increase the antihypertensive activities of Amlodipine.Approved
Amyl NitriteAvanafil may increase the vasodilatory activities of Amyl Nitrite.Approved
AprepitantThe serum concentration of Avanafil can be increased when it is combined with Aprepitant.Approved, Investigational
AtazanavirThe serum concentration of Avanafil can be increased when it is combined with Atazanavir.Approved, Investigational
AtenololAvanafil may increase the antihypertensive activities of Atenolol.Approved
AtomoxetineThe serum concentration of Avanafil can be increased when it is combined with Atomoxetine.Approved
BenazeprilAvanafil may increase the antihypertensive activities of Benazepril.Approved, Investigational
BendroflumethiazideAvanafil may increase the antihypertensive activities of Bendroflumethiazide.Approved
BepridilAvanafil may increase the antihypertensive activities of Bepridil.Approved, Withdrawn
BetaxololAvanafil may increase the antihypertensive activities of Betaxolol.Approved
BethanidineAvanafil may increase the antihypertensive activities of Bethanidine.Approved
BietaserpineAvanafil may increase the antihypertensive activities of Bietaserpine.Experimental
BimatoprostAvanafil may increase the antihypertensive activities of Bimatoprost.Approved, Investigational
BisoprololAvanafil may increase the antihypertensive activities of Bisoprolol.Approved
BoceprevirThe serum concentration of Avanafil can be increased when it is combined with Boceprevir.Approved, Withdrawn
BortezomibThe serum concentration of Avanafil can be increased when it is combined with Bortezomib.Approved, Investigational
BosentanThe serum concentration of Avanafil can be decreased when it is combined with Bosentan.Approved, Investigational
BQ-123Avanafil may increase the antihypertensive activities of BQ-123.Investigational
BretyliumAvanafil may increase the antihypertensive activities of Bretylium.Approved
BrigatinibThe serum concentration of Avanafil can be decreased when it is combined with Brigatinib.Approved
BrimonidineAvanafil may increase the antihypertensive activities of Brimonidine.Approved
BucindololAvanafil may increase the hypotensive activities of Bucindolol.Investigational
BunazosinAvanafil may increase the hypotensive activities of Bunazosin.Investigational
BupranololAvanafil may increase the antihypertensive activities of Bupranolol.Approved
CadralazineAvanafil may increase the antihypertensive activities of Cadralazine.Experimental
CafedrineAvanafil may increase the antihypertensive activities of Cafedrine.Investigational
CandesartanAvanafil may increase the antihypertensive activities of Candesartan.Experimental
Candesartan cilexetilAvanafil may increase the antihypertensive activities of Candesartan cilexetil.Approved
CandoxatrilAvanafil may increase the antihypertensive activities of Candoxatril.Experimental
CaptoprilAvanafil may increase the antihypertensive activities of Captopril.Approved
CarbamazepineThe metabolism of Avanafil can be increased when combined with Carbamazepine.Approved, Investigational
CarteololAvanafil may increase the antihypertensive activities of Carteolol.Approved
CarvedilolAvanafil may increase the hypotensive activities of Carvedilol.Approved, Investigational
CeliprololAvanafil may increase the antihypertensive activities of Celiprolol.Approved, Investigational
CeritinibThe serum concentration of Avanafil can be increased when it is combined with Ceritinib.Approved
ChlorothiazideAvanafil may increase the antihypertensive activities of Chlorothiazide.Approved, Vet Approved
ChlorthalidoneAvanafil may increase the antihypertensive activities of Chlorthalidone.Approved
CicletanineAvanafil may increase the antihypertensive activities of Cicletanine.Investigational
CilazaprilAvanafil may increase the antihypertensive activities of Cilazapril.Approved
ClarithromycinThe serum concentration of Avanafil can be increased when it is combined with Clarithromycin.Approved
ClemastineThe serum concentration of Avanafil can be increased when it is combined with Clemastine.Approved
ClonidineAvanafil may increase the antihypertensive activities of Clonidine.Approved
CloranololAvanafil may increase the antihypertensive activities of Cloranolol.Experimental
ClotrimazoleThe serum concentration of Avanafil can be increased when it is combined with Clotrimazole.Approved, Vet Approved
CobicistatThe serum concentration of Avanafil can be increased when it is combined with Cobicistat.Approved
ConivaptanThe serum concentration of Avanafil can be increased when it is combined with Conivaptan.Approved, Investigational
CrizotinibThe serum concentration of Avanafil can be increased when it is combined with Crizotinib.Approved
CryptenamineAvanafil may increase the antihypertensive activities of Cryptenamine.Approved
CyclopenthiazideAvanafil may increase the antihypertensive activities of Cyclopenthiazide.Experimental
CyclosporineThe serum concentration of Avanafil can be increased when it is combined with Cyclosporine.Approved, Investigational, Vet Approved
CyclothiazideAvanafil may increase the antihypertensive activities of Cyclothiazide.Approved
DabrafenibThe serum concentration of Avanafil can be decreased when it is combined with Dabrafenib.Approved
DapoxetineDapoxetine may increase the orthostatic hypotensive activities of Avanafil.Investigational
DarunavirThe serum concentration of Avanafil can be increased when it is combined with Darunavir.Approved
DasatinibThe serum concentration of Avanafil can be increased when it is combined with Dasatinib.Approved, Investigational
DebrisoquinAvanafil may increase the antihypertensive activities of Debrisoquin.Approved, Investigational
DeferasiroxThe serum concentration of Avanafil can be decreased when it is combined with Deferasirox.Approved, Investigational
DelaprilAvanafil may increase the antihypertensive activities of Delapril.Experimental
DelavirdineThe serum concentration of Avanafil can be increased when it is combined with Delavirdine.Approved
DeserpidineAvanafil may increase the antihypertensive activities of Deserpidine.Approved
DiazoxideAvanafil may increase the antihypertensive activities of Diazoxide.Approved
DiethylnorspermineAvanafil may increase the antihypertensive activities of Diethylnorspermine.Investigational
DihydralazineAvanafil may increase the antihypertensive activities of Dihydralazine.Investigational
DihydroergotamineThe serum concentration of Avanafil can be increased when it is combined with Dihydroergotamine.Approved
DiltiazemThe serum concentration of Avanafil can be increased when it is combined with Diltiazem.Approved
DorzolamideAvanafil may increase the antihypertensive activities of Dorzolamide.Approved
DoxazosinAvanafil may increase the hypotensive activities of Doxazosin.Approved
DoxycyclineThe serum concentration of Avanafil can be increased when it is combined with Doxycycline.Approved, Investigational, Vet Approved
DronedaroneThe serum concentration of Avanafil can be increased when it is combined with Dronedarone.Approved
EfonidipineAvanafil may increase the antihypertensive activities of Efonidipine.Approved, Investigational
EnalaprilAvanafil may increase the antihypertensive activities of Enalapril.Approved, Vet Approved
EnalaprilatAvanafil may increase the antihypertensive activities of Enalaprilat.Approved
EndralazineAvanafil may increase the antihypertensive activities of Endralazine.Experimental
EnzalutamideThe serum concentration of Avanafil can be decreased when it is combined with Enzalutamide.Approved
EpanololAvanafil may increase the antihypertensive activities of Epanolol.Experimental
EpoprostenolAvanafil may increase the antihypertensive activities of Epoprostenol.Approved
EprosartanAvanafil may increase the antihypertensive activities of Eprosartan.Approved
Erythrityl TetranitrateAvanafil may increase the vasodilatory activities of Erythrityl Tetranitrate.Approved, Investigational
ErythromycinThe serum concentration of Avanafil can be increased when it is combined with Erythromycin.Approved, Vet Approved
EthanolEthanol may increase the hypotensive activities of Avanafil.Approved
EtravirineThe serum concentration of Avanafil can be decreased when it is combined with Etravirine.Approved
FelodipineAvanafil may increase the antihypertensive activities of Felodipine.Approved, Investigational
FenoldopamAvanafil may increase the antihypertensive activities of Fenoldopam.Approved
Ferulic acidAvanafil may increase the antihypertensive activities of Ferulic acid.Experimental
FluconazoleThe serum concentration of Avanafil can be increased when it is combined with Fluconazole.Approved
FluvoxamineThe serum concentration of Avanafil can be increased when it is combined with Fluvoxamine.Approved, Investigational
FosamprenavirThe serum concentration of Avanafil can be increased when it is combined with Fosamprenavir.Approved
FosaprepitantThe serum concentration of Avanafil can be increased when it is combined with Fosaprepitant.Approved
FosinoprilAvanafil may increase the antihypertensive activities of Fosinopril.Approved
FosphenytoinThe metabolism of Avanafil can be increased when combined with Fosphenytoin.Approved
Fusidic AcidThe serum concentration of Avanafil can be increased when it is combined with Fusidic Acid.Approved
GuanabenzAvanafil may increase the antihypertensive activities of Guanabenz.Approved, Investigational
GuanadrelAvanafil may increase the antihypertensive activities of Guanadrel.Approved
GuanazodineAvanafil may increase the antihypertensive activities of Guanazodine.Experimental
GuanethidineAvanafil may increase the antihypertensive activities of Guanethidine.Approved
GuanfacineAvanafil may increase the antihypertensive activities of Guanfacine.Approved, Investigational
GuanoclorAvanafil may increase the antihypertensive activities of Guanoclor.Experimental
GuanoxabenzAvanafil may increase the antihypertensive activities of Guanoxabenz.Experimental
GuanoxanAvanafil may increase the antihypertensive activities of Guanoxan.Experimental
HexamethoniumAvanafil may increase the antihypertensive activities of Hexamethonium.Experimental
HydralazineAvanafil may increase the antihypertensive activities of Hydralazine.Approved
HydrochlorothiazideAvanafil may increase the antihypertensive activities of Hydrochlorothiazide.Approved, Vet Approved
HydroflumethiazideAvanafil may increase the antihypertensive activities of Hydroflumethiazide.Approved, Investigational
IdelalisibThe serum concentration of Avanafil can be increased when it is combined with Idelalisib.Approved
ImatinibThe serum concentration of Avanafil can be increased when it is combined with Imatinib.Approved
ImidaprilAvanafil may increase the antihypertensive activities of Imidapril.Investigational
IndapamideAvanafil may increase the antihypertensive activities of Indapamide.Approved
IndenololAvanafil may increase the antihypertensive activities of Indenolol.Withdrawn
IndinavirThe serum concentration of Avanafil can be increased when it is combined with Indinavir.Approved
IndoraminAvanafil may increase the hypotensive activities of Indoramin.Withdrawn
IrbesartanAvanafil may increase the antihypertensive activities of Irbesartan.Approved, Investigational
IsavuconazoniumThe serum concentration of Avanafil can be increased when it is combined with Isavuconazonium.Approved, Investigational
Isosorbide DinitrateAvanafil may increase the vasodilatory activities of Isosorbide Dinitrate.Approved
Isosorbide MononitrateAvanafil may increase the vasodilatory activities of Isosorbide Mononitrate.Approved
IsradipineThe serum concentration of Avanafil can be increased when it is combined with Isradipine.Approved
ItraconazoleThe serum concentration of Avanafil can be increased when it is combined with Itraconazole.Approved, Investigational
IvacaftorThe serum concentration of Avanafil can be increased when it is combined with Ivacaftor.Approved
KetanserinAvanafil may increase the antihypertensive activities of Ketanserin.Investigational
KetoconazoleThe serum concentration of Avanafil can be increased when it is combined with Ketoconazole.Approved, Investigational
LabetalolAvanafil may increase the hypotensive activities of Labetalol.Approved
LacidipineAvanafil may increase the antihypertensive activities of Lacidipine.Approved, Investigational
LatanoprostAvanafil may increase the antihypertensive activities of Latanoprost.Approved, Investigational
LercanidipineAvanafil may increase the antihypertensive activities of Lercanidipine.Approved, Investigational
LinsidomineAvanafil may increase the antihypertensive activities of Linsidomine.Experimental
LisinoprilAvanafil may increase the antihypertensive activities of Lisinopril.Approved, Investigational
LofexidineAvanafil may increase the antihypertensive activities of Lofexidine.Approved, Investigational
LopinavirThe serum concentration of Avanafil can be increased when it is combined with Lopinavir.Approved
LorcaserinThe risk or severity of adverse effects can be increased when Lorcaserin is combined with Avanafil.Approved
LosartanAvanafil may increase the antihypertensive activities of Losartan.Approved
LovastatinThe serum concentration of Avanafil can be increased when it is combined with Lovastatin.Approved, Investigational
LuliconazoleThe serum concentration of Avanafil can be increased when it is combined with Luliconazole.Approved
LumacaftorThe metabolism of Avanafil can be increased when combined with Lumacaftor.Approved
MacitentanAvanafil may increase the antihypertensive activities of Macitentan.Approved
ManidipineAvanafil may increase the antihypertensive activities of Manidipine.Approved, Investigational
MecamylamineAvanafil may increase the antihypertensive activities of Mecamylamine.Approved
MethoserpidineAvanafil may increase the antihypertensive activities of Methoserpidine.Experimental
MethyldopaAvanafil may increase the antihypertensive activities of Methyldopa.Approved
Methylpropylpropanediol dinitrateAvanafil may increase the vasodilatory activities of Methylpropylpropanediol dinitrate.Experimental
MetipranololAvanafil may increase the antihypertensive activities of Metipranolol.Approved
MetolazoneAvanafil may increase the antihypertensive activities of Metolazone.Approved
MetoprololAvanafil may increase the antihypertensive activities of Metoprolol.Approved, Investigational
MetyrosineAvanafil may increase the antihypertensive activities of Metyrosine.Approved
MibefradilAvanafil may increase the antihypertensive activities of Mibefradil.Investigational, Withdrawn
MifepristoneThe serum concentration of Avanafil can be increased when it is combined with Mifepristone.Approved, Investigational
MinoxidilAvanafil may increase the antihypertensive activities of Minoxidil.Approved
MirodenafilThe risk or severity of adverse effects can be increased when Mirodenafil is combined with Avanafil.Investigational
MitotaneThe serum concentration of Avanafil can be decreased when it is combined with Mitotane.Approved
MoexiprilAvanafil may increase the antihypertensive activities of Moexipril.Approved
MolsidomineMolsidomine may increase the hypotensive activities of Avanafil.Approved, Investigational
MoxonidineAvanafil may increase the antihypertensive activities of Moxonidine.Approved, Investigational
MuzolimineAvanafil may increase the antihypertensive activities of Muzolimine.Experimental
NadololAvanafil may increase the antihypertensive activities of Nadolol.Approved
NaftopidilAvanafil may increase the antihypertensive activities of Naftopidil.Investigational
NebivololAvanafil may increase the antihypertensive activities of Nebivolol.Approved, Investigational
NefazodoneThe serum concentration of Avanafil can be increased when it is combined with Nefazodone.Approved, Withdrawn
NelfinavirThe serum concentration of Avanafil can be increased when it is combined with Nelfinavir.Approved
NetupitantThe serum concentration of Avanafil can be increased when it is combined with Netupitant.Approved
NevirapineThe serum concentration of Avanafil can be increased when it is combined with Nevirapine.Approved
NicardipineAvanafil may increase the antihypertensive activities of Nicardipine.Approved
NicorandilAvanafil may increase the antihypertensive activities of Nicorandil.Approved, Investigational
NiguldipineAvanafil may increase the antihypertensive activities of Niguldipine.Experimental
NilotinibThe serum concentration of Avanafil can be increased when it is combined with Nilotinib.Approved, Investigational
NilvadipineAvanafil may increase the antihypertensive activities of Nilvadipine.Approved, Investigational
NimodipineAvanafil may increase the antihypertensive activities of Nimodipine.Approved
NisoldipineAvanafil may increase the antihypertensive activities of Nisoldipine.Approved
NitrendipineAvanafil may increase the antihypertensive activities of Nitrendipine.Approved, Investigational
NitroglycerinAvanafil may increase the vasodilatory activities of Nitroglycerin.Approved, Investigational
NitroprussideAvanafil may increase the antihypertensive activities of Nitroprusside.Approved
OlaparibThe serum concentration of Avanafil can be increased when it is combined with Olaparib.Approved
OlmesartanAvanafil may increase the antihypertensive activities of Olmesartan.Approved, Investigational
OmapatrilatAvanafil may increase the antihypertensive activities of Omapatrilat.Investigational
OsimertinibThe serum concentration of Avanafil can be increased when it is combined with Osimertinib.Approved
OxprenololAvanafil may increase the antihypertensive activities of Oxprenolol.Approved
PalbociclibThe serum concentration of Avanafil can be increased when it is combined with Palbociclib.Approved
PargylineAvanafil may increase the antihypertensive activities of Pargyline.Approved
PenbutololAvanafil may increase the antihypertensive activities of Penbutolol.Approved, Investigational
Pentaerythritol TetranitrateAvanafil may increase the vasodilatory activities of Pentaerythritol Tetranitrate.Approved
PentobarbitalThe metabolism of Avanafil can be increased when combined with Pentobarbital.Approved, Vet Approved
PentoliniumAvanafil may increase the antihypertensive activities of Pentolinium.Approved
PerindoprilAvanafil may increase the antihypertensive activities of Perindopril.Approved
PhenobarbitalThe metabolism of Avanafil can be increased when combined with Phenobarbital.Approved
PhenoxybenzamineAvanafil may increase the antihypertensive activities of Phenoxybenzamine.Approved
PhentolamineAvanafil may increase the antihypertensive activities of Phentolamine.Approved
PhenytoinThe metabolism of Avanafil can be increased when combined with Phenytoin.Approved, Vet Approved
PinacidilAvanafil may increase the antihypertensive activities of Pinacidil.Withdrawn
PindololAvanafil may increase the antihypertensive activities of Pindolol.Approved
Platelet Activating FactorAvanafil may increase the antihypertensive activities of Platelet Activating Factor.Experimental
PolythiazideAvanafil may increase the antihypertensive activities of Polythiazide.Approved
PosaconazoleThe serum concentration of Avanafil can be increased when it is combined with Posaconazole.Approved, Investigational, Vet Approved
PrazosinAvanafil may increase the hypotensive activities of Prazosin.Approved
PrimidoneThe metabolism of Avanafil can be increased when combined with Primidone.Approved, Vet Approved
Propatyl nitrateAvanafil may increase the vasodilatory activities of Propatyl nitrate.Experimental, Investigational
PropranololAvanafil may increase the antihypertensive activities of Propranolol.Approved, Investigational
QuinaprilAvanafil may increase the antihypertensive activities of Quinapril.Approved, Investigational
RamiprilAvanafil may increase the antihypertensive activities of Ramipril.Approved
RanolazineThe serum concentration of Avanafil can be increased when it is combined with Ranolazine.Approved, Investigational
RemikirenAvanafil may increase the antihypertensive activities of Remikiren.Approved
RescinnamineAvanafil may increase the antihypertensive activities of Rescinnamine.Approved
ReserpineAvanafil may increase the antihypertensive activities of Reserpine.Approved, Investigational
RibociclibThe serum concentration of Avanafil can be increased when it is combined with Ribociclib.Approved
RifabutinThe metabolism of Avanafil can be increased when combined with Rifabutin.Approved
RifampicinThe metabolism of Avanafil can be increased when combined with Rifampicin.Approved
RifapentineThe metabolism of Avanafil can be increased when combined with Rifapentine.Approved
RilmenidineAvanafil may increase the antihypertensive activities of Rilmenidine.Investigational
RiociguatAvanafil may increase the antihypertensive activities of Riociguat.Approved
RucaparibThe serum concentration of Avanafil can be increased when it is combined with Rucaparib.Approved, Investigational
SaprisartanAvanafil may increase the antihypertensive activities of Saprisartan.Experimental
SapropterinSapropterin may increase the hypotensive activities of Avanafil.Approved, Investigational
SaquinavirThe serum concentration of Avanafil can be increased when it is combined with Saquinavir.Approved, Investigational
SarilumabThe therapeutic efficacy of Avanafil can be decreased when used in combination with Sarilumab.Approved
SelexipagAvanafil may increase the antihypertensive activities of Selexipag.Approved
SildenafilThe serum concentration of Avanafil can be increased when it is combined with Sildenafil.Approved, Investigational
SilodosinAvanafil may increase the hypotensive activities of Silodosin.Approved
SiltuximabThe serum concentration of Avanafil can be decreased when it is combined with Siltuximab.Approved
SimeprevirThe serum concentration of Avanafil can be increased when it is combined with Simeprevir.Approved
SitaxentanAvanafil may increase the antihypertensive activities of Sitaxentan.Approved, Investigational, Withdrawn
SpiraprilAvanafil may increase the antihypertensive activities of Spirapril.Approved
St. John's WortThe serum concentration of Avanafil can be decreased when it is combined with St. John's Wort.Investigational, Nutraceutical
StiripentolThe serum concentration of Avanafil can be increased when it is combined with Stiripentol.Approved
SulfisoxazoleThe serum concentration of Avanafil can be increased when it is combined with Sulfisoxazole.Approved, Vet Approved
TadalafilThe risk or severity of adverse effects can be increased when Tadalafil is combined with Avanafil.Approved, Investigational
TalinololAvanafil may increase the antihypertensive activities of Talinolol.Investigational
TamsulosinAvanafil may increase the hypotensive activities of Tamsulosin.Approved, Investigational
TelaprevirThe serum concentration of Avanafil can be increased when it is combined with Telaprevir.Approved, Withdrawn
TelithromycinThe serum concentration of Avanafil can be increased when it is combined with Telithromycin.Approved
TelmisartanAvanafil may increase the antihypertensive activities of Telmisartan.Approved, Investigational
TemocaprilAvanafil may increase the antihypertensive activities of Temocapril.Experimental, Investigational
TenitramineAvanafil may increase the vasodilatory activities of Tenitramine.Experimental
TerazosinAvanafil may increase the hypotensive activities of Terazosin.Approved
TerlipressinAvanafil may increase the antihypertensive activities of Terlipressin.Approved, Investigational
TetrahydropalmatineAvanafil may increase the antihypertensive activities of Tetrahydropalmatine.Investigational
TheodrenalineAvanafil may increase the antihypertensive activities of Theodrenaline.Investigational
TiboloneAvanafil may increase the antihypertensive activities of Tibolone.Approved, Investigational
TiclopidineThe serum concentration of Avanafil can be increased when it is combined with Ticlopidine.Approved
TicrynafenAvanafil may increase the antihypertensive activities of Ticrynafen.Withdrawn
TimololAvanafil may increase the antihypertensive activities of Timolol.Approved
TocilizumabThe serum concentration of Avanafil can be decreased when it is combined with Tocilizumab.Approved
TolazolineAvanafil may increase the antihypertensive activities of Tolazoline.Approved, Vet Approved
TolonidineAvanafil may increase the antihypertensive activities of Tolonidine.Experimental
TorasemideAvanafil may increase the antihypertensive activities of Torasemide.Approved
TrandolaprilAvanafil may increase the antihypertensive activities of Trandolapril.Approved
TravoprostAvanafil may increase the antihypertensive activities of Travoprost.Approved
TreprostinilAvanafil may increase the antihypertensive activities of Treprostinil.Approved, Investigational
TrichlormethiazideAvanafil may increase the antihypertensive activities of Trichlormethiazide.Approved, Vet Approved
TrimazosinAvanafil may increase the hypotensive activities of Trimazosin.Experimental
TrimethaphanAvanafil may increase the antihypertensive activities of Trimethaphan.Approved, Investigational
TrolnitrateAvanafil may increase the vasodilatory activities of Trolnitrate.Experimental
UdenafilThe risk or severity of adverse effects can be increased when Udenafil is combined with Avanafil.Approved, Investigational
UnoprostoneAvanafil may increase the antihypertensive activities of Unoprostone.Approved, Investigational
UrapidilAvanafil may increase the hypotensive activities of Urapidil.Investigational
ValsartanAvanafil may increase the antihypertensive activities of Valsartan.Approved, Investigational
VardenafilThe risk or severity of adverse effects can be increased when Vardenafil is combined with Avanafil.Approved
VemurafenibThe serum concentration of Avanafil can be decreased when it is combined with Vemurafenib.Approved
VenlafaxineThe serum concentration of Avanafil can be increased when it is combined with Venlafaxine.Approved
VerapamilThe serum concentration of Avanafil can be increased when it is combined with Verapamil.Approved
VincamineAvanafil may increase the antihypertensive activities of Vincamine.Experimental
VinpocetineAvanafil may increase the antihypertensive activities of Vinpocetine.Investigational
VoriconazoleThe serum concentration of Avanafil can be increased when it is combined with Voriconazole.Approved, Investigational
XipamideAvanafil may increase the antihypertensive activities of Xipamide.Experimental
XylometazolineAvanafil may increase the antihypertensive activities of Xylometazoline.Approved
ZiprasidoneThe serum concentration of Avanafil can be increased when it is combined with Ziprasidone.Approved
ZofenoprilAvanafil may increase the antihypertensive activities of Zofenopril.Experimental
Food Interactions
  • When taken with a high-fat meal, time to maximum plasma concentration is prolonged- Tmax = 1 hour 20 minutes

References

General References
  1. Gur S, Sikka SC, Hellstrom WJ: Novel phosphodiesterase-5 (PDE5) inhibitors in the alleviation of erectile dysfunction due to diabetes and ageing-induced oxidative stress. Expert Opin Investig Drugs. 2008 Jun;17(6):855-64. doi: 10.1517/13543784.17.6.855 . [PubMed:18491987]
  2. Bruzziches R, Francomano D, Gareri P, Lenzi A, Aversa A: An update on pharmacological treatment of erectile dysfunction with phosphodiesterase type 5 inhibitors. Expert Opin Pharmacother. 2013 Jul;14(10):1333-44. doi: 10.1517/14656566.2013.799665. Epub 2013 May 16. [PubMed:23675780]
  3. Kedia GT, Uckert S, Assadi-Pour F, Kuczyk MA, Albrecht K: Avanafil for the treatment of erectile dysfunction: initial data and clinical key properties. Ther Adv Urol. 2013 Feb;5(1):35-41. doi: 10.1177/1756287212466282. [PubMed:23372609]
External Links
KEGG Drug
D03217
PubChem Compound
9869929
PubChem Substance
175427065
ChemSpider
8045620
BindingDB
235766
ChEBI
66876
ChEMBL
CHEMBL1963681
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Avanafil
ATC Codes
G04BE10 — Avanafil
FDA label
Download (465 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedBasic ScienceAvanfil ADME / Semen Exposure / Sperm Function1
1CompletedPreventionHealthy Volunteers1
1CompletedTreatmentErectile Dysfunction (ED)8
1CompletedTreatmentRenal1
2CompletedTreatmentErectile Dysfunction (ED)1
3CompletedTreatmentErectile Dysfunction (ED)5
3CompletedTreatmentSexual Function and Fertility Disorders NEC-Erectile Dysfunction1
4CompletedTreatmentErectile Dysfunction (ED)2
4CompletedTreatmentVision1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
FormRouteStrength
TabletOral100 mg
TabletOral200 mg
TabletOral50 mg
TabletOral100 mg/1
TabletOral200 mg/1
TabletOral50 mg/1
Prices
Not Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US6656935No2000-09-132020-09-13Us
US7501409No2003-05-052023-05-05Us

Properties

State
Solid
Experimental Properties
Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.0297 mg/mLALOGPS
logP2.42ALOGPS
logP2.78ChemAxon
logS-4.2ALOGPS
pKa (Strongest Acidic)12.53ChemAxon
pKa (Strongest Basic)5.54ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count9ChemAxon
Hydrogen Donor Count3ChemAxon
Polar Surface Area125.39 Å2ChemAxon
Rotatable Bond Count9ChemAxon
Refractivity131.75 m3·mol-1ChemAxon
Polarizability50.87 Å3ChemAxon
Number of Rings4ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleYesChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9958
Blood Brain Barrier-0.7165
Caco-2 permeable-0.61
P-glycoprotein substrateSubstrate0.672
P-glycoprotein inhibitor INon-inhibitor0.6724
P-glycoprotein inhibitor IIInhibitor0.9038
Renal organic cation transporterNon-inhibitor0.5282
CYP450 2C9 substrateNon-substrate0.7215
CYP450 2D6 substrateNon-substrate0.795
CYP450 3A4 substrateSubstrate0.6184
CYP450 1A2 substrateNon-inhibitor0.5
CYP450 2C9 inhibitorNon-inhibitor0.5841
CYP450 2D6 inhibitorNon-inhibitor0.7495
CYP450 2C19 inhibitorNon-inhibitor0.5892
CYP450 3A4 inhibitorNon-inhibitor0.549
CYP450 inhibitory promiscuityHigh CYP Inhibitory Promiscuity0.5277
Ames testNon AMES toxic0.6096
CarcinogenicityNon-carcinogens0.8809
BiodegradationNot ready biodegradable0.9929
Rat acute toxicity2.5077 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.6671
hERG inhibition (predictor II)Inhibitor0.8671
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 pyrimidinecarboxamides. These are compounds containing a pyrimidine ring which bears a carboxamide.
Kingdom
Organic compounds
Super Class
Organoheterocyclic compounds
Class
Diazines
Sub Class
Pyrimidines and pyrimidine derivatives
Direct Parent
Pyrimidinecarboxamides
Alternative Parents
Anisoles / Benzylamines / Phenoxy compounds / Dialkylarylamines / Methoxybenzenes / Alkyl aryl ethers / Aminopyrimidines and derivatives / Secondary alkylarylamines / Chlorobenzenes / Aryl chlorides
show 12 more
Substituents
Pyrimidinecarboxamide / Anisole / Benzylamine / Phenol ether / Dialkylarylamine / Methoxybenzene / Phenoxy compound / Alkyl aryl ether / Aminopyrimidine / Chlorobenzene
show 30 more
Molecular Framework
Aromatic heteromonocyclic compounds
External Descriptors
monocarboxylic acid amide, organochlorine compound, pyrimidines, aromatic amide, prolinols (CHEBI:66876)

Targets

Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Inhibitor
General Function
Metal ion binding
Specific Function
Plays a role in signal transduction by regulating the intracellular concentration of cyclic nucleotides. This phosphodiesterase catalyzes the specific hydrolysis of cGMP to 5'-GMP (PubMed:9714779, ...
Gene Name
PDE5A
Uniprot ID
O76074
Uniprot Name
cGMP-specific 3',5'-cyclic phosphodiesterase
Molecular Weight
99984.14 Da
References
  1. Kedia GT, Uckert S, Assadi-Pour F, Kuczyk MA, Albrecht K: Avanafil for the treatment of erectile dysfunction: initial data and clinical key properties. Ther Adv Urol. 2013 Feb;5(1):35-41. doi: 10.1177/1756287212466282. [PubMed:23372609]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Vitamin d3 25-hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation react...
Gene Name
CYP3A4
Uniprot ID
P08684
Uniprot Name
Cytochrome P450 3A4
Molecular Weight
57342.67 Da
References
  1. Bruzziches R, Francomano D, Gareri P, Lenzi A, Aversa A: An update on pharmacological treatment of erectile dysfunction with phosphodiesterase type 5 inhibitors. Expert Opin Pharmacother. 2013 Jul;14(10):1333-44. doi: 10.1517/14656566.2013.799665. Epub 2013 May 16. [PubMed:23675780]

Drug created on March 19, 2008 10:18 / Updated on December 01, 2017 15:38