U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

Details

Stereochemistry ABSOLUTE
Molecular Formula C23H26ClN7O3
Molecular Weight 483.9515
Optical Activity UNSPECIFIED
Defined Stereocenters 1 / 1
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of AVANAFIL

SMILES

COc1ccc(cc1Cl)CN=c2c(cnc([nH]2)N3CCC[C@@]3([H])CO)C(=NCc4ncccn4)O

InChI

InChIKey=WEAJZXNPAWBCOA-INIZCTEOSA-N
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

HIDE SMILES / InChI

Description
Curator's Comment:: description was created based on several sources, including http://www.fiercepharma.com/marketing/vivus-announces-operational-update; https://www.ncbi.nlm.nih.gov/pubmed/?term=22704456

Avanafil is a PDE5 inhibitor approved for erectile dysfunction by FDA and by EMA. Avanafil is known by the trademark names Stendra and Spedra and was developed by Vivus Inc. Avanafil selectively inhibits PDE5, thus inhibiting the degradation of cyclic guanosine monophosphate (cGMP) found in the smooth muscle of the corpus cavernosa of the penis. The physiologic mechanism of erection of the penis involves release of nitric oxide (NO) in the corpus cavernosum during sexual stimulation. NO then activates the enzyme guanylate cyclase, which results in increased levels of cGMP, producing smooth muscle relaxation in the corpus cavernosum and allowing inflow of blood. Avanafil has no direct relaxant effect on isolated human corpus cavernosum, but enhances the effect of NO by inhibiting PDE5, which is responsible for degradation of cGMP in the corpus cavernosum. Because sexual stimulation is required to initiate the local release of nitric oxide, the inhibition of PDE5 has noeffect in the absence of sexual stimulation. The advantage of avanafil is that it has very fast onset of action compared with other PDE5 inhibitors. It is absorbed quickly, reaching a maximum concentration in about 30–45 minutes. About two-thirds of the participants were able to engage in sexual activity within 15 minutes.

Originator

Curator's Comment:: STENDRA is a registered U.S. trademark of VIVUS, Inc.

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
5.2 nM [IC50]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Curative
STENDRA

Approved Use

Indicated for the treatment of erectile dysfunction.

Launch Date

1.33548474E12
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
2231.63 ng/mL
100 mg 1 times / day steady-state, oral
dose: 100 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
[NO STEREO] AVANAFIL plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
2630 ng/mL
100 mg single, oral
dose: 100 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
AVANAFIL plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
7339.13 ng × h/mL
100 mg 1 times / day steady-state, oral
dose: 100 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
[NO STEREO] AVANAFIL plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
7148.67 ng × h/mL
100 mg single, oral
dose: 100 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
AVANAFIL plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
8.66 h
100 mg 1 times / day steady-state, oral
dose: 100 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
[NO STEREO] AVANAFIL plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
7.53 h
100 mg single, oral
dose: 100 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
AVANAFIL plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
5 h
single, oral
AVANAFIL plasma
Homo sapiens
population: UNKNOWN
age: ADULT
sex: MALE
food status: UNKNOWN
Funbound

Funbound

ValueDoseCo-administeredAnalytePopulation
1%
single, oral
AVANAFIL plasma
Homo sapiens
population: UNKNOWN
age: ADULT
sex: MALE
food status: UNKNOWN
Doses

Doses

DosePopulationAdverse events​
100 mg 1 times / day steady, oral
Recommended
Dose: 100 mg, 1 times / day
Route: oral
Route: steady
Dose: 100 mg, 1 times / day
Sources: Page: p. 99
unhealthy
Disc. AE: Dizziness, Pigmentation disorder...
AEs leading to
discontinuation/dose reduction:
Dizziness (2 patients)
Pigmentation disorder (1 patient)
Chest discomfort (1 patient)
Headache (1 patient)
Diarrhea (1 patient)
Dyspepsia (1 patient)
Pruritus (1 patient)
Eye swelling (1 patient)
Sources: Page: p. 99
200 mg 1 times / day steady, oral
Recommended
Dose: 200 mg, 1 times / day
Route: oral
Route: steady
Dose: 200 mg, 1 times / day
Sources: Page: p. 99
unhealthy
Disc. AE: Back pain, Headache...
AEs leading to
discontinuation/dose reduction:
Back pain (1 patient)
Headache (2 patients)
Erection increased (1 patient)
Sources: Page: p. 99
50 mg 1 times / day steady, oral
Dose: 50 mg, 1 times / day
Route: oral
Route: steady
Dose: 50 mg, 1 times / day
Sources: Page: p. 99
unhealthy
Disc. AE: Palpitations, Dizziness...
AEs leading to
discontinuation/dose reduction:
Palpitations (1 patient)
Dizziness (1 patient)
Heart rate increased (1 patient)
Sources: Page: p. 99
AEs

AEs

AESignificanceDosePopulation
Chest discomfort 1 patient
Disc. AE
100 mg 1 times / day steady, oral
Recommended
Dose: 100 mg, 1 times / day
Route: oral
Route: steady
Dose: 100 mg, 1 times / day
Sources: Page: p. 99
unhealthy
Diarrhea 1 patient
Disc. AE
100 mg 1 times / day steady, oral
Recommended
Dose: 100 mg, 1 times / day
Route: oral
Route: steady
Dose: 100 mg, 1 times / day
Sources: Page: p. 99
unhealthy
Dyspepsia 1 patient
Disc. AE
100 mg 1 times / day steady, oral
Recommended
Dose: 100 mg, 1 times / day
Route: oral
Route: steady
Dose: 100 mg, 1 times / day
Sources: Page: p. 99
unhealthy
Eye swelling 1 patient
Disc. AE
100 mg 1 times / day steady, oral
Recommended
Dose: 100 mg, 1 times / day
Route: oral
Route: steady
Dose: 100 mg, 1 times / day
Sources: Page: p. 99
unhealthy
Headache 1 patient
Disc. AE
100 mg 1 times / day steady, oral
Recommended
Dose: 100 mg, 1 times / day
Route: oral
Route: steady
Dose: 100 mg, 1 times / day
Sources: Page: p. 99
unhealthy
Pigmentation disorder 1 patient
Disc. AE
100 mg 1 times / day steady, oral
Recommended
Dose: 100 mg, 1 times / day
Route: oral
Route: steady
Dose: 100 mg, 1 times / day
Sources: Page: p. 99
unhealthy
Pruritus 1 patient
Disc. AE
100 mg 1 times / day steady, oral
Recommended
Dose: 100 mg, 1 times / day
Route: oral
Route: steady
Dose: 100 mg, 1 times / day
Sources: Page: p. 99
unhealthy
Dizziness 2 patients
Disc. AE
100 mg 1 times / day steady, oral
Recommended
Dose: 100 mg, 1 times / day
Route: oral
Route: steady
Dose: 100 mg, 1 times / day
Sources: Page: p. 99
unhealthy
Back pain 1 patient
Disc. AE
200 mg 1 times / day steady, oral
Recommended
Dose: 200 mg, 1 times / day
Route: oral
Route: steady
Dose: 200 mg, 1 times / day
Sources: Page: p. 99
unhealthy
Erection increased 1 patient
Disc. AE
200 mg 1 times / day steady, oral
Recommended
Dose: 200 mg, 1 times / day
Route: oral
Route: steady
Dose: 200 mg, 1 times / day
Sources: Page: p. 99
unhealthy
Headache 2 patients
Disc. AE
200 mg 1 times / day steady, oral
Recommended
Dose: 200 mg, 1 times / day
Route: oral
Route: steady
Dose: 200 mg, 1 times / day
Sources: Page: p. 99
unhealthy
Dizziness 1 patient
Disc. AE
50 mg 1 times / day steady, oral
Dose: 50 mg, 1 times / day
Route: oral
Route: steady
Dose: 50 mg, 1 times / day
Sources: Page: p. 99
unhealthy
Heart rate increased 1 patient
Disc. AE
50 mg 1 times / day steady, oral
Dose: 50 mg, 1 times / day
Route: oral
Route: steady
Dose: 50 mg, 1 times / day
Sources: Page: p. 99
unhealthy
Palpitations 1 patient
Disc. AE
50 mg 1 times / day steady, oral
Dose: 50 mg, 1 times / day
Route: oral
Route: steady
Dose: 50 mg, 1 times / day
Sources: Page: p. 99
unhealthy
OverviewDrug as perpetrator​

Drug as perpetrator​

TargetModalityActivityMetaboliteClinical evidence
no
no
no
no
no
no
no
no
no
no
not significant
not significant
unlikely [IC50 1 uM]
weak [Ki 15.2 uM]
weak (co-administration study)
Comment: Increased AUC by 2.0% and decreased Cmax by 14% using rosiglitazone
Page: 138.0
weak [Ki 2.9 uM]
weak (co-administration study)
Comment: Increased AUC and Cmax of omeprazole by 5.9% and 8.6%, respectively;
Page: 138.0
weak [Ki 43.9 uM]
weak (co-administration study)
Comment: Increased AUC and Cmax of desipramine by 5.7% and 5.2%, respectively;
Page: 138.0
weak
weak
no (co-administration study)
Comment: Did not alter changes in PT, INR, AUC, or Cmax of warfarin
Page: 9.0
weak
no (co-administration study)
Comment: Did not affect PK of amlodipine; no in vivo study to evaluate CYP3A4 induction by avanafil was conducted by the sponsor
Page: 138.0
Drug as victim

Drug as victim

TargetModalityActivityMetaboliteClinical evidence
weak
yes
yes (co-administration study)
Comment: ritonavir increased Cmax and AUC equal to approximately 2-fold and 13-fold, respectively;
Page: 8.0
yes
yes (co-administration study)
Comment: Ketoconazole increased systemic exposure (AUC) and maximum concentration (Cmax) equal to 13-fold and 3-fold, respectively; ritonavir increased Cmax and AUC equal to approximately 2-fold and 13-fold, respectively; erythromycin increased STENDRA 200 mg single-dose Cmax and AUC equal to approximately 2-fold and 3-fold, respectively; amlodipine increased the Cmax and AUC of avanafil by approximately 22% and 70%, respectively; The Cmax and AUC of amlodipine decreased by approximately 9% and 4%, respectively;
Page: 8.0
Tox targets

Tox targets

TargetModalityActivityMetaboliteClinical evidence
PubMed

PubMed

TitleDatePubMed
Gateways to clinical trials.
2006 Dec
Gateways to clinical trials.
2006 Oct
Gateways to clinical trials.
2006 Sep
Looking to the future for erectile dysfunction therapies.
2008
Novel phosphodiesterase-5 (PDE5) inhibitors in the alleviation of erectile dysfunction due to diabetes and ageing-induced oxidative stress.
2008 Jun
Tolerability and pharmacokinetics of avanafil, a phosphodiesterase type 5 inhibitor: a single- and multiple-dose, double-blind, randomized, placebo-controlled, dose-escalation study in healthy Korean male volunteers.
2010 Jun
Avanafil, a new rapid-onset phosphodiesterase 5 inhibitor for the treatment of erectile dysfunction.
2010 Nov
Avanafil for the treatment of erectile dysfunction: initial data and clinical key properties.
2013 Feb
Patents

Sample Use Guides

The starting dose is 100 mg taken as early as approximately 15 minutes before sexual activity, on an as needed basis. Take STENDRA no more than once a day. Based on efficacy and/or tolerability, the dose may be increased to 200 mg taken as early as approximately 15 minutes before sexual activity, or decreased to 50 mg taken approximately 30 minutes before sexual activity. Use the lowest dose that provides benefit. May be taken with or without food.
Route of Administration: Oral
In Vitro Use Guide
Unknown
Name Type Language
AVANAFIL
DASH   INN   MART.   MI   ORANGE BOOK   USAN   VANDF   WHO-DD  
INN   USAN  
Official Name English
AVANAFIL [MI]
Common Name English
AVANAFIL [ORANGE BOOK]
Common Name English
AVANAFIL [VANDF]
Common Name English
AVANAFIL [INN]
Common Name English
AVANAFIL [WHO-DD]
Common Name English
(S)-4-(3-CHLORO-4-METHOXYBENZYLAMINO)-2-(2-HYDROXYMETHYLPYRROLIDIN-1-YL)-N-PYRIMIDIN-2-YLMETHYL-5-PYRIMIDINECARBOXAMIDE
Systematic Name English
STENDRA
Brand Name English
SPEDRA
Brand Name English
AVANAFIL [USAN]
Common Name English
AVANAFIL [MART.]
Common Name English
4-((3-CHLORO-4-METHOXYBENZYL)AMINO)-2-((2S)-2-(HYDROXYMETHYL)PYRROLIDIN-1-YL)-N-(PYRIMIDIN-2-YLMETHYL)PYRIMIDINE-5-CARBOXAMIDE
Systematic Name English
5-PYRIMIDINECARBOXAMIDE, 4-(((3-CHLORO-4-METHOXYPHENYL)METHYL)AMINO)-2-((2S)-2-(HYDROXYMETHYL)-1-PYRROLIDINYL)-N-(2-PYRIMIDINYLMETHYL)-
Systematic Name English
TA-1790
Code English
Classification Tree Code System Code
WHO-ATC G04BE10
Created by admin on Sat Jun 26 01:01:17 UTC 2021 , Edited by admin on Sat Jun 26 01:01:17 UTC 2021
EMA ASSESSMENT REPORTS SPEDRA (AUTHORIZED: ERECTILE DYSFUNCTIONS)
Created by admin on Sat Jun 26 01:01:17 UTC 2021 , Edited by admin on Sat Jun 26 01:01:17 UTC 2021
NCI_THESAURUS C2127
Created by admin on Sat Jun 26 01:01:17 UTC 2021 , Edited by admin on Sat Jun 26 01:01:17 UTC 2021
LIVERTOX 78
Created by admin on Sat Jun 26 01:01:17 UTC 2021 , Edited by admin on Sat Jun 26 01:01:17 UTC 2021
NDF-RT N0000175599
Created by admin on Sat Jun 26 01:01:17 UTC 2021 , Edited by admin on Sat Jun 26 01:01:17 UTC 2021
Code System Code Type Description
ChEMBL
CHEMBL1963681
Created by admin on Sat Jun 26 01:01:17 UTC 2021 , Edited by admin on Sat Jun 26 01:01:17 UTC 2021
PRIMARY
MESH
C553414
Created by admin on Sat Jun 26 01:01:17 UTC 2021 , Edited by admin on Sat Jun 26 01:01:17 UTC 2021
PRIMARY
CAS
330784-47-9
Created by admin on Sat Jun 26 01:01:17 UTC 2021 , Edited by admin on Sat Jun 26 01:01:17 UTC 2021
PRIMARY
DRUG CENTRAL
4305
Created by admin on Sat Jun 26 01:01:17 UTC 2021 , Edited by admin on Sat Jun 26 01:01:17 UTC 2021
PRIMARY
MERCK INDEX
M2145
Created by admin on Sat Jun 26 01:01:17 UTC 2021 , Edited by admin on Sat Jun 26 01:01:17 UTC 2021
PRIMARY Merck Index
WIKIPEDIA
Avanafil
Created by admin on Sat Jun 26 01:01:17 UTC 2021 , Edited by admin on Sat Jun 26 01:01:17 UTC 2021
PRIMARY
PUBCHEM
9869929
Created by admin on Sat Jun 26 01:01:17 UTC 2021 , Edited by admin on Sat Jun 26 01:01:17 UTC 2021
PRIMARY
EPA CompTox
330784-47-9
Created by admin on Sat Jun 26 01:01:17 UTC 2021 , Edited by admin on Sat Jun 26 01:01:17 UTC 2021
PRIMARY
DRUG BANK
DB06237
Created by admin on Sat Jun 26 01:01:17 UTC 2021 , Edited by admin on Sat Jun 26 01:01:17 UTC 2021
PRIMARY
EVMPD
SUB34916
Created by admin on Sat Jun 26 01:01:17 UTC 2021 , Edited by admin on Sat Jun 26 01:01:17 UTC 2021
PRIMARY
FDA UNII
DR5S136IVO
Created by admin on Sat Jun 26 01:01:17 UTC 2021 , Edited by admin on Sat Jun 26 01:01:17 UTC 2021
PRIMARY
NCI_THESAURUS
C74354
Created by admin on Sat Jun 26 01:01:17 UTC 2021 , Edited by admin on Sat Jun 26 01:01:17 UTC 2021
PRIMARY
INN
8572
Created by admin on Sat Jun 26 01:01:17 UTC 2021 , Edited by admin on Sat Jun 26 01:01:17 UTC 2021
PRIMARY
RXCUI
1291301
Created by admin on Sat Jun 26 01:01:17 UTC 2021 , Edited by admin on Sat Jun 26 01:01:17 UTC 2021
PRIMARY RxNorm
IUPHAR
7448
Created by admin on Sat Jun 26 01:01:17 UTC 2021 , Edited by admin on Sat Jun 26 01:01:17 UTC 2021
PRIMARY