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

Details

Stereochemistry ACHIRAL
Molecular Formula C23H32N6O4S
Molecular Weight 488.605
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of VARDENAFIL

SMILES

CCCc1nc(C)c2c(=O)nc(-c3cc(ccc3OCC)S(=O)(=O)N4CCN(CC)CC4)[nH]n12

InChI

InChIKey=SECKRCOLJRRGGV-UHFFFAOYSA-N
InChI=1S/C23H32N6O4S/c1-5-8-20-24-16(4)21-23(30)25-22(26-29(20)21)18-15-17(9-10-19(18)33-7-3)34(31,32)28-13-11-27(6-2)12-14-28/h9-10,15H,5-8,11-14H2,1-4H3,(H,25,26,30)

HIDE SMILES / InChI

Description
Curator's Comment:: http://www.accessdata.fda.gov/drugsatfda_docs/label/2014/021400s017lbl.pdf

Vardenafil (Levitra) is an oral therapy for the treatment of erectile dysfunction. It is a selective inhibitor of cyclic guanosine monophosphate (cGMP)-specific phosphodiesterase type 5 (PDE5). Penile erection is a hemodynamic process initiated by the relaxation of smooth muscle in the corpus cavernosum and its associated arterioles. During sexual stimulation, nitric oxide is released from nerve endings and endothelial cells in the corpus cavernosum. Nitric oxide activates the enzyme guanylate cyclase resulting in increased synthesis of cyclic guanosine monophosphate (cGMP) in the smooth muscle cells of the corpus cavernosum. The cGMP in turn triggers smooth muscle relaxation, allowing increased blood flow into the penis, resulting in erection. The tissue concentration of cGMP is regulated by both the rates of synthesis and degradation via phosphodiesterases (PDEs). The most abundant PDE in the human corpus cavernosum is the cGMPspecific phosphodiesterase type 5 (PDE5); therefore, the inhibition of PDE5 enhances erectile function by increasing the amount of cGMP.

CNS Activity

Curator's Comment:: Vardenafil crossed the BBB

Originator

Curator's Comment:: # Bayer

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
1 nM [Ki]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Levitra

Approved Use

LEVITRA is a phosphodiesterase 5 (PDE5) inhibitor indicated for the treatment of erectile dysfunction.

Launch Date

1061164800000
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
30.1 ng/mL
10 mg single, oral
dose: 10 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
VARDENAFIL plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
22.83 ng × h/mL
10 mg single, oral
dose: 10 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
VARDENAFIL plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
2.21 h
10 mg single, oral
dose: 10 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
VARDENAFIL plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
Doses

Doses

DosePopulationAdverse events​
2.4 mg 12 times / day multiple, respiratory
Highest studied dose
Dose: 2.4 mg, 12 times / day
Route: respiratory
Route: multiple
Dose: 2.4 mg, 12 times / day
Sources:
healthy, 27.5 years (range: 24-31 years)
Health Status: healthy
Age Group: 27.5 years (range: 24-31 years)
Sex: M+F
Sources:
120 mg single, oral
Highest studied dose
Dose: 120 mg
Route: oral
Route: single
Dose: 120 mg
Sources:
healthy, adult
Health Status: healthy
Age Group: adult
Sex: M
Sources:
Other AEs: Back pain, Myalgia...
Other AEs:
Back pain
Myalgia
Abnormal vision
Sources:
2.4 mg single, respiratory
Highest studied dose
Dose: 2.4 mg
Route: respiratory
Route: single
Dose: 2.4 mg
Sources:
healthy, adult
Health Status: healthy
Age Group: adult
Sex: M+F
Sources:
10 mg 1 times / day steady, oral
Recommended
Dose: 10 mg, 1 times / day
Route: oral
Route: steady
Dose: 10 mg, 1 times / day
Sources:
unhealthy, adult
Disc. AE: Headache, Flushing...
AEs leading to
discontinuation/dose reduction:
Headache (19 patients)
Flushing (10 patients)
Rhinitis (5 patients)
Tachycardia (4 patients)
Nausea (5 patients)
Liver function test abnormal (4 patients)
Dizziness (3 patients)
Hypesthesia (3 patients)
Abdominal pain (3 patients)
Palpitations (3 patients)
Sources:
AEs

AEs

AESignificanceDosePopulation
Abnormal vision
120 mg single, oral
Highest studied dose
Dose: 120 mg
Route: oral
Route: single
Dose: 120 mg
Sources:
healthy, adult
Health Status: healthy
Age Group: adult
Sex: M
Sources:
Back pain
120 mg single, oral
Highest studied dose
Dose: 120 mg
Route: oral
Route: single
Dose: 120 mg
Sources:
healthy, adult
Health Status: healthy
Age Group: adult
Sex: M
Sources:
Myalgia
120 mg single, oral
Highest studied dose
Dose: 120 mg
Route: oral
Route: single
Dose: 120 mg
Sources:
healthy, adult
Health Status: healthy
Age Group: adult
Sex: M
Sources:
Flushing 10 patients
Disc. AE
10 mg 1 times / day steady, oral
Recommended
Dose: 10 mg, 1 times / day
Route: oral
Route: steady
Dose: 10 mg, 1 times / day
Sources:
unhealthy, adult
Headache 19 patients
Disc. AE
10 mg 1 times / day steady, oral
Recommended
Dose: 10 mg, 1 times / day
Route: oral
Route: steady
Dose: 10 mg, 1 times / day
Sources:
unhealthy, adult
Abdominal pain 3 patients
Disc. AE
10 mg 1 times / day steady, oral
Recommended
Dose: 10 mg, 1 times / day
Route: oral
Route: steady
Dose: 10 mg, 1 times / day
Sources:
unhealthy, adult
Dizziness 3 patients
Disc. AE
10 mg 1 times / day steady, oral
Recommended
Dose: 10 mg, 1 times / day
Route: oral
Route: steady
Dose: 10 mg, 1 times / day
Sources:
unhealthy, adult
Hypesthesia 3 patients
Disc. AE
10 mg 1 times / day steady, oral
Recommended
Dose: 10 mg, 1 times / day
Route: oral
Route: steady
Dose: 10 mg, 1 times / day
Sources:
unhealthy, adult
Palpitations 3 patients
Disc. AE
10 mg 1 times / day steady, oral
Recommended
Dose: 10 mg, 1 times / day
Route: oral
Route: steady
Dose: 10 mg, 1 times / day
Sources:
unhealthy, adult
Liver function test abnormal 4 patients
Disc. AE
10 mg 1 times / day steady, oral
Recommended
Dose: 10 mg, 1 times / day
Route: oral
Route: steady
Dose: 10 mg, 1 times / day
Sources:
unhealthy, adult
Tachycardia 4 patients
Disc. AE
10 mg 1 times / day steady, oral
Recommended
Dose: 10 mg, 1 times / day
Route: oral
Route: steady
Dose: 10 mg, 1 times / day
Sources:
unhealthy, adult
Nausea 5 patients
Disc. AE
10 mg 1 times / day steady, oral
Recommended
Dose: 10 mg, 1 times / day
Route: oral
Route: steady
Dose: 10 mg, 1 times / day
Sources:
unhealthy, adult
Rhinitis 5 patients
Disc. AE
10 mg 1 times / day steady, oral
Recommended
Dose: 10 mg, 1 times / day
Route: oral
Route: steady
Dose: 10 mg, 1 times / day
Sources:
unhealthy, adult
Overview

OverviewOther

Drug as perpetrator​Drug as victim

Drug as victim

TargetModalityActivityMetaboliteClinical evidence
major
yes (co-administration study)
Comment: label: coadministration with ketoconazole (inhibitor) increased mean AUC and Cmax of vardenafil by 10-fold and 4-fold, respectively; coadministration with erythromycin (CYP3A4 substrate) increased mean AUC and Cmax of vardenafil, respectively; coadministration with indinavir (CYP3A4 inhibitor) increased mean AUC and Cmax of vardenafil by 16 fold and 7 fold, respectively; Ritonavir co-administered with vardenafil resulted in a 49-fold increase in vardenafil AUC and a 13­ fold increase in vardenafil Cmax;
Page: 19
minor
minor
minor
minor
yes
yes
yes
Tox targets

Tox targets

PubMed

PubMed

TitleDatePubMed
PDE-5 inhibition and sexual response: pharmacological mechanisms and clinical outcomes.
2002
Vardenafil: a review of its use in erectile dysfunction.
2003
Vardenafil enhances clitoral and vaginal blood flow responses to pelvic nerve stimulation in female dogs.
2003 Apr
Vardenafil reverses erectile dysfunction induced by paroxetine in rats.
2003 Apr
[How effective are PDE-5 inhibitors?].
2003 Apr
Sustained efficacy and tolerability of vardenafil, a highly potent selective phosphodiesterase type 5 inhibitor, in men with erectile dysfunction: results of a randomized, double-blind, 26-week placebo-controlled pivotal trial.
2003 Apr
The phosphodiesterase inhibitor 'war'.
2003 Apr
US advertising campaign begins for alternative to sildenafil.
2003 Aug 30
Oral drug treatment of erectile dysfunction.
2003 Dec
Vardenafil: a new approach to the treatment of erectile dysfunction.
2003 Dec
Effective treatment of erectile dysfunction with vardenafil.
2003 Jan
New phosphodiesterase type 5 inhibitors in the management of erectile dysfunction.
2003 Jun
Proceedings of the 99th meeting of the Food and Drug Administration Cardiovascular and Renal Drugs Advisory Committee. May 29th and 30th, 2003.
2003 Jun 17
[New PDE-5 inhibitor for treatment of impotence. 9 out of 10 have erections again].
2003 Jun 26
Gateways to clinical trials. March 2003.
2003 Mar
Effect of high-fat breakfast and moderate-fat evening meal on the pharmacokinetics of vardenafil, an oral phosphodiesterase-5 inhibitor for the treatment of erectile dysfunction.
2003 Mar
Gateways to clinical trials.
2003 May
Effects of medical or surgical castration on erectile function in an animal model.
2003 May-Jun
Switching patients with erectile dysfunction from sildenafil citrate to tadalafil: results of a European multicenter, open-label study of patient preference.
2003 Nov
Overview of phosphodiesterase 5 inhibition in erectile dysfunction.
2003 Nov 6
New tools 2003.
2003 Nov-Dec
[Drug therapy of erectile dysfunction--the current status].
2003 Oct
Phosphodiesterase type 5 inhibitors: a biochemical and clinical correlation survey.
2003 Oct
Safety and efficacy of vardenafil for the treatment of men with erectile dysfunction after radical retropubic prostatectomy.
2003 Oct
New drugs and dosage forms.
2003 Oct 1
Novel PDE5 inhibitors for the treatment of male erectile dysfunction.
2003 Oct-Nov
Efficacy and tolerability of vardenafil for treatment of erectile dysfunction in patient subgroups.
2003 Sep
Phosphodiesterase 5 inhibitors in male sexual dysfunction.
2003 Sep
Vardenafil (levitra) for erectile dysfunction.
2003 Sep 29
Structure of the catalytic domain of human phosphodiesterase 5 with bound drug molecules.
2003 Sep 4
FDA approves new drug for treatment of erectile dysfunction in men.
2003 Sep-Oct
[Comparison of efficacy and safety of phosphodiesterase type 5 inhibitors in the treatment of erectile dysfunction].
2004 Apr
Tadalafil and vardenafil.
2004 Apr
Novel phosphodiesterase type 5 inhibitors: assessing hemodynamic effects and safety parameters.
2004 Apr
Role of the cardiologist: clinical aspects of managing erectile dysfunction.
2004 Apr
Vardenafil: a novel type 5 phosphodiesterase inhibitor for the treatment of erectile dysfunction.
2004 Apr
Pills for erectile dysfunction: now there are three.
2004 Apr
Treatment of erectile dysfunction.
2004 Apr
Tadalafil (Cialis) and vardenafil (Levitra) recently approved drugs for erectile dysfunction.
2004 Feb
Drug approval highlights for 2003.
2004 Feb
Cardioprotection with phosphodiesterase-5 inhibition--a novel preconditioning strategy.
2004 Feb
Cialis is here. The soft sell.
2004 Feb 2
[Treatment of erectile dysfunction].
2004 Feb 29
Are they better than Viagra? Two new drugs for erectile dysfunction work like Viagra and carry similar risks and benefits. Their subtle differences, however, may make a difference for some men.
2004 Jan
Sustained efficacy and tolerability with vardenafil over 2 years of treatment in men with erectile dysfunction.
2004 Mar
Vardenafil--PDE5 inhibitor number 3.
2004 Mar
Pharmacokinetics, pharmacodynamics, and efficacy of phosphodiesterase type 5 inhibitors.
2004 Mar
Therapy of ED: PDE-5 Inhibitors.
2004 Mar-Apr
Emerging oral drugs for erectile dysfunction.
2004 May
The efficacy and safety of flexible-dose vardenafil (levitra) in a broad population of European men.
2004 May
Patents

Sample Use Guides

For most patients, the starting dose is 10 mg, up to once daily. Increase to 20 mg or decrease to 5 mg based on efficacy/tolerability.
Route of Administration: Oral
Treatment with vardenafil at concentrations of 50, 100, and 250 umol/L increased expression of PlGF in a dose-dependent manner in human umbilical vein endothelial cells.
Name Type Language
VARDENAFIL
EMA EPAR   HSDB   INN   MART.   MI   USAN   VANDF   WHO-DD  
INN   USAN  
Official Name English
VARDENAFIL [USAN]
Common Name English
VARDENAFIL [EMA EPAR]
Common Name English
VARDENAFIL [VANDF]
Common Name English
VARDENAFIL [WHO-DD]
Common Name English
VARDENAFIL [HSDB]
Common Name English
VARDENAFIL [INN]
Common Name English
VARDENAFIL [MART.]
Common Name English
1-((3-(3,4-DIHYDRO-5-METHYL-4-OXO-7-PROPYLIMIDAZO(5,1-F)-AS-TRIAZIN-2-YL)-4-ETHOXYPHENYL)SULFONYL)-4-ETHYLPIPERAZINE
Common Name English
VIVANZA
Brand Name English
BAY-389456
Code English
VARDENAFIL [MI]
Common Name English
BAY38-9456
Code English
Classification Tree Code System Code
EMA ASSESSMENT REPORTS LEVITRA (AUTHORIZED: ERECTILE DYSFUNCTIONS)
Created by admin on Sat Jun 26 03:33:38 UTC 2021 , Edited by admin on Sat Jun 26 03:33:38 UTC 2021
NDF-RT N0000020026
Created by admin on Sat Jun 26 03:33:38 UTC 2021 , Edited by admin on Sat Jun 26 03:33:38 UTC 2021
FDA ORPHAN DRUG 679319
Created by admin on Sat Jun 26 03:33:38 UTC 2021 , Edited by admin on Sat Jun 26 03:33:38 UTC 2021
WHO-ATC G04BE09
Created by admin on Sat Jun 26 03:33:38 UTC 2021 , Edited by admin on Sat Jun 26 03:33:38 UTC 2021
WHO-VATC QG04BE09
Created by admin on Sat Jun 26 03:33:38 UTC 2021 , Edited by admin on Sat Jun 26 03:33:38 UTC 2021
LIVERTOX 1022
Created by admin on Sat Jun 26 03:33:38 UTC 2021 , Edited by admin on Sat Jun 26 03:33:38 UTC 2021
NCI_THESAURUS C2127
Created by admin on Sat Jun 26 03:33:38 UTC 2021 , Edited by admin on Sat Jun 26 03:33:38 UTC 2021
NDF-RT N0000175599
Created by admin on Sat Jun 26 03:33:38 UTC 2021 , Edited by admin on Sat Jun 26 03:33:38 UTC 2021
EMA ASSESSMENT REPORTS VIVANZA (AUTHORIZED: ERECTILE DYSFUNCTIONS)
Created by admin on Sat Jun 26 03:33:38 UTC 2021 , Edited by admin on Sat Jun 26 03:33:38 UTC 2021
Code System Code Type Description
INN
7950
Created by admin on Sat Jun 26 03:33:38 UTC 2021 , Edited by admin on Sat Jun 26 03:33:38 UTC 2021
PRIMARY
MESH
C426063
Created by admin on Sat Jun 26 03:33:38 UTC 2021 , Edited by admin on Sat Jun 26 03:33:38 UTC 2021
PRIMARY
WIKIPEDIA
VARDENAFIL
Created by admin on Sat Jun 26 03:33:38 UTC 2021 , Edited by admin on Sat Jun 26 03:33:38 UTC 2021
PRIMARY
NCI_THESAURUS
C66650
Created by admin on Sat Jun 26 03:33:38 UTC 2021 , Edited by admin on Sat Jun 26 03:33:38 UTC 2021
PRIMARY
HSDB
7304
Created by admin on Sat Jun 26 03:33:38 UTC 2021 , Edited by admin on Sat Jun 26 03:33:38 UTC 2021
PRIMARY
IUPHAR
7320
Created by admin on Sat Jun 26 03:33:38 UTC 2021 , Edited by admin on Sat Jun 26 03:33:38 UTC 2021
PRIMARY
LACTMED
Vardenafil
Created by admin on Sat Jun 26 03:33:38 UTC 2021 , Edited by admin on Sat Jun 26 03:33:38 UTC 2021
PRIMARY
RXCUI
306674
Created by admin on Sat Jun 26 03:33:38 UTC 2021 , Edited by admin on Sat Jun 26 03:33:38 UTC 2021
PRIMARY RxNorm
PUBCHEM
135400189
Created by admin on Sat Jun 26 03:33:38 UTC 2021 , Edited by admin on Sat Jun 26 03:33:38 UTC 2021
PRIMARY
EPA CompTox
224785-90-4
Created by admin on Sat Jun 26 03:33:38 UTC 2021 , Edited by admin on Sat Jun 26 03:33:38 UTC 2021
PRIMARY
ChEMBL
CHEMBL1520
Created by admin on Sat Jun 26 03:33:38 UTC 2021 , Edited by admin on Sat Jun 26 03:33:38 UTC 2021
PRIMARY
CAS
224785-90-4
Created by admin on Sat Jun 26 03:33:38 UTC 2021 , Edited by admin on Sat Jun 26 03:33:38 UTC 2021
PRIMARY
DRUG BANK
DB00862
Created by admin on Sat Jun 26 03:33:38 UTC 2021 , Edited by admin on Sat Jun 26 03:33:38 UTC 2021
PRIMARY
FDA UNII
UCE6F4125H
Created by admin on Sat Jun 26 03:33:38 UTC 2021 , Edited by admin on Sat Jun 26 03:33:38 UTC 2021
PRIMARY
DRUG CENTRAL
2809
Created by admin on Sat Jun 26 03:33:38 UTC 2021 , Edited by admin on Sat Jun 26 03:33:38 UTC 2021
PRIMARY
MERCK INDEX
M11394
Created by admin on Sat Jun 26 03:33:38 UTC 2021 , Edited by admin on Sat Jun 26 03:33:38 UTC 2021
PRIMARY Merck Index
EVMPD
SUB20047
Created by admin on Sat Jun 26 03:33:38 UTC 2021 , Edited by admin on Sat Jun 26 03:33:38 UTC 2021
PRIMARY