Details
Stereochemistry | ABSOLUTE |
Molecular Formula | C23H26ClN7O3 |
Molecular Weight | 483.951 |
Optical Activity | UNSPECIFIED |
Defined Stereocenters | 1 / 1 |
E/Z Centers | 0 |
Charge | 0 |
SHOW SMILES / InChI
SMILES
COC1=CC=C(CNC2=C(C=NC(=N2)N3CCC[C@H]3CO)C(=O)NCC4=NC=CC=N4)C=C1Cl
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
DescriptionCurator'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
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.
Approval Year
Cmax
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
2231.63 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/20637970/ |
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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/20637970/ |
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
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
7339.13 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/20637970/ |
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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/20637970/ |
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
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
8.66 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/20637970/ |
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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/20637970/ |
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
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
1% |
single, oral |
AVANAFIL plasma | Homo sapiens population: UNKNOWN age: ADULT sex: MALE food status: UNKNOWN |
Doses
Dose | Population | Adverse 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 Health Status: unhealthy Sex: M+F Sources: Page: p. 99 |
Disc. AE: Dizziness, Pigmentation disorder... AEs leading to discontinuation/dose reduction: Dizziness (2 patients) Sources: Page: p. 99Pigmentation disorder (1 patient) Chest discomfort (1 patient) Headache (1 patient) Diarrhea (1 patient) Dyspepsia (1 patient) Pruritus (1 patient) Eye swelling (1 patient) |
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 Health Status: unhealthy Sex: M+F Sources: Page: p. 99 |
Disc. AE: Back pain, Headache... AEs leading to discontinuation/dose reduction: Back pain (1 patient) Sources: Page: p. 99Headache (2 patients) Erection increased (1 patient) |
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 Health Status: unhealthy Sex: M+F Sources: Page: p. 99 |
Disc. AE: Palpitations, Dizziness... AEs leading to discontinuation/dose reduction: Palpitations (1 patient) Sources: Page: p. 99Dizziness (1 patient) Heart rate increased (1 patient) |
AEs
AE | Significance | Dose | Population |
---|---|---|---|
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 Health Status: unhealthy Sex: M+F Sources: Page: p. 99 |
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 Health Status: unhealthy Sex: M+F Sources: Page: p. 99 |
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 Health Status: unhealthy Sex: M+F Sources: Page: p. 99 |
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 Health Status: unhealthy Sex: M+F Sources: Page: p. 99 |
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 Health Status: unhealthy Sex: M+F Sources: Page: p. 99 |
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 Health Status: unhealthy Sex: M+F Sources: Page: p. 99 |
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 Health Status: unhealthy Sex: M+F Sources: Page: p. 99 |
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 Health Status: unhealthy Sex: M+F Sources: Page: p. 99 |
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 Health Status: unhealthy Sex: M+F Sources: Page: p. 99 |
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 Health Status: unhealthy Sex: M+F Sources: Page: p. 99 |
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 Health Status: unhealthy Sex: M+F Sources: Page: p. 99 |
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 Health Status: unhealthy Sex: M+F Sources: Page: p. 99 |
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 Health Status: unhealthy Sex: M+F Sources: Page: p. 99 |
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 Health Status: unhealthy Sex: M+F Sources: Page: p. 99 |
Overview
CYP3A4 | CYP2C9 | CYP2D6 | hERG |
---|---|---|---|
Drug as perpetrator
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
Page: 15.0 |
no | |||
Page: 9.0 |
no | |||
Page: 9.0 |
no | |||
Page: 9.0 |
no | |||
Page: 9.0 |
no | |||
Page: 15.0 |
no | |||
Page: 15.0 |
no | |||
Page: 15.0 |
no | |||
Page: 15.0 |
no | |||
Page: 15.0 |
no | |||
Page: 15.0 |
not significant | |||
Page: 15.0 |
not significant | |||
Page: 15.0 |
unlikely [IC50 1 uM] | |||
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/202276Orig1s000ClinPharmR.pdf#page=138 Page: 138.0 |
weak [Ki 15.2 uM] | weak (co-administration study) Comment: Increased AUC by 2.0% and decreased Cmax by 14% using rosiglitazone Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/202276Orig1s000ClinPharmR.pdf#page=138 Page: 138.0 |
||
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/202276Orig1s000ClinPharmR.pdf#page=138 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; Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/202276Orig1s000ClinPharmR.pdf#page=138 Page: 138.0 |
||
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/202276Orig1s000ClinPharmR.pdf#page=138 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; Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/202276Orig1s000ClinPharmR.pdf#page=138 Page: 138.0 |
||
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/202276Orig1s000ClinPharmR.pdf#page=138 Page: 138.0 |
weak | |||
Page: 9.0 |
weak | no (co-administration study) Comment: Did not alter changes in PT, INR, AUC, or Cmax of warfarin Page: 9.0 |
||
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/202276Orig1s000ClinPharmR.pdf#page=138 Page: 138.0 |
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 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/202276Orig1s000ClinPharmR.pdf#page=138 Page: 138.0 |
Drug as victim
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/202276Orig1s000ClinPharmR.pdf#page=158 Page: 158.0 |
weak | |||
Page: 8.0 |
yes | yes (co-administration study) Comment: ritonavir increased Cmax and AUC equal to approximately 2-fold and 13-fold, respectively; Page: 8.0 |
||
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
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/202276Orig1s000PharmR.pdf#page=29 Page: 29.0 |
PubMed
Title | Date | PubMed |
---|---|---|
Gateways to clinical trials. | 2004 Jul-Aug |
|
Gateways to clinical trials. | 2006 Sep |
|
Novel phosphodiesterase-5 (PDE5) inhibitors in the alleviation of erectile dysfunction due to diabetes and ageing-induced oxidative stress. | 2008 Jun |
|
Selective phosphodiesterase inhibitors: a promising target for cognition enhancement. | 2009 Jan |
|
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 |
|
An update on pharmacological treatment of erectile dysfunction with phosphodiesterase type 5 inhibitors. | 2013 Jul |
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
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Code | English |
Classification Tree | Code System | Code | ||
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WHO-ATC |
G04BE10
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EMA ASSESSMENT REPORTS |
SPEDRA (AUTHORIZED: ERECTILE DYSFUNCTIONS)
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NCI_THESAURUS |
C2127
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LIVERTOX |
NBK548149
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NDF-RT |
N0000175599
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66876
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CHEMBL1963681
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QQ-36
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C553414
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330784-47-9
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4305
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100000128159
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m2145
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Avanafil
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9869929
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DB06237
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SUB34916
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DR5S136IVO
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C74354
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8572
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1291301
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DR5S136IVO
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7448
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ACTIVE MOIETY