Sildenafil

Generic Name
Sildenafil
Brand Names
Liqrev, Revatio, Viagra, Vizarsin, Sildenafil Actavis, Sildenafil ratiopharm, Granpidam, Sildenafil Teva, Mysildecard
Drug Type
Small Molecule
Chemical Formula
C22H30N6O4S
CAS Number
139755-83-2
Unique Ingredient Identifier
3M7OB98Y7H
Background

In eliciting its mechanism of action, sildenafil ultimately prevents or minimizes the breakdown of cyclic guanosine monophosphate (cGMP) by inhibiting cGMP specific phosphodiesterase type 5 (PDE5) . The result of doing so allows cGMP present in both the penis and pulmonary vasculature to elicit smooth muscle relaxation and vasodilation that subsequently facilitates relief in pulmonary arterial hypertension and the increased flow of blood into the spongy erectile tissue of the penis that consequently allows it to grow in size and become erect and rigid .

Interestingly enough, it is precisely via this mechanism why sildenafil was at first researched as a potential treatment for angina - or chest pain associated with inadequate blood flow to the heart - before being serendipitously indicated for treating erectile dysfunction in the late 1980s . Nevertheless, it is because of this mechanism that sildenafil is also indicated for treating pulmonary arterial hypertension but is also additionally notorious for interacting with various anti-anginal or anti-hypertensive agents to develop potentially rapid, excessive, and/or fatal hypotensive crises .

Regardless, sildenafil, among a variety of other similar or related PDE5 inhibitors, has become a common and effective treatment for erectile dysfunction and since its formal approval for medical use in the public in 1998 , continues to see millions of prescriptions written for it internationally. Although the medication has historically been most popularly recognized as Pfizer's brand name Viagra, sildenafil is currently available generically and even as a non-prescription over the counter medication in some countries .

Indication

Sildenafil is a phosphodiesterase-5 (PDE5) inhibitor that is predominantly employed for two primary indications:

(1) the treatment of erectile dysfunction ; and

(2) treatment of pulmonary hypertension, where:

a) the US FDA specifically indicates sildenafil for the treatment of pulmonary arterial hypertension (PAH) (WHO Group I) in adults to improve exercise ability and delay clinical worsening . The delay in clinical worsening was demonstrated when sildenafil was added to background epoprostenol therapy . Studies establishing effectiveness were short-term (12 to 16 weeks), and included predominately patients with New York Heart Association (NYHA) Functional Class II-III symptoms and idiopathic etiology (71%) or associated with connective tissue disease (CTD) (25%) ;

b) the Canadian product monograph specifically indicates sildenafil for the treatment of primary pulmonary arterial hypertension (PPH) or pulmonary hypertension secondary to connective tissue disease (CTD) in adult patients with WHO functional class II or III who have not responded to conventional therapy . In addition, improvement in exercise ability and delay in clinical worsening was demonstrated in adult patients who were already stabilized on background epoprostenol therapy ; and

c) the EMA product information specifically indicates sildenafil for the treatment of adult patients with pulmonary arterial hypertension classified as WHO functional class II and III, to improve exercise capacity . Efficacy has been shown in primary pulmonary hypertension and pulmonary hypertension associated with connective tissue disease . The EMA label also indicates sildenafil for the treatment of pediatric patients aged 1 year to 17 years old with pulmonary arterial hypertension . Efficacy in terms of improvement of exercise capacity or pulmonary hemodynamics has been shown in primary pulmonary hypertension and pulmonary hypertension associated with congenital heart disease .

Associated Conditions
Erectile Dysfunction, NYHA Functional Class II-III Pulmonary arterial hypertension, Premature Ejaculation, Pulmonary Arterial Hypertension (PAH)
Associated Therapies
-

Sildenafil IV Bolus Study

Phase 1
Completed
Conditions
Interventions
First Posted Date
2008-12-02
Last Posted Date
2021-02-01
Lead Sponsor
Pfizer's Upjohn has merged with Mylan to form Viatris Inc.
Target Recruit Count
12
Registration Number
NCT00800592
Locations
🇧🇪

Pfizer Investigational Site, Bruxelles, Belgium

Study to Compare the Blood Levels of Sildenafil Following Administration of an Experimental Tablet vs. the Conventional Oral Tablet in Healthy Subjects.

Phase 1
Completed
Conditions
Interventions
First Posted Date
2008-11-21
Last Posted Date
2021-02-01
Lead Sponsor
Pfizer's Upjohn has merged with Mylan to form Viatris Inc.
Target Recruit Count
18
Registration Number
NCT00795938
Locations
🇺🇸

Pfizer Investigational Site, New Haven, Connecticut, United States

Evaluation of Sildenafil for the Treatment of Moderate Congestive Heart Failure

Phase 4
Withdrawn
Conditions
Interventions
First Posted Date
2008-11-19
Last Posted Date
2023-06-26
Lead Sponsor
University of New Mexico
Registration Number
NCT00793338
Locations
🇺🇸

Clinical Translational Science Center, Albuquerque, New Mexico, United States

Effects of Viagra on Heart Function in Patients With Heart Failure

First Posted Date
2008-10-29
Last Posted Date
2014-07-02
Lead Sponsor
MetroHealth Medical Center
Target Recruit Count
10
Registration Number
NCT00781508
Locations
🇺🇸

MetroHealth Medical Center, Cleveland, Ohio, United States

Study Evaluating the Addition of Sildenafil to Bosentan Therapy in Pulmonary Arterial Hypertension

Phase 3
Withdrawn
Conditions
Interventions
First Posted Date
2008-10-28
Last Posted Date
2009-11-13
Lead Sponsor
University Health Network, Toronto
Registration Number
NCT00780728

Taste Test of a New Formulation of Sildenafil (Revatio)

Completed
Conditions
Interventions
First Posted Date
2008-10-08
Last Posted Date
2021-02-01
Lead Sponsor
Pfizer's Upjohn has merged with Mylan to form Viatris Inc.
Target Recruit Count
4
Registration Number
NCT00768573
Locations
🇺🇸

Pfizer Investigational Site, Cambridge, Massachusetts, United States

Evaluating the Effectiveness of Sildenafil at Improving Health Outcomes and Exercise Ability in People With Diastolic Heart Failure (The RELAX Study)

Phase 3
Completed
Conditions
Interventions
First Posted Date
2008-10-01
Last Posted Date
2014-07-23
Lead Sponsor
Duke University
Target Recruit Count
216
Registration Number
NCT00763867
Locations
🇺🇸

Brigham and Women's Hospital, Boston, Massachusetts, United States

🇺🇸

Duke University Medical Center, Durham, North Carolina, United States

🇺🇸

University of Utah Health Sciences Center, Murray, Utah, United States

and more 7 locations

Combination Chemotherapy With Sildenafil Plus Carboplatin and Paclitaxel in Patients With Advanced Non-small Cell Lung Cancer

First Posted Date
2008-09-15
Last Posted Date
2011-09-07
Lead Sponsor
Hamamatsu University
Target Recruit Count
120
Registration Number
NCT00752115
Locations
🇯🇵

Hamamatsu University School of Medicine, Hamamatsu, Japan

An Open-Label, Extension Study Evaluating the Safety, Toleration, and Efficacy of Sildenafil in Women With Sexual Arousal Disorder

First Posted Date
2008-09-04
Last Posted Date
2021-02-01
Lead Sponsor
Pfizer's Upjohn has merged with Mylan to form Viatris Inc.
Target Recruit Count
267
Registration Number
NCT00746967
Locations
🇺🇸

Pfizer Investigational Site, Cheyenne, Wyoming, United States

The Assessment of Right Ventricular Contractility in Response to Sildenafil

Phase 3
Terminated
Conditions
Interventions
First Posted Date
2008-08-27
Last Posted Date
2021-04-19
Lead Sponsor
The Hospital for Sick Children
Target Recruit Count
10
Registration Number
NCT00742014
Locations
🇨🇦

The Hospital for Sick Children, Toronto, Ontario, Canada

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