Overview

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)

Research Report

Published: Jul 14, 2025

Sildenafil (DB00203): A Comprehensive Monograph on its Pharmacology, Clinical Utility, and Developmental History

Executive Summary

Sildenafil is a small molecule drug that functions as a potent and selective inhibitor of phosphodiesterase type 5 (PDE5), an enzyme critical to the regulation of blood flow in specific tissues.[1] It is globally recognized under its original brand name, Viagra, for the treatment of erectile dysfunction (ED), and as Revatio for the management of pulmonary arterial hypertension (PAH).[3] The discovery of sildenafil represents a landmark case of pharmaceutical serendipity; it was initially investigated in the late 1980s and early 1990s as a potential treatment for angina pectoris, a form of cardiovascular disease.[1] When clinical trials revealed its limited efficacy for angina but a pronounced and unexpected effect on penile erections, the drug's developmental trajectory was famously redirected.[6]

The pharmacological basis of sildenafil's action lies in its ability to enhance the nitric oxide (NO)/cyclic guanosine monophosphate (cGMP) signaling pathway. By inhibiting PDE5, sildenafil prevents the degradation of cGMP, leading to prolonged smooth muscle relaxation and vasodilation in the corpus cavernosum of the penis and the pulmonary vasculature.[1] This mechanism requires sexual stimulation to initiate the release of NO, meaning the drug facilitates a natural physiological response rather than inducing an artificial one.[1]

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Clinical Trials

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Title	Posted	Study ID	Phase	Status	Sponsor
Sildenafil for Post-capillary Pulmonary Hypertension in Patients Undergoing Cardiac Surgery	2011/11/29	NCT01481350	Phase 2	Completed	University of Turin, Italy
Comparison of Efficacy Different Treatment Regimens in Pulmonary Hypertension Secondary to Lung Disease and or Hypoxia	2011/10/10	NCT01449253	Phase 4	UNKNOWN	All India Institute of Medical Sciences, New Delhi
SPHERIC-1. Sildenafil and Pulmonary HypERtension In COPD	2011/09/28	NCT01441934	Phase 3	UNKNOWN	Italian Association of Hospital Pneumologists
Lybrido for Female Sexual Dysfunction	2011/09/13	NCT01432665	Phase 2	Completed	Emotional Brain NY Inc.
Role of Sildenafil Citrate in Patients With Unexplained Recurrent Miscarriages	2011/08/18	NCT01419392	Phase 4	UNKNOWN	Ain Shams University
Renin-Angiotensin and Fibrinolysis in Humans: Effect of Long-Term PDE5 Inhibition on Glucose Homeostasis	2011/08/04	NCT01409993	Phase 4	Terminated	Vanderbilt University
Study of Sildenafil to Treat Newborns With Persistent Pulmonary Hypertension	2011/08/03	NCT01409031	Phase 2	Terminated	University of Colorado, Denver
Pharmacokinetic Effects of QTI571 on Sildenafil and Bosentan in Pulmonary Arterial Hypertension Participants	2011/07/12	NCT01392469	Phase 3	Completed	Novartis Pharmaceuticals
Effects of Sildenafil in Resistant Hypertensives and Genetic Polymorphism	2011/07/12	NCT01392638	Not Applicable	Completed	University of Campinas, Brazil
Responsiveness of Exercise Tests in Pulmonary Arterial Hypertension	2011/07/11	NCT01391104	Not Applicable	Completed	Laval University

FDA Drug Approvals

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Approved Product	Manufacturer	NDC Code	Route	Strength	Effective Date
Sildenafil	Reyoung Corporation	82647-210	ORAL	25 mg in 1 1	4/14/2022
Sildenafil	Medsource Pharmaceuticals	45865-833	ORAL	20 mg in 1 1	12/24/2018
Revatio	Viatris Specialty LLC	58151-385	ORAL	10 mg in 1 mL	12/18/2024
Sildenafil Citrate	ANI Pharmaceuticals, Inc.	70954-408	ORAL	50 mg in 1 1	9/5/2023
SILDENAFIL	Northwind Pharmaceuticals, LLC	51655-131	ORAL	20 mg in 1 1	11/6/2014
SILDENAFIL CITRATE	NIVAGEN PHARMACEUTICALS, INC.	75834-272	ORAL	25 mg in 1 1	12/20/2023
SILDENAFIL CITRATE	Proficient Rx LP	71205-657	ORAL	100 mg in 1 1	7/6/2023
Sildenafil	Northwind Pharmaceuticals, LLC	51655-172	ORAL	20 mg in 1 1	4/24/2023
Sildenafil	Taro Pharmaceuticals U.S.A. Inc.	51672-4231	ORAL	10 mg in 1 mL	12/12/2023
Sildenafil	CALVIN, SCOTT AND COMPANY, INCORPORATED	17224-460	ORAL	20 mg in 1 1	12/3/2019

EMA Drug Approvals

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Approved Product	Authorization Holder	Status	Issued Date
No EMA approvals found for this drug.

HSA Drug Approvals

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Approved Product	Manufacturer	Approval Number	Dosage Form	Strength	Approval Date
No HSA approvals found for this drug.

NMPA Drug Approvals

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Approved Product	Company	Approval Number	Drug Type	Dosage Form	Approval Date
No NMPA approvals found for this drug.

PPB Drug Approvals

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Approved Product	Registration No.	Company	Licence No.	Strength	Registration Date
No PPB approvals found for this drug.

TGA Drug Approvals

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Approved Product	ARTG ID	Sponsor	Registration Type	Status	Registration Date
No TGA approvals found for this drug.

Health Canada Drug Approvals

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Approved Product	Company	DIN	Dosage Form	Strength	Market Date
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CIMA AEMPS Drug Approvals

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Approved Product	Company	Registration Number	Pharmaceutical Form	Prescription Type	Status
No CIMA AEMPS (Spain) approvals found for this drug.

Philippines FDA Drug Approvals

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Approved Product	Company	License Number	Dosage Form	Strength	Approval Date
No Philippines FDA approvals found for this drug.

Saudi SFDA Drug Approvals

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Approved Product	Company	License Number	Dosage Form	Strength	Approval Date
No Saudi SFDA approvals found for this drug.

Malaysia NPRA Drug Approvals

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No Malaysia NPRA approvals found for this drug.

UK EMC Drug Information

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Medicine Name	MA Holder	MA Number	Pharmaceutical Form	Active Ingredient	Authorization Date
No UK EMC drug information found for this drug.