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
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]
Clinical Trials
Title | Posted | Study ID | Phase | Status | Sponsor |
|---|---|---|---|---|---|
2025/06/26 | Phase 1 | Not yet recruiting | |||
2025/05/01 | Phase 2 | Recruiting | |||
2025/03/13 | Phase 4 | Recruiting | |||
2025/03/06 | Phase 1 | Completed | |||
2025/01/29 | Phase 2 | Recruiting | |||
2025/01/20 | Phase 1 | Not yet recruiting | Aspargo Labs, Inc | ||
2025/01/16 | Not Applicable | Recruiting | |||
2024/10/18 | Phase 4 | Recruiting | Charitable Union for the Research and Education of Peyronie's Disease | ||
2024/08/20 | Not Applicable | Completed | Muhammad Aamir Latif | ||
2024/07/26 | Phase 2 | Not yet recruiting |
FDA Drug Approvals
Approved Product | Manufacturer | NDC Code | Route | Strength | Effective Date |
|---|---|---|---|---|---|
| Camber Pharmaceuticals, Inc. | 31722-709 | ORAL | 25 mg in 1 1 | 5/17/2018 | |
| PD-Rx Pharmaceuticals, Inc. | 43063-982 | ORAL | 20 mg in 1 1 | 9/15/2023 | |
| Exelan Pharmaceuticals, Inc. | 76282-645 | ORAL | 100 mg in 1 1 | 8/3/2022 | |
| Proficient Rx LP | 63187-813 | ORAL | 20 mg in 1 1 | 12/1/2018 | |
| Northwind Pharmaceuticals, LLC | 51655-468 | ORAL | 100 mg in 1 1 | 1/24/2023 | |
| NIVAGEN PHARMACEUTICALS, INC. | 75834-240 | ORAL | 50 mg in 1 1 | 12/20/2023 | |
| NuCare Pharmaceuticals,Inc. | 68071-2217 | ORAL | 20 mg in 1 1 | 1/20/2022 | |
| Mylan Pharmaceuticals Inc. | 0378-1660 | ORAL | 100 mg in 1 1 | 7/20/2018 | |
| Reyoung Corporation | 82647-211 | ORAL | 50 mg in 1 1 | 4/14/2022 | |
| PD-Rx Pharmaceuticals, Inc. | 43063-941 | ORAL | 50 mg in 1 1 | 4/25/2023 |
EMA Drug Approvals
Approved Product | Authorization Holder | Status | Issued Date |
|---|---|---|---|
Authorised | 9/21/2009 | ||
Authorised | 11/30/2009 | ||
Authorised | 9/13/1998 | ||
Authorised | 11/14/2016 | ||
Authorised | 11/14/2016 | ||
Authorised | 10/28/2005 | ||
Authorised | 12/23/2009 | ||
Authorised | 12/10/2009 |
HSA Drug Approvals
Approved Product | Manufacturer | Approval Number | Dosage Form | Strength | Approval Date |
|---|---|---|---|---|---|
| SILDENAFIL STADA® FILM COATED TABLET 100MG | SIN15090P | TABLET, FILM COATED | 100mg | 9/22/2016 | |
| Revatio Film-Coated Tablets 20mg | SIN13244P | TABLET, FILM COATED | 20.0 mg/unit | 3/30/2007 | |
| INTAGRA 100 FILM COATED TABLET 100 MG | SIN16779P | TABLET, FILM COATED | 100 mg | 5/12/2023 | |
| Ernafil Tablet 100 mg | SIN14151P | TABLET, FILM COATED | 100.00 mg | 5/18/2012 | |
| SYNERRV SILDENAFIL FILM-COATED TABLETS 100MG | SIN16067P | TABLET, FILM COATED | 100mg | 12/29/2020 | |
| INTAGRA 50 FILM COATED TABLET 50 MG | SIN16778P | TABLET, FILM COATED | 50 mg | 5/12/2023 | |
| A-Sildenafil Tablets 100mg | SIN14394P | TABLET, FILM COATED | 100 mg | 8/19/2013 | |
| SILDENAFIL PHARMATHEN FILM-COATED TABLET 50MG | SIN15175P | TABLET, FILM COATED | 50mg | 2/14/2017 | |
| VIAGRA TABLET 100 mg | SIN10806P | TABLET, FILM COATED | 100mg | 3/17/1999 | |
| MAXIGRA 100 FILM-COATED TABLETS 100MG | SIN16684P | TABLET, FILM COATED | 100 mg | 2/6/2023 |
NMPA Drug Approvals
Approved Product | Company | Approval Number | Drug Type | Dosage Form | Approval Date |
|---|---|---|---|---|---|
| No NMPA approvals found for this drug. | |||||
PPB Drug Approvals
Approved Product | Registration No. | Company | Licence No. | Strength | Registration Date |
|---|---|---|---|---|---|
| No PPB approvals found for this drug. | |||||
TGA Drug Approvals
Health Canada Drug Approvals
Approved Product | Company | DIN | Dosage Form | Strength | Market Date |
|---|---|---|---|---|---|
| No Health Canada approvals found for this drug. | |||||
CIMA AEMPS Drug Approvals
Approved Product | Company | Registration Number | Pharmaceutical Form | Prescription Type | Status |
|---|---|---|---|---|---|
| VIZARSIN 100 mg COMPRIMIDOS RECUBIERTOS CON PELICULA EFG | Krka D.D. Novo Mesto | 09551009 | COMPRIMIDO RECUBIERTO CON PELÍCULA | Medicamento Sujeto A Prescripción Médica | Not Commercialized |
| VIAGRA 50 MG COMPRIMIDOS RECUBIERTOS CON PELICULA | 98077007IP | COMPRIMIDO RECUBIERTO CON PELÍCULA | Medicamento Sujeto A Prescripción Médica | Commercialized | |
| SILDENAFILO SANDOZ 100 mg COMPRIMIDOS EFG | Sandoz Farmaceutica S.A. | 71464 | COMPRIMIDO | Medicamento Sujeto A Prescripción Médica | Commercialized |
| Vizarsin 50 mg comprimidos bucodispersables | Krka D.D. Novo Mesto | 109551020 | COMPRIMIDO BUCODISPERSABLE | Medicamento Sujeto A Prescripción Médica | Commercialized |
| VIZARSIN 50 mg COMPRIMIDOS RECUBIERTOS CON PELICULA EFG | Krka D.D. Novo Mesto | 09551007 | COMPRIMIDO RECUBIERTO CON PELÍCULA | Medicamento Sujeto A Prescripción Médica | Commercialized |
| VIZARSIN 50 mg COMPRIMIDOS RECUBIERTOS CON PELICULA EFG | Krka D.D. Novo Mesto | 09551006 | COMPRIMIDO RECUBIERTO CON PELÍCULA | Medicamento Sujeto A Prescripción Médica | Commercialized |
| VIZARSIN 100 MG COMPRIMIDOS BUCODISPERSABLES | Krka D.D. Novo Mesto | 109551025 | COMPRIMIDO BUCODISPERSABLE | Medicamento Sujeto A Prescripción Médica | Commercialized |
| VIAGRA 100 MG COMPRIMIDOS RECUBIERTOS CON PELICULA | 98077011IP1 | COMPRIMIDO RECUBIERTO CON PELÍCULA | Medicamento Sujeto A Prescripción Médica | Not Commercialized | |
| VIAGRA COMPRIMIDOS RECUBIERTOS | 98077014IP | COMPRIMIDO RECUBIERTO CON PELÍCULA | Medicamento Sujeto A Prescripción Médica | Not Commercialized | |
| VIZARSIN 25 mg COMPRIMIDOS RECUBIERTOS CON PELICULA EFG | Krka D.D. Novo Mesto | 09551002 | COMPRIMIDO RECUBIERTO CON PELÍCULA | Medicamento Sujeto A Prescripción Médica | Commercialized |
Philippines FDA Drug Approvals
Approved Product | Company | License Number | Dosage Form | Strength | Approval Date |
|---|---|---|---|---|---|
| No Philippines FDA approvals found for this drug. | |||||
Saudi SFDA Drug Approvals
Approved Product | Company | License Number | Dosage Form | Strength | Approval Date |
|---|---|---|---|---|---|
| No Saudi SFDA approvals found for this drug. | |||||
Malaysia NPRA Drug Approvals
Approved Product | Company | Registration Number | Dosage Form | Strength | Approval Date |
|---|---|---|---|---|---|
| No Malaysia NPRA approvals found for this drug. | |||||
UK EMC Drug Information
Medicine Name | MA Holder | MA Number | Pharmaceutical Form | Active Ingredient | Authorization Date |
|---|---|---|---|---|---|
| No UK EMC drug information found for this drug. | |||||
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