Wikipedia:WikiProject Chemicals/Chembox validation/VerifiedDataSandbox and Sildenafil: Difference between pages

{{Short description|Drug for erectile dysfunction and hypertension}}

{{Redirect|Viagra|other uses|Viagra (disambiguation)}}

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{{Use dmy dates|date=February 2024}}

{{cs1 config | name-list-style=vanc | display-authors=6}}

{{Blacklisted-links|1=

* http://www.viagra.com/

*: ''Triggered by <code>viagra(?!nde\.ct\.it\b)</code> on the global blacklist''|bot=Cyberbot II|invisible=true}}

{{Infobox drug

| Verifiedfields = changed

| Watchedfields = changed

| verifiedrevid = 477173085

| image = Sildenafil structure.svg

| alt =

| width = 250

| alt2 =

<!-- Clinical data -->

| pronounce = {{IPAc-en|s|ɪ|l|ˈ|d|ɛ|n|ə|f|ɪ|l}} {{respell|sil|DEN|ə-fil}}

| tradename = Viagra, others

| DailyMedID = Sildenafil

| pregnancy_AU = B1

| pregnancy_AU_comment = <ref name="Drugs.com pregnancy">{{cite web | title=Sildenafil Use During Pregnancy | website=Drugs.com | date=7 October 2019 | url=https://www.drugs.com/pregnancy/sildenafil.html | access-date=6 October 2020 | archive-date=12 October 2020 | archive-url=https://web.archive.org/web/20201012160551/https://www.drugs.com/pregnancy/sildenafil.html | url-status=live }}</ref>

| pregnancy_category =

| routes_of_administration = [[Oral administration|Oral]], [[Intravenous therapy|intravenous]], [[sublingual administration|sublingual]]

| class =

| ATC_prefix = G04

| ATC_suffix = BE03

| ATC_supplemental =

<!-- Legal status -->

| legal_AU = S4

| legal_AU_comment =

| legal_BR = <!-- OTC, A1, A2, A3, B1, B2, C1, C2, C3, C4, C5, D1, D2, E, F -->

| legal_BR_comment =

| legal_CA = Rx-only

| legal_CA_comment =

| legal_DE = <!-- Anlage I, II, III or Unscheduled -->

| legal_DE_comment =

| legal_NZ = <!-- Class A, B, C -->

| legal_NZ_comment =

| legal_UK = P

| legal_UK_comment = /&nbsp;[[Prescription drug|POM]]<ref>{{cite web | title=Viagra 25mg film-coated tablets - Summary of Product Characteristics (SmPC) | website=(emc) | date=7 August 2020 | url=https://www.medicines.org.uk/emc/product/1072/smpc | access-date=6 October 2020}}</ref><ref>{{cite web | title=Viagra Connect 50 mg film-coated tablets - Summary of Product Characteristics (SmPC) | website=(emc) | date=5 December 2017 | url=https://www.medicines.org.uk/emc/product/8725/smpc | access-date=6 October 2020 | archive-date=9 October 2020 | archive-url=https://web.archive.org/web/20201009144326/https://www.medicines.org.uk/emc/product/8725/smpc | url-status=live }}</ref>

| legal_US = Rx-only

| legal_US_comment = <ref name="Viagra FDA label" />

| legal_EU = Rx-only

| legal_EU_comment = <ref name="Viagra EPAR">{{cite web | title=Viagra EPAR | website=[[European Medicines Agency]] | date=17 September 2018 | url=https://www.ema.europa.eu/en/medicines/human/EPAR/viagra | access-date=6 October 2020 | archive-date=11 October 2020 | archive-url=https://web.archive.org/web/20201011024432/https://www.ema.europa.eu/en/medicines/human/EPAR/viagra | url-status=live }}</ref><ref name="Revatio EPAR">{{cite web | title=Revatio EPAR | website=[[European Medicines Agency]] | date=17 September 2018 | url=https://www.ema.europa.eu/en/medicines/human/EPAR/revatio | access-date=6 October 2020 | archive-date=11 November 2020 | archive-url=https://web.archive.org/web/20201111211205/https://www.ema.europa.eu/en/medicines/human/EPAR/revatio | url-status=live }}</ref>

| legal_UN = <!-- N I, II, III, IV / P I, II, III, IV -->

| legal_UN_comment =

<!-- Pharmacokinetic data -->

| bioavailability = 41% (mean)<ref>{{cite journal | vauthors = Nichols DJ, Muirhead GJ, Harness JA | title = Pharmacokinetics of sildenafil after single oral doses in healthy male subjects: absolute bioavailability, food effects and dose proportionality | journal = British Journal of Clinical Pharmacology | volume = 53 | issue = Suppl 1 | pages = 5S–12S | date = 6 March 2002 | pmid = 11879254 | pmc = 1874258 | doi = 10.1046/j.0306-5251.2001.00027.x }}</ref>

| protein_bound = ~96%

| metabolism = [[Liver]]: [[CYP3A4]] (major route), [[CYP2C9]] (minor route)

| metabolites = ''N''-desmethylsildenafil (~50% potency for PDE₅)

| onset = 20 minutes

| elimination_half-life = 3–4 hours

| duration_of_action =

| excretion = Feces (~80%), urine (~13%)<ref name="Viagra FDA label"/>

<!-- Identifiers -->

| index2_label = citrate

| CAS_number_Ref = {{cascite|correct|CAS}}

| CAS_number2_Ref = {{cascite|correct|CAS}}

| CAS_number2 = 171599-83-0

| CAS_supplemental =

| PubChem = 135398744

| PubChem2 = 135413523

| IUPHAR_ligand =

| DrugBank2_Ref = {{drugbankcite|correct|drugbank}}

| DrugBank2 = DBSALT000347

| ChemSpiderID = 5023

| ChemSpiderID2_Ref = {{chemspidercite|correct|chemspider}}

| ChemSpiderID2 = 56586

| UNII2_Ref = {{fdacite|correct|FDA}}

| UNII2 = BW9B0ZE037

| KEGG2_Ref = {{keggcite|correct|kegg}}

| KEGG2 = D02229

| ChEBI_Ref = {{ebicite|correct|EBI}}

| ChEBI = 9139

| ChEBI2_Ref = {{ebicite|correct|EBI}}

| ChEBI2 = 58987

| ChEMBL_Ref = {{ebicite|correct|EBI}}

| ChEMBL2_Ref = {{ebicite|correct|EBI}}

| ChEMBL2 = 1737

| NIAID_ChemDB =

| PDB_ligand = VIA

| synonyms =

<!-- Chemical and physical data -->

| IUPAC_name = 5-{2-Ethoxy-5-[(4-methylpiperazin-1-yl)sulfonyl]phenyl}-1-methyl-3-propyl-1,6-dihydro-6''H''-pyrazolo[4,3-''d'']pyrimidin-7-one

| C=22 | H=30 | N=6 | O=4 | S=1

| SMILES = CCCC1=NN(C2=C1N=C(NC2=O)C3=C(C=CC(=C3)S(=O)(=O)N4CCN(CC4)C)OCC)C

| StdInChI_Ref = {{stdinchicite|changed|chemspider}}

| StdInChI = 1S/C22H30N6O4S/c1-5-7-17-19-20(27(4)25-17)22(29)24-21(23-19)16-14-15(8-9-18(16)32-6-2)33(30,31)28-12-10-26(3)11-13-28/h8-9,14H,5-7,10-13H2,1-4H3,(H,23,24,29)

| StdInChI_comment =

| StdInChIKey_Ref = {{stdinchicite|changed|chemspider}}

| StdInChIKey = BNRNXUUZRGQAQC-UHFFFAOYSA-N

| density =

| density_notes =

| melting_point =

| melting_high =

| melting_notes =

| boiling_point =

| boiling_notes =

| solubility =

| sol_units =

| specific_rotation =

<!-- Definition and uses -->

'''Sildenafil''', sold under the brand name '''Viagra''', among others, is a [[medication]] used to treat [[erectile dysfunction]] and [[pulmonary hypertension|pulmonary arterial hypertension]].<ref name="Viagra FDA label" /><ref name=AHFS2014>{{cite web|title=Sildenafil Citrate|url=https://www.drugs.com/monograph/sildenafil-citrate.html|publisher=The American Society of Health-System Pharmacists|access-date=1 December 2014|archive-date=23 April 2020|archive-url=https://web.archive.org/web/20200423210530/https://www.drugs.com/monograph/sildenafil-citrate.html|url-status=live}}</ref> It is also sometimes used [[off-label]] for the treatment of certain symptoms in secondary [[Raynaud's phenomenon]].<ref name="Raynaud's treatment - sildenafil + other PDE5 inhibitors" /> It is unclear if it is effective for treating sexual dysfunction in females.<ref name=AHFS2014/> It can be taken [[oral administration|orally]] (swallowed by mouth), [[intravenous|intravenously]] (injection into a vein), or through the [[sublingual administration|sublingual route]] (dissolved under the tongue).<ref name=AHFS2014/><ref name=sublingual/> Onset when taken orally is typically within twenty minutes and lasts for about two hours.<ref name=AHFS2014/>

<!-- Side effects and interactions -->

Common side effects include [[headache]]s, [[heartburn]], and flushed skin.<ref name=AHFS2014/> Caution is advised in those with [[cardiovascular disease]].<ref name=AHFS2014/> Rare but serious side effects include vision problems, [[hearing loss]], and [[prolonged erection]] (priapism) that can lead to damage to the [[human penis|penis]].<ref name=AHFS2014/> Sildenafil should not be taken by people on [[Nitrovasodilator|nitric oxide donors]] such as [[Medical use of nitroglycerin|nitroglycerin]] (glycerin trinitrate), as this may result in a serious drop in [[blood pressure]].<ref name=AHFS2014/>

<!-- Mechanism of action -->

Sildenafil acts by blocking [[cGMP-specific phosphodiesterase type 5|phosphodiesterase 5]] (PDE₅), an [[enzyme]] that promotes breakdown of [[Cyclic guanosine monophosphate|cGMP]], which regulates blood flow in the penis.<ref name=AHFS2014/> It requires [[sexual arousal]] to work, and does not by itself cause or increase sexual arousal.<ref name=AHFS2014/> It also results in dilation of the blood vessels in the lungs.<ref name=AHFS2014/>

<!-- History, society and culture -->

[[Pfizer]] originally discovered the medication in 1989 while looking for a treatment for [[angina]].<ref name=Gold2018>{{cite journal | vauthors = Goldstein I, Burnett AL, Rosen RC, Park PW, Stecher VJ | title = The Serendipitous Story of Sildenafil: An Unexpected Oral Therapy for Erectile Dysfunction | journal = Sexual Medicine Reviews | volume = 7 | issue = 1 | pages = 115–128 | date = January 2019 | pmid = 30301707 | doi = 10.1016/j.sxmr.2018.06.005 | s2cid = 52945888 }}</ref> It was approved for medical use in the United States and in the European Union in 1998.<ref name="Viagra EPAR" /><ref name=AHFS2014/><ref name=Gold2018/><ref>{{cite web | title=Drug Approval Package: Viagra (sildenafil citrate) NDA #020895 | website=U.S. [[Food and Drug Administration]] (FDA) | date=27 March 1998 | url=https://www.accessdata.fda.gov/drugsatfda_docs/NDA/98/viagra/viagra_toc.cfm | access-date=15 February 2021 | archive-date=31 March 2021 | archive-url=https://web.archive.org/web/20210331145847/https://www.accessdata.fda.gov/drugsatfda_docs/NDA/98/viagra/viagra_toc.cfm | url-status=live }}</ref> In 2021, it was the 157th most commonly prescribed medication in the United States, with more than 3{{nbsp}}million prescriptions.<ref>{{cite web | title=The Top 300 of 2021 | url=https://clincalc.com/DrugStats/Top300Drugs.aspx | website=ClinCalc | access-date=14 January 2024 | archive-date=15 January 2024 | archive-url=https://web.archive.org/web/20240115223848/https://clincalc.com/DrugStats/Top300Drugs.aspx | url-status=live }}</ref><ref>{{cite web | title = Sildenafil - Drug Usage Statistics | website = ClinCalc | url = https://clincalc.com/DrugStats/Drugs/Sildenafil | access-date = 14 January 2024 | archive-date = 8 July 2020 | archive-url = https://web.archive.org/web/20200708061504/https://clincalc.com/DrugStats/Drugs/Sildenafil | url-status = live }}</ref> It is available as a [[generic medication]].<ref>{{cite news |vauthors=Gordon S |title=Generic Viagra: Two versions of sildenafil hit the market today |website=CBS News |url=https://www.cbsnews.com/news/generic-viagra-two-versions-of-sildenafil-hit-the-market-today/ |date=11 December 2017 |access-date=24 November 2018 |archive-date=25 November 2018 |archive-url=https://web.archive.org/web/20181125073951/https://www.cbsnews.com/news/generic-viagra-two-versions-of-sildenafil-hit-the-market-today/ |url-status=live }}</ref><ref>{{cite web | title=Competitive Generic Therapy Approvals | website=U.S. [[Food and Drug Administration]] (FDA) | date=3 March 2023 | url=https://www.fda.gov/drugs/generic-drugs/competitive-generic-therapy-approvals | access-date=6 March 2023 | archive-date=12 February 2022 | archive-url=https://web.archive.org/web/20220212032835/https://www.fda.gov/drugs/generic-drugs/competitive-generic-therapy-approvals | url-status=live }}</ref> In the United Kingdom, it is available [[over the counter]].<ref>{{cite news |vauthors=LaMattina J |title=With Viagra Now Available Over-The-Counter In The U.K., Will The U.S. Follow Suit? |url=https://www.forbes.com/sites/johnlamattina/2018/05/01/with-viagra-now-available-over-the-counter-in-the-uk-will-the-us-follow-suit/ |access-date=24 November 2018 |work=Forbes |archive-date=25 November 2018 |archive-url=https://web.archive.org/web/20181125074100/https://www.forbes.com/sites/johnlamattina/2018/05/01/with-viagra-now-available-over-the-counter-in-the-uk-will-the-us-follow-suit/ |url-status=live }}</ref>

{{TOC limit}}

==Medical uses==

[[File:Viagra Tablette.jpg|thumb|Pfizer Viagra tablet in the trademark blue diamond shape]]

===Sexual dysfunction===

The primary indication of sildenafil is treatment of erectile dysfunction (inability to sustain a satisfactory erection to complete [[sexual intercourse]]). Its use is now one of the standard treatments for erectile dysfunction, including for males with [[diabetes mellitus]].<ref name="Vardi">{{cite journal | vauthors = Vardi M, Nini A | title = Phosphodiesterase inhibitors for erectile dysfunction in patients with diabetes mellitus | journal = The Cochrane Database of Systematic Reviews | issue = 1 | pages = CD002187 | date = January 2007 | volume = 2009 | pmid = 17253475 | pmc = 6718223 | doi = 10.1002/14651858.CD002187.pub3 }}</ref>

====Antidepressant-associated sexual dysfunction====

Tentative evidence suggests that sildenafil may help males who experience [[antidepressant]]-induced [[erectile dysfunction]].<ref name="Taylor">{{cite journal | vauthors = Taylor MJ, Rudkin L, Bullemor-Day P, Lubin J, Chukwujekwu C, Hawton K | title = Strategies for managing sexual dysfunction induced by antidepressant medication | journal = The Cochrane Database of Systematic Reviews | issue = 5 | pages = CD003382 | date = May 2013 | pmid = 23728643 | doi = 10.1002/14651858.CD003382.pub3 | url = https://kclpure.kcl.ac.uk/portal/en/publications/strategies-for-managing-sexual-dysfunction-induced-by-antidepressant-medication(5f0f0033-e139-42cc-9590-d3b5cad1bb25).html | doi-access = free | access-date = 30 November 2019 | archive-date = 10 October 2020 | archive-url = https://web.archive.org/web/20201010111725/https://kclpure.kcl.ac.uk/portal/en/publications/strategies-for-managing-sexual-dysfunction-induced-by-antidepressant-medication(5f0f0033-e139-42cc-9590-d3b5cad1bb25).html/ | url-status = live }}</ref>

===Pulmonary hypertension===

While sildenafil improves some markers of disease in people with [[Pulmonary hypertension|pulmonary arterial hypertension]], it does not appear to affect the risk of death or serious side effects.<ref name="Wang">{{cite journal | vauthors = Wang RC, Jiang FM, Zheng QL, Li CT, Peng XY, He CY, Luo J, Liang ZA | title = Efficacy and safety of sildenafil treatment in pulmonary arterial hypertension: a systematic review | journal = Respiratory Medicine | volume = 108 | issue = 3 | pages = 531–7 | date = March 2014 | pmid = 24462476 | doi = 10.1016/j.rmed.2014.01.003 | url = http://www.resmedjournal.com/article/S0954-6111(14)00023-7/pdf | access-date = 5 November 2016 | doi-access = free | archive-date = 29 August 2021 | archive-url = https://web.archive.org/web/20210829060021/https://www.resmedjournal.com/article/S0954-6111%2814%2900023-7/pdf | url-status = live }}</ref>

===Raynaud's phenomenon===

Sildenafil and other [[PDE5 inhibitor]]s are used off-label to alleviate [[vasospasm]] and treat severe ischemia and ulcers in fingers and toes for people with secondary [[Raynaud's phenomenon]];<ref name="Raynaud's treatment - sildenafil + other PDE5 inhibitors" /><ref name="Raynaud's treatments" /> these drugs have moderate efficacy for reducing the frequency and duration of vasospastic episodes.<ref name="Raynaud's treatment - sildenafil + other PDE5 inhibitors">{{cite journal | vauthors = Roustit M, Blaise S, Allanore Y, Carpentier PH, Caglayan E, Cracowski JL | title = Phosphodiesterase-5 inhibitors for the treatment of secondary Raynaud's phenomenon: systematic review and meta-analysis of randomised trials | journal = Annals of the Rheumatic Diseases | volume = 72 | issue = 10 | pages = 1696–9 | date = October 2013 | pmid = 23426043 | doi = 10.1136/annrheumdis-2012-202836 | quote = PDE-5 inhibitors appear to have significant but moderate efficacy in secondary [Raynaud's phenomenon]. | s2cid = 33666968 }}</ref> {{As of|2016|post=,}} their role more generally in Raynaud's was not clear.<ref name="Raynaud's treatments">{{cite journal | vauthors = Linnemann B, Erbe M | title = Raynaud's phenomenon and digital ischaemia--pharmacologic approach and alternative treatment options | journal = VASA. Zeitschrift für Gefässkrankheiten | volume = 45 | issue = 3 | pages = 201–12 | date = 2016 | pmid = 27129065 | doi = 10.1024/0301-1526/a000526 | quote = Phosphodiesterase inhibitors (e.g., sildenafil) can also improve [Raynaud's phenomenon] symptoms and ulcer healing }}</ref>

===High-altitude pulmonary edema===

Sildenafil has been studied for [[high-altitude pulmonary edema]], but its use is currently not recommended for that indication.<ref>{{cite journal | vauthors = Nieto Estrada VH, Molano Franco D, Medina RD, Gonzalez Garay AG, Martí-Carvajal AJ, Arevalo-Rodriguez I | title = Interventions for preventing high altitude illness: Part 1. Commonly-used classes of drugs | journal = The Cochrane Database of Systematic Reviews | volume = 6 | pages = CD009761 | date = June 2017 | issue = 12 | pmid = 28653390 | pmc = 6481751 | doi = 10.1002/14651858.CD009761.pub2 }}</ref>

==Adverse effects==

In [[clinical trial]]s, the most common [[Adverse drug reaction|adverse effects]] of sildenafil use included [[headache]], [[Flushing (physiology)|flushing]], [[indigestion]], [[nasal congestion]], and impaired vision, including [[photophobia]] and blurred vision.<ref name="Viagra FDA label" /> Some sildenafil users have complained of seeing everything tinted blue ([[cyanopsia]]).<ref>{{cite web | url = http://www.visionweb.com/content/consumers/dev_consumerarticles.jsp?RID=85 | title = Viagra and Vision | date = 29 October 2001 | publisher = VisionWeb | access-date = 5 November 2016 |archive-url = https://web.archive.org/web/20170610174402/http://www.visionweb.com/content/consumers/dev_consumerarticles.jsp?RID=85 | archive-date = 10 June 2017}}</ref> This cyanopsia can be explained because Sildenafil, while selective for PDE5, does have some affinity for PDE6, which is the phosphodiesterase found in the retina. Patients thus taking the drug may experience colorvision abnormalities. Some complained of blurriness and loss of [[peripheral vision]]. In July 2005, the US [[Food and Drug Administration]] (FDA) updated labeling for Cialis, Levitra, and Viagra to reflect a small number of post-marketing reports of sudden vision loss, while acknowledging that "...it is not possible to determine whether these oral medicines for erectile dysfunction were the cause of the loss of eyesight or whether the problem is related to other factors such as high blood pressure or diabetes, or to a combination of these problems."<ref>{{cite press release | title = FDA Updates Labeling for Viagra, Cialis and Levitra for Rare Post-Marketing Reports of Eye Problems | url = https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/2005/ucm108458.htm | publisher = U.S. [[Food and Drug Administration]] (FDA) | access-date=5 November 2016 | archive-url = https://web.archive.org/web/20161022204628/https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/2005/ucm108458.htm | archive-date = 22 October 2016 | date = 8 July 2005}}</ref> A careful review of pooled data from clinical trials containing well documented information about the dose and duration of exposure to the drug for a large number of patients, yields no evidence for an increased risk of [[Anterior ischemic optic neuropathy|non-arteritic anterior ischemic optic neuropathy]] or other adverse ocular events associated with PDE-5 inhibitor use.<ref name="Laties">{{cite journal | vauthors = Laties AM | title = Vision disorders and phosphodiesterase type 5 inhibitors: a review of the evidence to date | journal = Drug Safety | volume = 32 | issue = 1 | pages = 1–18 | date = January 2009 | pmid = 19132801 | doi = 10.2165/00002018-200932010-00001 | s2cid = 207296076 }}</ref>

Rare but serious adverse effects found through [[postmarketing surveillance]] include [[Priapism|prolonged erections]], severe [[Hypotension|low blood pressure]], [[myocardial infarction]] (heart attack), [[Ventricular tachycardia|ventricular arrhythmias]], [[stroke]], increased [[intraocular pressure]], and sudden [[hearing loss]].<ref name="Viagra FDA label" /> In October 2007, the FDA announced that the labeling for all [[PDE5]] inhibitors, including sildenafil, required a more prominent warning of the potential risk of sudden hearing loss.<ref>{{cite web | title = FDA Announces Revisions to Labels for Cialis, Levitra and Viagra | url = https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/2007/ucm109012.htm | publisher = U.S. [[Food and Drug Administration]] (FDA) | access-date = 5 November 2016 | archive-url = https://web.archive.org/web/20161022203200/https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/2007/ucm109012.htm | archive-date = 22 October 2016 | date = 18 October 2007}}</ref>

=== Interactions ===

Care should be exercised by people who are also taking [[Protease inhibitor (pharmacology)|protease inhibitors]] for the treatment of [[HIV/AIDS|HIV infection]]. Protease inhibitors inhibit the metabolism of sildenafil, effectively multiplying the plasma levels of sildenafil, increasing the incidence and severity of side effects. Those using protease inhibitors are recommended to limit their use of sildenafil to no more than one 25&nbsp;mg dose every 48 hours.<ref name="Viagra FDA label" /> Other drugs that interfere with the metabolism of sildenafil include [[erythromycin]] and [[cimetidine]], both of which can also lead to prolonged plasma half-life levels.<ref>{{cite journal | vauthors = Schwartz BG, Kloner RA | title = Drug interactions with phosphodiesterase-5 inhibitors used for the treatment of erectile dysfunction or pulmonary hypertension | journal = Circulation | volume = 122 | issue = 1 | pages = 88–95 | date = July 2010 | pmid = 20606131 | doi = 10.1161/CIRCULATIONAHA.110.944603 | s2cid = 13207143 | doi-access = free }}</ref>

The use of sildenafil and an [[Alpha-1 blocker|α₁ blocker]] (typically prescribed for [[hypertension]] or for urologic conditions, such as [[benign prostatic hypertrophy]]) at the same time may lead to low blood pressure, but this effect does not occur if they are taken at least 4 hours apart.<ref name="Kloner">{{cite journal | vauthors = Kloner RA | title = Pharmacology and drug interaction effects of the phosphodiesterase 5 inhibitors: focus on alpha-blocker interactions | journal = The American Journal of Cardiology | volume = 96 | issue = 12B | pages = 42M–46M | date = December 2005 | pmid = 16387566 | doi = 10.1016/j.amjcard.2005.07.011 }}</ref>

===Contraindications===

[[Contraindications]] include:<ref name="Viagra FDA label">{{cite web | title=Viagra- sildenafil citrate tablet, film coated | website=DailyMed | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=0b0be196-0c62-461c-94f4-9a35339b4501 | access-date=6 October 2020 | archive-date=13 August 2020 | archive-url=https://web.archive.org/web/20200813210523/https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=0b0be196-0c62-461c-94f4-9a35339b4501 | url-status=live }}</ref>

* Concomitant use of nitric oxide donors, organic nitrites and nitrates,<ref name="ACC/AHA">{{cite journal | vauthors = Cheitlin MD, Hutter AM, Brindis RG, Ganz P, Kaul S, Russell RO, Zusman RM | title = ACC/AHA expert consensus document. Use of sildenafil (Viagra) in patients with cardiovascular disease. American College of Cardiology/American Heart Association | journal = Journal of the American College of Cardiology | volume = 33 | issue = 1 | pages = 273–82 | date = January 1999 | pmid = 9935041 | doi = 10.1016/S0735-1097(98)00656-1 | doi-access = free }}</ref> such as:

** [[Nitroglycerin (drug)|nitroglycerin]]

** [[isosorbide mononitrate]]

** [[isosorbide dinitrate]]

** [[sodium nitroprusside]]

** [[alkyl nitrites]] (commonly known as "[[poppers]]")

* Concomitant use of [[soluble guanylyl cyclase]] stimulators, such as [[riociguat]]

* Known hypersensitivity to sildenafil

Sildenafil should not be used if sexual activity is inadvisable due to underlying cardiovascular risk factors.<ref>{{Cite news|url=https://www.rxlist.com/viagra-drug.htm#warnings_precautions|title=Viagra (Sildenafil Citrate): Side Effects, Interactions, Warning, Dosage & Uses|work=RxList|access-date=11 July 2018|archive-date=12 July 2018|archive-url=https://web.archive.org/web/20180712002957/https://www.rxlist.com/viagra-drug.htm#warnings_precautions|url-status=live}}</ref>

==Nonmedical use==

===Recreational use===

Sildenafil's popularity with young adults has increased over the years.<ref name=USAToday>{{cite news|vauthors=Peterson K|url=http://usatoday30.usatoday.com/news/health/2001-03-21-viagra-abuse.htm|title=Young men add Viagra to their drug arsenal|work=[[USA Today]]|date=21 March 2001|access-date=27 December 2013|archive-date=4 September 2014|archive-url=https://web.archive.org/web/20140904174441/http://usatoday30.usatoday.com/news/health/2001-03-21-viagra-abuse.htm|url-status=live}}</ref> Sildenafil's brand name, Viagra, is widely recognized in popular culture, and the drug's association with treating erectile dysfunction has led to its recreational use.<ref name=JAPA>{{cite journal | vauthors = Smith KM, Romanelli F | title = Recreational use and misuse of phosphodiesterase 5 inhibitors | journal = Journal of the American Pharmacists Association | volume = 45 | issue = 1 | pages = 63–72; quiz 73–5 | year = 2005 | pmid = 15730119 | doi = 10.1331/1544345052843165 }}</ref> The reasons behind such use include the belief that the drug increases libido, improves sexual performance,<ref name=JAPA/> or permanently increases penis size.<ref>{{cite web|url=http://www.theonlineclinic.co.uk/news/2012/12/24/SildenafilWillNotAffectLibidoFact.aspx|title=Sildenafil Will Not Affect Libido - Fact!|access-date=15 July 2016|archive-date=21 August 2016|archive-url=https://web.archive.org/web/20160821085902/http://www.theonlineclinic.co.uk/news/2012/12/24/SildenafilWillNotAffectLibidoFact.aspx|url-status=live}}</ref> Studies on the effects of sildenafil when used recreationally are limited, but suggest it has little effect when used by those who do not have erectile dysfunction. In one study, a 25&nbsp;mg dose was shown to cause no significant change in erectile quality, but did reduce the postejaculatory [[Refractory period (sex)|refractory time]].<ref name=Mondaini>{{cite journal | vauthors = Mondaini N, Ponchietti R, Muir GH, Montorsi F, Di Loro F, Lombardi G, Rizzo M | title = Sildenafil does not improve sexual function in men without erectile dysfunction but does reduce the postorgasmic refractory time | journal = International Journal of Impotence Research | volume = 15 | issue = 3 | pages = 225–8 | date = June 2003 | pmid = 12904810 | doi = 10.1038/sj.ijir.3901005 | s2cid = 22508049 | doi-access = }}</ref> This study also noted a significant [[placebo effect]] in the control group.<ref name=Mondaini/>

Unprescribed recreational use of sildenafil and other PDE5 inhibitors is noted as particularly high among users of illegal drugs.<ref name="pmid">{{cite journal | vauthors = McCambridge J, Mitcheson L, Hunt N, Winstock A | title = The rise of Viagra among British illicit drug users: 5-year survey data | journal = Drug and Alcohol Review | volume = 25 | issue = 2 | pages = 111–3 | date = March 2006 | pmid = 16627299 | doi = 10.1080/09595230500537167 | s2cid = 40250895 }}<br>- {{cite journal | vauthors = Eloi-Stiven ML, Channaveeraiah N, Christos PJ, Finkel M, Reddy R | title = Does marijuana use play a role in the recreational use of sildenafil? | journal = The Journal of Family Practice | volume = 56 | issue = 11 | pages = E1-4 | date = November 2007 | pmid = 17976333 }}</ref> Sildenafil is sometimes used to counteract the effects of other substances, often illicit.<ref name=JAPA/> Some users mix it with [[methylenedioxymethamphetamine]] ([[MDMA]], ecstasy), other stimulants, or opiates in an attempt to compensate for the common side effect of erectile dysfunction, a combination known as "[[sextasy]]", "rockin' and rollin,'" "hammerheading," or "trail mix".<ref name=JAPA/> Mixing it with [[amyl nitrite]], another [[vasodilator]], is particularly dangerous and potentially fatal.<ref name=JAPA/>

===Jet lag research===

The 2007 [[Ig Nobel Prize]] in aviation went to Patricia V. Agostino, Santiago A. Plano, and [[Diego Golombek|Diego A. Golombek]] of [[Universidad Nacional de Quilmes]], Argentina, for their discovery that sildenafil helps treat [[jet lag]] recovery in [[hamster]]s.<ref>{{cite web |url=http://www.improbable.com/ig/ig-pastwinners.html#ig2007 |title=The 2007 Ig Nobel Prize Winners |publisher=Improbable Research |date=4 October 2007 |access-date=10 February 2009 |archive-date=26 January 2013 |archive-url=https://web.archive.org/web/20130126124951/http://www.improbable.com/ig/ig-pastwinners.html#ig2007 |url-status=dead }}</ref><ref name="pmid17519328">{{cite journal | vauthors = Agostino PV, Plano SA, Golombek DA | title = Sildenafil accelerates reentrainment of circadian rhythms after advancing light schedules | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 104 | issue = 23 | pages = 9834–9 | date = June 2007 | pmid = 17519328 | pmc = 1887561 | doi = 10.1073/pnas.0703388104 | bibcode = 2007PNAS..104.9834A | doi-access = free }}</ref>

===Sports===

Professional athletes have been documented using sildenafil, believing the opening of their blood vessels will enrich their muscles. In turn, they believe it will enhance their performances.<ref>{{cite news | vauthors = Thompson T, Red C, O'Keefffe M, Vinton N|title=Source: Roger Clemens, host of athletes pop Viagra to help onfield performance |work=[[Daily News (New York)|Daily News]] |date=10 June 2008 |url=http://www.nydailynews.com/sports/baseball/yankees/source-roger-clemens-host-athletes-pop-viagra-onfield-performance-article-1.171270 |access-date=10 February 2009| url-status=live| archive-url=https://web.archive.org/web/20200814120852/https://www.nydailynews.com/sports/baseball/yankees/source-roger-clemens-host-athletes-pop-viagra-onfield-performance-article-1.171270| archive-date=14 August 2020}}</ref><ref>{{cite news | vauthors = Busbee J | url=https://sports.yahoo.com/blogs/nfl-shutdown-corner/bears-brandon-marshall-says-nfl-players-viagra-field-184549686--nfl.html | title = Bears' Brandon Marshall says some NFL players use Viagra … ON THE FIELD | work = [[Yahoo! Sports]] | date = 28 November 2012 | access-date = 28 November 2012 | archive-date = 5 March 2016 | archive-url = https://web.archive.org/web/20160305041235/https://sports.yahoo.com/blogs/nfl-shutdown-corner/bears-brandon-marshall-says-nfl-players-viagra-field-184549686--nfl.html | url-status = dead}}</ref>

===Analogs===

[[Acetildenafil]] and other synthetic [[structural analog]]s of sildenafil which are [[cGMP-specific phosphodiesterase type 5|PDE5 inhibitors]] have been found as adulterants in a number of "herbal" aphrodisiac products sold over-the-counter.<ref>{{cite journal | vauthors = Venhuis BJ, de Kaste D | title = Towards a decade of detecting new analogues of sildenafil, tadalafil and vardenafil in food supplements: a history, analytical aspects and health risks | journal = Journal of Pharmaceutical and Biomedical Analysis | volume = 69 | pages = 196–208 | date = October 2012 | pmid = 22464558 | doi = 10.1016/j.jpba.2012.02.014 }}</ref> These analogs have not undergone any of the rigorous testing that drugs like sildenafil have passed, and thus have unknown side-effect profiles.<ref>{{cite journal | vauthors = Oh SS, Zou P, Low MY, Koh HL | title = Detection of sildenafil analogues in herbal products for erectile dysfunction | journal = Journal of Toxicology and Environmental Health. Part A | volume = 69 | issue = 21 | pages = 1951–8 | date = November 2006 | pmid = 16982533 | doi = 10.1080/15287390600751355 | bibcode = 2006JTEHA..69.1951S | s2cid = 40831895 }}</ref> Some attempts have been made to ban these drugs, but progress has been slow so far, as, even in those jurisdictions that have laws targeting designer drugs, the laws are drafted to ban analogs of illegal drugs of abuse, rather than analogs of prescription medicines. However, at least one court case has resulted in a product being taken off the market.<ref>{{cite journal | vauthors = Venhuis BJ, Blok-Tip L, de Kaste D | title = Designer drugs in herbal aphrodisiacs | journal = Forensic Science International | volume = 177 | issue = 2–3 | pages = e25-7 | date = May 2008 | pmid = 18178354 | doi = 10.1016/j.forsciint.2007.11.007 }}</ref>

The US [[Food and Drug Administration]] (FDA) has banned numerous products claiming to be ''[[Eurycoma longifolia]]'' that, in fact, contain only analogs of sildenafil.<ref>{{cite web|url=https://www.fda.gov/ICECI/EnforcementActions/WarningLetters/2005/ucm075981.htm|title=FDA letter to Libidus distributor|url-status=dead|website=U.S. [[Food and Drug Administration]] (FDA)|date=11 July 2006|archive-url=https://web.archive.org/web/20160304202145/https://www.fda.gov/ICECI/EnforcementActions/WarningLetters/2005/ucm075981.htm|archive-date=4 March 2016}}</ref><ref>{{cite web|url=https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/2006/ucm108690.htm|title=FDA Warns Consumers About Dangerous Ingredients in "Dietary Supplements" Promoted for Sexual Enhancement|url-status=dead|website=U.S. [[Food and Drug Administration]] (FDA)|archive-date=18 January 2017|archive-url=https://web.archive.org/web/20170118090958/https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/2006/ucm108690.htm|date=12 July 2006}}</ref><ref>{{cite web|url=https://www.fda.gov/ForConsumers/ConsumerUpdates/ucm048386.htm|title=Hidden Risks of Erectile Dysfunction 'Treatments' Sold Online|date=21 February 2009|website=U.S. [[Food and Drug Administration]] (FDA)|access-date=8 December 2020|archive-date=23 April 2019|archive-url=https://web.archive.org/web/20190423031555/https://www.fda.gov/ForConsumers/ConsumerUpdates/ucm048386.htm|url-status=live}}</ref> Sellers of such fake herbals typically respond by just changing the names of their products.

==Detection in biological fluids==

Sildenafil and/or N-desmethylsildenafil, its major active metabolite, may be quantified in plasma, serum, or whole blood to assess pharmacokinetic status in those receiving the drug therapeutically, to confirm the diagnosis in potential poisoning victims, or to assist in the forensic investigation in a case of fatal overdose.<ref>R. Baselt, ''Disposition of Toxic Drugs and Chemicals in Man'', 9th edition, Biomedical Publications, Seal Beach, CA, 2011, pp. 1552–53. {{cite web |url=http://www.biomedicalpublications.com/dt9.pdf |title=Sildenafil | website=Biomedical Publications |access-date=1 July 2011 |url-status=dead |archive-url=https://web.archive.org/web/20110910161559/http://www.biomedicalpublications.com/dt9.pdf |archive-date=10 September 2011 }}</ref>

==Mechanism of action==

[[File:1udt.png|thumb|Crystal structure of human PDE5 with bound sildenafil, PDB entry {{PDBe|1udt}}<ref>{{cite journal | vauthors = Sung BJ, Hwang KY, Jeon YH, Lee JI, Heo YS, Kim JH, Moon J, Yoon JM, Hyun YL, Kim E, Eum SJ, Park SY, Lee JO, Lee TG, Ro S, Cho JM | title = Structure of the catalytic domain of human phosphodiesterase 5 with bound drug molecules | journal = Nature | volume = 425 | issue = 6953 | pages = 98–102 | date = September 2003 | pmid = 12955149 | doi = 10.1038/nature01914 | s2cid = 4404590 | bibcode = 2003Natur.425...98S }}</ref>]]

Sildenafil protects [[cyclic guanosine monophosphate]] (cGMP) from degradation by [[cGMP-specific phosphodiesterase type 5]] (PDE5) in the [[corpus cavernosum penis|corpus cavernosum]]. [[Nitric oxide]] (NO) in the corpus cavernosum of the penis binds to [[guanylate cyclase]] receptors, which results in increased levels of cGMP, leading to [[smooth muscle]] relaxation ([[vasodilation]]) of the intimal cushions of the [[Helicine arteries of penis|helicine arteries]]. This smooth muscle relaxation leads to vasodilation and increased inflow of blood into the spongy tissue of the penis, causing an erection.<ref name="WebbDJ">{{cite journal | vauthors = Webb DJ, Freestone S, Allen MJ, Muirhead GJ | title = Sildenafil citrate and blood-pressure-lowering drugs: results of drug interaction studies with an organic nitrate and a calcium antagonist | journal = The American Journal of Cardiology | volume = 83 | issue = 5A | pages = 21C–28C | date = March 1999 | pmid = 10078539 | doi = 10.1016/S0002-9149(99)00044-2 }}</ref> [[Robert F. Furchgott]], [[Ferid Murad]], and [[Louis Ignarro]] won the [[Nobel Prize in Physiology or Medicine]] in 1998 for their independent study of the metabolic pathway of nitric oxide in smooth muscle vasodilation.

The molecular mechanism of smooth muscle relaxation involves the enzyme [[CGMP-dependent protein kinase]], also known as PKG. This kinase is activated by cGMP and it phosphorylates multiple targets in the smooth muscle cells, namely [[Myosin-light-chain phosphatase|myosin light chain phosphatase]], [[RHOA|RhoA]], [[Inositol trisphosphate receptor|IP3 receptor]], [[phospholipase C]], and others.<ref name=":0">{{cite journal | vauthors = Francis SH, Busch JL, Corbin JD, Sibley D | title = cGMP-dependent protein kinases and cGMP phosphodiesterases in nitric oxide and cGMP action | journal = Pharmacological Reviews | volume = 62 | issue = 3 | pages = 525–63 | date = September 2010 | pmid = 20716671 | pmc = 2964902 | doi = 10.1124/pr.110.002907 }}</ref> Overall, this results in a decrease in intracellular calcium and desensitizing proteins to the effects of calcium, engendering smooth muscle relaxation.<ref name=":0" />

Sildenafil is a potent and selective inhibitor of [[cGMP-specific phosphodiesterase type 5]] (PDE5), which is responsible for degradation of cGMP in the [[corpus cavernosum penis|corpus cavernosum]]. The molecular structure of sildenafil is similar to that of cGMP and acts as a competitive binding agent of PDE5 in the corpus cavernosum, resulting in more cGMP and increased penile response to sexual stimulation.<ref name="WebbDJ"/><ref name="goldsteinI">{{cite journal | vauthors = Goldstein I, Lue TF, Padma-Nathan H, Rosen RC, Steers WD, Wicker PA | title = Oral sildenafil in the treatment of erectile dysfunction. Sildenafil Study Group | journal = The New England Journal of Medicine | volume = 338 | issue = 20 | pages = 1397–1404 | date = May 1998 | pmid = 9580646 | doi = 10.1056/NEJM199805143382001 | doi-access = free }}</ref> Without sexual stimulation, and therefore lack of activation of the NO/cGMP system, sildenafil should not cause an erection. Other drugs that operate by the same mechanism include [[tadalafil]] (Cialis) and [[vardenafil]] (Levitra).

Sildenafil is broken down in the liver by hepatic metabolism using cytochrome p450 enzymes, mainly CYP450 3A4 (major route), but also by CYP2C9 (minor route) hepatic isoenzymes. The major product of metabolisation by these enzymes is N-desmethylated sildenafil, which is metabolised further. This metabolite also has an affinity for the PDE receptors, about 40% of that of sildenafil. Thus, the metabolite is responsible for about 20% of sildenafil's action. Sildenafil is excreted as metabolites predominantly in the feces (about 80% of administered oral dose) and to a lesser extent in the urine (around 13% of the administered oral dose). If taken with a high-fat meal, absorption is reduced; the time taken to reach the maximum plasma concentration increases by around one hour, and the maximum concentration itself is decreased by nearly one-third.<ref name=RxListCP>{{cite web | url = http://www.rxlist.com/viagra-drug/clinical-pharmacology.htm | title = Viagra Clinical Pharmacology | year = 2008 | access-date = 20 August 2008 | publisher = RxList.com | archive-date = 14 January 2012 | archive-url = https://web.archive.org/web/20120114040129/http://www.rxlist.com/viagra-drug/clinical-pharmacology.htm | url-status = live }}</ref>

==Route of administration==

* When taken [[Oral administration|orally]], sildenafil for erectile dysfunction results in an average time to onset of erections of 27 minutes (ranging from 12 to 70 minutes).<ref>{{cite journal | vauthors = Eardley I, Ellis P, Boolell M, Wulff M | title = Onset and duration of action of sildenafil for the treatment of erectile dysfunction | journal = British Journal of Clinical Pharmacology | volume = 53 | issue = Suppl 1 | pages = 61S–65S | year = 2002 | pmid = 11879261 | pmc = 1874251 | doi = 10.1046/j.0306-5251.2001.00034.x }}</ref>

* [[Sublingual administration|Sublingual]] use of sildenafil for erectile dysfunction results in an average onset of action of 15 minutes and lasting for an average of 40 minutes.<ref name=sublingual>{{cite journal | vauthors = Deveci S, Peşkircioğlu L, Aygün C, Tekin MI, Dirim A, Ozkardeş H | title = Sublingual sildenafil in the treatment of erectile dysfunction: faster onset of action with less dose | journal = International Journal of Urology | volume = 11 | issue = 11 | pages = 989–92 | date = November 2004 | pmid = 15509203 | doi = 10.1111/j.1442-2042.2004.00933.x | s2cid = 28302024 | doi-access = }}</ref>

{{anchor|spray}}

==Chemical synthesis==

The preparation steps for synthesis of sildenafil are:<ref>{{cite journal|journal = Org Process Res Dev| volume = 2005 |issue =1 |pages = 88–97 |doi = 10.1021/op040019c| title = Synthesis of Commercial Phosphodiesterase(V) Inhibitors | vauthors = Dunn PJ | year = 2005| s2cid = 93589067 }}</ref>

# [[Methylation]] of 3-propylpyrazole-5-carboxylic acid ethyl [[ester]] with hot [[dimethyl sulfate]]

# [[Hydrolysis]] with [[aqueous]] [[sodium hydroxide]] (NaOH) to free [[acid]]

# [[Nitration]] with [[oleum]]/fuming [[nitric acid]]

# [[Carboxamide]] formation with [[refluxing]] [[thionyl chloride]]/NH₄OH

# [[Redox|Reduction]] of [[nitro group]] to [[amino group]]

# [[Acylation]] with 2-ethoxybenzoyl chloride

# [[Cyclization]]

# [[Sulfonation]] to the chlorosulfonyl derivative

# [[Condensation reaction|Condensation]] with 1-methylpiperazine.

==History==

Sildenafil (compound UK-92,480) was synthesized by a group of pharmaceutical chemists led by [[Simon Campbell]]<ref name="RPS2014">{{cite journal |title=Scientist who developed Viagra receives knighthood in New Year's Honours |journal=The Pharmaceutical Journal |publisher=Royal Pharmaceutical Society |year=2014 |issn=2053-6186 |doi=10.1211/pj.2014.20067494 |url=https://pharmaceutical-journal.com/article/news/scientist-who-developed-viagra-receives-knighthood-in-new-years-honours |access-date=14 January 2023 |archive-date=14 January 2023 |archive-url=https://web.archive.org/web/20230114090526/https://pharmaceutical-journal.com/article/news/scientist-who-developed-viagra-receives-knighthood-in-new-years-honours |url-status=live }}</ref> working at Pfizer's [[Sandwich, Kent]], research facility in England. It was initially studied for use in [[hypertension]] (high blood pressure) and [[angina pectoris]] (a symptom of [[ischaemic heart disease]]).<ref name="pmid16883306">{{cite journal |vauthors=Ghofrani HA, Osterloh IH, Grimminger F |title=Sildenafil: from angina to erectile dysfunction to pulmonary hypertension and beyond |journal=Nat Rev Drug Discov |volume=5 |issue=8 |pages=689–702 |date=August 2006 |pmid=16883306 |pmc=7097805 |doi=10.1038/nrd2030}}</ref> The first clinical trials were conducted in [[Morriston Hospital]] in [[Swansea]].<ref>{{cite web| title=Research | url=http://www.abm.university-trust.wales.nhs.uk/page.cfm?orgId=743&pid=29457 | date= 4 July 2008 | access-date=6 August 2008|archive-url = https://web.archive.org/web/20080926034946/http://www.abm.university-trust.wales.nhs.uk/page.cfm?orgId=743&pid=29457|url-status = dead|archive-date = 26 September 2008|publisher = Abertawe Bro Morgannwg University Health Board|website = ABM|quote = Our clinicians regularly offer patients the opportunity to take part in trials of new drugs and treatments. Morriston Hospital in Swansea, was the first in the world to trial Viagra!}}</ref> Phase I [[clinical trial]]s under the direction of [[Ian Osterloh]] suggested the drug had little effect on angina, but it could induce marked penile [[erection]]s.<ref name="autogenerated47">{{cite journal | vauthors = Boolell M, Allen MJ, Ballard SA, Gepi-Attee S, Muirhead GJ, Naylor AM, Osterloh IH, Gingell C | title = Sildenafil: an orally active type 5 cyclic GMP-specific phosphodiesterase inhibitor for the treatment of penile erectile dysfunction | journal = International Journal of Impotence Research | volume = 8 | issue = 2 | pages = 47–52 | date = June 1996 | pmid = 8858389 }}</ref><ref>{{cite journal |vauthors=Terrett NK, Bell AS, Brown D, Elllis P | title = Sildenafil (Viagra), a potent and selective inhibitor of Type 5 cGMP phosphodiesterase with utility for the treatment of male erectile dysfunction | journal = Bioorg Med Chem Lett | year = 1996 | volume = 6 | pages = 1819–24 | doi = 10.1016/0960-894X(96)00323-X |issue=15 }}<!--not indexed on Medline--></ref> Pfizer therefore decided to market it for erectile dysfunction, rather than for angina; this decision became an often-cited example of [[drug repositioning]].<ref>{{cite journal | vauthors = Ashburn TT, Thor KB | title = Drug repositioning: identifying and developing new uses for existing drugs | journal = Nature Reviews. Drug Discovery | volume = 3 | issue = 8 | pages = 673–83 | date = August 2004 | pmid = 15286734 | doi = 10.1038/nrd1468 | s2cid = 205475073 }}</ref><ref>{{cite book|last1=Institute of Medicine|title=Drug Repurposing and Repositioning: Workshop Summary|date=2014|publisher=National Academies Press|isbn=9780309302043|url=https://www.nap.edu/catalog/18731/drug-repurposing-and-repositioning-workshop-summary|access-date=11 June 2017|archive-date=22 April 2019|archive-url=https://web.archive.org/web/20190422054824/https://www.nap.edu/catalog/18731/drug-repurposing-and-repositioning-workshop-summary|url-status=live}}</ref> The drug was [[patent]]ed in 1996, approved for use in erectile dysfunction by the FDA on 27 March 1998, becoming the first oral treatment approved to treat erectile dysfunction in the United States, and offered for sale in the United States later that year.<ref>{{cite journal| vauthors = Kling J |title=From hypertension to angina to Viagra|journal=Mod. Drug Discov.|year=1998|volume=1|pages=31–38|url=<!--http://pubs.acs.org/hotartcl/mdd/98/novdec/viagra.html deadlink not required in present instance. The article is present as a TOC entry at http://pubs.acs.org/subscribe/archive/mdd/toc/1198toc.html . -->|issn = 1532-4486|oclc = 41105083}} <!--Not indexed on PubMed--></ref> It soon became a great success: annual sales of Viagra peaked in 2008 at US$1.934 billion.<ref>{{cite web|url=https://www.sec.gov/Archives/edgar/data/78003/000119312511048877/dex13.htm|title=Portions of the 2010 Financial Report|access-date=15 July 2016|archive-date=10 June 2019|archive-url=https://web.archive.org/web/20190610193252/https://www.sec.gov/Archives/edgar/data/78003/000119312511048877/dex13.htm|url-status=live}}</ref>{{globalise-inline|date=December 2023}}

==Counterfeits==

{{further|Counterfeit medications}}

Counterfeit Viagra, despite generally being cheaper,<ref name="record_2015">{{cite web|url=https://www.bbc.com/news/health-36266826|title=Record amount of counterfeit Viagra seized|website=www.bbc.com|date=12 May 2016|access-date=26 December 2016|url-status=live|archive-url=https://web.archive.org/web/20161119084035/http://www.bbc.com/news/health-36266826|archive-date=19 November 2016}}</ref> can contain harmful substances or substances that affect how Viagra works, such as blue printer ink, [[amphetamine]]s, [[metronidazole]], [[boric acid]], and [[rat poison]].<ref name="accessrx_2">{{cite news|vauthors=Amerman D|title=Counterfeit Viagra, Cialis, Levitra: The Ultimate Guide|url=https://www.accessrx.com/blog/erectile-dysfunction/counterfeit-viagra-cialis-levitra-ultimate-guide/|work=AccessRx|date=22 May 2012|access-date=10 January 2017|archive-date=10 January 2017|archive-url=https://web.archive.org/web/20170110162756/https://www.accessrx.com/blog/erectile-dysfunction/counterfeit-viagra-cialis-levitra-ultimate-guide/|url-status=live}}</ref>

Viagra is one of the world's most counterfeited medicines.<ref>{{cite news|vauthors=Moran B|title=Cracking Down on Counterfeit Drugs — NOVA Next {{!}} PBS|url=https://www.pbs.org/wgbh/nova/next/body/uncovering-counterfeit-medicines/|publisher=PBS NOVA Next|date=20 August 2013|access-date=10 January 2017|archive-date=10 January 2017|archive-url=https://web.archive.org/web/20170110163116/http://www.pbs.org/wgbh/nova/next/body/uncovering-counterfeit-medicines/|url-status=live}}</ref><ref>{{cite news|vauthors=Somra G|title=Online pharmacies suspected of counterfeit drug sales|url=http://www.cnn.com/2015/08/31/health/counterfeit-medications/|publisher=CNN|date=31 August 2015|access-date=10 January 2017|archive-date=10 January 2017|archive-url=https://web.archive.org/web/20170110162602/http://www.cnn.com/2015/08/31/health/counterfeit-medications/|url-status=live}}</ref> According to a 2012 Pfizer study, around 80% of sites claiming to sell Viagra were selling counterfeits.<ref name="accessrx_2"/>

An October 2023 release stated that erectile dysfunction medicines were the most seized drugs by the [[Interpol]]<ref>{{cite web | url=https://www.forbes.com/sites/britneynguyen/2023/10/31/erectile-dysfunction-medication-the-most-seized-drug-during-global-crackdown-interpol-says/ | title=Erectile Dysfunction Medication the Most Seized Drug During Global Crackdown, Interpol Says | website=[[Forbes]] }}</ref> accounting for 22% of seizures.<ref>{{cite web | url=https://www.interpol.int/News-and-Events/News/2023/Global-illicit-medicines-targeted-by-INTERPOL-operation | title=Global illicit medicines targeted by INTERPOL operation | access-date=10 December 2023 | archive-date=10 December 2023 | archive-url=https://web.archive.org/web/20231210191359/https://www.interpol.int/News-and-Events/News/2023/Global-illicit-medicines-targeted-by-INTERPOL-operation | url-status=live }}</ref> International networks may be active.<ref>{{cite web | url=https://www.jpost.com/business-and-innovation/article-739678 | title=Israeli-made AI exposes international fake Viagra network | date=19 April 2023 | access-date=10 December 2023 | archive-date=10 December 2023 | archive-url=https://web.archive.org/web/20231210191358/https://www.jpost.com/business-and-innovation/article-739678 | url-status=live }}</ref><ref>{{cite web | url=https://www.cbp.gov/newsroom/local-media-release/counterfeit-viagra-pills-footwear-belts-car-emblems-and-headphones | title=Counterfeit Viagra Pills, Footwear, Belts, Car Emblems and Headphones Worth over $32 Million Seized at the LA/Long Beach Seaport &#124; U.S. Customs and Border Protection | access-date=10 December 2023 | archive-date=10 December 2023 | archive-url=https://web.archive.org/web/20231210191528/https://www.cbp.gov/newsroom/local-media-release/counterfeit-viagra-pills-footwear-belts-car-emblems-and-headphones | url-status=live }}</ref>

==Society and culture==

===Marketing and sales===

[[File:CBP with bag of seized counterfeit Viagra.jpg|right|thumb|upright|Bulk bag of counterfeit Viagra]]{{Further|Medicalisation of sexuality}}

In the US, even though sildenafil is available only by prescription from a doctor, it was advertised directly to consumers on TV (famously being endorsed by former [[United States Senate|United States Senator]] [[Bob Dole]] and [[Association football|football]] star [[Pelé]]). Numerous sites on the Internet offer Viagra for sale after an "online consultation", often a simple web questionnaire.<ref>{{cite journal | vauthors = Ciment J | title = Health situation in former communist bloc is dire, says Unicef | journal = BMJ | volume = 319 | issue = 7221 | pages = 1324 | date = November 1999 | pmid = 10567131 | pmc = 1174637 | doi = 10.1136/bmj.319.7221.1324g }}</ref><ref>{{cite news |url=http://www.dailyrecord.co.uk/news/uk-world-news/chemists-plan-to-sell-viagra-on-the-internet-991948 |title=Chemists plan to sell Viagra on the internet |vauthors=Devine A |work=[[Daily Record (Scotland)|Daily Record]] |date=29 September 2008 |access-date=30 April 2012 |archive-date=1 November 2012 |archive-url=https://web.archive.org/web/20121101013346/http://www.dailyrecord.co.uk/news/uk-world-news/chemists-plan-to-sell-viagra-on-the-internet-991948 |url-status=live }}</ref> The Viagra name has become so well known that many fake [[aphrodisiac]]s now call themselves "[[herbal viagra]]" or are presented as blue tablets imitating the shape and colour of Pfizer's product. Viagra is also informally known as "vitamin V", "the blue pill", or "blue diamond", as well as various other nicknames.

Viagra and other products for sexual dysfunction, termed ''sexuopharmaceuticals,'' proliferated new types of specialised marketing for such products.<ref name=":12">{{Cite journal | vauthors = Gurevich M, Cormier N, Leedham U, Brown-Bowers A |date=August 2018 |title=Sexual dysfunction or sexual discipline? Sexuopharmaceutical use by men as prevention and proficiency |journal=Feminism & Psychology |volume=28 |issue=3 |pages=309–330 |doi=10.1177/0959353517750682 |issn=0959-3535 |s2cid=149254089}}</ref> Viagra and similar prescription pharmaceuticals were promoted by images in media to the extent of becoming a cultural icon, at the time a relatively new phenomenon known to be permitted only in the United States and New Zealand and which is believed to have significantly contributed to norms regarding male sexuality.<ref name=":varesbraun">{{Cite journal | vauthors = Vares T, Braun V |date=July 2006 |title=Spreading the Word, but What Word is That? Viagra and Male Sexuality in Popular Culture |journal=Sexualities |volume=9 |issue=3 |pages=315–332 |doi=10.1177/1363460706065055 |issn=1363-4607 |s2cid=146569195}}</ref> One author notes that although the effect of Viagra is only limited to penile blood vessels, advertisements routinely use imagery of couples hugging, smiling and dancing, with the author claiming that pharmaceutical companies were deceptive in the use of such advertisements.<ref name=":17">{{Cite journal | vauthors = Tiefer L |date=1 May 2001 |title=A new view of women's sexual problems: Why new? Why now? |url=https://www.tandfonline.com/doi/full/10.1080/00224490109552075 |journal=The Journal of Sex Research |volume=38 |issue=2 |pages=89–96 |doi=10.1080/00224490109552075 |issn=0022-4499 |s2cid=144377564}}</ref>

In 2000, Viagra sales accounted for 92% of the global market for prescribed erectile dysfunction pills.<ref name="pmid10718028">{{cite journal | vauthors = Keith A | title = The economics of Viagra | journal = Health Affairs | volume = 19 | issue = 2 | pages = 147–57 | year = 2000 | pmid = 10718028 | doi = 10.1377/hlthaff.19.2.147 | doi-access = free }}</ref> By 2007, Viagra's global share had plunged to about 50%<ref>{{cite web|title=Cialis gaining market share worldwide | vauthors = McGuire S | work = Medical Marketing & Media | date = 1 January 2007 | url = http://www.allbusiness.com/marketing-advertising/marketing-advertising-measures/10557040-1.html | publisher = Haymarket Media | access-date = 10 February 2009 |archive-url = https://web.archive.org/web/20090103220918/http://www.allbusiness.com/marketing-advertising/marketing-advertising-measures/10557040-1.html|archive-date = 3 January 2009}}</ref> due to several factors, including the entry of Cialis and Levitra, along with several counterfeits and clones, and reports of vision loss in people taking PDE5 inhibitors.<ref>{{cite journal |url=http://pubs.acs.org/cen/coverstory/83/8325/8325viagra.html |title=Viagra |vauthors=Mullin R |journal=[[Chemical & Engineering News]] |volume=83 |issue=25 |date=20 June 2005 |access-date=20 August 2008 |archive-date=12 October 2008 |archive-url=https://web.archive.org/web/20081012045710/http://pubs.acs.org/cen/coverstory/83/8325/8325viagra.html |url-status=live }}</ref><ref>{{cite news |url=https://www.nytimes.com/2005/12/04/business/yourmoney/04impotence.html |title=Sales of Impotence Drugs Fall, Defying Expectations |vauthors=Berenson A |work=[[The New York Times]] |date=4 December 2005 |access-date=20 August 2008 |archive-date=11 October 2007 |archive-url=https://web.archive.org/web/20071011031227/http://nytimes.com/2005/12/04/business/yourmoney/04impotence.html |url-status=live }}</ref> In 2008, the FDA forced Pfizer to remove ''Viva Cruiser'', an [[advergame]] for Viagra, from appearing on [[Forbes]], after the game failed to disclose risk information about the drug.<ref>{{Cite web|url=https://www.cbsnews.com/news/pfizer-courting-more-controversy-with-viagra-advergaming/|title=Pfizer Courting More Controversy with Viagra 'Advergaming'|website=CBS News|date=3 September 2008|access-date=19 December 2019|archive-date=19 December 2019|archive-url=https://web.archive.org/web/20191219232459/https://www.cbsnews.com/news/pfizer-courting-more-controversy-with-viagra-advergaming/|url-status=live}}</ref><ref>{{Cite web|url=https://www.engadget.com/2008/11/24/fda-gave-pfizer-hard-time-over-viagra-game/|title=FDA gave Pfizer hard time over Viagra game|website=Engadget|date=24 November 2008|access-date=19 December 2019|archive-date=6 May 2018|archive-url=https://web.archive.org/web/20180506121913/https://www.engadget.com/2008/11/24/fda-gave-pfizer-hard-time-over-viagra-game/|url-status=live}}</ref>

In February 2007, it was announced that [[Boots UK|Boots]], the UK pharmacy chain, would try [[Over-the-counter drug|over-the-counter]] sales of Viagra in stores in [[Manchester|Manchester, England]]. Males between the ages of 30 and 65 would be eligible to buy four tablets after a consultation with a [[pharmacist]].<ref>{{cite news |url=http://news.bbc.co.uk/2/hi/health/6351171.stm |title=Over-the-counter Viagra piloted |date=11 February 2007 |work=BBC News |access-date=10 February 2009 |archive-date=9 January 2009 |archive-url=https://web.archive.org/web/20090109140423/http://news.bbc.co.uk/2/hi/health/6351171.stm |url-status=live }}</ref> In 2017, the [[Medicines and Healthcare products Regulatory Agency]] (MHRA) enacted legislation that expanded this nationwide,<ref>{{cite news |url=https://www.bbc.com/news/health-42155489 |title=Viagra can be sold over the counter |date=28 November 2017 |work=BBC News |access-date=5 April 2018 |archive-date=22 February 2021 |archive-url=https://web.archive.org/web/20210222234502/https://www.bbc.com/news/health-42155489 |url-status=live }}</ref> allowing a particular branded formulation of Sildenafil, Viagra Connect (50&nbsp;mg), to be sold over the counter and without a prescription throughout the UK from early 2018. While the sale remains subject to a consultation with a pharmacist, the other restrictions from the trial have been removed, allowing customers over the age of 18 to purchase an unlimited number of pills.<ref name="The Independent">{{cite news |url=https://www.independent.co.uk/life-style/health-and-families/viagra-buy-without-prescription-over-counter-uk-pharmacies-male-impotence-erectile-dysfunction-a8275461.html |title=Viagra now available over the counter without prescription in the UK |date=27 March 2018 |newspaper=The Independent |access-date=5 April 2018 |archive-date=26 March 2021 |archive-url=https://web.archive.org/web/20210326040400/https://www.independent.co.uk/life-style/health-and-families/viagra-buy-without-prescription-over-counter-uk-pharmacies-male-impotence-erectile-dysfunction-a8275461.html |url-status=live }}</ref> The decision was made, in part, to reduce online sales of counterfeit and potentially dangerous erectile dysfunction treatments.

In May 2013, [[Pfizer]], which manufactures Viagra, told the [[Associated Press]] they will begin selling the drug directly to people on its website.<ref>{{cite news|title=Pfizer to sell Viagra online, in first for Big Pharma: AP|url=https://www.cbsnews.com/news/pfizer-to-sell-viagra-online-in-first-for-big-pharma-ap/|work=CBS News|access-date=6 May 2013|agency=Associated Press|archive-date=8 December 2013|archive-url=https://web.archive.org/web/20131208051657/http://www.cbsnews.com/news/pfizer-to-sell-viagra-online-in-first-for-big-pharma-ap/|url-status=live}}</ref>

Pfizer's patents on Viagra expired outside the US in 2012; in the US they were set to expire, but Pfizer settled litigation with each of Mylan and Teva which agreed that both companies could introduce generics in the US on 11 December 2017.<ref>{{cite news|vauthors=Helfand C|title=The coming generics threat to Pfizer's Viagra brand just got scarier|url=http://www.fiercepharma.com/sales-and-marketing/coming-generics-threat-to-pfizer-s-viagra-brand-just-got-scarier|work=FiercePharma|date=14 April 2015|access-date=9 September 2017|archive-date=9 September 2017|archive-url=https://web.archive.org/web/20170909142637/http://www.fiercepharma.com/sales-and-marketing/coming-generics-threat-to-pfizer-s-viagra-brand-just-got-scarier|url-status=live}}</ref><ref>{{cite news|title=Viagra to go generic in 2017 according to Pfizer agreement|url=https://www.cbsnews.com/news/viagra-to-go-generic-in-2017-according-to-pfizer-agreement/|work=CBS News|date=17 December 2013|access-date=19 November 2017|archive-date=1 December 2017|archive-url=https://web.archive.org/web/20171201042527/https://www.cbsnews.com/news/viagra-to-go-generic-in-2017-according-to-pfizer-agreement/|url-status=live}}</ref> In December 2017, Pfizer released its own generic version of Viagra.<ref>{{cite news | title=Sex, Drugs and That Little Blue Pill | vauthors=Nocera J | url=https://www.bloomberg.com/view/articles/2017-12-06/viagra-history-from-sex-icon-to-generic-drug | date=6 December 2017 | access-date=10 December 2017 | publisher=Bloomberg | archive-date=6 December 2017 | archive-url=https://web.archive.org/web/20171206161327/https://www.bloomberg.com/view/articles/2017-12-06/viagra-history-from-sex-icon-to-generic-drug | url-status=live }}</ref><ref>{{cite news | title=Why Pfizer Is About to Slash Viagra's Price in Half | url=http://fortune.com/2017/12/06/viagra-generic-pfizer-price/ | vauthors=Mukherjee S | date=6 December 2017 | access-date=6 December 2017 | work=Fortune | archive-date=7 December 2017 | archive-url=https://web.archive.org/web/20171207030004/http://fortune.com/2017/12/06/viagra-generic-pfizer-price/ | url-status=live }}</ref>

{{As of|2018}}, the US [[Food and Drug Administration]] has approved fifteen drug manufacturers to market generic sildenafil in the United States. Seven of these companies are based in India.<ref>{{cite news | vauthors =Chandna H | title =Pfizer to lose patent of drug Viagra, Indian companies gear up with copycat versions: Pfizer's patent for the formulation of Viagra, used to treat impotence in men, ends in the US in 2020. | newspaper =[[Hindustan Times]] | location =[[New Delhi]] | date =7 August 2018 | url =https://www.hindustantimes.com/business-news/pfizer-to-lose-patent-of-drug-viagra-indian-companies-gear-up-with-copycat-versions/story-jrBkWfXF1A6fO7insmqmCN.html | access-date =10 August 2018 | archive-date =17 April 2021 | archive-url =https://web.archive.org/web/20210417213245/https://www.hindustantimes.com/business-news/pfizer-to-lose-patent-of-drug-viagra-indian-companies-gear-up-with-copycat-versions/story-jrBkWfXF1A6fO7insmqmCN.html | url-status =live }}</ref><ref>{{cite news | title =Set to conquer US, Indian 'Viagras' may give Pfizer a hard Time | newspaper =[[The Economic Times]] | location =[[Mumbai]] | date =3 August 2018 | url =https://economictimes.indiatimes.com/industry/healthcare/biotech/healthcare/set-to-conquer-us-indian-viagras-may-give-pfizer-a-hard-time/articleshow/65304880.cms | access-date =10 August 2010 | archive-date =22 December 2020 | archive-url =https://web.archive.org/web/20201222184012/https://economictimes.indiatimes.com/industry/healthcare/biotech/healthcare/set-to-conquer-us-indian-viagras-may-give-pfizer-a-hard-time/articleshow/65304880.cms | url-status =live }}</ref>

===Regional issues===

====United States====

In 1992, Pfizer filed a patent covering the substance sildenafil and its use to treat cardiovascular diseases.<ref>{{US patent|5250534}}</ref> This would be marketed as Revatio. The patent was published in 1993 and expired in 2012. The patent on Revatio (indicated for pulmonary arterial hypertension rather than erectile dysfunction) expired in late 2012. [[generic drug|Generic versions]] of this low-dose form of sildenafil have been available in the US from a number of manufacturers, including Greenstone, Mylan, and Watson, since early 2013.<ref>{{cite news |url=http://www.zacks.com/stock/news/86972/Pfizers-Revatio-Goes-Generic |title=Pfizer's Revatio Goes Generic |date=15 November 2012 |publisher=Zacks Equity Research |access-date=5 October 2013 |archive-date=12 October 2013 |archive-url=https://web.archive.org/web/20131012062327/http://www.zacks.com/stock/news/86972/Pfizers-Revatio-Goes-Generic |url-status=live }}</ref> Health care providers may prescribe generic sildenafil for erectile dysfunction.<ref name="Skinner March 2016"/> For a time, the generic was not available in the same dosages as branded Viagra, so using dosages typically required for treating ED required patients to take multiple pills.<ref name="Skinner March 2016"/>

In 1994, Pfizer filed a patent covering the use of sildenafil to treat erectile dysfunction.<ref>{{US patent|6469012}}</ref> This would be marketed as Viagra. This patent was published in 2002 and expired in 2019. [[Teva Pharmaceutical Industries|Teva]] sued to have the latter patent invalidated, but Pfizer prevailed in an August 2011 federal district court case.<ref>{{cite news |url=https://www.bloomberg.com/news/2011-08-15/pfizer-wins-viagra-patent-infringement-case-against-teva-pharmaceuticals.html |title=Pfizer Wins Viagra Patent Infringement Case Against Teva Pharmaceuticals |date=15 August 2011 |publisher=Bloomberg |access-date=1 April 2012 |vauthors=Milford P |archive-date=11 January 2015 |archive-url=https://web.archive.org/web/20150111001411/http://www.bloomberg.com/news/2011-08-15/pfizer-wins-viagra-patent-infringement-case-against-teva-pharmaceuticals.html |url-status=live }}</ref> An agreement with Pfizer allowed Teva to begin to provide the generic drug in December 2017.<ref name="Skinner March 2016"/>

In the United States, Pfizer received two patents for sildenafil: one for its indication to treat cardiovascular disease (marketed as Revatio) and another for its indication to treat erectile dysfunction (marketed as Viagra). The substance is the same under both brand names.<ref name="Skinner March 2016"/>

Sildenafil is available as a generic drug in the United States, labeled for pulmonary arterial hypertension.<ref name="Skinner March 2016">{{cite web|vauthors=Skinner G|title=Yes, There Is a Way to Get Generic Viagra|url=http://www.consumerreports.org/drugs/yes-there-is-a-way-to-get-generic-viagra/|website=Consumer Reports|access-date=4 May 2016|date=4 March 2016|archive-date=2 May 2016|archive-url=https://web.archive.org/web/20160502201031/http://www.consumerreports.org/drugs/yes-there-is-a-way-to-get-generic-viagra/|url-status=live}}</ref>

In the US, Revatio and Viagra are marketed by [[Viatris]] after Upjohn was spun off from Pfizer.<ref>{{cite web | title=Pfizer Completes Transaction to Combine Its Upjohn Business with Mylan | publisher=Pfizer | via=Business Wire | date=16 November 2020 | url=https://www.businesswire.com/news/home/20201116005378/en/ | access-date=17 June 2024}}</ref><ref>{{cite web | title=Revatio | website=Pfizer | url=https://www.pfizer.com/products/product-detail/revatio | access-date=17 June 2024 | archive-date=17 June 2024 | archive-url=https://web.archive.org/web/20240617051424/https://www.pfizer.com/products/product-detail/revatio | url-status=live }}</ref><ref>{{cite web | title=Viagra | website=Pfizer | url=https://www.pfizer.com/products/product-detail/viagra | access-date=17 June 2024}}</ref><ref>{{cite web | title=Brands | website=Viatris | date=16 November 2020 | url=https://www.viatris.com/en/products/brands | access-date=17 June 2024 | archive-date=17 June 2024 | archive-url=https://web.archive.org/web/20240617060406/https://www.viatris.com/en/products/brands | url-status=live }}</ref>

====Brazil====

Pfizer's patent on sildenafil citrate expired in Brazil in 2010.<ref>{{cite web|url=http://www.in-pharmatechnologist.com/Industry-Drivers/Viagra-patent-expires-in-June-says-Brazilian-court|title=Viagra patent expires in June, says Brazilian court|last=in-PharmaTechnologist.com|access-date=15 July 2016|archive-date=17 April 2012|archive-url=https://web.archive.org/web/20120417233636/http://www.in-pharmatechnologist.com/Industry-Drivers/Viagra-patent-expires-in-June-says-Brazilian-court|url-status=live}}</ref>

====Canada====

In Canada, Pfizer's patent 2,324,324 for Revatio (sildenafil used to treat pulmonary hypertension) was found invalid by the Federal Court in June 2010, on an application by [[Ratiopharm]] Inc.<ref>{{cite web |url=http://www.canadiantechnologyiplaw.com/2010/06/articles/intellectual-property/patents-1/revatio-patent-ruled-invalid-for-lack-of-sound-prediction-and-obviousness/ |publisher=Stikeman Elliott |work=Canadian Technology & IP Law |title=Revatio patent ruled invalid for lack of sound prediction and obviousness |date=18 June 2010 |access-date=14 November 2012 |archive-url=https://web.archive.org/web/20160303205830/http://www.canadiantechnologyiplaw.com/2010/06/articles/intellectual-property/patents-1/revatio-patent-ruled-invalid-for-lack-of-sound-prediction-and-obviousness/ |archive-date=3 March 2016 }}</ref><ref>{{cite web |url=http://canlii.ca/en/ca/fct/doc/2010/2010fc612/2010fc612.html |title=''Pfizer Canada Inc. v. Ratiopharm Inc.'', 2010 FC 612 |publisher=CanLII |access-date=27 December 2013 |archive-date=15 January 2013 |archive-url=https://archive.today/20130115095754/http://canlii.ca/en/ca/fct/doc/2010/2010fc612/2010fc612.html |url-status=live }}</ref>

On 8 November 2012, the Supreme Court of Canada ruled that Pfizer's patent 2,163,446 on Viagra was invalid from the beginning because the company did not provide full disclosure in its application. The decision, ''[[Teva Canada Ltd. v. Pfizer Canada Inc.]]'', pointed to section 27(3)(b) of The Patent Act which requires that disclosure must include sufficient information "to enable any person skilled in the art or science to which it pertains" to produce it. It added further: "As a matter of policy and sound statutory interpretation, patentees cannot be allowed to 'game' the system in this way. This, in my view, is the key issue in this appeal."<ref>{{cite CanLII|litigants=Teva Canada Ltd. v. Pfizer Canada Inc.|link=|year=2012|court=scc|num=60|pinpoint=par. 80|parallelcite=|date=8 November 2012|courtname=|juris=}}</ref>

Teva Canada launched Novo-Sildenafil, a generic version of Viagra, on the day the Supreme Court of Canada released its decision.<ref>{{cite news |url=https://www.thestar.com/business/2012/11/08/supreme_court_ruling_could_lead_to_cheaper_versions_of_viagra.html |work=[[Toronto Star]] |vauthors=Spears J |title=Supreme Court ruling could lead to cheaper versions of Viagra |date=8 November 2012 |access-date=14 November 2012 |archive-date=10 March 2013 |archive-url=https://web.archive.org/web/20130310084530/http://www.thestar.com/business/2012/11/08/supreme_court_ruling_could_lead_to_cheaper_versions_of_viagra.html |url-status=live }}</ref><ref>{{cite web |url=http://digitaljournal.com/article/336456 |work=Digital Journal |title=Canadian Supreme court rules Viagra patent invalid |vauthors=Hanly K |date=8 November 2012 |access-date=14 November 2012 |archive-date=11 November 2012 |archive-url=https://web.archive.org/web/20121111141433/http://digitaljournal.com/article/336456 |url-status=live }}</ref><ref>{{cite news |publisher=[[CBC News]] |url=http://www.cbc.ca/news/business/viagra-patent-tossed-out-by-supreme-court-1.1216466 |title=Viagra patent tossed out by Supreme Court: Decision allows generic versions of drug to be produced |access-date=14 November 2012 |date=8 November 2012 |archive-date=18 September 2013 |archive-url=https://web.archive.org/web/20130918100438/http://www.cbc.ca/news/business/viagra-patent-tossed-out-by-supreme-court-1.1216466 |url-status=live }}</ref> To remain competitive, Pfizer then reduced the price of Viagra in Canada.<ref>{{cite news |work=Financial Post |url=http://business.financialpost.com/2012/11/22/pfizer-canada-drops-viagra-price-generic-201/ |title=Pfizer Canada drops Viagra price after generic versions get Supreme Court green light |access-date=9 February 2013 |date=22 November 2012 |archive-date=30 November 2012 |archive-url=https://web.archive.org/web/20121130095322/http://business.financialpost.com/2012/11/22/pfizer-canada-drops-viagra-price-generic-201/ |url-status=live }}</ref> However, on 9 November 2012, Pfizer filed a motion for a re-hearing of the appeal in the Supreme Court of Canada,<ref>{{cite web |url=http://www.scc-csc.gc.ca/case-dossier/info/dock-regi-eng.aspx?cas=33951 |access-date=14 November 2012 |title=SCC Case Information, Docket No. 33951 |date=January 2001 |archive-date=27 December 2013 |archive-url=https://web.archive.org/web/20131227180306/http://www.scc-csc.gc.ca/case-dossier/info/dock-regi-eng.aspx?cas=33951 |url-status=live }}</ref> on the grounds that the court accidentally exceeded its jurisdiction by voiding the patent.<ref>{{cite news |vauthors=Makin K |work=The Globe and Mail |date=15 November 2012 |access-date=15 November 2012 |url=https://www.theglobeandmail.com/news/national/in-rare-move-pfizer-asks-supreme-court-to-reconsider-ruling-that-killed-viagra-patent/article5347670/ |title=In rare move, Pfizer asks Supreme Court to reconsider ruling that killed Viagra patent |archive-date=5 February 2013 |archive-url=https://web.archive.org/web/20130205050909/http://www.theglobeandmail.com/news/national/in-rare-move-pfizer-asks-supreme-court-to-reconsider-ruling-that-killed-viagra-patent/article5347670/ |url-status=live }}</ref> Finally, on 22 April 2013, the Supreme Court of Canada invalidated Pfizer's patent altogether.<ref>{{cite web |title=The Supreme Court of Canada holds Pfizer's Viagra patent invalid |vauthors=Henderson GL, D'Iorio H |work=Lexology |date=22 April 2013 |url=http://www.lexology.com/library/detail.aspx?g=63099904-cd62-4b40-a2e2-5112612e2da8 |access-date=27 December 2013 |archive-date=27 December 2013 |archive-url=https://web.archive.org/web/20131227123421/http://www.lexology.com/library/detail.aspx?g=63099904-cd62-4b40-a2e2-5112612e2da8 |url-status=live }}</ref>

====China====

{{unreferenced section|date=July 2024}}

Manufacture and sale of sildenafil citrate drugs is common in China, where Pfizer's patent claim is not widely enforced.

====Egypt====

Egypt approved Viagra for sale in 2002, but soon afterwards allowed local companies to produce generic versions of the drug, citing the interests of poor people who would not be able to afford Pfizer's price.<ref>{{cite news |title=Seeking Investment, Egypt Tries Patent Laws |vauthors=Allam A |url=https://www.nytimes.com/2002/10/04/business/seeking-investment-egypt-tries-patent-laws.html |newspaper=New York Times |date=4 October 2002 |access-date=1 April 2013 |archive-date=20 May 2013 |archive-url=https://web.archive.org/web/20130520125620/http://www.nytimes.com/2002/10/04/business/seeking-investment-egypt-tries-patent-laws.html |url-status=live }}</ref>

====European Union====

[[File:Sildenafil 100 milligram tablets - (prescription in the European Union) - Transgender shows the four-pack of 100 milligrams of tablet - Image 002n) - Transgender zeigt den Vierpack der je 100 Milligramm Tablette - Bild 002.jpg|thumb|upright=0.7|Sildenafil 100 milligram tablets (prescription in the European Union)]]

Pfizer's patent on sildenafil citrate expired in some member countries of the European Union, Austria, Denmark, France, Germany, Ireland, Italy, The Netherlands, Spain, Sweden, the United Kingdom, and Switzerland in June 2013.<ref>{{cite web|title=Actavis Launches Generic Viagra in Europe as Patents Expire|date=24 June 2013|url=https://finance.yahoo.com/news/actavis-launches-generic-viagra-r-120020258.html|access-date=25 October 2013|archive-date=29 October 2013|archive-url=https://web.archive.org/web/20131029201715/http://finance.yahoo.com/news/actavis-launches-generic-viagra-r-120020258.html|url-status=live}}</ref><ref name="What">{{cite web |url=http://www.accessrx.com/research/viagra-patent-expires |title=What Will Happen When Viagra Goes Generic? |vauthors=Edwards J |date=21 October 2009 |publisher=AccessRx.com |access-date=25 March 2011 |archive-date=23 April 2011 |archive-url=https://web.archive.org/web/20110423201812/http://www.accessrx.com/research/viagra-patent-expires |url-status=dead }}</ref><ref>{{cite news|title=Is Viagra about to lose its pulling power in the UK?|url=https://www.theguardian.com/business/shortcuts/2013/jun/03/viagra-lose-patent-pfizer-generic|newspaper=The Guardian|access-date=13 June 2013|date=3 June 2013|archive-date=30 October 2013|archive-url=https://web.archive.org/web/20131030182608/http://www.theguardian.com/business/shortcuts/2013/jun/03/viagra-lose-patent-pfizer-generic|url-status=live}}</ref> A UK patent held by Pfizer on the use of [[PDE5 inhibitor]]s (see below) as treatment of impotence was invalidated in 2000 because of [[Inventive step and non-obviousness|obviousness]]; this decision was upheld on appeal in 2002.<ref>{{cite news |url=https://www.telegraph.co.uk/money/main.jhtml?xml=/money/2002/01/24/cnviag24.xml |title=Viagra ruling upsets Pfizer |date=23 January 2002 |publisher=Telegraph Media Group Limited |access-date=10 February 2009 | location=London | vauthors = Murray R |url-status=dead |archive-url = https://web.archive.org/web/20090822222900/http://www.telegraph.co.uk/finance/2750418/Viagra-ruling-upsets-Pfizer.html|archive-date = 22 August 2009}}</ref><ref>{{cite web|url=http://www.urotoday.com/browse_categories/erectile_dysfunction/pfizer_loses_uk_battle_on_viagra_patent.html| title=Pfizer Loses UK Battle on Viagra Patent |date=17 June 2002 |publisher=Thomson Reuters |work=UroToday |access-date=10 February 2009|url-status = dead|archive-url = https://web.archive.org/web/20070625060239/http://www.urotoday.com/browse_categories/erectile_dysfunction/pfizer_loses_uk_battle_on_viagra_patent.html|archive-date = 25 June 2007}}</ref>

====India====

{{unreferenced section|date=July 2024}}

Manufacture and sale of sildenafil citrate drugs known as "generic Viagra" is common in India, where Pfizer's patent claim does not apply. Brand names include Kamagra ([[Ajanta Pharma]]), Silagra ([[Cipla]]), Edegra ([[Sun Pharmaceutical]]), Penegra ([[Zydus Cadila]]), Manly (Cooper Pharma) and Zenegra ([[Samprada Singh|Alkem Laboratories]]).

====New Zealand====

Sildenafil was reclassified in New Zealand in 2014 so it could be bought over the counter from a pharmacist. It is thought that this reduced sales over the Internet and was safer as males could be referred for medical advice if appropriate.<ref>{{cite news|title=Viagra from the pharmacist: insight from reclassification in New Zealand|url=https://pharmaceutical-journal.com/article/opinion/viagra-from-the-pharmacist-insight-from-reclassification-in-new-zealand|vauthors=Gauld N|access-date=2 April 2018|publisher=Pharmaceutical Journal|date=31 January 2018|archive-date=17 May 2021|archive-url=https://web.archive.org/web/20210517195302/https://pharmaceutical-journal.com/article/opinion/viagra-from-the-pharmacist-insight-from-reclassification-in-new-zealand|url-status=live}}</ref>

====South Korea====

In 1999 South Korea granted two patents to Pfizer related to sildenafil. The first document guaranteed sole production and sale of the substance until 2012, while the second gave Pfizer the exclusive use to treating erectile dysfunction with sildenafil until 2014.<ref>{{Cite web|date=14 March 2012|title=Generic Viagra developers queue up, but may have to wait|url=http://www.koreaherald.com/view.php?ud=20120314001093|access-date=28 December 2021|website=The Korea Herald|archive-date=28 December 2021|archive-url=https://web.archive.org/web/20211228061652/http://www.koreaherald.com/view.php?ud=20120314001093|url-status=live}}</ref> In 2011 [[Hanmi Pharmaceutical]] and [[CJ CheilJedang]] launched a suit against the exclusive use patent. The Korean Court system made a ruling against Pfizer in June 2012, allowing for the unhindered domestic production of generic prescription sildenafil.<ref>{{Cite news|date=1 June 2012|title=Approved Viagra copies flood drugstores in Korea|work=Reuters|url=https://www.reuters.com/article/us-korea-viagra-idUSBRE8500KF20120601|access-date=28 December 2021|archive-date=28 December 2021|archive-url=https://web.archive.org/web/20211228061651/https://www.reuters.com/article/us-korea-viagra-idUSBRE8500KF20120601|url-status=live}}</ref>

During 2012 Viagra lost its position as the top selling erectile dysfunction treatment in South Korea. This development was credited largely "due to the introduction of generic products." Generic sildenafil became publicly available in May. Sales of PalPal by Hanmi Pharmaceuticals totalled ₩22 billion or about 86% the market share of Viagra that year.<ref>{{Cite web|date=10 April 2013|title=Viagra loses top spot in Korean market|url=http://www.koreaherald.com/view.php?ud=20130410000803|access-date=28 December 2021|website=The Korea Herald|archive-date=28 December 2021|archive-url=https://web.archive.org/web/20211228061651/http://www.koreaherald.com/view.php?ud=20130410000803|url-status=live}}</ref> By 2017 there were over 50 generic sildenafil pills available. During that year Viagra sales slumped to 38% that of Palpal.<ref>{{Cite web|date=12 December 2017|title=Hanmi leads erectile dysfunction drug sales|url=http://www.koreabiomed.com/news/articleView.html?idxno=2104|access-date=28 December 2021|website=KBR|language=ko|archive-date=28 December 2021|archive-url=https://web.archive.org/web/20211228061652/http://www.koreabiomed.com/news/articleView.html?idxno=2104|url-status=live}}</ref>

====United Kingdom====

There were 2,958,199 prescriptions for Sildenafil in 2016 in England, compared with 1,042,431 in 2006.<ref>{{cite web | title=Viagra prescriptions almost triple in a decade | website=The Pharmaceutical Journal | date=12 February 2021 | url=https://pharmaceutical-journal.com/article/news/viagra-prescriptions-almost-triple-in-a-decade | access-date=1 July 2024 | archive-date=1 July 2024 | archive-url=https://web.archive.org/web/20240701041224/https://pharmaceutical-journal.com/article/news/viagra-prescriptions-almost-triple-in-a-decade | url-status=live }}</ref>

In 2018, Viagra Connect, a particular formulation of Sildenafil marketed by Pfizer, became available for sale without a prescription in the UK,<ref name="The Independent"/> in an attempt to widen availability and reduce demand for counterfeit products.

== References ==

{{Reflist}}

== External links ==

{{Sister project links|Sildenafil}}

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{{Nitric oxide signaling modulators}}

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