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词条 Sildenafil
释义

  1. Medical uses

     Sexual dysfunction  Antidepressant-associated sexual dysfunction  Pulmonary hypertension  Raynaud's phenomenon  High-altitude pulmonary edema 

  2. Adverse effects

     Interactions  Contraindications 

  3. Nonmedical use

     Recreational use  Jet lag research  Sports  Analogs 

  4. Detection in biological fluids

  5. Mechanism of action

  6. Route of administration

  7. Chemical synthesis

  8. History

  9. Society and culture

     Marketing and sales  Counterfeits  Regional issues  European Union  United Kingdom  United States  Canada  India  China  New Zealand  Other countries 

  10. References

  11. External links

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  • http://www.viagra.com/

Triggered by viagra(?!nde\\.ct\\.it\\b) on the global blacklist|bot=Cyberbot II|invisible=true}}

{{Drugbox
| Verifiedfields = changed
| Watchedfields = changed
| verifiedrevid = 477173085
| IUPAC_name = 52-Ethoxy-5-[(4-methylpiperazin-1-yl)sulfonyl]phenyl1-methyl-3-propyl-1,6-dihydro-7H-pyrazolo[4,3-d]pyrimidin-7-one
| image = Sildenafil structure.svg
| width = 250
| image2 = Sildenafil-from-xtal-3D-balls.png
| pronounce = {{IPAc-en|s|ɪ|l|ˈ|d|ɛ|n|ə|f|ɪ|l}} {{respell|sil|DEN|ə-fil}}
| tradename = Viagra, Revatio, others
| Drugs.com = {{drugs.com|monograph|sildenafil-citrate}}
| MedlinePlus = a699015
| licence_EU = yes
| licence_US = Sildenafil
| pregnancy_AU = B1
| pregnancy_US = B
| legal_AU = S4
| legal_CA = Rx-only
| legal_UK = P
| legal_US = Rx-only
| legal_status = Rx-only
| routes_of_administration = By mouth (tablets), IV
| bioavailability = 41% (mean)[1]
| protein_bound = ~96%
| metabolism = Liver: CYP3A4 (major route), CYP2C9 (minor route)
| metabolites = N-desmethylsildenafil (~50% potency for PDE5)
| elimination_half-life = 3–4 hours
| excretion = Feces (~80%), urine (~13%)[2]
| CAS_number_Ref = {{cascite|correct|??}}
| CAS_number = 139755-83-2
| CAS_number2_Ref = {{cascite|changed|??}}
| CAS_number2 = 171599-83-0
| index2_label = Citrate
| ATC_prefix = G04
| ATC_suffix = BE03
| ChEBI_Ref = {{ebicite|changed|EBI}}
| ChEBI = 9139
| PubChem = 5212
| DrugBank_Ref = {{drugbankcite|correct|drugbank}}
| DrugBank = DB00203
| ChemSpiderID_Ref = {{chemspidercite|changed|chemspider}}
| ChemSpiderID = 5023
| UNII_Ref = {{fdacite|correct|FDA}}
| UNII = 3M7OB98Y7H
| KEGG_Ref = {{keggcite|correct|kegg}}
| KEGG = D08514
| ChEMBL_Ref = {{ebicite|correct|EBI}}
| ChEMBL = 192
| PDB_ligand = VIA
| C=22 | H=30 | N=6 | O=4 | S=1
| molecular_weight = 474.5764 g/mol
| 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)
| StdInChIKey_Ref = {{stdinchicite|changed|chemspider}}
| StdInChIKey = BNRNXUUZRGQAQC-UHFFFAOYSA-N
}}Sildenafil, sold as the brand name Viagra among others, is a medication used to treat erectile dysfunction and pulmonary arterial hypertension.[2] It is unclear if it is effective for treating sexual dysfunction in women.[2] It is taken by mouth or injection into a vein.[2] Onset is typically within 20 minutes and lasts for about 2 hours.[2]

Common side effects include headaches, heartburn, and flushed skin.[2] Caution is advised in those with cardiovascular disease.[2] Rare but serious side effects include a prolonged erection that can lead to damage to the penis, vision problems, and hearing loss.[2] Sildenafil should not be taken by people on nitrates such as nitroglycerin (glycerin trinitrate), as this may result in a serious drop in blood pressure.[2]

Sildenafil acts by blocking phosphodiesterase 5 (PDE5), an enzyme that promotes breakdown of cGMP, which regulates blood flow in the penis.[2] It requires sexual arousal, however, to work.[2] It also results in dilation of the blood vessels in the lungs.[2]

Pfizer originally discovered the medication in 1989 while looking for a treatment for heart related chest pain.[3] It was approved for medical use in the United States and Europe in 1998.[2][3] In the United States about 2 million prescriptions were written for sildenafil in 2016.[4] In 2017 it became available as a generic medication.[5] In the United Kingdom it is available over the counter.[6] As of 2018 in the United States the wholesale cost is less than US$1 per dose.[7]{{TOC limit}}

Medical uses

Sexual dysfunction

The primary indication of sildenafil is treatment of erectile dysfunction (inability to sustain a satisfactory erection to complete intercourse). Its use is now one of the standard treatments for erectile dysfunction, including for men with diabetes mellitus.[8]

Antidepressant-associated sexual dysfunction

Tentative evidence suggests that sildenafil may help men who experience antidepressant-induced erectile dysfunction.[9]

Pulmonary hypertension

While sildenafil improves some markers of disease in people with pulmonary arterial hypertension, it does not appear to affect the risk of death or serious side effects {{as of|2014|lc=y}}.[10]

Raynaud's phenomenon

Sildenafil and other PDE5 inhibitors are used off-label to alleviate vasospasm and treat severe ischemia and ulcers in fingers and toes for people with secondary Raynaud's phenomenon;[24][25] these drugs have moderate efficacy for reducing the frequency and duration of vasospastic episodes.[11] {{As of|2016|post=,}} their role more generally in Raynaud's was not clear.[12]

High-altitude pulmonary edema

Sildenafil has been studied for high-altitude pulmonary edema but its use is currently not recommended for that indication.[13]

Adverse effects

In clinical trials, the most common adverse effects of sildenafil use included headache, flushing, indigestion, nasal congestion, and impaired vision, including photophobia and blurred vision.[2] Some sildenafil users have complained of seeing everything tinted blue (cyanopsia).[14] Some complained of blurriness and loss of peripheral vision. In July 2005, the FDA found that sildenafil could lead to vision impairment in rare cases[15] and a number of studies have linked sildenafil use with non-arteritic anterior ischemic optic neuropathy.[16]

Rare but serious adverse effects found through postmarketing surveillance include prolonged erections, severe low blood pressure, myocardial infarction (heart attack), ventricular arrhythmias, stroke, increased intraocular pressure, and sudden hearing loss.[2] 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.[17]

Interactions

Care should be exercised by people who are also taking protease inhibitors for the treatment of 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 mg dose every 48 hours.[2] 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.

The use of sildenafil and an 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.[18]

Contraindications

Contraindications include:[19]{{rp|11}}

  • Concomitant use of nitric oxide donors, organic nitrites and nitrates,[20] such as:
    • 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[21]

Nonmedical use

Recreational use

Sildenafil's popularity with young adults has increased over the years.[22] Sildenafil's trade name, Viagra, is widely recognized in popular culture, and the drug's association with treating erectile dysfunction has led to its recreational use.[23] The reasons behind such use include the belief that the drug increases libido, improves sexual performance,[23] or permanently increases penis size.[24] Studies on the effects of viagra when used recreationally are limited, but suggest it has little effect when used by those not suffering from erectile dysfunction. In one study, a 25-mg dose was shown to cause no significant change in erectile quality, but did reduce the postejaculatory refractory time.[25] This study also noted a significant placebo effect in the control group.[25]

Unprescribed recreational use of sildenafil and other PDE5 inhibitors is noted as particularly high among users of illegal drugs.[26] Sildenafil is sometimes used to counteract the effects of other substances, often illicit.[23] 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'" or "trail mix".[23] Mixing with amyl nitrite is particularly dangerous and potentially fatal.[23]

Jet lag research

The 2007 Ig Nobel Prize in Aviation went to Patricia V. Agostino, Santiago A. Plano, and Diego A. Golombek of Universidad Nacional de Quilmes, Argentina, for their discovery that sildenafil helps treat jet lag recovery in hamsters.[27][28]

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.[29][30]

Analogs

Acetildenafil and other synthetic structural analogs of sildenafil which are PDE5 inhibitors have been found as adulterants in a number of "herbal" aphrodisiac products sold over-the-counter.[31] These analogs have not undergone any of the rigorous testing that drugs like sildenafil have passed, and thus have unknown side-effect profiles.[32] 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.[33]

The US FDA has banned numerous products claiming to be Eurycoma longifolia that, in fact, contain only analogs of sildenafil.[34][35][36] 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.[37]

Mechanism of action

Sildenafil protects cyclic guanosine monophosphate (cGMP) from degradation by cGMP-specific phosphodiesterase type 5 (PDE5) in the 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. This smooth muscle relaxation leads to vasodilation and increased inflow of blood into the spongy tissue of the penis, causing an erection.[39] 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.

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. 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 better erections.[39] 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.[40]

Route of administration

  • When taken by mouth sildenafil for erectile dysfunction results in an average time to onset of erections of 27 minutes (ranging from 12 to 70 minutes).[41]
  • Under the tongue use of sildenafil for erectile dysfunction results in an average onset of action of 15 minutes and lasting for an average of 40 minutes.[42]
{{anchor|spray}}

There are also mouth spray preparations of sildenafil for faster onset of action.

Chemical synthesis

The preparation steps for synthesis of sildenafil are:[43]

  1. Methylation of 3-propylpyrazole-5-carboxylic acid ethyl ester with hot dimethyl sulfate
  2. Hydrolysis with aqueous sodium hydroxide (NaOH) to free acid
  3. Nitration with oleum/fuming nitric acid
  4. Carboxamide formation with refluxing thionyl chloride/NH4OH
  5. Reduction of nitro group to amino group
  6. Acylation with 2-ethoxybenzoyl chloride
  7. Cyclization
  8. Sulfonation to the chlorosulfonyl derivative
  9. Condensation with 1-methylpiperazine.

History

Sildenafil (compound UK-92,480) was synthesized by a group of pharmaceutical chemists 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). The first clinical trials were conducted in Morriston Hospital in Swansea.[44] Phase I clinical trials under the direction of Ian Osterloh suggested the drug had little effect on angina, but it could induce marked penile erections.[45][46] Pfizer therefore decided to market it for erectile dysfunction, rather than for angina; this decision became an often-cited example of drug repositioning.[47][48] The drug was patented 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.[49] It soon became a great success: annual sales of Viagra peaked in 2008 at US$1.934 billion.[50]

Society and culture

Marketing and sales

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 Senator Bob Dole and football star Pelé). Numerous sites on the Internet offer Viagra for sale after an "online consultation", often a simple web questionnaire.[51][52] The Viagra name has become so well known, many fake aphrodisiacs 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.

In 2000, Viagra sales accounted for 92% of the global market for prescribed erectile dysfunction pills.[53] By 2007, Viagra's global share had plunged to about 50%[54] 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.[55][56]

In February 2007, it was announced that Boots, the UK pharmacy chain, would try over-the-counter sales of Viagra in stores in Manchester, England. Men between the ages of 30 and 65 would be eligible to buy four tablets after a consultation with a pharmacist.[57] In 2017, the Medicines and Healthcare products Regulatory Agency enacted legislation that expanded this nationwide.,[58] allowing a particular branded formulation of Sildenafil, Viagra Connect (50 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 [59] The decision was made, in part, to reduce online sales of counterfeit and potentially dangerous erectile dysfunction treatments.

On 6 May 2013, Pfizer, which manufactures Viagra, told the Associated Press they will begin selling the drug directly to patients on its website.[60]

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.[61][62] In December 2017, Pfizer released its own generic version of Viagra.[63][64]

As of 2018, the U.S. Food and Drug Administration has approved 15 drug manufacturers to market generic sildenafil in the United States. Seven of these companies are based in India. This is likely to lead to dramatic price reductions.[65][66]

Counterfeits

{{further|Counterfeit medications}}

Counterfeit Viagra, despite generally being cheaper,[67] can contain harmful substances or substances that affect how Viagra works, such as blue printer ink, amphetamines, metronidazole, boric acid, and rat poison.[68]

Viagra is one of the world's most counterfeited medicines.[69][70] According to a Pfizer study, around 80% of sites claiming to sell Viagra were selling counterfeits.[68]

Regional issues

European Union

Pfizer's patent on sildenafil citrate expired in some member countries of the EU, Austria, Denmark, France, Germany, Ireland, Italy, The Netherlands, Spain, Sweden, the United Kingdom and Switzerland on 21 June 2013.[71][72][73] A UK patent held by Pfizer on the use of PDE5 inhibitors (see below) as treatment of impotence was invalidated in 2000 because of obviousness; this decision was upheld on appeal in 2002.[74][75]

United Kingdom

There were 2,958,199 prescriptions for Sildenafil in 2016 in England, compared with 1,042,431 in 2006.[76]

In 2018, Viagra Connect, a particular formulation of Sildenafil marketed by Pfizer, became available for sale without a prescription in the UK,[59] in an attempt to widen availability and reduce demand for counterfeit products.

United States

Sildenafil is available as a generic drug in the United States, labelled for pulmonary arterial hypertension.[77] {{As of|2016}} branded pills cost about 50 times more than generic ones.[77] In the United States {{as of|2015|lc=y}} the branded 50 mg pill cost is between 25.17 and US$37.88.[78]

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 trade names.[77]

In 1992, Pfizer filed a patent covering the substance sildenafil and its use to treat cardiovascular diseases.[79] 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 versions of this low-dose form of sildenafil have been available in the U.S. from a number of manufacturers, including Greenstone, Mylan, and Watson, since early 2013.[80] Health care providers may prescribe generic sildenafil for erectile dysfunction.[77] However, the generic is not available in the same dosages as branded Viagra, so using dosages typically required for treating ED requires patients to take multiple pills.[77]

In 1994, Pfizer filed a patent covering the use of sildenafil to treat erectile dysfunction.[81] This would be marketed as Viagra. This patent was published in 2002 and will expire in 2019. Teva sued to have the latter patent invalidated, but Pfizer prevailed in an August 2011 federal district court case.[82] An agreement with Pfizer allowed Teva to begin to provide the generic drug in December 2017.[77]

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.[83][84]

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."[85]

Teva Canada launched Novo-Sildenafil, a generic version of Viagra, on the day the Supreme Court of Canada released its decision.[86][87][88] To remain competitive, Pfizer then reduced the price of Viagra in Canada.[89] However, on 9 November 2012, Pfizer filed a motion for a re-hearing of the appeal in the Supreme Court of Canada,[90] on the grounds that the court accidentally exceeded its jurisdiction by voiding the patent.[91] Finally, on 22 April 2013, the Supreme Court of Canada invalidated Pfizer's patent altogether.[92]

India

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

China

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

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 men could be referred for medical advice if appropriate.[93]

Other countries

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.[94]

Pfizer's patent on sildenafil citrate expired in Brazil in 2010.[95]

References

1. ^{{cite journal | last1 = Nichols | first1 = DJ | last2 = Muirhead | first2 = GJ | last3 = Harness | first3 = 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 | date = 6 March 2002 | volume = 53 | pages = 5S–12S | doi = 10.1046/j.0306-5251.2001.00027.x | pmid = 11879254 | pmc = 1874258}}
2. ^1 2 3 4 5 6 7 8 9 10 11 {{cite web|title=Sildenafil Citrate|url=https://www.drugs.com/monograph/sildenafil-citrate.html|publisher=The American Society of Health-System Pharmacists|accessdate=1 December 2014}}
3. ^1 {{cite journal |last1=Goldstein |first1=I |last2=Burnett |first2=AL |last3=Rosen |first3=RC |last4=Park |first4=PW |last5=Stecher |first5=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=6 October 2018 |doi=10.1016/j.sxmr.2018.06.005 |pmid=30301707}}
4. ^{{cite web |title=The Top 300 of 2019 |url=https://clincalc.com/DrugStats/Top300Drugs.aspx |website=clincalc.com |accessdate=21 November 2018 |language=en}}
5. ^{{cite news |title=Generic Viagra: Two versions of sildenafil hit the market today |url=https://www.cbsnews.com/news/generic-viagra-two-versions-of-sildenafil-hit-the-market-today/ |accessdate=24 November 2018 |language=en}}
6. ^{{cite news |last1=LaMattina |first1=John |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/ |accessdate=24 November 2018 |work=Forbes |language=en}}
7. ^{{cite web |title=NADAC as of 2018-11-21 |url=https://data.medicaid.gov/Drug-Pricing-and-Payment/NADAC-as-of-2018-11-21/j5j5-fxwa |website=Centers for Medicare and Medicaid Services |accessdate=24 November 2018 |language=en}}
8. ^{{cite journal | last1 = Vardi | first1 = M | last2 = Nini | first2 = A | title = Phosphodiesterase Inhibitors for Erectile Dysfunction in Patients with Diabetes Mellitus | journal = The Cochrane Database of Systematic Reviews | date = 24 January 2007 | issue = 1 | page = CD002187 | doi = 10.1002/14651858.CD002187.pub3 | pmid = 17253475 }}
9. ^{{cite journal | last1 = Taylor | first1 = MJ | last2 = Rudkin | first2 = L | last3 = Bullemor-Day | first3 = P | last4 = Lubin | first4 = J | last5 = Chukwujekwu | first5 = C | last6 = Hawton | first6 = K | title = Strategies for Managing Sexual Dysfunction Induced by Antidepressant Medication | journal = The Cochrane Database of Systematic Reviews | date = 31 May 2013 | issue = 5 | page = CD003382 | doi = 10.1002/14651858.CD003382.pub3 | pmid = 23728643 }}
10. ^{{cite journal | last1 = Wang | first1 = RC | last2 = Jiang | first2 = FM | last3 = Zheng | first3 = QL | last4 = Li | first4 = CT | last5 = Peng | first5 = XY | last6 = He | first6 = CY | last7 = Luo | first7 = J | last8 = Liang | first8 = ZA | title = Efficacy and Safety of Sildenafil Treatment in Pulmonary Arterial Hypertension: a Systematic Review | journal = Respiratory Medicine | date = March 2014 | volume = 108 | issue = 3 | pages = 513–17 | doi = 10.1016/j.rmed.2014.01.003 | pmid = 24462476 | url = http://www.resmedjournal.com/article/S0954-6111(14)00023-7/pdf | accessdate = 5 November 2016}}
11. ^1 {{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 = 1696–99 | 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].}}
12. ^1 {{cite journal | vauthors = Linnemann B, Erbe M | title = Raynaud's phenomenon and digital ischaemia – pharmacologic approach and alternative treatment options | journal = VASA | 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 }}
13. ^{{cite journal |last1=Nieto Estrada |first1=Víctor H |last2=Molano Franco |first2=Daniel |last3=Medina |first3=Roger David |last4=Gonzalez Garay |first4=Alejandro G |last5=Martí-Carvajal |first5=Arturo J |last6=Arevalo-Rodriguez |first6=Ingrid |title=Interventions for preventing high altitude illness: Part 1. Commonly-used classes of drugs |journal=Cochrane Database of Systematic Reviews |volume=6 |pages=CD009761 |date=27 June 2017 |doi=10.1002/14651858.CD009761.pub2 |pmid=28653390}}
14. ^{{cite web | url = http://www.visionweb.com/content/consumers/dev_consumerarticles.jsp?RID=85 | title = Viagra and Vision | date = 29 October 2001 | publisher = VisionWeb | accessdate = 5 November 2016}}
15. ^{{cite web | title = FDA Updates Labeling for Viagra, Cialis and Levitra for Rare Post-Marketing Reports of Eye Problems | url = http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/2005/ucm108458.htm | publisher = U.S. Food and Drug Administration | accessdate=5 November 2016 | archiveurl = https://web.archive.org/web/20161022204628/http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/2005/ucm108458.htm | archivedate = 22 October 2016 | date = 8 July 2005}}
16. ^{{cite journal | last1 = Laties | first1 = AM | title = Vision Disorders and Phosphodiesterase Type 5 Inhibitors: a Review of the Evidence to Date | journal = Drug Safety | date = January 2009 | volume = 32 | issue = 1 | pages=1–18 | doi = 10.2165/00002018-200932010-00001 | pmid = 19132801 }}
17. ^{{cite web | title = FDA Announces Revisions to Labels for Cialis, Levitra and Viagra | url = http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/2007/ucm109012.htm | publisher = U.S. Food and Drug Administration | accessdate = 5 November 2016 | archiveurl = https://web.archive.org/web/20161022203200/http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/2007/ucm109012.htm | archivedate = 22 October 2016 | date = 18 October 2007}}
18. ^{{cite journal | last1 = Kloner | first1 = RA | title = Pharmacology and Drug Interaction Effects of the Phosphodiesterase 5 Inhibitors: Focus on α-Blocker Interactions | journal = The American Journal of Cardiology | date = 26 December 2005 | volume = 96 | issue = 12 (Suppl. 2) | pages = 42–46 | doi = 10.1016/j.amjcard.2005.07.011 | pmid = 16387566 }}
19. ^1 2 3 4 {{cite web | title = Viagra (sildenafil citrate) Tablets, for Oral Use. Full Prescribing Information | url = http://labeling.pfizer.com/ShowLabeling.aspx?id=652 | publisher = Pfizer Labs. Division of Pfizer, Inc., NY, NY 10017 | accessdate = 5 November 2016}}
20. ^{{cite journal | last1 = Cheitlin | first1 = MD | last2 = Hutter | first2 = AM Jr | last3 = Brindis | first3 = RG | last4 = Ganz | first4 = P | last5 = Kaul | first5 = S | last6 = Russell | first6 = RO Jr | last7 = Zusman | first7 = RM | title = ACC/AHA Expert Consensus Document. Use of Sildenafil (Viagra) in Patients with Cardiovascular Disease | journal = Journal of the American College of Cardiology | date = 15 November 1999 | volume = 34 | issue = 6 | pages = 273–82 | doi = 10.1016/S0735-1097(98)00656-1 | pmid = 9935041 }}
21. ^{{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=2018-07-11|language=en}}
22. ^{{cite news|author=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}}
23. ^1 2 3 4 {{cite journal |vauthors=Smith KM, Romanelli F | title = Recreational use and misuse of phosphodiesterase 5 inhibitors | journal = J Am Pharm Assoc (2003) | volume = 45 | issue = 1 | pages = 63–72; quiz 73–75 | year = 2005 | pmid = 15730119 | doi = 10.1331/1544345052843165 }}
24. ^{{cite web|url=http://www.theonlineclinic.co.uk/news/2012/12/24/SildenafilWillNotAffectLibidoFact.aspx|title=Sildenafil Will Not Affect Libido - Fact!|accessdate=15 July 2016}}
25. ^1 {{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 = Int. J. Impot. Res. | volume = 15 | issue = 3 | pages = 225–28 |date=June 2003 | pmid = 12904810 | doi = 10.1038/sj.ijir.3901005 }}
26. ^{{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 Alcohol Rev | volume = 25 | issue = 2 | pages = 111–13 |date=March 2006 | pmid = 16627299 | doi = 10.1080/09595230500537167 }}
- {{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 = J Fam Pract | volume = 56 | issue = 11 | pages = E1–4 |date=November 2007 | pmid = 17976333 | doi = }}
27. ^{{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 |accessdate=10 February 2009}}
28. ^{{cite journal |vauthors=Agostino PV, Plano SA, Golombek DA | title = Sildenafil accelerates reentrainment of circadian rhythms after advancing light schedules | journal = Proc. Natl. Acad. Sci. U.S.A. | volume = 104 | issue = 23 | pages = 9834–39 |date=June 2007 | pmid = 17519328 | pmc = 1887561 | doi = 10.1073/pnas.0703388104 }}
29. ^{{cite news |author=Teri Thompson |author2=Christian Red |author3=Michael O'Keefffe |author4=Nathaniel Vinton |title=Source: Roger Clemens, host of athletes pop Viagra to help onfield performance |work=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 |accessdate=10 February 2009}}
30. ^{{cite web | author = 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 | publisher = Yahoo! Sports | date = 28 November 2012 | accessdate = 28 November 2012 }}
31. ^{{cite journal | doi = 10.1016/j.jpba.2012.02.014 |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 |year = 2006–2012 | volume=69 | pages=196–208 | pmid=22464558}}
32. ^{{cite journal | doi = 10.1080/15287390600751355 | 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 |year = 2006 | volume=69 | issue=21 | pages=1951–58 | pmid=16982533}}
33. ^{{cite journal |vauthors=Venhuis BJ, Blok-Tip L, de Kaste D | title = Designer drugs in herbal aphrodisiacs | journal=Forensic Science International | year=2008 | volume=177 |issue=2–3 | pages = 25–27 | pmid=18178354 | doi = 10.1016/j.forsciint.2007.11.007}}
34. ^FDA letter to Libidus distributor
35. ^FDA Warns Consumers About Dangerous Ingredients in "Dietary Supplements" Promoted for Sexual Enhancement
36. ^Hidden Risks of Erectile Dysfunction "Treatments" Sold Online
37. ^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=Archived copy |accessdate=1 July 2011 |deadurl=yes |archiveurl=https://web.archive.org/web/20110910161559/http://www.biomedicalpublications.com/dt9.pdf |archivedate=10 September 2011 |df= }}
38. ^{{Cite journal| last1 = Sung | first1 = B. J.| last2 = Hwang | first2 = K.| last3 = Jeon | first3 = Y.| last4 = Lee | first4 = J. I.| last5 = Heo | first5 = Y. S.| last6 = Kim | first6 = J.| last7 = Moon | first7 = J.| last8 = Yoon | first8 = J.| last9 = Hyun | first9 = Y. L.| last10 = Kim| doi = 10.1038/nature01914 | first10 = E.| last11 = Eum | first11 = S.| last12 = Park | first12 = S. Y.| last13 = Lee | first13 = J. O.| last14 = Lee | first14 = T.| last15 = Ro | first15 = S.| last16 = Cho | first16 = J.| title = Structure of the catalytic domain of human phosphodiesterase 5 with bound drug molecules| journal = Nature| volume = 425| issue = 6953| pages = 98–102| year = 2003| pmid = 12955149| pmc =}}
39. ^1 {{cite journal|author1=Webb, D.J. |author2=Freestone, S. |author3=Allen, M.J. |author4=Muirhead, G.J. |title=Sildenafil citrate and blood-pressure-lowering drugs: results of drug interaction studies with an organic nitrate and a calcium antagonist|date=4 March 1999|journal=Am. J. Cardiol.|volume=83|issue=5A|pages=21C–28C|pmid=10078539|doi=10.1016/S0002-9149(99)00044-2}}
40. ^{{cite web| url = http://www.rxlist.com/viagra-drug/clinical-pharmacology.htm | title = Viagra Clinical Pharmacology | year = 2008 | accessdate = 20 August 2008 | publisher = RxList.com}}
41. ^{{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=Br J Clin Pharmacol |volume=53 Suppl 1 |issue= |pages=61S–65S |year=2002 |pmid=11879261 |pmc=1874251 |doi= 10.1046/j.0306-5251.2001.00034.x|url=}}
42. ^{{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=Int. J. Urol. |volume=11 |issue=11 |pages=989–92 |year=2004 |pmid=15509203 |doi=10.1111/j.1442-2042.2004.00933.x |url=}}
43. ^{{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 | author = Dunn PJ | year = 2005}}
44. ^{{cite web| title=Research | url=http://www.abm.university-trust.wales.nhs.uk/page.cfm?orgId=743&pid=29457 | date= 4 July 2008 | accessdate=6 August 2008|archiveurl = https://web.archive.org/web/20080926034946/http://www.abm.university-trust.wales.nhs.uk/page.cfm?orgId=743&pid=29457|deadurl = yes|archivedate = 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!}}
45. ^{{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 = Int. J. Impot. Res. | volume = 8 | issue = 2 | pages = 47–52 |date=June 1996 | pmid = 8858389 | doi = }}
46. ^{{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 }}
47. ^{{cite journal|last1=Ashburn|first1=TT|last2=Thor|first2=KB|title=Drug repositioning: identifying and developing new uses for existing drugs.|journal=Nature Reviews. Drug Discovery|date=August 2004|volume=3|issue=8|pages=673–83|doi=10.1038/nrd1468|pmid=15286734}}
48. ^{{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}}
49. ^{{cite journal|author=Kling J|title=From hypertension to angina to Viagra|journal=Mod. Drug Discov.|year=1998|volume=1|pages=31–38|url=|issn = 1532-4486|oclc = 41105083}}
50. ^{{cite web|url=https://www.sec.gov/Archives/edgar/data/78003/000119312511048877/dex13.htm|title=Portions of the 2010 Financial Report|accessdate=15 July 2016}}
51. ^{{cite journal|pmc=1174637 |title=Missouri fines internet pharmacy |year=1999|volume=319|issue=7221|doi=10.1136/bmj.319.7221.1324g|journal=BMJ|page=1324|pmid=10567131|last1=Ciment|first1=J}}
52. ^{{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|author=Devine, Amy |work=Daily Record |date=29 September 2008 |accessdate=30 April 2012}}
53. ^{{cite journal | author = Keith A | title = The economics of Viagra | journal = Health Aff (Millwood) | volume = 19 | issue = 2 | pages = 147–57 | year = 2000 | pmid = 10718028 | doi = 10.1377/hlthaff.19.2.147 }}
54. ^{{cite web|title=Cialis gaining market share worldwide | author = 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 | accessdate = 10 February 2009 |archiveurl = https://web.archive.org/web/20090103220918/http://www.allbusiness.com/marketing-advertising/marketing-advertising-measures/10557040-1.html|archivedate = 3 January 2009}}
55. ^{{cite journal |url=http://pubs.acs.org/cen/coverstory/83/8325/8325viagra.html |title=Viagra |author=Mullin, Rick |journal=Chemical & Engineering News |volume=83 |issue=25 |date=20 June 2005 |accessdate=20 August 2008}}
56. ^{{cite news |url=https://www.nytimes.com/2005/12/04/business/yourmoney/04impotence.html |title=Sales of Impotence Drugs Fall, Defying Expectations |author=Berenson, Alex |work=The New York Times |date=4 December 2005 |accessdate=20 August 2008 }}
57. ^{{cite news |url=http://news.bbc.co.uk/2/hi/health/6351171.stm |title=Over-the-counter Viagra piloted |date=11 February 2007 |publisher=BBC News |accessdate=10 February 2009}}
58. ^{{cite news |url=https://www.bbc.com/news/health-42155489 |title=Viagra can be sold over the counter |date=28 November 2017 |publisher=BBC News |accessdate=5 April 2018}}
59. ^1 {{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 |publisher=The Independent |accessdate=5 April 2018}}
60. ^{{cite web|title=Pfizer to sell Viagra online, in first for Big Pharma: AP|url=http://www.cbsnews.com/news/pfizer-to-sell-viagra-online-in-first-for-big-pharma-ap/|publisher=CBS News|accessdate=6 May 2013}}
61. ^{{cite news|last1=Helfand|first1=Carly|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}}
62. ^{{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/|publisher=CBS News|date=17 December 2013}}
63. ^{{cite news | title=Sex, Drugs and That Little Blue Pill | first=Joe | last=Nocera | url=https://www.bloomberg.com/view/articles/2017-12-06/viagra-history-from-sex-icon-to-generic-drug | date=6 December 2017 | accessdate=10 December 2017 | publisher=Bloomberg}}
64. ^{{cite new | title=Why Pfizer Is About to Slash Viagra's Price in Half | url=http://fortune.com/2017/12/06/viagra-generic-pfizer-price/ | first=Sy | last=Mukherjee | date=6 December 2017 | accessdate=6 December 2017 | work=Fortune}}
65. ^{{cite news | last = Chandna | first =Himani | 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 | pages = | language = | publisher = | date =August 7, 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 | accessdate =August 10, 2018 }}
66. ^{{cite news | last = | first = | title =Set to conquer US, Indian 'Viagras' may give Pfizer a hard Time | newspaper =The Economic Times | location =Mumbai | pages = | language = | publisher = | date =August 3, 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 | accessdate =August 10, 2010 }}
67. ^{{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|deadurl=bot: unknown|archiveurl=https://www.webcitation.org/6n3Lm88RW?url=http://www.bbc.com/news/health-36266826|archivedate=26 December 2016|df=}}
68. ^1 {{cite news|last1=Amerman|first1=Don|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}}
69. ^{{cite news|last1=Moran|first1=Barbara|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}}
70. ^{{cite news|last1=CNN|first1=Gena Somra|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}}
71. ^{{cite web|title=Actavis Launches Generic Viagra in Europe as Patents Expire|url=https://finance.yahoo.com/news/actavis-launches-generic-viagra-r-120020258.html|accessdate=25 October 2013}}
72. ^{{cite web |url=http://www.accessrx.com/research/viagra-patent-expires |title=What Will Happen When Viagra Goes Generic? |author=Jim Edwards |date=21 October 2009 |publisher=AccessRx.com |accessdate=25 March 2011 }}
73. ^{{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|accessdate=13 June 2013|date=2013-06-03}}
74. ^{{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 |accessdate=10 February 2009 | location=London | first=Rosie | last=Murray-|archiveurl = https://web.archive.org/web/20090822222900/http://www.telegraph.co.uk/finance/2750418/Viagra-ruling-upsets-Pfizer.html|archivedate = 22 August 2009}}
75. ^{{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 |accessdate=10 February 2009|deadurl = yes|archiveurl = https://web.archive.org/web/20070625060239/http://www.urotoday.com/browse_categories/erectile_dysfunction/pfizer_loses_uk_battle_on_viagra_patent.html|archivedate = 25 June 2007}}
76. ^{{cite news|title=Viagra prescriptions almost triple in a decade|url=http://www.pharmaceutical-journal.com/20203430.article|accessdate=8 October 2017|publisher=Pharmaceutical Journal|date=21 August 2017}}
77. ^1 2 3 4 5 {{cite web|last1=Skinner|first1=Ginger|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|accessdate=4 May 2016|date=4 March 2016}}
78. ^{{cite news|last1=Langreth|first1=Robert|title=Decoding Big Pharma's Secret Drug Pricing Practices|url=https://www.bloomberg.com/graphics/2016-drug-prices/|accessdate=15 July 2016|publisher=Bloomberg|date=29 June 2016}}
79. ^{{US patent|5250534}}
80. ^{{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 |accessdate=5 October 2013}}
81. ^{{US patent|6469012}}
82. ^{{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 |accessdate=1 April 2012}}
83. ^{{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=Revation patent ruled invalid for lack of sound prediction and obviousness |date=18 June 2010 |accessdate=14 November 2012 }}
84. ^{{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}}
85. ^{{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=}}
86. ^{{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 |author=John Spears |title=Supreme Court ruling could lead to cheaper versions of Viagra |date=8 November 2012 |accessdate=14 November 2012}}
87. ^{{cite web |url=http://digitaljournal.com/article/336456 |work=Digital Journal |title=Canadian Supreme court rules Viagra patent invalid |author=Ken Hanly |date=8 November 2012 |accessdate=14 November 2012}}
88. ^{{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 |accessdate=14 November 2012 |date=8 November 2012}}
89. ^{{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 |accessdate=9 February 2013 |date=22 November 2012 }}
90. ^{{cite web | url=http://www.scc-csc.gc.ca/case-dossier/info/dock-regi-eng.aspx?cas=33951 |accessdate=14 November 2012 |title=SCC Case Information, Docket No. 33951|date=January 2001 }}
91. ^{{cite news |author=Kirk Makin |work=The Globe and Mail |date=15 November 2012 |accessdate=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}}
92. ^{{cite web |title=The Supreme Court of Canada holds Pfizer's Viagra patent invalid |author1=Gowling Lafleur Henderson LLP |author2=Hélène D'Iorio |work=Lexology |date=22 April 2013 | url=http://www.lexology.com/library/detail.aspx?g=63099904-cd62-4b40-a2e2-5112612e2da8 | accessdate=27 December 2013}}
93. ^{{cite news|title=Viagra from the pharmacist: insight from reclassification in New Zealand|url=https://www.pharmaceutical-journal.com/20204320.article?|accessdate=2 April 2018|publisher=Pharmaceutical Journal|date=31 January 2018}}
94. ^{{cite news |title=Seeking Investment, Egypt Tries Patent Laws |first=Abeer |last=Allam |url=https://www.nytimes.com/2002/10/04/business/seeking-investment-egypt-tries-patent-laws.html |newspaper=New York Times |date=4 October 2002 |accessdate=1 April 2013 }}
95. ^{{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|accessdate=15 July 2016}}

External links

{{Sister project links|Sildenafil}}
  • FDA Information
  • [https://www.nlm.nih.gov/medlineplus/druginfo/meds/a699015.html MedlinePLUS information, including side effects]
  • U.S. National Library of Medicine: Drug Information Portal – Sildenafil
  • Viagra at The Periodic Table of Videos (University of Nottingham)
{{Sexual dysfunction pharmacotherapies}}{{Drugs for erectile dysfunction and premature ejaculation}}{{Management of pulmonary arterial hypertension}}{{PDE inhibitors}}{{Piperazines}}{{Authority control}}

9 : Erectile dysfunction drugs|Lactams|PDE5 inhibitors|Pfizer products|Phenol ethers|Piperazines|Products introduced in 1998|Pyrazolopyrimidines|RTT
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