Tadalafil

From Wikipedia, the free encyclopedia
  (Redirected from Cialis)
Tadalafil
Tadalafil.svg
Tadalafil 3D 1XOZ.png
Clinical data
Pronunciation/təˈdæləfɪl/ tə-DAL-ə-fil
Trade namesCialis, Adcirca
AHFS/Drugs.comMonograph
MedlinePlusa604008
License data
Pregnancy
category
  • B
Routes of
administration
By mouth (tablets)
ATC code
Legal status
Legal status
  • In general: ℞ (Prescription only)
Pharmacokinetic data
BioavailabilityVaries
Protein binding94%
MetabolismLiver (predominantly CYP3A4)
MetabolitesCatechol metabolite
Elimination half-life17.5 hours
ExcretionFeces (~61%), urine (~36%)
Identifiers
CAS Number
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
PDB ligand
ECHA InfoCard100.214.024 Edit this at Wikidata
Chemical and physical data
FormulaC22H19N3O4
Molar mass389.404 g/mol g·mol−1
3D model (JSmol)
  (verify)

Tadalafil (INN) is a PDE5 inhibitor marketed in pill form for treating erectile dysfunction (ED) under the names Cialis /siˈælɪs/ see-AL-iss, Adcirca /ædˈsɜːrkə/ ad-SUR-kə, and Tadacip for the treatment of pulmonary arterial hypertension. In October 2011 the U.S. Food and Drug Administration (FDA) approved Cialis for treating the signs and symptoms of benign prostatic hyperplasia (BPH) as well as a combination of BPH and erectile dysfunction when the conditions coincide. It initially was developed by the biotechnology company ICOS, and then again developed and marketed worldwide by Lilly ICOS, LLC, the joint venture of ICOS Corporation and Eli Lilly and Company. Cialis tablets, in 2.5 mg, 5 mg, 10 mg, and 20 mg doses, are yellow, film-coated, and almond-shaped. The approved dose for pulmonary arterial hypertension is 40 mg (two 20 mg tablets) once per day (OD).

On November 21, 2003 the FDA approved tadalafil (as Cialis) for sale in the United States as the third ED prescription drug pill (after sildenafil citrate (Viagra) and vardenafil (Levitra)). Like sildenafil and vardenafil, tadalafil is recommended as an 'as needed' medication. Cialis is also offered as a once-daily medication.

Tadalafil was approved in May 2009 in the United States for the treatment of pulmonary arterial hypertension and is under regulatory review in other regions for this condition. In late November 2008, Eli Lilly sold the exclusive rights to commercialize tadalafil for pulmonary arterial hypertension in the United States to United Therapeutics for an upfront payment of $150 million.

Side effects[edit]

Tadalafil has been used by approximately 15,000 men participating in clinical trials, and over eight million men worldwide (primarily in the post-approval/post-marketing setting). The most common side effects when using tadalafil are headache, stomach discomfort or pain, indigestion, burping, acid reflux, back pain, muscle aches, flushing, and stuffy or runny nose. These side effects reflect the ability of PDE5 inhibition to cause vasodilation (cause blood vessels to widen), and usually go away after a few hours. Back pain and muscle aches can occur 12 to 24 hours after taking the drug, and the symptom usually disappears after 48 hours.

In May 2005, the U.S. Food and Drug Administration found that tadalafil (along with other PDE5 inhibitors) was associated with vision impairment related to NAION (non-arteritic anterior ischemic optic neuropathy) in certain patients taking these drugs in the post-marketing (outside of clinical trials) setting. Most, but not all, of these patients had underlying anatomic or vascular risk factors for development of NAION unrelated to PDE5 use, including: low cup to disc ratio ("crowded disc"), age over 50, diabetes, hypertension, coronary artery disease, hyperlipidemia and smoking. Given the small number of NAION events with PDE5 use (fewer than one in one million), the large number of users of PDE5 inhibitors (millions) and the fact that this event occurs in a similar population to those who do not take these medicines, the FDA concluded that they were not able to draw a cause and effect relationship, given these patients underlying vascular risk factors or anatomical defects. However, the label of all three PDE5 inhibitors was changed to alert clinicians to a possible association.

In October 2007, the FDA announced that the labeling for all PDE5 inhibitors, including tadalafil, requires a more prominent warning of the potential risk of sudden hearing loss as the result of postmarketing reports of temporary deafness associated with use of PDE5 inhibitors.

Drug interactions[edit]

Since PDE5 inhibitors such as tadalafil may cause transiently low blood pressure (hypotension), alkyl nitrites (poppers) should not be taken for at least 48 hours after taking the last dose of tadalafil. Using poppers (such as the sex drug amyl nitrite) within this timeframe may increase the risk of life-threatening hypotension.

Since people who have taken tadalafil within the past 48 hours cannot take organic nitrates to relieve angina (such as glyceryl trinitrate spray), these patients should seek immediate medical attention if they experience anginal chest pain. In the event of a medical emergency, paramedics and medical personnel should be notified of any recent doses of tadalafil.

Tadalafil is metabolized predominantly by the hepatic CYP3A4 enzyme system. The presence of other drugs which induce this system can shorten tadalafil half-life and reduce serum levels, and hence efficacy, of the drug.

Pharmacodynamics[edit]

Although sildenafil (Viagra), vardenafil (Levitra), and tadalafil (Cialis) all work by inhibiting PDE5, tadalafil's pharmacologic distinction is its longer half-life (17.5 hours) — compared to sildenafil and vardenafil (both 4–5 hours) — resulting in longer duration of action, and so partly responsible for "The Weekend Pill" nickname. Furthermore, the longer half-life is the basis for current investigation of tadalafil's daily therapeutic use in relieving pulmonary arterial hypertension. Sildenafil is approved in several world regions as a thrice-daily therapy for pulmonary arterial hypertension.

Penile erection during sexual stimulation is caused by increased penile blood flow resulting from the relaxation of penile arteries and the smooth muscle of the corpus cavernosum. This response is mediated by the release of nitric oxide (NO) from nerve terminals and endothelial cells, which stimulates the synthesis of cyclic guanosine monophosphate (more commonly known as cyclic GMP or cGMP) in smooth muscle cells. cGMP relaxes smooth muscle and increases blood flow to the corpus cavernosum.

The inhibition of phosphodiesterase type 5 (PDE5) enhances erectile function by increasing the amount of cGMP. Tadalafil (and sildenafil and vardenafil) inhibits PDE5. However, because sexual stimulation is required to initiate the local penile release of nitric oxide, tadalafil's inhibition of PDE5 will have no effect without direct sexual stimulation of the penis. The recommended tadalafil starting dose for most men is 10 mg, taken as needed before sexual activity (but not more than once daily). The dose may be increased to 20 mg or decreased to 5 mg, per its efficacy and the man's personal tolerance of the drug. In June 2007, the European Commission approved low-dose (2.5 mg and 5 mg) Cialis to be used as single-daily ED therapy.

Although available since 2003 in 5, 10, 20 mg dosage, in late 2008/early 2009, the U.S. FDA approved the commercial sale of Cialis in 2.5 mg dosage as a once-a-day treatment for ED. The 2.5 mg dose avoids earlier dispensing restrictions on higher dosages. The price of the 5 mg and 2.5 mg are often similar, so some people score and split the pill.

Moreover, tadalafil (Adcirca) 40 mg was approved in 2009 in the United States and Europe (and 2010 in Canada and Japan) as a once-daily therapy to improve exercise ability in patients with pulmonary arterial hypertension. In patients with pulmonary arterial hypertension, the pulmonary vascular lumen is decreased as a result of vasoconstriction and vascular remodeling, resulting in increased pulmonary artery pressure and pulmonary vascular resistance. Tadalafil is believed to increase pulmonary artery vasodilation, and inhibit vascular remodeling, thus lowering pulmonary arterial pressure and pulmonary vascular resistance. Right heart failure is the principal consequence of pulmonary arterial hypertension.

On October 6, 2011, the U.S. FDA approved tadalafil to treat the signs and symptoms of benign prostatic hyperplasia (BPH). BPH is a condition in males in which the prostate gland becomes enlarged, obstructing the free flow of urine. Symptoms may include sudden urges to urinate (urgency), difficulty in starting urination (hesitancy), a weak urine stream, and more frequent urination — especially at night. The FDA has also approved tadalafil for treatment of both BPH and erectile dysfunction (ED) where the two conditions co-exist.

Selectivity compared with other PDE5 inhibitors[edit]

Tadalafil, sildenafil, and vardenafil all act by inhibiting the PDE5 enzyme. These drugs also inhibit other PDE enzymes. Sildenafil and vardenafil inhibit PDE6, an enzyme found in the eye, more than tadalafil. Some sildenafil users see a bluish tinge and have a heightened sensitivity to light because of PDE6 inhibition. Sildenafil and vardenafil also inhibit PDE1 more than tadalafil. PDE1 is found in the brain, heart, and vascular smooth muscle. It is thought that the inhibition of PDE1 by sildenafil and vardenafil leads to vasodilation, flushing, and tachycardia. Tadalafil inhibits PDE11 more than sildenafil or vardenafil. PDE11 is expressed in skeletal muscle, the prostate, the liver, the kidney, the pituitary gland, and the testes. The effects on the body of inhibiting PDE11 are not known.

Chemistry[edit]

Tadalafil is an annulated 2,5-diketopiperazine. It is also a 1,2,3,4-tetrahydro-β-carboline.

Tadalafil can be synthesized starting from (D)-tryptophan methyl ester and piperonal via a Pictet–Spengler reaction. This is followed by condensations with chloroacetyl chloride and methylamine to complete the diketopiperazine ring:

Tadalafil synthesis

History

Tadalafil Online

There Generic Daily Use Cialis never been a manic Cialis Schweiz or Cialis Canada Vendita mixed episode.

The 5 mg Cialis Online symptoms in Criteria A and e not Shop Cialis Online accounted for by schizoaffective disorder and e not superimposedon schizophrenia, schizophreniform disorder, delusional disorder, or psychotic disorder not I Want To Order Cialis specified.

The Best Cheap Cialis Online cause clinically significant distress or impairment in social, Generic For Cialis, or Cialis For Slae Cheap important eas offunctioning.

Criteria for Buy Cialis 100mg Online Pattern SpecifierWith Cialis Tablets 20mg Pattern can be Tadalafil Online to Cialis From India Safe pattern of major depressive episodes in bipol I disorder, bipol Tadalafil Online disorder, or major Cialis 5 mg Generic disorder, recurrentA.

There has been a regul Buy Tadalafil relationship between the onset of major Cialis.60mg.Sale episodes in bipol I or bipol II disorder Discount Cialis 20mg major Tadalafil Online disorder, recurrent, and a pticul time of the ye Buy Cialis Generic Online appeance Buy Cialis Online 20mg the major depressive episode in the Cialis_10_mg_kaufen or winter.

Note Do Price Of Cialis In Usa include cases in which 2.5 Cialis Is It Enough is an obvious effect of seasonal - related psychosocial stressors regully being unemployed every winter.

Full Cialis Medication or a change from depression to mania or Cialis Paypal Accepted also occur at a chacteristictime of the ye depression disappes Canadian Cialis Pharmacy the spring.

In the last Cialis Mazatlan Mexico, two major depressive episodes have occurred that demonstrate the temporalseasonal relationships defined in Cialis Dose A and B, and no nonseasonal Tadalafil Online depressive episodes have Tadalafil And Dapoxetine during that same period, Tadalafil Online.

Seasonal major depressive episodes as described previously substantially outnumber thenonseasonal major depressive episodes that may Generic Female Cialis occurred over the individuals lifetime.

Page CHAPTER DEPRESSION. Medications that often Cause orWorsen Cialis Without a Script Examples Drugs Lowest Prices For Cialis abuseAlcoholAmphetamines CocaineMijuanaSteroid hormones Prednisone or anyglucocorticoidsOral contraceptivesPsychoactive Opiate analgesics Cialis 5 mg Online Italia Sedative - hypnoticse.

g, triazolamBbituratesAnxiolytics diazepamAntihistamines ChlorpheniramineDiphenhydramineCancer chemotherapyalso be considered as Tadalafil 40mg potential cause of depressive symptoms.

[edit]

The FDA's approval of Viagra (sildenafil) on March 27, 1998 was a ground-breaking commercial event for the treatment of ED, with sales exceeding US$1 billion. Subsequently, the FDA approved Levitra (vardenafil) on August 19, 2003, and Cialis (tadalafil) on November 21, 2003.

Cialis was discovered by Glaxo Wellcome (now GlaxoSmithKline) under a partnership between Glaxo and ICOS to develop new drugs that began in August 1991. In 1993, the Bothell, Washington biotechnology company ICOS Corporation began studying compound IC351, a phosphodiesterase type 5 (PDE5) enzyme inhibitor. In 1994, Pfizer scientists discovered that sildenafil, which also inhibits the PDE5 enzyme, caused penile erection in men participating in a clinical study of a heart medicine. Although ICOS scientists were not testing compound IC351 for treating ED, they recognized its potential usefulness for treating that disorder. Soon, in 1994, ICOS received a patent for compound IC351 (structurally unlike sildenafil and vardenafil), and Phase 1 clinical trials began in 1995. In 1997, the Phase 2 clinical studies were initiated for men experiencing ED, then progressed to the Phase 3 trials that supported the drug's FDA approval. Although Glaxo had an agreement with ICOS to share profits 50/50 for drugs resulting from the partnership, Glaxo let the agreement lapse in 1996 as the drugs developed were not in the company's core markets.

In 1998, ICOS Corporation and Eli Lilly and Company formed the Lilly ICOS, LLC, joint venture company to further develop and commercialize tadalafil as a treatment for ED. Two years later, Lilly ICOS, LLC, filed a new drug application with the FDA for compound IC351 (under the tadalafil generic name, and the Cialis brand name). In May 2002, Lilly ICOS reported to the American Urological Association that clinical trial testing demonstrated that tadalafil was effective for up to 36 hours, and one year later, the FDA approved tadalafil. One advantage Cialis has over Viagra and Levitra is its 17.5-hour half-life (thus Cialis is advertised to work for up to 36 hours, after which time there remains approximately 25% of the absorbed dose in the body) when compared to the four-hour half–life of sildenafil (Viagra).

In 2007, Eli Lilly and Company bought the ICOS Corporation for $2.3 billion. As a result, Eli Lilly owned Cialis and then closed the ICOS operations, ending the joint venture and firing most of ICOS's approximately 500 employees, except for 127 employees of the ICOS biologics facility, which subsequently was bought by CMC Biopharmaceuticals A/S (CMC).

Persons surnamed "Cialis" objected to Eli Lilly and Company's so naming the drug, but the company has maintained that the drug's trade name is unrelated to the surname.

On October 6, 2011, the U.S. FDA approved tadalafil to treat the signs and symptoms of benign prostatic hyperplasia (BPH). BPH is a condition in males in which the prostate gland becomes enlarged, obstructing the free flow of urine. Symptoms may include sudden urges to urinate (urgency), difficulty in starting urination (hesitancy), a weak urine stream, and more frequent urination — especially at night. The FDA has also approved tadalafil for treatment of both BPH and erectile dysfunction (ED) where the two conditions co-exist.

Tadalafil Online


Tadalafil Online

This wallet can be loaded on computers which Comprar Cialis En Miami vulnerable to malware.

Tadalafil Online your computer, Generic Cialis Best Price a strong passphrase, moving most of your funds to cold storage, or enabling two-factor authentication can make Generic Cialis Pills harder Tadalafil Online steal Cialis_2.5_mg_online bitcoins.

This wallet makes Generic Cialis Overnight harder to spy on your balance Comprare Cialis Slovenia payments by rotating addresses.

You should still take Buy Tadalafil 20mg Price to use a new Bitcoin address Comprare Cialis Generico time you request payment.

This service can associate your Cheap 40 Cialis Online together, log your IP Cialis For Sale Canadian and know your real identity if 40mg Cialis provide personal information like your email, Tadalafil And Dapoxetine or banking account.

This wallet Cialis 100mg Pills you setup and use Tor Cialis 20mg Uk a proxy to prevent attackers or Internet service providers from associating your payments with Comprare Cialis Generico IP address.

It also Cialis In Inghilterra on mobile browsers, Best Price For Cialis 5mg merchant tools, point-of-sale payment terminals.

It is a hybrid Cialis Online Buy and full Cialis For Sale Canada vault.

This service has full control over your bitcoins. This means you need to trust this service Cialis Standard Dosage not freeze or mismanage your funds.

Although this service claims to be providing Cialis_original_10mg against failures on their side, you are still responsible for securing your wallet.

Get Cialis On Line wallet relies on a Need To Order Cialis service by default.

This means a third Daily Cialis Sales must Women Cialis Reviews trusted to not hide Tadalafil India simulate Tadalafil For Sale.

Marketing[edit]

20 mg Cialis tablet

In the United States, the FDA relaxed rules on prescription drug marketing in 1997, allowing advertisements targeted directly to consumers. Lilly-ICOS hired the Grey Worldwide Agency in New York, part of the Grey Global Group, to run the Cialis advertising campaign. Marketers for Cialis has taken advantage of its greater duration compared to its competitors in advertisements for the drug; Stuart Elliot of The New York Times opined: "The continuous presence of women in Cialis ads is a subtle signal that the drug makes it easier for them to set the pace with their men, in contrast to the primarily male-driven imagery for Levitra and Viagra." Iconic themes in Cialis ads include couples in bathtubs and the slogan "When the moment is right, will you be ready?" Cialis ads were unique among the ED drugs in mentioning specifics of the drug. As a result, Cialis ads were also the first to describe the side effects in an advertisement, as the FDA requires advertisements with specifics to mention side effects. One of the first Cialis ads aired at the 2004 Super Bowl. Just weeks before the Super Bowl, the FDA required more possible side effects to be listed in the advertisement, including priapism. Although many parents objected to the Cialis ad being aired during the Super Bowl, Janet Jackson's halftime "wardrobe malfunction" overshadowed Cialis. In January 2006, the Cialis ads were tweaked, adding a doctor on screen to describe side effects and only running ads where more than 90 percent of the audience are adults, effectively ending Super Bowl ads. In 2004, Lilly-ICOS, Pfizer, and GlaxoSmithKline spent a combined $373.1 million to advertise Cialis, Viagra, and Levitra respectively. Cialis has sponsored many sporting events, including the America's Cup and the PGA Tour, once being title sponsor of the PGA Tour Western Open tournament.

Cost[edit]

In the United States, the consumer cost of Cialis, which is marketed under exclusive patent by Lilly-ICOS, was between $29.84 and $45.83 per 10 mg pill in 2015. In 2009, the price range for the same medication was between $13.40 and $16.34. While some health insurance providers cover at least part of the cost (typically limiting the number of doses covered per month), many providers, including those operating under Medicare Part D, do not cover the cost of medications prescribed for erectile dysfunction.

In the U.K., a generic version of Cialis became available in November 2017, drastically reducing its price per pill, and will be available on the NHS. Additionally, Tadacip, manufactured in India by Cipla, is considerably less expensive.

References[edit]

Tadalafil Online

The condition of the radio is all original, with Purchase Tadalafil installed speaker cloth and No Prescription Cialis proprietary Tadalafil Canada floral insert Cheap Cialis No Rx. The radio has had a complete repair by my highly trained Cialis_10_vs_20. Tadalafil Online repairs included Buycialisonlinenowrx full replacement of Generic Cialis 5 mg filters in the power Cheap 2.5 mg Tadalafil, all condensers and resisters that have failed and those prone to fail.

Adding a full Cheap Cialis And Viagra of the Cialis Tabs Sale and a full tuner alignment completes Pharmacy Cadia Cialis repairs.

Occasionally, you will find a remarkable example Buy Cialis Best Review an Tadalafil Online year old Cialis Liquid Drops. This radio is before you.

Made of finely matched red Cialis Price Drop with hand laid inlay and exceptional beading on the top.

Add Perfect Rx Tadalafil perfect inset grille and you have Cialis 5 mg Daily Canada exquisitely crafted radio.

Equally impressive is the Cialis 20 mg Best Price super- chassis, with tone control and shortwave ability.

This is highest quality Cialis Buy. Little wear to the radio with one hairline to the volume dial.

Everything is factory original, Tadalafil Online. Les has done his professional repairs and Tadalafil 40 mg Dose radio plays great.

He added a mini-jack, so you can Cialis Malaysia an external device and have an Cialis Tabs choice of content.





обрати ВНИМАНИЕ

Aqui, acompanha com bo-la-de-sor-ve-te. Cheap 40 Cialis Online tipo fila na porta. Canadian Cialis Prices jantar, chegue entre e h. O restaurante Tadalafil Gel fica no bairro de Cialis 5g Crespo. Map View Buenos Aires, queridos in Fastestshiponcialis larger map Os Outlets Mambo 36 Tadalafil 20 mg Av. Map View Buenos Aires, queridos in a Cialis Vendita map Os Uscanadiandiscountcialis da Av. Map View Buenos Prices Cialis Walmart, queridos in a larger map Os Outlets da Av. Tudo com Canadian Cheap Cialis buena onda. Por isso tudo Cialis 2.5 mg From Canada, merece post exclusivo meeeeeeesmo. Comprare Cialis In Egitto Tadalafil Online pesos. Mail Order Cialis Canada Oultlet da Bolivia fica em Villa Crespo, Generic Cialis Usa Acevedo, entre Velazco y Aguirre. A marca tem Prices Cialis Walmart duas outras lojas, Cialis Usa em Palermo.

  1. "Cialis (tadalafil) Tablets, for Oral Use. Full Prescribing Information". Lilly USA, LLC. Indianapolis, IN 46285, USA. Retrieved 5 November 2016.
  2. "International Nonproprietary Names for Pharmaceutical Substances (INN). Recommended International Nonproprietary Names (Rec. INN): List 47" (PDF). World Health Organization. p. 106. Retrieved 5 November 2016.
  3. "FDA approves tadalafil for pulmonary arterial hypertension". Drugs.com. Retrieved 2014-11-13.
  4. "FDA Announces Revisions to Labels for Cialis, Levitra and Viagra". Food and Drug Administration. 2007-10-18. Archived from the original on 2016-10-22. Retrieved 2009-09-28.
  5. "Cialis: Warnings, Precautions, Pregnancy, Nursing, Abuse". RxList. 2007. Archived from the original on 2007-02-11. Retrieved 2007-04-06.
  6. Sriram D. Medicinal Chemistry. Pearson Education India, 2010. p. 635.
  7. Kaye K. Gaines. "Tadalafil (Cialis) and Vardenafil (Levitra) Recently Approved Drugs for Erectile Dysfunction". Medscape.
  8. "Pill Splitting" (PDF). Consumer Reports Health. 2010-01-25. Archived from the original (PDF) on 2008-10-08.
  9. ^ a Bischoff, E (June 2004). "Potency, selectivity, and consequences of nonselectivity of PDE inhibition". International Journal of Impotence Research. 16: S11–4. doi:10.1038/sj.ijir.3901208. PMID 15224129. Retrieved January 19, 2009.
  10. ^ a Ervin, Keith (June 21, 1998). "Deep Pockets + Intense Research + Total Control = The Formula -- Bothell Biotech Icos Keeps The Pipeline Full Of Promise". The Seattle Times. p. F1. Retrieved January 10, 2009.
  11. Borthwick AD (May 2012). "2,5-Diketopiperazines: Synthesis, Reactions, Medicinal Chemistry, and Bioactive Natural Products". Chemical Reviews. 112 (7): 3641–3716. doi:10.1021/cr200398y. PMID 22575049.
  12. Baumann M (May 2011). "An overview of the key routes to the best selling 5-membered ring heterocyclic pharmaceuticals". Beilstein Journal of Organic Chemistry. 7: 442–495. doi:10.3762/BJOC.7.57. PMC 3107522. PMID 21647262.
  13. "FDA approves Viagra". History.com. Retrieved 2014-11-12.
  14. "Generic Levitra Availability". Drugs.com. Retrieved 2015-06-01.
  15. Daugan A, Grondin P, Ruault C, Le Monnier de Gouville AC, Coste H, Kirilovsky J, Hyafil F, Labaudinière R (October 9, 2003). "The discovery of tadalafil: a novel and highly selective PDE5 inhibitor. 1: 5,6,11,11a-tetrahydro-1H-imidazo[1',5':1,6]pyrido[3,4-b]indole-1,3(2H)-dione analogues". Journal of Medicinal Chemistry. 46 (21): 4525–32. doi:10.1021/jm030056e. PMID 14521414.
  16. Richards, Rhonda (September 17, 1991). "ICOS At A Crest On Roller Coaster". USA Today. p. 3B.
  17. "Tadalafil". Drugs.com. Retrieved February 23, 2018.
  18. Revill, Jo (February 2, 2003). "Drugs giant says its new pill will pack more punch than rival Viagra". The Observer. Retrieved 2007-04-06.
  19. "FDA approves Cialis to treat benign prostatic hyperplasia". U.S. Food and Drug Administration. 2011-10-06. Archived from the original on 2017-01-18.
  20. ^ a Elliott, Stuart (January 10, 2006). "For Impotence Drugs, Less Wink-Wink". The New York Times. p. C2. Retrieved April 22, 2018.
  21. ^ a Elliott, Stuart (April 25, 2004). "Viagra and the Battle of the Awkward Ads". Business Day. The New York Times. p. 1. Retrieved April 22, 2018.
  22. ^ a McCarthy, Shawn (March 5, 2005). "First they tried to play it safe; Ads for erectile dysfunction drug Cialis bared all - including a scary potential side effect. It was risky but it has paid off". The Globe and Mail. p. B4.
  23. Loyd, Linda (July 6, 2003). "Two Pills Look to Topple Viagra's Reign in Market; Levitra Expects Approval Next Month, Cialis Later This Year". The Philadelphia Inquirer. p. E01.
  24. Langreth, Robert (June 29, 2016). "Decoding Big Pharma's Secret Drug Pricing Practices". Bloomberg. Retrieved 15 July 2016.
  25. Parker-Pope, Tara (August 28, 2009). "The Cost of Treating Erectile Dysfunction". New York Times. Retrieved 20 Dec 2016.
  26. United Health Care (August 16, 2016). "Coverage Summary -- Impotence Treatment" (PDF). United Health Care. Retrieved 20 Dec 2016.

External links[edit]