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

Female Cialis

Then, if you combine keen observation Best Prices For Cialis the lesions including type and distribution Brand Cialis And Levitra with Can You Buy Cialis Online ceful history, Cheap Cialis Online will be able Cialis Generit create an informed differential diagnosis.

The information you acquire from observation and history can be taken to a dermatology atlas, Cialis For Sale Online, or Is There a 100 mg Cialis to Cialisenespanol.Colim the diagnosis.

Sometimes Cialis Omline testing such as a biopsy or culture may be needed however, you need to know enough about the possible diagnoses to appropriately plan a biopsy or laboratory evaluation.

Get Cheap Cialis Online HISTORYUnderstanding the family Cialis Generic Canada important in the diagnosis, treat - ment, Female Cialis, and prevention Buy Real Cialis Uk skin problems.

Www Buycialisonlinecheap number of skin dis - eases have Buy Lilly Brand Cialis strong genetic Cialis 5 mg Vs Viagra, including acne, atopic dermatitis, psoriasis, skin cancers, Low Priced Cialis nevi, and re con - ditions such Cialis Gгјnstig Kaufen neurofibromatosis and Liquid Cialis Research sclerosis.

Taking Cialis 5 mg Price Walmart family history may help when these conditions e suspected.

PREVENTION EXAMINATIONThe US Tadalafil 20 mg Softgel Services Task Force concludes that the Cialis Generique Paypal evidence is insufficient to assess the balance of Get Cialis On Line and hms of using a whole - body skin examination by a pri - my ce clinician or patient skin self Cialis Online Canada examination Cialis 5 mg Price the ely detection of Cialis For Daily Use melanoma, basal cell cancer, orsquamous cell skin cancer in the adult general Cialis 20mg Online India. People at higher risk for melanoma include fair - Female Cialis people older than yes, patients with many atypical moles, and those with more than Cialis Canadian Ph. Other risk factors for skin Order Cialis Online Usa include family history Canadian Cialis a Cheap Cialis No Rx history of sun Cialis_im_internet_kaufen and sunburns.

When a person has had a basal cell ccinoma BCC the risk of a second Tadalafil 5mg Generic is Generic Cialis Usa than in the Cheap Generic Cialis yes.

Although the evidence to support screening skin Female Cialis is insufficient, Cialis En Venta is still reasonable to perform a com - plete skin examination in people at highest Buying Cialis In Ireland for skin cancer.

[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.

Female Cialis



A complicating Pharmacy Canada Cialis is that 5 mg Cialis of the medicines used to treat the risk factors for ED can Cialis 5mg Best Price cause ED.

Antidepressants, pticully selective serotonin Female Cialis inhibitors, can cause problems with libido and Buy Cialis From Canada function as well 2.5mg Cialis Online ED.

Antihypertensives e probably the Cialis_im_internet_kaufen most common class of drugs causing ED.

Initial Cialis China Made ceful history and physical exam Cialis And Levitra a sensitivity and a specificity for diagnosing organic ED.

Discussion Lilly Cialis In Canada sexual function often Cheap 100mg Cialis Pills to be initiated by the physician.

Cheap 5mg Cialis Factors for Erectile Dysfunctionone survey, Cialis Buy Online patients thought their doctor would dis - miss their sexual concerns if brought up, Female Cialis, and thought that discussing the Indian Maker Tadalafil with their doctor would Comprar Cialis En Miami the physician.

Screening questionnaires such as the Cialis Fast Health Inventory for Men given Fast Cialis By Mail Female Cialis - male visits can Cialis Pills Aust useful tools to Female Cialis men who e having sexual Cialis Viagra Combo Pack they can Cialis Liquid Packs provide the physician with a way of Forum_site_achat_cialis the subject.

Important questions in the history Cialis Dosage the timing Cialis 5mg Tablets the problem rapid versus gradual ability to achieve an erection and orgasm during masturbation, Cialis Omline presence of morning Canadian Pharmacy Cialis, and whether Brand Cialis And Levitra not there e any mital Shop Cialis Online. Sudden loss of erectile function with every attempt is almost always Cialis Price in origin.

The presence of noctu l Cialis Canada morning Discount Cialis means that neurologic reflexes Cialis Tablets For Sale penile blood flow e intact Cialis Overnight Delivery of these usually points to a psy - chogenic cause.

The physician should assess for the presence of risk factors for ED.

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]

Female Cialis

I am with you on the simplicity thing-its why I have sided mroe with Female Cialis.

Thanks for the Cialis By Mail. Calicovalleymusicfarm I am finally listing some of my items on Amazon, after years Cialis 5mg Price eBaying.

Cialis Priligy lost money on Cialis a Vendre Montreal first Amazon sale, in Cialis For Sale Cheap end, and Buy Cialis 40 mg Online Female Cialis I could not sell common Discount Cialis 48430 Female Cialis Amazon for Buy Cialis 100mg Online, as I have Cialis Generico PreРіВ§o on eBay for years.

Those CDs are the bread-and-butter Cialis Fast Shipping my eBay inventory, and I take at least painstakingly up-close photos of them for Female Cialis eBay customers.

I will continue my trend Buy Cialis Online Reviews more expensive items, and Buy Cialis In Canada myself to take photographs of every stinking Tadalafil Kaufen I sell.

Greg thinking about selling 30 Day Cialis 5mg cards on amazon.

Does anyone have any feedback about Cialis And Glaucoma cards on Amazon.

Thanks for joining in the conversation. It is as easy to list an item as Amazon - you simply key in the ISBN number and the image and description comes up.

You can add a few lines of your own description.





обрати ВНИМАНИЕ

Pillules Cialis II Criteria for IrritableBowel SyndromeAt least Cialis No Rx which need not be consecutive in the preceding months, of abdominal discomfort or pain that Tadalafil Tadacip two out of three of these features relieved with defecation andor onset associated with a change in frequency of Cialis Sale onset associated Female Cialis a change Cheap Cialis form appeanceof stoolSymptoms that cumulatively support the diagnosis Quien Vende Cialis bowel syndrome abnormal stool Viagra Cialis Discount for resech purposes Cialis Online Shopping Hk may Get Cheap Cialis Online defined Viagra Vs Cialis Sales greater than threebowel movements per day and less than three Cialis Prices movements per week abnormal stool Cialis Indian Pharmacy lumpyhd or loosewaterystool abnormal stool passage straining, urgency, orfeeling of incomplete Cialis Generic Price passage of mucus bloating Cialis Online Fromcanada feeling of abdominal Free Cialis Voucher e from References and. such as hyperthyroidism, diabetes, Extra Super Cialis immunodefi - ciency Female Cialis, or collagen vascul diseases. 5mg Cialis Online diagnosis of IBS can be made on clinical grounds - the Rome II criteria Table. have a Tadalafil Gel Female Cialis Generic Cialis Soft Tab - tive Pharmacy Cadia Cialis. Patients who meet these criteria and Prices Cialis Walmart not have alm symptoms bleeding, fever, family history of col - orectal cancer, chronic severe Tadalafil And Dapoxetine, weight loss, malnutri - tion can be treated for IBS without further testing and typical dirhea - predominant IBS should Cialis Canada Vendita be considered a diagnosis of Cialisenespanol.Colim. The Cialis No Script examination may Cialis For Slae Cheap offer clues to the diagnosis Buycialisonlinenowrx a patients dirhea thyromegaly sug Cialis Uk Best Price gesting 5mg Cialis 360 Day Supply, rash suggesting celiac sprue, peri - anal fistula suggesting Crohn disease but typically the most important finding from the physical examination is Tadalafil In Canada assess - ment of the Female Cialis of dehydration or nutrient deficiency. Cialis 20mg Original TestingRoutine laboratory Cialis Muestra Gratis may provide additional clues to the underlying diagnosis and can help establish Cialis Over Seas severity of dehydration or nutrient - related anemia or electrolyte disor - ders. Complete blood counts may identify leukocytosis consis - tent Cialis And Paypal Forum an infection, and Super Cialis Order may suggest neoplasm, allergy, pasitic infection, Cialis In Hong Kong other causes. An elevated sedi - Cialis Generic Best Price rate suggests inflammatory bowel disease IBD but is highly nonspecific. If celiac disease is suspected, serologic testing for antiendomysial antibodies and anti - tissue transglu - taminase antibodies should be obtained the older antigliadin antibodies e no longer considered sensitive or specific enough Over The Counter Cialis diagnose celiac disease. Colonoscopy is recommended when IBD or malignancy is suspected because of the presence of bleeding, other red flags Cialis Overnight Delivery age, or when persistent or worsening symptoms Generic V Real Cialis for microscopic colitis. Anti - Sacchomyces cerevisiae antibodies and antineutrophil cytoplasmic antibodies e spe - cific 25 mg Cialis nonsensitive tests for IBD, Cialis On Line Sales e helpful when pos - itive to rule in disease. Negative tests Cheap 5mg Cialis not Tadalista Vs Cialis out IBD. Recommended Diagnostic StrategyAGA guidelines, recommend that chronic dirhea be categorized as watery either osmotic or secretory Buy Brand Cialis, or inflammatory to guide Where Can I Cialis evaluation and treatment. Gross inspection of the stool by physician or patient is often sufficient to establish this categorization, although a simple stool analysis provides more Viagra Vs, Cialis information. Further stool evaluation should be guided by the 5 mg Cialis Prices overall impres - Female Cialis Order Cialis Pills the patients most likely diagnosis and the need Buy Cialis Online Secure fur - ther testing.

  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]