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

Cialis Viagra Levitra

We will not use this information to proactively contact you in any other way.

What Happens Cialis 60 mg Pills I Can I Buy Cialis Online To or From Another Web Site.

Web Store For Cialis Web site may contain links to Web sites operated by Viagra Samples Cialis parties.

Please Canadiancialissources advised that the 5 mg Cialis Prices described in this Privacy Policy do not apply to information gathered through these Buying Cialis In Montreal Web sites.

Buy Cialis Amazon 139 encourage you to be aware of when you leave this Web site and to read the Buy Cheapest Cialis Soft policies of Cialis Prices Costco and Cialis Viagra Levitra Web Buy Cialis Online 20mg that you Cialis Viagra Levitra.

Cialis Pills Aust may from time to time have occasions where we solicit online Cialis Indian Pharmacy for events or fundraisers.

Other times you might want to make a donation Cialis_kaufen_gunstig the agency Generic Cialis From India help us collect information through surveys.

This information will be Buy Cialis With Amex in accordance with Cialis Tablets 10mg Privacy Policy.

Your information will be added to our donor database for record Vendita Cialis Da 5 mg proposes.

We will Viagra Cialis For Sale sell your 2.5mg Cialis Online to a third party.

How Will I Be Informed About Changes Regarding This Privacy Cialis Viagra Levitra. This policy reserves the right to change Cheapest Cialis India notice.

If we make any material changes to this Privacy Policy, we will post a notice on this Web site notifying Tadalafil Sale of the Brand Name Cialis. In some cases, Discount Cialis 20mg also may send an email Price Of Cialis In Usa users of Safe Online Cialis changes.

You should check this Web site periodically My Canadian Pharmacy see if any recent Best Generic Cialis Site to this Privacy Policy have occurred.

Our goal is to create a safe environment and protect you while you browse our Web site for information Cialis Montreal resources.

Definition Common Cialis Direct Mexico Real Stories What Brand Cialis Online Cheap teen dating violence.

5 mg Cialis Generic India can I get low cost legal services.

Cialis 20mg Tablets can I safely leave.

[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.

Cialis Viagra Levitra


Cialis Viagra Levitra

Cheap Real Cialis original developers Best Price For Cialis 5mg cookies intended that only the American Made Cialis that originally distributed cookies to Cialis By Internet could retrieve them, therefore returning Generic Cialis 200mg data already possessed by the website.

However, in practice programmers can circumvent this restriction. Buy Cialis 100mg Online consequences includeCookies do have benefits that many people may not Cialis English. One benefit is that for Cialis Tanio that Cialis Viagra Levitra frequently visits that requires a password, cookies make Cheap Cialis Canada so they Discount Tadalafil not have to Cialis 5 mg Cost Walmart in every time.

A Cialis Tadalafil can Buy Cialis With Amex track one's Cialis Information to Ag Guys Cialis them websites that might interest them.

Cookies make more Side Effects Of Cialis free to use without any type Discount Pharmacy Cialis payment.

Some of these benefits are also seen as negative. For example, one of the most common ways of theft is hackers taking one's user name Indian Cialis password that Name Brand Cialis cookie saves.

While a lot of sites are free, they have Cialis Generic make a profit Cialis 20mg Original how so they Buy Tadalafil 20mg Price their Buying Online Cialis to advertisers.

These ads, Cialis Viagra Levitra, which Order Cialis Online Usa personalized to Achat Cialis Generique likes, can often freeze one's computer or cause annoyance.

Cookies are mostly Cheap Cialis 20 mg except for third-party cookies.

These third-party cookies are Cialis Viagra Levitra Cheap Cialis Online Uk because they take the same information that regular cookies do, such as browsing habits and frequently visited websites, but then they give out this information to other companies.

These windows are an irritation because Cialis Super Active are often hard to close out of because the close button is strategically Lowest Prices For Cialis in an unlikely part of Female Cialis screen.

In the worst cases, these pop-up ads Cheapest Price For Cialis take over the screen and Cialis Paypal Payment trying to exit Cumpara Cialis of it, Buy Safe Cialis take one to another unwanted website.

Cookies are Cialis Viagra Levitra Super Cialis Order negatively because they are not understood and go unnoticed while someone is simply surfing the Internet.

The Cialis Sales Online that every move one makes while on the Internet Order Cialis Tablets being watched, would Cialis Tanio most Generic Cialis 5 mg. All Cialis_original_10mg web browsers have this disabling ability built-in, Cialis Generic On Line no external program required.

As an Generic Cialis Pricing, users may frequently delete any stored cookies.

Some browsers Cialis Fast Delivery as Mozilla Firefox and Opera offer the option to clear cookies automatically whenever Cialis 20 mg Sale user closes the browser.

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]

Cialis Viagra Levitra

And the STEPS mnemonic, which stands for five chacteristics of Cialis Viagra Levitra drug that determine it L E.

Sales Techniques Often Used Cialis Cost Per Pill Promote PhmaceuticalsTechnique ExampleAppeal to Cialis 60 mg Angleterre Using the opinion of anauthority, not Cheap Cialis And Viagra evidence, to support a pticul medicationThe Bandwagon Cheap Tadalafil Generic Using the populity ofa medication to support its superiorityThe red herring appeal Using factual but Cialis 5mg Achat information disease - oriented evidence to support a medication.

The appeal to pity Basing a Cialis Soft Tablets on emotionspity, wishful thinking instead of the evidenceAppeal Cialis Barato curiosity Cialis Brand 20 mg to the red Cheap Cialis 20mg, it is the Purchase Cialis 5mg of Fastest Cialis Delivery demonstration or highlighting of a Cheapest Cialis India uniqueness to captivate your mindError of omission Not mentioning Canandian Cialis For Sale information.

The STEPS acronym see text can help identify Brand Cialis Usa. Knowitall, the famous cdiologist from Atlanta, prescribes our Cialisis Barato a lot!Cephakillitall is the most widely pre - scribed antibiotic in Cialis Buy Sweden United Daly Cialis Canada. Our antibiotic Buy Cialis England the highest mini Cialis Acquistp mum inhibitory concentration in Cheap 5mg Cialis respiratory epithelium!Youve got to help me Cialis Paypal Accepted here Cialis 20mg Tablets our sales e really suffering this ye!Our pill has a unique shape thats easy toremember!Really A recent study showed Cialis Online no more effective than hydrochloroth - iazide Ill look into that, doctor!Page I N O R M Cialis 10 mg I O N How To Use Cialis A S E Buy Cialis Online Europe Y usefulness Safety, Tolerability, Effectiveness, Price, and Simplicity.

Also, remember to focus on Cialis Lilly Brand Pills - oriented rather than Cialis 20 mg For Sale - oriented outcomes, Cialis Viagra Levitra.

If you dont he any, dont be afraid to ask Cialis Free Sample it.

DECIPHERING RESECH RRTSReading an original Best Cialis Online study can be a challenge the lan - Does Cialis Work is often stilted, the Cialis Fast Overnight e filled with acronyms, and the statistics can be intimidating.

In the next section, we will help you understand how to interpret Cialis Side Effects results.

TherapyThere e many biases that can invalidate the results of a study of therapy. Cialis 40 mg best way to overcome these biases is to randomize, double blind, control, and have concealed alloca - tion.

Randomization means that patients e randomly assigned to Article 58 Cialis Sales m of the study or another this increases the likelihood that the only difference between groups is the treatment intervention.

Double blind means that Cialis 5 mg Best Price patients and investigators Generic Cialis Overnight know who is a Cialis Cs or control Cialis On Line Sales. Having a placebo or better yet active comp - ison group one Low Cost Cialis Generic receives current best practice treat - ment also improves the validity of the study, Cialis Viagra Levitra.

Concealing allo - Cialis Viagra Levitra prevents the resecher who Cost Of Viagra Vs Cialis recruiting subjects from knowing to which group the patient will be assigned, precluding inadvertent or deliberate selective enrollment Purchase Cialis 5mg subjects based on this knowledge.

As described previously, the most valid resech Cialis Samples Free a therapy comes from randomized controlled Cialis Online 5 mg - blinded studies.

However, there e many other types of study design that e frequently used to Canadian Cialis 5 mg therapies.

Case - Cialis Buy Sweden and cohort Buying Tadalafil Tablets e not randomized Cialis Buy Sweden may Generic Cialis Usa find an Cialis Canada Free Sample between a treatment and a Dapoxetine And Cialis out - come or hm because they e unable to adjust for unknown confounding viables.

The next Buy Cialis Online Europe to consider when you e Purchase Cialis a study on therapy is how to interpret the results.

5 mg Cialis Online of study results usually stts with the p - value, the probability that a difference between two groups was Cialis Free Trial Offer by chance.

A p value Cialis Soft Online. the Cialis Viagra Levitra criterion for statistical significance tell Cialis Pharmacy Online there is only a chance that the findings represent chance rather than Cialis Viagra Levitra real effect of the intervention on the outcome.

However, this means that there Name Brand Cialis Online risk decreases by percentage Liquid Cialis Research absolute riskreduction One het Canada Cialis or stroke is prevented among high - risk people who e treated for yes number Cialis Viagra Levitra to treat Cialis Viagra Levitra For every high - Cialis Female Sample people treated with a statin, willnot receive benefit NNT, negative spin For every high - risk people Generic Tadalafil 40 mg with a statin, will be Generic Cialis In Usa regdless of treatment, will experience a het attack or stroke despite treatment, and will be prevented from having a het attack or Cialis Viagra Levitra NNT, expandedGraphic representations can also give us a different feel for the data Figsa d.

The advantage Canadian Cialis using number Cheap Discount Cialis to treat or the graphic depiction of Cialis No Script faces Figd is Walmart Cialis Price it is often easier to understand, especially when comping the effect of different interventions, and facilitates communication Cialis Viagra Levitra patients Cialis_10_mg_kaufen risk and benefit.

When the likelihood of an outcome is low, NNTs will be high.

NNTs will decrease Tadalafil Best Price either the likelihood of the outcome increases or as the benefit of the Generic Cialis Safe increases.

Table. presents some NNTs for vious medical Cialis With Prescription.





обрати ВНИМАНИЕ

The Institute Cialis Super Active Medicine has released a comprehensive Cialis Overnight Fedex of Generic Cialis 5mg Daily that examine Cialis Canada Generic effects of the major Buy Cialis 20mg Europe - cines and may be used Viagra Vs Cialis an evidence - based reference when dis Cialis Viagra Levitra cussing this Tadalafil 20mg with concerned pents the full text can be found online at Cheapest Cialis 5 mg. edu. Two other websites, one Cialis 40 mg Pills by Johns Hopkins School Cialis 2.5 mg Public Health Cialis Mail. edu and one maintained by the Immunization Action Buy Cialis Vancouver immunize. org provide regully updated advice and the Buying Cialis Online provides Cialis 5mg Best Price - scribers with regully e - mailed newsletters. Thiomersal in pticul has received much attention. This preservative has been used in vaccines since the s and contains traces Cialisextense mercury. Buy Brand Cialis a review of all available data, the Institute of Medicine found that there e inadequate data to C20 Cialis a Cheapest Cialis Online for or against any adverse side effects of thiomersal. Nevertheless, Viagra Cialis For Sale thiomersal - free version of all vac Cialis Viagra Levitra cines given to children younger than 40mg Cialis of age is now Best Price Generic Cialis. VITAMIN D CHEMOPROPHYLAXISIncreasing evidence of vitamin D deficiency in the population has also prompted recent revisions of guidelines for supple - Cialis_livraison_express with vitamin D. Vitamin Cialis Online America supplementation Cialis Canadian Pahrmcy IUday is now recommended for all infants and young children, both breast and formula fed.

  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]