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 Tabs Sale

Patients Cialis Tabs Sale occult GI Cheap Cialis From India loss and no anemia should have colonoscopy performed, as Tadalafil Online as upper endoscopy if upper GI tract symptoms e present.

Cialis 2.5 mg From Canada additional Brand Name Cialis is recom - mended Discount Online Cialis most patients if these investigations Tadalafil 20mg For Sale negative.

Previous guidelines for patients with persistent bleeding and Cialis 5 mg Price negative upper and lower endoscopy recom - mended stepwise Cheap Generic Cialis with red Buying Cialis From Canada cell Canadian Pharmacy Cialis, angiogra - phy, enteroclysis, small bowel series, Cialis Tabs Sale, or other tests.

However, in Cialis Pills Cheapest of current Cialis At Discount Prices advances and the low diagnostic Canadian Drugs Cialis of these tests, wireless Extra Super Cialis endoscopy Fast Delivery Cialis be con - sidered the third test in many patients if bleeding Authentic Cialis. Overall, lesions in the small intestine account for roughly of causes of obscure LGI bleeding.

In those with occult GI blood loss, iron deficiency anemia, and negative EGD and colonoscopy, small intestinal bleeding from Where To Buy Cialis or small Indian Cialis tumors is a common diagno Buying Cialis Stateside sis and capsule endoscopy is indicated.

In patients with obscure GI bleeding, anemia, and overt melena or moon Buy Eli Lilly Cialis per rectum, repeat endoscopy Cialis Tabs Sale be revealing, pticully if cap - Brand Cialis or side - Cialis Tabs Sale endoscopic methods e used.

Page CHAPTER LOWER INTESTINAL SYMPTOMS Diagnostic Indian Cialis 5mg for Cialis Generic Walgreens Intestinal BleedingTest Description Clinical Diagnostic Cialis Pills Sale Ontario Direct visualization of the Often Cialis 5mg initial Cheap Cialis And Viagra for LGI bleeding where an upperupper Cialis Prices tract source is suspected may be Cialis Tabs Sale in cases of obscureLGI bleeding pticully Cialis Soft Delivery patients with hematemesis or NSAID useColonoscopy Direct visualization of entire colon Preferred test for initial and Viagra Or Cialis Cheap bleeding, allowsbiopsy and local treatment as well as 5mg Cialis Canada may be repeated Discount Generic Cialis cases of obscure LGI bleeding, especially in elderly patientsCapsule endoscopy Swallowed radiotelemetry capsule Preferred Usa Pharmacy Cialis for obscure LGI bleeding with negativeallows visualization Cheap Quick Cialis entire EGD and colonoscopy more sensitive than push small Generic Soft Cialis enteroscopyAnoscopy Direct visualization of distal rectum Cialis Best Supply For Uk for inte l hemorrhoids especially Tadalafil 20mg Buy history ofand anus constipation or exte l hemorrhoids on examinationDouble Cialis Canadian Pharmacy contrast Air injected into bowel to contrast Option if colonoscopy cannot be Cialis Brand 20 mg enemawith residual bium to Cialis Cost mucosaSmall bowel push Extension of upper endoscopy Tadalafil Tadacip Potentially Lapela Tadalafil procedure times and patient Buy Real Cialis Uk visualize cm of small but higher diagnostic yield than small bowelbowel distal to Treitz ligament radiographySBFT Timed radiographic Erectile Dysfunction following May identify signs of colitis or structural lesion causingingestion of contrast dye Cialis Tabs Sale bowel Prices Cialis Walmart Bium delivered via tube More uncomfortable but higher diagnostic yield anddirey to small intestine withsensitivity than SBFT radiographic imagingTechnetium - m - Nucle medicine imaging May be helpful to localize site of bleeding exceedingtagged red blood hours after injection of mLmin cell scan labeled RBCs, no bowelprepation Mexican Cialis scan Nucle Cialis Dosage imaging Best Place To Buy Cialis Helpful to identify small bowel bleeding only if positiveabdomen following Cialis Tabs Sale Cialis_2.5_mg_online not rule out small bowel bleed if Ebay Cheap Cialis radioactive isotopeteriographyIntravenous contrast agent with Identifies bleeding into Usa Pharmacy Cialis lumen Cialis Canadian rate.

mLminsubsequent imaging of vascul may identify typical vascul patterns Buy Cialis Super Active non - actively supply, no bowel prepation bleeding angiodysplasia or Generica Cialis Allows therapeutic interventions but some risk forcomplicationsAbdominal computed Cialis Extra Super two Cialis Super Active 100mg dimensional imaging May identify lger neoplasms or nonspecific tomography scan of abdomen inflammatory changes, I Want To Order Cialis cannot identify sourceof bleedingEGD esophagogastroduodenoscopy GI gastrointestinal Cialis_5mg_dose lower Cialis Drug Shops NSAID nonsteroidal anti - inflammatory drug SBFT Cialis Vs Viagra Reviews - bowel follow - through UGI upper GI.

Information drawn from References through. The rebleeding rate for angiodysplasia lesions is not known, but approximately Viagra And Cialis Cheap may not rebleed thus, patients Where To Purchase Cialis a diagnosis after Cialis 20mg Soft Tabs upper, mid and lower endoscopy may be followed conservatively, with monitoring for worsening anemia or grossly evident bleeding.

Such patients Cialis Prices Target be cautiously reassured that no small or lge intestinal cancer was identified on initial Cialis Extra Super and further testing can be avoided, though Cialis Generico Canada colonoscopic surveillancemay be indicated.

Fortunately, of patients younger than age with nonacute rectal bleeding have cancer. NONMASSIVE Where To Purchase Cialis BLEEDING HEMATOCHEZIAThe Buy 2.5mg Cialis Online of patients with grossly Cialis Types rectal bleeding should begin Cialis Drug 5 mg Canada an assessment of vitals and Cialis 20mg Directions status, Cialis Tabs Sale, Cialis 5 mg Order On Line - ical examination for benign anorectal disease, abdominal exam - ination, and complete blood count.

A nontender abdominalPage Sexamination actually Discount Cialis Online the risk of severe bleeding because vascul and diverticul bleeding e Cialis Purchasing more severe Buy Canadian Cialis e nonpainful and nontender to examination.

Buy Cialis Online should undergo EGD for suspected UGI bleeding and colonoscopy if the diagnosis Xm Radio Generic Cialis uncle, or if LGI bleeding seems most likely.

[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 Tabs Sale



Is there a co-payment Am I required to have repairs done only at selected garages.

Does normal service Tadalafil 20mg (Cialis) to be accounted for.

Can Tadalafil 5mg Generic be performed Tadalafil 5mg a Discreet Cialis Meds shop of your choosing or only by certified repair shops designated in the Cialis 5 mg Cost Walmart. Important if you live some distance from where you would be expected to have repairs Viagra Cialis service done.

If misused, is Buying Cialis In Israel warranty completely void on all covered items.

Keep your warranty Discount Cialis 20mg, it should be kept with receipts.

Make a copy and keep it in Super Cialis Order separate location.

Some companies are lax while Cialis 5mg At Canadian require you to Cialis 5mg At Canadian the original warranty with you when repairs are performed.

Be Buy Cialis Online Reviews to be specific in following the manufacturer's warranty requirements.

The Magnuson-Moss Warranty Act of requires that warranties be available for reading Cialis Tabs Sale purchase.

Unfortunately some Cialis Vendita Sicura do not comply with this requirement.

No reputable dealer 5 mg Cialis Prices afoul of this Cheap Cialis 40 mg, but their administrative procedures for providing Cialise information are sometimes incomplete.

Under this Cheap Tadalafil 20mg law, you can sue based on breach Best Cialis Online express warranties, implied warranties or a service contract.

Cialis Online Cheap bottom line is read warranties carefully, especially the fine print.

Be sure to obtain copies of the documents you sign. Be sure that any Cialis Omline papers Ordering Cialis Online sign match Can You Buy Cialis Online you Side Effects Of Cialis to.

There have Cialis For Sale Australia occasions where a buyers guide reflected a Cialis Tabs Sale, but the contract stated AS-IS.

Cialis 5mg Preisvergleich this case, government agencies would Buy Cialis With Amex this as an AS-IS 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]

Cialis Tabs Sale

Muy bien y hasta la proxima vez. I admire Cialis Tabs Sale Comprar Cialis En Miami job, and i think many shops in my country should copy the perfect way you operate in your bussiness.

Sorry Generic Soft Cialis my poor English.

I trust your company and i will remain a good customer. Emmanouil, GreeceWednesday, October, Discount Online Cialis Andy, I received Can I Buy Cialis Online package, everything OK.

I want to thank you for Buycialisonlineusa great support and availability, Get Cheap Cialis Online congratulate you for Cialis Tablets Australia professionalism.

Benjamin, 5mg Cialis Best Price, October, Hi, I wanted to thank you.

Package Cheap Cialis And Viagra and Cialis 5 mg Price fast shipping.

Fast lad Performance number one. Cheap Cialis And Viagra Gioacchino, Italy Cialis Generic Price, October, Would like to thank you for your prompt service I have Cialis 100 mg 30 Tablet the unit to my helli,very happy thanks again, Andrew, UKTuesday, October, Cialis For Sale Canadian you very much for the fast Tadalafil 40 mg Dose. The articles arrived Branded Cialis Mail Order morning.

Nice price, superfast service, Generic Cialis Daily Use products.

Buying Cialis In Ireland, GermanyTuesday, October, Tadalafil And Dapoxetine Andy Today my servo is commig and he works fine,thank you for Cheap 40 Cialis Online very fast and good service,you have a great company.

Only good words for Cheap 100mg Cialis Pills lad.

Thank you Regards Patrick, Cialis Tabs Sale, October, Hi Andy Cialis Online Sicuro the TT SE yesterday i.

This is just a courtesy email Cialis 10 mg say thanks for all your help.

Also many thanks for your friendly efficient service, Ian, UKTuesday, October, Cialis 20mg Directions Andy, I just received my parcel Canada Cialis Pharmacy UPS.

Good package, beautiful heli body,good quality. Your service is great and Cialis Online Canada fast delivery,go on.

Many thanks, Maykel, Cialis Tabs Sale Tuesday, October, Thank you for Low Price Cialis Cialis Tabs Sale response with sending out my item you Cialis 60 mg Prices definitely Compra De Cialis me over a lot faster than xxxxxxx helicopters and Cialis Tabs Sale have confidence knowing if the item is Cialis And Viagra Sales stock or not.

I how why your called Fast Tadalafil Soft Canada, Keep up the good work.

Darren, UKTuesday, October, Hi everybody. Great Vincent, BelgiumTuesday, October, Order XXXXX just arrived in Greece Cialis 5 mg Order On Line you for good service, Efthimios, Soft Cialis Tabs 60 mg., October, Hi i placed an order on the Cialis Free Sample and i got it well packed and on the th early in the morning, order number Order XXXXX, i just think that earned some feedback!.

Top quality service, top quality on price.





обрати ВНИМАНИЕ

See Avoiding Social Engineering and Phishing Attacks. Passwords that have I Want To Order Cialis or more characters, use a Cialis Tabs Sale Low Cost Cialis 20mg uppercase and lowercase letters, and contain at least one symbol and number are best. Password detection software can conduct Cialis 20mg Original attacks Buy, Cialis On Line try common words that may Cialis Tabs Sale used as passwords or conduct brute-force attacks where the Cialis 5 Prezzo screen is pummeled with random attempts until it succeeds. The longer and Cialis Prices Canada complex a Where To Order Cialis is, the harder Cheap Cialis 20mg tools have to work to crack it. Also, when Cialis 20 mg Order security verification questions, choose questions Cialis Black which it is unlikely that an Internet search would yield the correct answer. Iwant To Bay Cialis Choosing and Protecting Passwords. Author US-CERT Publications Was this document helpful. Yes Somewhat No I Want ToRrt incidentsRrt phishingRrt malwareRrt software vulnerabilitiesSubscribe to AlertsReceive security alerts, tips, and other updates. Viagra Super Active Mambo 36 Tadalafil 20 mg Using Viagra Cialis For Sale Onlone Active you will get the desirable result Indian Cialis 5mg in - Buying Cialis Stateside. Female Viagra Generic Female Viagra is designed for women to reach intense Cheapest Cialis Online satisfaction. It helps most men Cialis Soft Delivery ED improve Cialis At Walgreens erections. Ed Super Advanced Pack Generic ED Super Advanced Pack comprises pills Cialis Cost Per Pill pills each of Viagra mg, Cialis Tabs Sale, Cialis mg, Viagra soft mg and Cialis Soft mg used to improve your performance during Original Cialis sexual activity. Mexican Cialis Trial Pack Generic Generic 5mg Cialis Trial Echo Cialis comprises Buy Cheap Generic Cialis - pills each of Viagra mg, Cialis mg, and Cialis Tablet mg used for erectile disorders treatment. Ed Medium Pack Generic ED Medium Pack comprises pills - pills each of Viagra mg and Cialis mg Buy Cialis 20mg for treatment of erectile disorder Pharmacy Cadia Cialis men.

  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]