Two files start the molecule in different rooms
Wikipedia says tadalafil 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 same page says, the Bothell, Washington company ICOS Corporation began studying compound IC351, a phosphodiesterase type 5 inhibitor. The 2008 review does not mention Glaxo in its development history. It says ICOS Corporation was started in 1990 and began the initial cardiovascular testing of a PDE5 inhibitor called IC351 in 1993.
Those are two verbs for one stretch of years. Discovery, on Wikipedia, sits with Glaxo Wellcome in a partnership. The laboratory start, in both files, sits with ICOS in Bothell in 1993. This note does not own a lab notebook that would pick a winner. A reader who wants a single inventor will not get one from the pages that actually opened.
The next years line up. Wikipedia says that in 1994 ICOS received a patent for compound IC351, structurally unlike sildenafil and vardenafil, and that phase 1 clinical trials began in 1995. The review says IC351 was patented in 1994 and phase 1 began in 1995. Wikipedia adds that phase 2 studies in men with erectile dysfunction began in 1997 and moved on to the phase 3 trials that supported FDA approval. It also says Glaxo had a 50/50 profit share and let that agreement lapse in 1996 because the drugs were not in the company's core markets. The review's history section skips that lapse and moves straight to the Lilly joint venture.
Sildenafil is the neighboring clock, not this page's subject. Both files put a 1994 heart-drug observation next to IC351: penile erection turned up in men taking what became sildenafil. Wikipedia says ICOS scientists were not testing IC351 for erectile dysfunction and still saw the possible use. The tablet on this page is the one that came out of IC351.
The brand name arrives with the application
Both files put Eli Lilly and Company with ICOS in 1998. Wikipedia says they formed Lilly ICOS, LLC, a joint venture to develop and commercialize tadalafil as a treatment for erectile dysfunction. The review uses the same year and the same joint venture, formed to market the newest PDE5 inhibitor.
The name Cialis is not in the 1993 lab sentence. It shows up when the application does. Wikipedia says that two years after 1998, Lilly ICOS filed a new drug application with the FDA for compound IC351 under the generic name tadalafil and the brand name Cialis. The review says tadalafil was officially born in 2000, when a new drug application was put forth for IC351 with that generic name and that trade name. "Officially born" is the review's phrase for a filing, not a birth certificate.
Europe and the United States then split. The review says tadalafil was approved for use in Europe in late 2002, and that on November 21, 2003, the FDA approved it for use in the United States. Wikipedia says tadalafil was approved for medical use in the United States in 2003, in the same sentence-cluster as vardenafil's US approval, and it does not print November 21. The Lilly label prints Initial U.S. Approval: 2003 and does not print the day. The day in this note is the review's day. The year is the label's year, and Wikipedia's year, and the review's year.
What the long clock became
The current label says the mean terminal half-life is 17.5 hours in healthy subjects. As-needed Cialis improved erectile function compared with placebo for up to 36 hours after the dose. Once-daily use for erectile dysfunction starts at 2.5 mg, and the dose may go to 5 mg. Benign prostatic hyperplasia uses 5 mg once a day. Those instructions are the product the history turned into. The schedules themselves are on Cialis daily versus as needed. The trial rows behind the 36-hour window are on tadalafil clinical trials.
Wikipedia's duration section calls the longer half-life, 17.5 hours against about 4 to 5 hours for sildenafil and vardenafil, part of the reason for the nickname "The Weekend Pill." That nickname is not a sentence on the Lilly label. A weekend is a story people tell about a 36-hour comparison window. The label's comparison is with placebo, in men who still needed sexual stimulation, with a once-a-day cap. It is not a promise that one tablet occupies a Saturday and a Sunday as a continuous erection.
The 2008 review ties the same 17.5-hour half-life to on-demand dosing and to once-daily dosing. It says that in January 2008 Lilly announced FDA approval of tadalafil once-daily dosing for erectile dysfunction. Wikipedia's October 2011 sentence is a later stamp: the US FDA approved tadalafil to treat the signs and symptoms of benign prostatic hyperplasia. The doses for those uses live on the current label. The announcement dates live on the review and on Wikipedia. This folder does not contain the 2008 or 2011 approval letters.
Pulmonary hypertension is a second approval
Wikipedia says tadalafil was approved in the United States in 2009 for pulmonary arterial hypertension. The same page's duration section uses the long half-life as the basis for daily treatment of that lung condition. That sentence is easy to paste onto the erectile-dysfunction daily tablet. It is a different approval.
The current Cialis label says the drug is also marketed as Adcirca for pulmonary arterial hypertension, and it tells patients not to take both Cialis and Adcirca. It also says not to take Cialis with other PDE5 inhibitors, including Adcirca. A walk-test number from a pulmonary-hypertension program does not belong in this development note. The 2009 year is Wikipedia's. The "do not take both" line is the label's.
The 21.6-hour line is the review's, not the 2026 label's
The 2008 review says the half-life of tadalafil is 17.5 hours in normal healthy men and 21.6 hours in elderly men. The 2026 Lilly label does not print 21.6. Its geriatric pharmacokinetics sentence says healthy men 65 and over had a lower oral clearance, resulting in 25% higher exposure, with no effect on peak concentration compared with healthy subjects 19 to 45 years old. It then says no dose adjustment is warranted based on age alone. Greater sensitivity in some older people should still be considered.
A history page that copies 21.6 into a current dosing talk is using a review and skipping the label that replaced it on the shelf. The 17.5-hour figure is the one both the review and the current label print for healthy men. The elderly figure a reader should take to a prescriber is the label's 25% higher exposure, not a number that stopped appearing in the file we opened.
Nitrates stay a hard stop on that same label, whatever year the tablet was approved. A long half-life is why the wait after a dose is long. It is not a reason to treat an old nitrate spray as safe. Chest pain is emergency care. The pharmacology of that interaction is on the trials note, not a second time here.
A path you can check
| Year | What the opened file says | File |
|---|---|---|
| 1991 | Partnership between Glaxo and ICOS begins. Wikipedia credits discovery to Glaxo Wellcome. | Wikipedia |
| 1993 | ICOS in Bothell starts work on IC351. The review calls it cardiovascular testing. | Wikipedia and the 2008 review |
| 1994 to 1995 | Patent, then phase 1 trials. | Both |
| 1996 | Glaxo lets the 50/50 agreement lapse. | Wikipedia |
| 1998 | Lilly and ICOS form Lilly ICOS to develop tadalafil for erectile dysfunction. | Both |
| 2000 | An application is filed under the name tadalafil and the brand Cialis. | Both |
| Late 2002 | Approval in Europe. | 2008 review |
| 2003 | US approval. The review prints November 21. The label prints the year. | Review and the Lilly label |
| January 2008 | The review says Lilly announced once-daily approval for erectile dysfunction. | 2008 review |
| 2009 | US approval for pulmonary arterial hypertension. | Wikipedia |
| October 2011 | Wikipedia says the FDA approved tadalafil for benign prostatic hyperplasia symptoms. | Wikipedia |
The fill, the imprint, and the pharmacy check are on the tadalafil medicine page. Julian Frost signs this note. The limit of a reading note is on the margin disclaimer. The label text is the Lilly CIALIS entry on DailyMed. The review that prints November 21 and the January 2008 announcement is Tadalafil in the treatment of erectile dysfunction.