tadalafil

this is cialis, the erection pill. the same molecule does three jobs. it helps men with erectile dysfunction get an erection, it eases the urinary symptoms of an enlarged prostate, and at 40 mg, under the name adcirca, it treats high blood pressure in the arteries of the lungs. a pde5 inhibitor with a 17.5-hour mean half-life, two decades of approved human trials, and a research channel selling two other molecules under its name.

tier S · libido · 9,000+ men dosed in trials

verdict

it is cialis, the erection pill. it is approved for erection problems, for the urinary symptoms of an enlarged prostate, and at the higher 40 mg dose, as adcirca, for high blood pressure in the arteries of the lungs. the approved evidence is enormous and mostly positive. the trouble starts at the label on the research vial, where the same word covers two other molecules.

if you're asking which tadalafil: the small doses are for erections and the prostate, and the big dose is for the lungs. the erectile-dysfunction and BPH world runs 2.5 to 20 mg as Cialis, and the pulmonary-arterial-hypertension world runs 40 mg once daily as Adcirca or Tadliq. PHIRST tested 2.5, 10, 20 and 40 mg in PAH and only the 40 mg arm met its prespecified endpoint. the 5 mg once-daily erectile data and the 40 mg PAH data come from separate trials, so each figure holds for its own dose and its own indication.

if you're asking about tadalafil citrate or amino tadalafil: the approved drug is plain tadalafil, the free base, and those two names describe something else. all 35 Drugs@FDA applications list the active ingredient as tadalafil, UNII 742SXX0ICT, free base, and every FDA and EMA authorisation is that free base, so a liquid sold as tadalafil citrate is describing a solution. amino tadalafil is a structurally distinct compound that the FDA names as its own undeclared substance in recall language, alongside nortadalafil and chloropretadalafil. it has no approval anywhere, and the analytical literature on it is chemistry, with no assessed toxicology.

if you're asking whether the 36-hour claim is real: a difference over placebo was still measurable at 36 hours in two label studies. in the first, 348 men randomized to placebo or 20 mg attempted intercourse at set intervals: at 33 to 39 hours, 88 of 137 on tadalafil (64%) had at least one successful attempt versus 49 of 133 on placebo (37%). in the second, n=483, the mean per-patient success rate at 36 hours was 62% at 20 mg versus 33% on placebo. the mean terminal half-life is 17.5 hours, which is what makes that window mechanically possible. the slogan describes a window in which the drug still beats placebo.

if you're asking about the muscle, pump and endurance angle: the one large trial of it failed. Victor 2017 randomized 331 boys with Duchenne muscular dystrophy across 63 sites to placebo or tadalafil 0.3 or 0.6 mg/kg/day for 48 weeks. six-minute walk decline was 51.0 m on placebo, 64.7 m on low dose (p=0.307) and 59.1 m on high dose (p=0.538). the authors classified it as Class I evidence that tadalafil does not slow ambulatory decline, and the open-label extension was stopped. the mechanistic work that justified running it, a 10-man Becker crossover, was clean and positive, and it stayed a 10-man result.

based on the FDA-approved labels, published trials and the public regulatory record. not medical advice.

why S-tier

S-tier because the S bar is drug-tier human evidence and tadalafil clears it several times over. Four NDAs, three separate indications, a 405-patient randomized PAH trial with a prespecified primary endpoint met at 40 mg, pooled erectile-dysfunction analyses at n=1,112 and n=1,913, a 1,089-man BPH trial, and over 9,000 men dosed across the worldwide programme. Twenty-three years of postmarketing surveillance sit on top of that. S still comes with limits. Urine flow rate stays flat in BPH, the Duchenne phase 3 failed on Class I evidence, and the endothelial and dementia literatures are small, mixed or class-level. Those limits describe what the compound does; the evidence itself is solid. The identity problem is what would move the tier. If the research channel's product were shown at scale to be a different molecule, the grade would attach to a name and the compound behind it would be unknown. The analytical record already shows that happening in the supplement channel.

the core tension

tadalafil is the best-evidenced compound most peptide shelves carry, and the worst-labelled. the approved record is enormous, with over 9,000 men dosed, 22 erectile-dysfunction trials behind one label section, a 405-patient PAH randomized trial and twenty-plus years of postmarketing surveillance. that record attaches to the labelled molecule. the research channel sells a free base as a citrate, sells a distinct analogue under a name one syllable away, and quotes selectivity tables that contradict the label they claim to be quoting, so the grade belongs to the compound and the vial stays an open question. the analytical literature says why. a retention time and a UV peak read the same on tadalafil and on at least one of its analogues.

what it is

Tadalafil is the drug sold as Cialis. It is a small molecule and a selective inhibitor of phosphodiesterase type 5, and it sits on a peptide board only because vendors stock it beside peptides. The FDA label gives the empirical formula C22H19N3O4 and a molecular weight of 389.41, chemical designation pyrazino[1',2':1,6]pyrido[3,4-b]indole-1,4-dione, 6-(1,3-benzodioxol-5-yl)-2,3,6,7,12,12a-hexahydro-2-methyl-, (6R,12aR)-. The label describes a crystalline solid practically insoluble in water. It has been approved for two decades. Drugs@FDA returns 35 applications under the generic name tadalafil, four NDAs and 31 ANDAs, every one naming the active ingredient as tadalafil, UNII 742SXX0ICT. Cialis (NDA 021368) was approved November 21, 2003 and now covers erectile dysfunction, BPH signs and symptoms, and the two together. Adcirca (NDA 022332) was approved May 22, 2009 for pulmonary arterial hypertension. Tadliq, an oral suspension, followed June 17, 2022, and Opsynvi, a macitentan combination, March 22, 2024. In the EU both sit under ATC G04BE08. Every approved product is the free base. The phrase 'tadalafil citrate' has no regulatory existence, and 'amino tadalafil' names a different molecule entirely.

what it does

It relaxes the smooth muscle in the walls of blood vessels, which lets more blood through them. That one action is why a single molecule covers three different complaints. Tadalafil inhibits PDE5, the enzyme that degrades cyclic GMP in smooth muscle. The label reports the in vitro selectivity numbers directly: more than 10,000-fold over PDE1, PDE2, PDE3, PDE4 and PDE7, more than 9,000-fold over PDE8, PDE9 and PDE10, 700-fold over PDE6, and only 14-fold over PDE11A1 and 40-fold over PDE11A4. In erectile dysfunction the measured effect is large. The pooled analysis of five 12-week randomized trials, 1,112 men, reported a 7.9-point gain on the 30-point IIEF erectile-function domain at 20 mg, 75% of intercourse attempts completed on SEP3, and 81% reporting improved erections versus 35% on placebo. In BPH the effect is real and modest, roughly a 2-point placebo-adjusted improvement in the 35-point IPSS symptom score, while objective urine flow stays where it was. In pulmonary arterial hypertension, PHIRST reported a placebo-adjusted 33-metre gain in six-minute walk distance at 40 mg once daily.

origin

The composition-of-matter patent, US5859006A, 'Tetracyclic derivatives; process of preparation and use', names Alain Claude-Marie Daugan as inventor and ICOS Corporation as assignee, with a January 19, 1995 GB priority and a January 12, 1999 grant. The development codes were IC-351 and LY450190. ICOS and Eli Lilly took it through registration together. The FDA approved Cialis on November 21, 2003 as a Type 1 New Molecular Entity. The EMA had already authorised it on November 12, 2002, and authorised Adcirca on October 1, 2008, roughly seven months ahead of the FDA. One piece of the story ended in court. EP(UK)1173181, the patent covering the 1 to 5 mg once-daily unit dose, was revoked for obviousness by the UK Supreme Court in Actavis Group PTC EHF and others v ICOS Corporation and another [2019] UKSC 15. The court held that a skilled team running routine clinical dose-ranging would have arrived at the low-dose daily regimen without inventive skill. The 5 mg daily regimen that the research channel now copies was, on the record, ordinary dose-finding.

why researchers are interested

Duration is the whole pitch, and this duration claim has label data behind it. A mean terminal half-life of 17.5 hours produces a measurable window out to 36 hours, which is why the once-daily 5 mg regimen exists at all. The second reason is that one 5 mg daily regimen moves two endpoints at once. In the combined ED and BPH trial, n=606, the 5 mg arm improved IPSS by 6.1 points versus 3.8 on placebo and the IIEF erectile domain by 6.5 versus 1.9, both p<.001. The third reason is availability. Thirty-one generic applications sit on the FDA register, which makes it cheap and easy to get.

does it work

Within its labelled indications, yes, and the record is unusually deep. Twenty-two trials of up to 24 weeks and over 4,000 patients sit behind the erectile-dysfunction label alone; over 9,000 men were dosed across the worldwide programme. Outside them the picture thins in specific places. In BPH the symptom score improves while the measured urine flow rate stays flat. The 331-boy Duchenne phase 3 missed its primary endpoint and every secondary. An 89-person double-blind trial put erectile score and flow-mediated dilation level with placebo, which cuts against the small positive endothelial studies. The dementia headline belongs to sildenafil, and it comes from cohort data that a Medicare analysis then failed to reproduce.

key facts

• molecular formula: C22H19N3O4
• molecular weight: 389.41 (FDA label; every approved product is the free base)
• amino acids: a tetracyclic PDE5 inhibitor with a benzodioxole substituent; it has no amino-acid sequence
• half-life: 17.5 h mean terminal (Cialis label); median Tmax 2 h, range 30 min to 6 h
• type: small-molecule PDE5 inhibitor, sold alongside peptides and stocked here for that reason
• CAS: UNII 742SXX0ICT (FDA unique ingredient identifier; the registry sweep recorded the UNII in place of a CAS number. aminotadalafil, a different molecule, is CAS 385769-84-6)
• 9,000+ men dosed, worldwide programme
• 17.5 h mean terminal half-life
• 35 drugs@FDA applications (4 NDA, 31 ANDA)
• 126 FDA recalls for undeclared tadalafil

frequently asked questions

What is tadalafil?

Tadalafil is Cialis, the erection pill. It is approved to treat erectile dysfunction and the urinary symptoms of an enlarged prostate (BPH), and at a higher dose, sold as Adcirca and Tadliq, high blood pressure in the arteries of the lungs (pulmonary arterial hypertension). On the research shelf the same word also gets stuck on two other molecules, sold as tadalafil citrate and amino tadalafil. Tadalafil itself is a small-molecule selective inhibitor of phosphodiesterase type 5, formula C22H19N3O4, molecular weight 389.41. Despite sitting on a peptide board it is a small-molecule drug. It is FDA-approved as Cialis (2003) for erectile dysfunction and BPH, as Adcirca (2009) and Tadliq (2022) for pulmonary arterial hypertension, and as part of the Opsynvi combination (2024). Thirty-one generic applications also sit on the FDA register.

What does tadalafil do?

It relaxes the smooth muscle in the walls of blood vessels, so more blood flows through them. That one action does three things. It helps many men with erectile dysfunction get an erection, it modestly eases the urinary symptoms of an enlarged prostate, and at the higher 40 mg dose it improves exercise ability in people with high blood pressure in the arteries of the lungs. Mechanically, tadalafil inhibits PDE5, the enzyme that breaks down cyclic GMP in smooth muscle. The pooled analysis of five 12-week randomized trials in 1,112 men reported a 7.9-point gain on the 30-point IIEF erectile-function domain at 20 mg, with 81% reporting improved erections against 35% on placebo. In BPH the placebo-adjusted IPSS symptom improvement runs about 2 points while objective urine flow stays flat. In pulmonary arterial hypertension, PHIRST reported a placebo-adjusted 33-metre gain in six-minute walk distance at 40 mg once daily.

How is tadalafil dosed in the published literature?

Small doses for erections and the prostate, one big dose for the lungs. The Cialis label covers erectile dysfunction and BPH at oral tablet strengths of 5, 10 and 20 mg, with 5 mg once daily as the strength carried through the BPH trials. The Adcirca and Tadliq labels cover pulmonary arterial hypertension at 40 mg once daily, with reductions for renal or hepatic impairment and for concomitant ritonavir. Each figure holds for the dose world it came from. Exact dosing belongs to the current FDA-approved label.

Is tadalafil FDA approved?

Yes. Drugs@FDA lists 35 applications under the generic name tadalafil: four NDAs (Cialis 2003, Adcirca 2009, Tadliq 2022, Opsynvi 2024) and 31 ANDAs. A fifth NDA, Entadfi (finasteride plus tadalafil, approved 2021), is marked discontinued, and the public record does not state a reason. The EMA authorised Cialis in November 2002 and Adcirca in October 2008, both under ATC G04BE08.

What are the side effects of tadalafil?

From the Cialis label's as-needed pooled tables, 20 mg versus placebo: headache 15% versus 5%, dyspepsia 10% versus 1%, back pain 6% versus 3%, myalgia 3% versus 1%, nasal congestion 3% versus 1%, flushing 3% versus 1%. Discontinuation for an adverse event ran 3.1% versus 1.4% on placebo. Rates are higher at the 40 mg pulmonary-hypertension dose, where headache reached 42% versus 15% on placebo. Any organic nitrate is contraindicated, as are guanylate cyclase stimulators such as riociguat. Postmarketing reports include non-arteritic anterior ischemic optic neuropathy, sudden hearing decrease, priapism, and Stevens-Johnson syndrome.

Is amino tadalafil the same thing as tadalafil?

No, it is a different molecule with a different structure, identified by NMR and mass spectrometry as (6R,12aR)-2-amino-6-(1,3-benzodioxol-5-yl)-2,3,6,7,12,12a-hexahydropyrazino[1',2':1,6]pyrido[3,4-b]indole-1,4-dione. The FDA names aminotadalafil, along with nortadalafil and chloropretadalafil, as its own undeclared substance in Class I recall language, separate from tadalafil. These analogues have no approved application anywhere, and what has been published on them is analytical chemistry, so the Cialis trial record describes tadalafil alone. Tadalafil citrate is a separate problem. Every FDA and EMA product is the free base, and all 35 Drugs@FDA applications list tadalafil free base, UNII 742SXX0ICT.

related peptides

• pt-141: the central MC4R route to the same complaint; tadalafil works on peripheral vasculature
• melanotan-ii: the melanocortin parent of PT-141; erections were the accidental finding
• kisspeptin-10: works on the upstream hormonal axis; tadalafil works on a vascular enzyme
• oxytocin: the other much-claimed, thinly-evidenced compound in this category

reptides grades the research record and cites the literature behind every call. research reference only; not medical advice.