tadalafil

Q: What is tadalafil?

Tadalafil is a small-molecule selective inhibitor of phosphodiesterase type 5, formula C22H19N3O4, molecular weight 389.41. It is not a peptide. 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.

Q: What does tadalafil do?

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. In BPH the placebo-adjusted IPSS symptom improvement runs about 2 points while objective urine flow does not move significantly. In pulmonary arterial hypertension, PHIRST reported a placebo-adjusted 33-metre gain in six-minute walk distance at 40 mg once daily.

Q: How is tadalafil dosed in the published literature?

In two separate dose worlds. 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. Evidence generated in one dose world does not transfer to the other. Exact dosing belongs to the current FDA-approved label.

Q: 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.

Q: 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.

Q: Is amino tadalafil the same thing as tadalafil?

No. Aminotadalafil is a structurally distinct compound, 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 it, along with nortadalafil and chloropretadalafil, as its own undeclared substance in Class I recall language, separate from tadalafil. None of these analogues has an approved application anywhere, and the published literature on them is analytical chemistry rather than toxicology. The Cialis trial record does not transfer to them. The phrase 'tadalafil citrate' is a separate problem: no FDA or EMA product is a citrate salt, and all 35 Drugs@FDA applications list tadalafil free base, UNII 742SXX0ICT.

cialis and adcirca. a 17.5-hour pde5 inhibitor with 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

one molecule, two dose worlds, three names on the research shelf. the approved record is enormous and mostly positive. the naming is where it goes wrong.

if you're asking which tadalafil — there are two dose worlds and they do not share evidence. 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 are separate literatures, and neither supports a claim made about the other.

if you're asking about tadalafil citrate or amino tadalafil — neither is the approved molecule. all 35 Drugs@FDA applications list the active ingredient as tadalafil, UNII 742SXX0ICT, free base; there is no citrate salt in any FDA or EMA authorisation, so a liquid sold as tadalafil citrate is describing a solution, not a salt. amino tadalafil is worse: it is a structurally distinct compound that the FDA names as its own undeclared substance in recall language, alongside nortadalafil and chloropretadalafil. no approval anywhere, and the analytical literature reports no assessed toxicology for it.

if you're asking whether the 36-hour claim is real — it comes from two label studies and it is narrower than the slogan. 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. so a measurable difference persists out to 36 hours. the mean terminal half-life is 17.5 hours, which is what makes that window mechanically possible.

if you're asking about the muscle, pump and endurance angle — the phase 3 that tested 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 small mechanistic work that preceded it, a 10-man Becker crossover, is real but tiny, and the trial that followed it did not replicate.

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 does not mean uncomplicated: urine flow rate does not move in BPH, the Duchenne phase 3 failed on Class I evidence, and the endothelial and dementia literatures are small, mixed or class-level. Those are limits on what the compound does, not doubts about whether the evidence exists. The identity problem is what would move the tier. If the research channel's product were shown at scale to be something other than the labelled molecule, the page would be grading a name rather than a compound. 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: over 9,000 men dosed, 22 erectile-dysfunction trials behind one label section, a 405-patient PAH randomized trial, twenty-plus years of postmarketing surveillance. almost none of that record attaches to what the research channel actually ships, because the 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. the compound is S-tier. the vial is a separate question, and the analytical literature says a retention time and a UV peak are not enough to answer it.

what it is

Tadalafil is a small molecule, not a peptide. 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)-. It is a selective inhibitor of phosphodiesterase type 5 and a crystalline solid described on the label as 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. No approved product anywhere is a citrate salt. The phrase 'tadalafil citrate' has no regulatory existence, and 'amino tadalafil' names a different molecule entirely.

what it does

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, with objective urine flow unmoved. 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 unlike most duration claims this one 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 is a different market structure from anything else on this board.

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. Urine flow rate does not move in BPH even where the symptom score does. The 331-boy Duchenne phase 3 missed its primary endpoint and every secondary. An 89-person double-blind trial found no between-group difference on either erectile score or flow-mediated dilation against placebo, which cuts against the small positive endothelial studies. The dementia headline is carried by sildenafil, not tadalafil, and comes from cohort data that a Medicare analysis then failed to reproduce.

claims vs the data

improves erectile function — supported — pooled analysis of five 12-week RCTs, n=1,112: IIEF erectile-function domain +7.9 points at 20 mg, 81% reporting improved erections vs 35% placebo. Once-daily integrated analysis, n=1,913, confirms at 2.5 and 5 mg.
works for 36 hours — partially true — label study 1, n=348: at 33 to 39 hours, 64% on 20 mg had at least one successful attempt vs 37% on placebo. Label study 2, n=483: mean per-patient success 62% vs 33% at 36 hours. A measurable window, not a 36-hour continuous effect, and mean terminal half-life is 17.5 hours.
improves urinary flow in BPH — contradicted — the symptom score moves and the flow rate does not. In both label BPH studies Qmax was not significantly different from placebo (+1.6 vs +1.2 mL/sec, and +1.6 vs +1.1). Porst 2011, n=325, reported no significant improvement in Qmax or postvoid residual. IPSS improves by roughly 2 points placebo-adjusted.
treats pulmonary arterial hypertension — supported — PHIRST, n=405, 16 weeks: placebo-adjusted six-minute walk +33 m (95% CI 15 to 50) at 40 mg. Only the 40 mg arm met prespecified significance; 2.5, 10 and 20 mg did not, and WHO functional class change was not significant.
improves muscle function, endurance or pump — contradicted — Victor 2017, n=331 boys with Duchenne muscular dystrophy, 48 weeks: primary endpoint missed at both doses (p=0.307 and p=0.538), no secondary endpoint met, open-label extension stopped. Authors classified it as Class I evidence that tadalafil does not slow ambulatory decline.
lowers dementia risk — weak — Adesuyan 2024, 269,725 men, adjusted HR 0.82 for PDE5-inhibitor initiation, but the effect is carried by sildenafil (HR 0.81) and the paper states it did not find strong evidence for tadalafil specifically. Desai 2022, Medicare claims with 76 confounders matched, found no reduction across four analytic approaches. Observational on both sides.
improves endothelial function — weak — Rosano 2005, n=32, found brachial flow-mediated dilation rising from 4.2% to 9.3% on alternate-day 20 mg. Pattanaik 2019, n=89 double-blind, found no between-group difference on either IIEF or FMD, with more adverse events on tadalafil. Small studies pointing opposite ways.
tadalafil citrate is a salt form of the drug — contradicted — there is no citrate salt in any FDA or EMA authorisation. All 35 Drugs@FDA products list the active ingredient as tadalafil, UNII 742SXX0ICT, free base. The formulation patent literature treats tadalafil as a poorly water-soluble free base needing a dispersion stabiliser or liquid vehicle. A liquid sold as a citrate is describing a solution.
amino tadalafil is a form of tadalafil — contradicted — aminotadalafil is a structurally distinct molecule, isolated from a supplement and characterised by NMR and mass spectrometry in Ulloa 2015. The FDA lists aminotadalafil, nortadalafil and chloropretadalafil as separate undeclared substances in its own Class I recall language. No approval anywhere, and the published record on it is analytical chemistry, with no toxicology study found.
a research-channel vial is the same molecule the trials used — unverified — nobody has published an assay survey of research-channel tadalafil solutions. The nearest data is the counterfeit-pharma and supplement literature: Trefi 2008 found seven of eight illicit formulations within 100 +/- 5% of stated content, and one that contained no tadalafil at all, only vardenafil and homosildenafil. Liu 2023 reports that N-cyclohexyl nortadalafil's MS2 spectrum below 300 m/z is highly similar to tadalafil and its UV spectrum almost identical.

key facts

molecular formula: C22H19N3O4
molecular weight: 389.41 (FDA label; free base, no approved citrate salt exists)
amino acids: not a peptide; a tetracyclic PDE5 inhibitor with a benzodioxole substituent
half-life: 17.5 h mean terminal (Cialis label); median Tmax 2 h, range 30 min to 6 h
type: small-molecule PDE5 inhibitor; not a peptide despite being sold alongside them
CAS: UNII 742SXX0ICT (FDA unique ingredient identifier; the registry sweep recorded the UNII, not 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 a small-molecule selective inhibitor of phosphodiesterase type 5, formula C22H19N3O4, molecular weight 389.41. It is not a peptide. 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?

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. In BPH the placebo-adjusted IPSS symptom improvement runs about 2 points while objective urine flow does not move significantly. 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?

In two separate dose worlds. 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. Evidence generated in one dose world does not transfer to the other. 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. Aminotadalafil is a structurally distinct compound, 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 it, along with nortadalafil and chloropretadalafil, as its own undeclared substance in Class I recall language, separate from tadalafil. None of these analogues has an approved application anywhere, and the published literature on them is analytical chemistry rather than toxicology. The Cialis trial record does not transfer to them. The phrase 'tadalafil citrate' is a separate problem: no FDA or EMA product is a citrate salt, 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 — upstream hormonal axis rather than 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.