S tier · elite
Tadalafil holds three separate FDA-approved indications supported by multiple replicated randomised placebo-controlled trials showing consistent, large separations on validated erectile function and urinary symptom endpoints.
tadalafil
Tadalafil is a long-acting phosphodiesterase type 5 inhibitor approved for erectile dysfunction, for the signs and symptoms of benign prostatic hyperplasia, and for the two conditions when they occur together. Its 17.5-hour terminal half-life gives it a substantially longer window of action than sildenafil.
the explanation
Tadalafil works like Viagra but lasts far longer, which is why it is sometimes called the weekend pill. It is approved both for erection problems and for urinary symptoms from an enlarged prostate.
regulatory status
FDA-approved (three indications)
Approved for erectile dysfunction (as needed or once daily), for the signs and symptoms of benign prostatic hyperplasia, and for ED and BPH occurring together. A separate brand and label cover pulmonary arterial hypertension. Widely approved internationally.
how it works · proposed mechanism
Tadalafil competitively inhibits phosphodiesterase type 5, preventing degradation of cyclic GMP in smooth muscle.
Prolonged cGMP elevation
By blocking PDE5, tadalafil sustains cGMP generated downstream of nitric oxide release during sexual stimulation. Its 17.5-hour terminal half-life extends this effect far beyond that of shorter-acting agents in the class.
Lower urinary tract smooth muscle
PDE5 is expressed in prostatic stroma, bladder neck and pelvic vasculature. cGMP-mediated relaxation there reduces lower urinary tract symptoms, which is the mechanistic basis of the separate BPH approval.
Systemic vasodilation
PDE5 inhibition in systemic vasculature modestly lowers blood pressure. This becomes clinically dangerous alongside nitric oxide donors and additive with alpha-blockers, both of which are explicitly addressed on the label.
what’s reported
evidence shape
5 sourcesThe composition of the cited literature by study type. This describes the shape of the evidence, not its quality — and it does not by itself set the grade.
⚠ the catch
Tadalafil's S grade covers erectile dysfunction and benign prostatic hyperplasia in diagnosed patients, and the approved-indication evidence does not establish benefit as a general performance or 'pump' enhancer in men without those conditions. The absolute nitrate contraindication, the NAION and sudden hearing loss signals, and the additive hypotension with alpha-blockers all persist across a 17.5-hour half-life, which makes casual unsupervised use materially different from the supervised context the trials studied.
key published findings
- Human trial (randomised, placebo-controlled, US Study B): IIEF erectile function domain score improved to 22.5 on tadalafil versus 13.6 on placebo; SEP2 (penetration) success rose from 43% to 77% and SEP3 (successful intercourse) from 23% to 64%.
- Human trial (randomised, placebo-controlled, US Study A): IIEF erectile function domain 19.5 versus 13.5 placebo; SEP2 62% versus 39%; SEP3 50% versus 25% — replicating the effect in an independent cohort.
- Human trial (once-daily, 24-week US Study H): IIEF erectile function domain 20.8 versus 14.6 placebo; SEP2 71% versus 51%; SEP3 57% versus 31%, establishing efficacy for the continuous-exposure regimen.
- Regulatory (label, pharmacokinetics): 'The mean terminal half-life is 17.5 hours in healthy subjects' — approximately four times that of sildenafil.
- Human observational: the PharMetrics Plus cohort with nested case-control analysis found an adjusted incidence rate ratio for ischaemic optic neuropathy across PDE5 inhibitors of 2.02 (95% CI 1.14-3.58).
limitations of the evidence
- Pivotal trials enrolled men with diagnosed erectile dysfunction or BPH; efficacy in men without either condition is not established by this evidence base.
- NAION and ocular risk estimates are observational and pooled across the PDE5 inhibitor class rather than being tadalafil-specific, and shared vascular risk factors limit causal inference.
- Trial endpoints are diary and questionnaire based, and blinding is imperfect because the drug produces recognisable side effects.
documented safety signals
- ABSOLUTE CONTRAINDICATION: administration to patients using any form of organic nitrate, due to potentially dangerous hypotension — a risk that persists longer than with shorter-acting PDE5 inhibitors given the 17.5-hour half-life.
- ABSOLUTE CONTRAINDICATION: co-administration with guanylate cyclase stimulators such as riociguat.
- Non-arteritic anterior ischaemic optic neuropathy has been reported rarely postmarketing; the label instructs immediate discontinuation and medical attention for sudden vision loss in one or both eyes.
- Sudden decrease or loss of hearing has been reported and requires prompt discontinuation and medical attention.
- Priapism: erections lasting greater than 4 hours require emergency medical attention, as untreated priapism can cause irreversible tissue damage.
- Additive blood pressure lowering with alpha-blockers; the label requires patients be stable on alpha-blocker therapy before initiating for ED, and states the combination is not recommended for the BPH indication.
- Additive hypotension with other antihypertensives and with alcohol.
- Caution in patients for whom sexual activity is inadvisable on cardiovascular grounds, and in recent cardiovascular events.
- Exposure is materially altered by CYP3A4 inhibitors and inducers.
- Caution in anatomical penile deformity and in conditions predisposing to priapism including sickle cell disease, multiple myeloma and leukaemia.
- Tadalafil is among the most frequently detected undeclared adulterants in 'natural' sexual-enhancement supplements, creating unintended exposure and nitrate-interaction risk in people who do not know they have taken it.
identity
| full name | Tadalafil |
| category | Sexual Health |
| modality | small molecule |
| formula | C22H19N3O4 |
| molar mass | 389.4 g/mol |
| cas | 171596-29-5 |
| half-life | 17.5 h (mean terminal, healthy subjects) |
laboratory handling
| storage | Marketed tablets are stored at controlled room temperature per the approved label. |
| solubility | Tadalafil is described in the label as practically insoluble in water and very slightly soluble in ethanol, which is reflected in its formulation as a solid oral tablet. |
| co-studied with | Documented interaction hazards rather than a regimen: absolute contraindication with organic nitrates and guanylate cyclase stimulators; additive hypotension with alpha-blockers, where the label requires alpha-blocker stability before initiation for ED and states the combination is not recommended for BPH; and altered exposure with CYP3A4 inhibitors and inducers. Combination with other PDE5 inhibitors, including undeclared PDE5 content in supplements, is a documented route to unintended overdose. |
Handling information describes laboratory practice for a research reagent. It is not a preparation guide for use in humans.
the receipts
5 citedDailyMed / US FDA · 2024 · official
US FDA Drugs@FDA · 2011 · official
JAMA Ophthalmology · 2022 · observational
others in Sexual Health