Tadalafil, sold as Cialis, is a phosphodiesterase type 5 (PDE5) inhibitor. It boosts the nitric oxide signal that relaxes smooth muscle in the penis, prostate, bladder and blood vessels. It is FDA-approved for erectile dysfunction (ED) and for urinary symptoms of an enlarged prostate (benign prostatic hyperplasia, BPH). Under the brand Adcirca, the same molecule is approved at a higher dose for pulmonary arterial hypertension (PAH).

What sets tadalafil apart from sildenafil is its long half-life of about 17.5 hours. That is why the label reports an effect up to 36 hours after a dose, and why it can be taken once daily. Outside medicine, anabolic steroid users report misusing it more often than other gym-goers. Small controlled trials in athletes found no meaningful performance benefit, and a large trial in muscular dystrophy found no functional benefit.

This page summarizes what the FDA labels, clinical trials and regulators report. It is for education only and is not medical advice.

Property	Detail
Drug class	Phosphodiesterase type 5 (PDE5) inhibitor
Brands / approval	Cialis (Eli Lilly): EU November 12, 2002; FDA November 21, 2003 (NDA 021368). Adcirca for PAH: FDA 2009. Generics available
Route	Oral tablet
Strengths	Cialis 5, 10 and 20 mg; Adcirca 20 mg
Labeled doses	ED as needed: 10 mg (range 5–20 mg), at most once a day. ED daily: 2.5–5 mg. BPH: 5 mg daily. PAH: 40 mg daily
Time to peak	Median 2 h (range 30 min–6 h)
Half-life (label)	17.5 h in healthy subjects; 35 h in PAH patients
Metabolism	Mainly CYP3A4 in the liver
US status	Prescription only (Rx)
WADA status	Not on the 2026 Prohibited List

What it is

Tadalafil has the formula C₂₂H₁₉N₃O₄ and a molecular weight of 389.4 g/mol (Cialis label; PubChem). It was discovered by a GlaxoSmithKline research team in France, starting from a beta-carboline lead compound, under the code GF196960. The discovery paper reported a PDE5 IC50 (the concentration that blocks half the enzyme’s activity) of 5 nM (Daugan et al., J Med Chem 2003).

Mechanism

During sexual stimulation, nerves and the lining of blood vessels release nitric oxide. Nitric oxide raises cyclic GMP (cGMP) in smooth muscle cells, the muscle relaxes, and blood flows into the penis. PDE5 is the enzyme that breaks cGMP down. Tadalafil blocks PDE5, so cGMP stays high for longer.

The label stresses one point: because the nitric oxide signal starts with sexual stimulation, tadalafil has no effect without it. It does not cause erections on its own.

PDE5 is also present in the prostate, bladder, blood vessels, lungs, platelets and skeletal muscle. This underlies the PAH use and the mild blood-pressure-lowering effect. For BPH, the label states that the mechanism of symptom relief has not been established.

Selectivity

Tadalafil’s in-vitro selectivity for PDE5 over other phosphodiesterases, from the label:

Enzyme	Main location	Selectivity for PDE5 over it
PDE1, PDE2, PDE4, PDE7	Heart, brain, blood vessels, liver, white cells	More than 10,000-fold
PDE3	Heart and blood vessels	More than 10,000-fold
PDE6	Retina (vision)	700-fold
PDE8, PDE9, PDE10	Various	More than 9,000-fold
PDE11A1 / PDE11A4	Prostate, testes, skeletal muscle	14-fold / 40-fold

Color-vision changes, which the label links to PDE6 inhibition, were rare with tadalafil (under 0.1% of patients in trials). PDE11 is the exception: tadalafil inhibits it at therapeutic concentrations in vitro, and the label states that the clinical consequence of this “has not been defined.”

Pharmacokinetics

From the Cialis and Adcirca labels (Cialis label; Adcirca label):

Parameter	Value
Time to peak (single dose)	30 min–6 h, median 2 h
Effect of food	None on rate or extent of absorption
Dose proportionality	Exposure rises in proportion to dose from 2.5 to 20 mg
Steady state (once daily)	Reached within 5 days; exposure ≈ 1.6× a single dose
Volume of distribution	≈ 63 L
Plasma protein binding	94%
Metabolism	CYP3A4 to a catechol, then methylation and glucuronidation; metabolites not expected to be active
Terminal half-life, healthy subjects	17.5 h (Cialis label); 15 h after a 40 mg dose (Adcirca label)
Terminal half-life, PAH patients	35 h
Excretion	≈ 61% in feces, ≈ 36% in urine, mostly as metabolites
Older men (65+)	≈ 25% higher exposure, no dose change needed for age alone

Two consequences follow from these numbers:

A long window. After a single dose, a meaningful amount remains for more than a day. This underlies both the 36-hour efficacy data and the 48-hour wait the label requires before nitrates.
Sensitivity to CYP3A4. Drugs that block or speed up CYP3A4 change tadalafil levels several-fold (see Interactions below). Renal impairment also roughly doubles exposure.

Approved medical use

The current Cialis label covers:

erectile dysfunction;
the signs and symptoms of BPH;
ED and BPH together;
starting BPH treatment together with finasteride, for up to 26 weeks.

Adcirca is approved for PAH (WHO Group 1) to improve exercise ability.

Cialis was authorized in the EU on November 12, 2002 (EMA) and approved by the FDA on November 21, 2003 (Drugs@FDA). Adcirca followed in 2009 (Drugs@FDA).

Use	Labeled dose
ED, as needed	Start 10 mg before sexual activity; adjust to 5 or 20 mg. Not more than once per day
ED, once daily	2.5 mg daily, may increase to 5 mg
BPH or ED with BPH	5 mg daily
PAH (Adcirca)	40 mg (two 20 mg tablets) once daily

The label lowers or caps doses in kidney or liver impairment and with strong CYP3A4 inhibitors. Severe liver impairment is not recommended. In men with creatinine clearance under 30 mL/min, the as-needed dose is capped at 5 mg once every 72 hours and daily use is not recommended.

What the research shows

Erectile dysfunction

Tadalafil was evaluated for ED in 22 clinical trials of up to 24 weeks in more than 4,000 patients (Cialis label). The main outcome was the erectile function (EF) domain of the IIEF questionnaire, scored 0–30, where higher is better.

Results from the two primary US trials of 20 mg taken as needed, 12 weeks:

Outcome (change from baseline)	Study A placebo	Study A 20 mg	Study B placebo	Study B 20 mg
EF domain score	−0.2	+6.9	+0.3	+9.3
Successful penetration (SEP2)	+2%	+26%	+2%	+32%
Erection lasting to completion (SEP3)	+5%	+34%	+4%	+44%

All tadalafil-versus-placebo differences had p under 0.001. Benefits were also shown in men with diabetes (EF score +7.3 on 20 mg vs +0.1 on placebo) and after nerve-sparing prostate removal (+5.3 vs +1.1).

Duration of effect

Two label trials tested whether a single dose still worked a day or more later:

Trial	Time after dose	Placebo	10 mg	20 mg
Study 1 (n = 348): men with at least 1 successful intercourse	22–26 h	37%	—	61%
Study 1	33–39 h	37%	—	64%
Study 2 (n = 483): mean share of successful attempts	24 h	42%	56%	67%
Study 2	36 h	33%	56%	62%

Onset can be fast in some men. In a 223-patient trial, 52% on 20 mg reported a successful erection within 30 minutes, compared with 35% on placebo.

Once-daily dosing

In two primary trials of 2.5–5 mg daily, taken without regard to timing of sex, the EF domain score improved by 6.1–9.7 points, compared with 0.9–1.2 points on placebo. In a 6-month trial, the effect did not diminish over time.

How it compares with other PDE5 inhibitors

A network meta-analysis of 82 randomized trials (47,626 patients) compared starting doses (Chen et al., Eur Urol 2015):

sildenafil 50 mg had the greatest efficacy but also the highest overall rate of adverse events;
tadalafil 10 mg had intermediate efficacy and the lowest overall rate of adverse events.

There is no clear “best” PDE5 inhibitor. The choice is a trade-off between strength of effect, side effects and how long the drug lasts.

Benign prostatic hyperplasia

The IPSS is a 0–35 urinary symptom score, where lower is better. In two 12-week trials of 5 mg daily (Cialis label):

Trial	Placebo change	Tadalafil 5 mg change	p-value
Study J (n = 410 in these arms)	−2.2	−4.8	under 0.001
Study K (n = 324)	−3.6	−5.6	0.004

Peak urine flow rose similarly on drug and placebo (1.6 vs 1.1–1.2 mL/sec), so tadalafil eases symptoms without measurably improving flow. When started together with finasteride, tadalafil’s added benefit shrank from 1.7 IPSS points at week 4 to 1.0 point at week 26. This is why the label limits the combination to 26 weeks.

Pulmonary arterial hypertension

The PHIRST trial randomized 405 patients with PAH to placebo or tadalafil 2.5, 10, 20 or 40 mg daily for 16 weeks (Galiè et al., Circulation 2009):

Only 40 mg met the prespecified significance level for the 6-minute walk distance.
The placebo-corrected gain was 33 m (95% CI 15–50).
The gain was 44 m in patients not on bosentan, and 23 m (95% CI −2 to 48) in those already taking it.
Clinical worsening occurred in 5% on 40 mg, compared with 16% on placebo (Adcirca label).

Exercise performance in healthy athletes

A small group of Italian crossover trials tested a single 20 mg dose in trained men:

Study	Design	Main finding
Di Luigi et al., Int J Sports Med 2008	14 athletes, maximal cycle test	No change in VO2max or in aerobic and anaerobic thresholds. Lower systolic blood pressure
Guidetti et al., Br J Sports Med 2008	12 athletes, 30-second sprint test	No change in mean or peak power. Slightly shorter time to peak power and higher lactate at 3 minutes
Di Luigi et al., AJP-Endo 2012	14 men, two 20 mg doses 36 h apart	No effect on performance. Smaller ACTH and cortisol rise during exercise

An earlier trial in 9 athletes found the opposite cortisol result: a larger salivary cortisol and testosterone rise after exercise on tadalafil (Di Luigi et al., JCEM 2008). The hormone findings are therefore inconsistent, and all of these studies are very small. The authors themselves concluded that 20 mg does not substantially influence physical performance in normoxia (normal oxygen levels).

Muscle disease and blood flow in muscle

In a crossover trial in 10 men with Becker muscular dystrophy, a single 20 mg dose restored the normal blunting of blood-vessel constriction in exercising forearm muscle (Martin et al., Sci Transl Med 2012). This is a blood-flow finding, not a strength or muscle-mass finding.

When tested for clinical benefit, it failed. A phase 3 trial randomized 331 boys with Duchenne muscular dystrophy to tadalafil 0.3 or 0.6 mg/kg/day or placebo for 48 weeks (Victor et al., Neurology 2017):

Arm	48-week decline in 6-minute walk distance	p vs placebo
Placebo	51.0 m	—
Tadalafil 0.3 mg/kg/day	64.7 m	0.307
Tadalafil 0.6 mg/kg/day	59.1 m	0.538

Secondary measures of muscle function were also unchanged. The Cialis label now records this trial as having failed to show “any benefit” on muscle strength and performance.

About “pumps” and muscle growth. Tadalafil is often promoted as boosting muscle blood flow, “pumps” or growth. No controlled human trial has shown that it increases muscle mass or strength. The athlete trials found no performance gain, and the large Duchenne trial found no functional benefit.

Testosterone and fertility

Tadalafil does not act on the hormonal axis. In the label’s studies, 10–20 mg daily for 6–9 months had no adverse effect on testosterone, LH or FSH (Cialis label).

The largest semen study randomized 253 men aged 45 or older to 20 mg daily or placebo for 9 months (Hellstrom et al., Eur Urol 2008):

a 50% or greater drop in sperm concentration occurred in 12.6% on tadalafil vs 2.1% on placebo;
this met the trial’s noninferiority margin, and sperm motility and shape were unaffected;
baseline levels returned in 8 of those 12 men during 6 months off the drug.

The label calls the clinical significance of the lower sperm concentrations “unknown.”

Side effects and risks

Common side effects

From the label’s eight placebo-controlled as-needed trials:

Side effect	Placebo	5 mg	10 mg	20 mg
Headache	5%	11%	11%	15%
Dyspepsia (indigestion)	1%	4%	8%	10%
Back pain	3%	3%	5%	6%
Myalgia (muscle pain)	1%	1%	4%	3%
Nasal congestion	1%	2%	3%	3%
Flushing	1%	2%	3%	3%
Pain in limb	1%	1%	3%	3%

Side effects were less frequent on the lower daily doses. In the BPH trials of 5 mg daily, headache occurred in 4.1% vs 2.3% on placebo.

Back pain and muscle aches are characteristic of tadalafil. They typically start 12–24 hours after a dose, feel like diffuse lower-back, buttock or thigh discomfort that worsens lying down, and resolve within 48 hours. Tests for muscle injury or inflammation found no underlying damage. About 0.5% of men stopped as-needed treatment because of it.

Nitrates: a dangerous combination

Tadalafil is contraindicated with any nitrate (for example nitroglycerin or isosorbide), regular or occasional. In a 150-man study, tadalafil 20 mg significantly amplified the blood-pressure drop from nitroglycerin at every time point up to 24 hours. By 48 hours the interaction was mostly gone. The label therefore requires at least 48 hours after the last tadalafil dose before a nitrate is given, even in an emergency, and only under close monitoring.

The same applies to guanylate cyclase stimulators such as riociguat, which the label also contraindicates.

Blood pressure, alpha-blockers and alcohol

On its own, 20 mg lowered supine blood pressure by only 1.6/0.8 mm Hg relative to placebo. The drop is larger with other blood-pressure-lowering agents:

Combined with	Placebo-subtracted blood-pressure drop
Doxazosin 8 mg (alpha-blocker)	9.8 mm Hg standing systolic
Angiotensin II receptor blockers	8/4 mm Hg
Bendrofluazide	6/4 mm Hg
Metoprolol	5/3 mm Hg
Alcohol 0.7 g/kg	More orthostatic hypotension and dizziness than alcohol alone

The label does not recommend tadalafil plus an alpha-blocker for BPH. For ED, men should be stable on the alpha-blocker before starting tadalafil at the lowest dose. Drinking 5 or more units of alcohol with tadalafil increases the chance of dizziness, fast heart rate and a drop in standing blood pressure.

Heart conditions

Sexual activity carries some cardiac risk. The label says tadalafil should not be used by men for whom sex is inadvisable. It is not recommended in men with any of the following, as they were excluded from trials:

heart attack in the last 90 days;
unstable angina, or angina during sex;
heart failure of NYHA class 2 or worse in the last 6 months;
uncontrolled arrhythmias, low blood pressure (under 90/50 mm Hg) or uncontrolled high blood pressure;
stroke in the last 6 months.

In 23 men with stable coronary disease, tadalafil 10 mg did not shorten the time to exercise-induced ischemia.

Vision and hearing

Sudden vision loss. Non-arteritic anterior ischemic optic neuropathy (NAION) is a stroke of the optic nerve. It has been reported rarely with all PDE5 inhibitors. Two observational studies cited on the label estimated roughly a doubled risk shortly after use (2.15, 95% CI 1.06–4.34; and 2.27, 95% CI 0.99–5.20). The label states that a causal link has not been established. Men with prior NAION or a “crowded” optic disc are at higher risk.

Sudden hearing loss has been reported in temporal association with PDE5 inhibitors, sometimes with tinnitus and dizziness.

Priapism

Erections lasting more than 4 hours, and priapism (painful erections lasting more than 6 hours), are rare. Untreated priapism can permanently damage erectile tissue and needs emergency care. Caution is advised in men with sickle cell anemia, multiple myeloma, leukemia or Peyronie’s disease.

Interactions through CYP3A4

Co-administered drug	Effect on tadalafil exposure (AUC)
Ketoconazole 400 mg daily	+312%
Ritonavir 200 mg twice daily	+124%
Rifampin 600 mg daily	−88%

Grapefruit juice, erythromycin, itraconazole and other HIV protease inhibitors are expected to raise levels. Carbamazepine, phenytoin and phenobarbital are expected to lower them. With strong CYP3A4 inhibitors, the label caps as-needed use at 10 mg every 72 hours and daily use at 2.5 mg. Tadalafil itself did not meaningfully change levels of warfarin, midazolam, lovastatin, theophylline or digoxin.

Overdose data

Single doses up to 500 mg in healthy subjects, and daily doses up to 100 mg in patients, produced adverse events similar to those at lower doses. A single 100 mg dose prolonged the QTc interval by 3.5 ms on average and raised heart rate by 3.1 beats per minute.

Who should not use it

The label contraindicates tadalafil in people who:

use any form of organic nitrate;
use a guanylate cyclase stimulator such as riociguat;
have had a serious allergic reaction to tadalafil, including Stevens-Johnson syndrome or exfoliative dermatitis.

Men should not take it together with other PDE5 inhibitors, including Adcirca. Cialis is not indicated for women or children.

Use outside medicine

In a survey of 219 gym members in San Francisco, the 40 anabolic steroid users took far more performance drugs than non-users (8.7 vs 3.7 on average). Erectile dysfunction drugs, specifically tadalafil and sildenafil, were among the prescription drugs they were more likely to misuse (Ip et al., Res Social Adm Pharm 2019). A 2026 review of six systematic reviews linked prolonged steroid use to suppressed testosterone and erectile dysfunction, although most of the included reviews were of low methodological quality (García Vidal et al., Actas Urol Esp 2026).

Tadalafil is not named on the WADA anti-doping list, so it is not prohibited in sport (WADA 2026 Prohibited List).

Tadalafil obtained outside a pharmacy carries its own risks:

Hidden in supplements. Of 776 adulterated supplements flagged in FDA warnings from 2007 to 2016, 353 (45.5%) were marketed for sexual enhancement (Tucker et al., JAMA Netw Open 2018). Sildenafil was the most common hidden drug in that group. A review describes PDE5 inhibitors as the main drugs found in “natural” sexual enhancement supplements worldwide (Yéléhé-Okouma et al., Fundam Clin Pharmacol 2021).
Unknown dose. A man who does not know he is taking a PDE5 inhibitor cannot avoid the nitrate interaction, and the dose is not controlled.

Key takeaways

A long-acting PDE5 inhibitor. The 17.5-hour half-life gives an effect up to 36 hours after a dose and allows once-daily use at 2.5–5 mg.
Works only with sexual stimulation. It amplifies the nitric oxide signal and does not cause erections on its own.
Approved for ED, BPH and PAH. In the main ED trials, 20 mg improved the erectile function score by 6.9–9.3 points, compared with about 0 on placebo.
No proven performance or muscle benefit. Small athlete trials found no gain in VO2max or power, and a 331-patient Duchenne trial found no functional benefit.
Never combine with nitrates. Allow at least 48 hours between the last dose and any nitrate. Alpha-blockers, other blood-pressure drugs, heavy drinking and strong CYP3A4 inhibitors also raise the risk.
Headache, indigestion and back pain are typical. Rare but serious events include priapism, sudden vision loss and sudden hearing loss.

Sources

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United Therapeutics Corporation. Adcirca (tadalafil) tablets, prescribing information. DailyMed; Drugs@FDA, NDA 022332.
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Cialis (Tadalafil)