A long-acting oral medication that widens blood vessels. Approved uses rest on consistent trial evidence. For longevity, continuous low daily dosing modestly lowers blood pressure and improves how well arteries relax; prescription records report fewer deaths among men who took it, but those men differ. Side effects are common, mostly mild; combining with nitrate heart medicines is dangerous. (Full Review)

Protocol

Standard continuous protocol

2.5–5 mg once daily

Taken indefinitely and without regard to sexual activity. Longevity-oriented telehealth clinics have standardized on 5 mg daily, the upper end of this range.

Best time of day

Evening or bedtime

Steady-state concentrations are essentially flat, so timing does not affect efficacy — only which hours carry the peak headache, flushing and blood-pressure nadir.

Single versus split dosing

Once-daily single dose

Splitting is unnecessary given the long half-life. Alternate-day dosing of a 5 mg tablet is the common variation where daily dosing produces cumulative side effects.

Time to effect

Erectile effect

30 minutes – 2 hours

From an on-demand dose. Continuous dosing reaches steady state in about five days.

Urinary symptoms

1–4 weeks

Improvement in frequency, urgency, stream and night-time waking is usually apparent by then.

Vascular measures

~4 weeks

Flow-mediated dilation, arterial stiffness and blood pressure. The anti-inflammatory effect appears only at twelve weeks or beyond.

Benefits

High: Restoration of erectile function; relief of lower urinary tract symptoms from prostate enlargement; improved vascular function and arterial stiffness; improved exercise capacity in pulmonary arterial hypertension

Medium: Lower all-cause mortality and major cardiovascular events; reduced vascular inflammation; improved cerebral blood flow in small-vessel disease

Low: Lower risk of Alzheimer's disease and dementia; relief of Raynaud phenomenon; facilitation of ureteral stone passage

Speculative: Improved skeletal muscle perfusion and exercise tolerance; metabolic and insulin-sensitizing effects; immune modulation in cancer

Contraindications

Organic nitrates and nitric oxide donors (nitroglycerin, isosorbide mononitrate and dinitrate, sodium nitroprusside, amyl or alkyl nitrites)

Riociguat and other soluble guanylate cyclase stimulators

Myocardial infarction within 90 days, stroke within 6 months, or life-threatening arrhythmia within 6 months

NYHA Class III–IV heart failure

Unstable angina, or angina occurring during intercourse

Uncontrolled hypertension above 170/100 mmHg, or hypotension below 90/50 mmHg

Severe hepatic impairment (Child-Pugh Class C)

Severe renal impairment (creatinine clearance below 30 mL/min) for continuous daily dosing

Prior NAION in either eye; hereditary degenerative retinal disorders including retinitis pigmentosa

Anatomical penile deformity, or a condition predisposing to priapism (sickle cell disease, multiple myeloma, leukemia)

Women outside pulmonary arterial hypertension; anyone under 18

Key Interactions

Alpha-blockers (doxazosin, terazosin, alfuzosin, tamsulosin, silodosin)

Antihypertensives and diuretics (angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, calcium channel blockers, beta-blockers, thiazide diuretics)

CYP3A4 inhibitors (ketoconazole, itraconazole, clarithromycin, erythromycin, ritonavir and other protease inhibitors, cobicistat, grapefruit or Seville orange juice)

CYP3A4 inducers (rifampicin, carbamazepine, phenytoin, phenobarbital, St. John's wort)

Over-the-counter medications (pseudoephedrine and phenylephrine decongestants, non-steroidal anti-inflammatory drugs, cimetidine, magnesium and aluminum antacids)

Supplements with additive vasodilatory or blood-pressure-lowering effects (L-Citrulline, L-Arginine, beetroot juice, garlic extract, hawthorn, magnesium, taurine, coenzyme Q10, hibiscus, potassium, omega-3 fatty acids)

Supplements affecting CYP3A4 (St. John's wort; grapefruit seed extract, bergamot, high-dose quercetin, resveratrol, berberine)

Other interventions (sauna and hot bathing, alcohol, intense heat exposure, prolonged fasting, aggressive sodium restriction)

Another phosphodiesterase type 5 inhibitor, intracavernosal alprostadil injection, or testosterone replacement

Risk & Side Effects

High: Headache; dyspepsia and reflux; back pain and myalgia; severe hypotension with nitrates or riociguat

Medium: Symptomatic hypotension and dizziness; discontinuation due to adverse effects; nasal congestion and flushing

Low: Non-arteritic anterior ischemic optic neuropathy; sudden sensorineural hearing loss; priapism and prolonged erection; hypersensitivity reactions; melanoma association

Speculative: Long-term consequences of continuous pathway suppression; masking of progressive vascular disease; blunting of exercise-induced vascular adaptation

Monitoring

Marker	Target	Why
Blood pressure (seated and standing)	110–125 / 70–80 mmHg seated; postural drop under 10 mmHg	Tadalafil lowers blood pressure; defines the safety margin
Resting heart rate	50–70 bpm	Detects the compensatory heart-rate rise that follows excessive vessel widening
hs-CRP	Under 0.5 mg/L	Tracks the anti-inflammatory effect that appears only after 12 weeks of continuous dosing
Interleukin-6	Under 1.5 pg/mL	The inflammation marker that moved most clearly in randomized trials of this drug class
Total and free testosterone	Total 600–900 ng/dL; free 15–25 ng/dL	Low androgens blunt response; predicts non-response before it is blamed on the drug
Fasting glucose and HbA1c	Glucose 75–90 mg/dL; HbA1c 4.8–5.4%	Diabetes both blunts erectile response and marks the group with the largest observational mortality benefit
Fasting insulin	Under 5 µIU/mL	Detects the insulin resistance that drives endothelial dysfunction
ApoB	Under 80 mg/dL, or under 60 mg/dL at high risk	Counts the artery-clogging particles that drive the vascular risk tadalafil does not treat
eGFR and creatinine	eGFR above 80 mL/min/1.73 m²	Determines the tadalafil dose ceiling, since impaired clearance raises exposure
ALT and AST	Under 25 U/L (men); under 22 U/L (women)	Tadalafil is cleared almost entirely by the liver, so liver capacity sets exposure
Prostate-specific antigen	Under 1.0 ng/mL at 40–50; under 2.0 ng/mL at 60+	Distinguishes benign enlargement from prostate cancer before attributing urinary symptoms to the former
Flow-mediated dilation	Above 7% brachial artery dilation	The direct readout of endothelial function that tadalafil is expected to improve
International Prostate Symptom Score	Under 8 (mild)	The primary efficacy measure for the urinary indication
International Index of Erectile Function-5	22–25	The primary efficacy measure for the erectile indication

Cadence: Baseline before the first dose. Seated and standing blood pressure at 2 weeks and after any dose increase; symptom scores and side-effect review at 4 and 12 weeks; a full biomarker panel at 3 months, and thereafter every 6–12 months indefinitely, with kidney and liver function annually and prostate-specific antigen annually in men over 45 with urinary symptoms.

Qualitative Assessment

Nocturia frequency — number of times waking to urinate per night
Sleep continuity and morning refreshment — whether reduced night waking translates into feeling better rested, and whether nasal congestion has begun to interfere
Spontaneous morning erections — an unprompted indicator of nocturnal endothelial and androgen function
Exercise tolerance and post-exertional dizziness — whether perfusion feels better or blood pressure feels lower during and after training
Headache, reflux and back ache burden — tracked weekly for the first month, since the trajectory determines whether the dose is right
Cold hands and feet — a crude but responsive marker of peripheral vasodilation
Sexual confidence and spontaneity — distinct from mechanical function, and the domain where continuous dosing is most often preferred over on-demand dosing

Tadalafil for Health & Longevity

Protocol

Benefits

Risk & Side Effects

Monitoring

Qualitative Assessment