Tadalafil
Also known as: Cialis
PDE5 Inhibitor | Erectile Function & Blood Flow
Overview
Tadalafil is a long-acting PDE5 inhibitor FDA-approved for erectile dysfunction (ED), benign prostatic hyperplasia (BPH), and pulmonary arterial hypertension (PAH). Its extended half-life of approximately 17.5 hours provides a therapeutic window of up to 36 hours, earning it the nickname 'the weekend pill.' Unlike shorter-acting PDE5 inhibitors, tadalafil is uniquely suited for daily low-dose use (2.5-5mg), which maintains steady-state plasma levels and allows for spontaneous sexual activity without timing constraints. Originally developed by ICOS Corporation and marketed by Eli Lilly as Cialis, tadalafil received FDA approval in 2003 for ED and has since become one of the most widely prescribed medications in its class. Beyond sexual health, tadalafil has gained attention for its cardiovascular and hemodynamic benefits, including improved endothelial function, reduced blood pressure, and enhanced exercise capacity.
Key benefits
- Long-acting duration with a 36-hour therapeutic window
- Daily low-dose option (2.5-5mg) eliminates timing constraints
- FDA-approved for both ED and BPH/LUTS
- Minimal food interaction compared to other PDE5 inhibitors
- Improved endothelial function and blood flow
- Lower incidence of visual side effects vs. sildenafil
- Potential benefits for exercise performance via enhanced blood flow
- Well-established long-term safety profile
Mechanism of action
Tadalafil selectively inhibits phosphodiesterase type 5 (PDE5), the enzyme responsible for degrading cyclic guanosine monophosphate (cGMP) in smooth muscle tissue. During sexual stimulation, nitric oxide (NO) is released in the corpus cavernosum, activating guanylate cyclase and increasing cGMP levels. Elevated cGMP causes smooth muscle relaxation in penile arteries and the corpus cavernosum, facilitating increased blood flow and erection. By blocking PDE5, tadalafil prolongs and amplifies this cGMP-mediated vasodilatory signaling cascade. PDE5 is also expressed in pulmonary vasculature, prostatic smooth muscle, and the bladder neck, which accounts for tadalafil's therapeutic effects in PAH and BPH/LUTS. Tadalafil has high selectivity for PDE5 over PDE6 (the retinal isoform), which contributes to its lower incidence of visual disturbances compared to sildenafil.
Molecular data
- Type
- Small molecule phosphodiesterase type 5 (PDE5) inhibitor
- Half-life
- ~17.5 hours
Indications
What the research community uses this compound for, with self-reported effectiveness.
Sexual Health
Urological
Cardiovascular
Performance
Dosing protocols
Common protocols by delivery method. Adjust the curve below to model accumulation in your own cycle.
Delivery method
| Protocol | Dose | Frequency | Duration |
|---|---|---|---|
| — | 10mg | As needed, at least 30 min before sexual activity | — |
| — | 20mg | As needed, max once per 24 hours | — |
| — | 2.5mg | Once daily, same time each day | — |
| — | 5mg | Once daily, same time each day | — |
| — | 5mg | Once daily | — |
| — | 5mg | Once daily | — |
| — | 12.5mg | Twice per week (e.g., training days) | — |
| — | 12.5mg | Every other day (EOD) | — |
| — | 12.5mg | Once daily | — |
| — | 40mg | Once daily | — |
Safety
Reported adverse effects, contraindications, and what to monitor on cycle.
Common side effects
- Headache (11-15% incidence, most common side effect)
- Dyspepsia / indigestion (4-13%)
- Back pain (3-9%, relatively unique to tadalafil among PDE5 inhibitors)
- Myalgia / muscle aches (1-7%, thought to be related to PDE11 inhibition)
- Nasal congestion / rhinitis (3-5%)
- Flushing (1-4%)
- Limb pain (1-3%)
- Dizziness (1-2%)
Rare side effects
- Non-arteritic anterior ischemic optic neuropathy (NAION) -- extremely rare, causal relationship uncertain
- Sudden sensorineural hearing loss -- extremely rare, causal relationship uncertain
- Priapism (prolonged erection >4 hours) -- rare but requires immediate medical attention
- Hypersensitivity reactions (rash, urticaria, facial edema, Stevens-Johnson syndrome)
- Exfoliative dermatitis
- Seizures
Contraindications
- Concurrent use of any organic nitrate medication (absolute contraindication)
- Concurrent use of guanylate cyclase stimulators (e.g., riociguat)
- Known hypersensitivity to tadalafil or any tablet excipient
- Severe hepatic impairment (Child-Pugh Class C)
- Recent stroke or myocardial infarction (within 90 days)
- Unstable angina or angina during sexual intercourse
- Uncontrolled hypertension (>170/100 mmHg) or hypotension (<90/50 mmHg)
- NYHA Class IV heart failure
- Hereditary degenerative retinal disorders (including retinitis pigmentosa)
- History of NAION (relative contraindication -- increased recurrence risk)
References
Primary literature and clinical-trial data informing this entry.