Prescription ·Strong evidence ·Reviewed May 2026
Tadalafil is a long-acting PDE5 inhibitor approved for erectile dysfunction (ED), benign prostatic hyperplasia (BPH), and pulmonary arterial hypertension (PAH). Its prolonged duration of action (up to 36 hours) distinguishes it from sildenafil and vardenafil, earning it the nickname 'the weekend pill.' Low-dose daily tadalafil (2.5-5 mg) is uniquely approved for combined ED and BPH symptom management.
The bottom line
Evidence rating strong. Most-documented uses: longest duration of action among pde5 inhibitors (up to 36 hours), daily dosing option eliminates need for timing with sexual activity, uniquely approved for both ed and bph. 10 sources indexed (2020–2025), with 3 interaction records on file.
Core mechanism
Selectively inhibits phosphodiesterase type 5 (PDE5), preventing degradation of cGMP in smooth muscle cells. This enhances nitric oxide-mediated vasodilation in the corpus cavernosum (for erection), the prostate and bladder (for BPH symptom relief), and the pulmonary vasculature (for PAH). Tadalafil is more selective for PDE5 over PDE6 than sildenafil, resulting in fewer visual side effects, but has more PDE11 inhibition (significance uncertain).2
Not significantly affected by food (unlike sildenafil); can be taken with or without meals. Bioavailability not precisely determined but clinical effect is reliable. Long half-life of 17.5 hours supports daily dosing.
Same mechanism as sildenafil + L-arginine. Tadalafil has a 36-hour half-life, making the interaction window much longer than sildenafil.
Recommendation: Use caution. Tadalafil's long duration means the vasodilatory interaction persists for 1-2 days. Start L-arginine at low doses.
L-Citrulline can raise plasma L-arginine and nitric-oxide signaling, while tadalafil preserves cGMP by inhibiting PDE5. A small randomized crossover pilot study found that L-citrulline-containing supplementation improved erectile function in men who were still using on-demand PDE5 inhibitors. The combination is usually a therapeutic synergy, but dizziness or flushing can occur if vasodilation becomes excessive.
Recommendation: Use L-citrulline with tadalafil only after you know how tadalafil affects your blood pressure. Start with a low L-citrulline dose, avoid combining it with nitrates or heavy alcohol use, and stop the supplement if you develop dizziness, faintness, or severe headache.
St. John's Wort can induce CYP3A4, the main metabolic pathway for tadalafil. This may lower tadalafil exposure and reduce its effectiveness for erectile dysfunction, BPH symptoms, or pulmonary hypertension indications. The risk is most relevant with daily or repeated St. John's Wort use, because enzyme induction builds over days and can persist after stopping.
Recommendation: Avoid St. John's Wort while using tadalafil unless your prescriber specifically approves it. If you stop St. John's Wort, do not change tadalafil dosing on your own; enzyme activity may take about a week or longer to normalize.
Numbered references. Citations throughout the page link here.
Zhou R, Che X, Zhou Z et al.. A Systematic Review and Meta-Analysis of the Efficacy and Safety of Tamsulosin Plus Tadalafil Compared With Tamsulosin Alone in Treating Males With Lower Urinary Tract Symptoms Secondary to Benign Prostrate Hyperplasia. American journal of men's health. 2023
Shafiee A, Bahri RA, Teymouri Athar MM et al.. Phosphodiesterase 5 (PDE-5) inhibitors (sildenafil, tadalafil, and vardenafil) effects on esophageal motility: a systematic review. BMC gastroenterology. 2023
Belkovsky M, Zogaib GV, Passerotti CC et al.. Tamsulosin vs. Tadalafil as medical expulsive therapy for distal ureteral stones: a systematic review and meta-analysis. International braz j urol : official journal of the Brazilian Society of Urology. 2023
Wang YL, Geng LG, He CB et al.. Chinese herbal medicine combined with tadalafil for erectile dysfunction: a systematic review and meta-analysis. Andrology. 2020
Cox D, Byrne B, Hammers DW et al.. Effect of Tadalafil on cardiac function and left ventricular dimensions in Duchenne muscular dystrophy: safety and cardiac MRI substudy results from a randomized, placebo-controlled trial. BMC cardiovascular disorders. 2025
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