Tadalafil
Long-acting PDE-5 inhibitor for erectile dysfunction, BPH, and pulmonary hypertension
Tadalafil is a selective phosphodiesterase type 5 (PDE-5) inhibitor approved for the treatment of erectile dysfunction (ED), benign prostatic hyperplasia (BPH), and pulmonary arterial hypertension (PAH). It is marketed under the trade names Cialis (ED and BPH) and Adcirca (PAH). With a half-life of approximately 17.5 hours and a duration of action of up to 36 hours, tadalafil is the longest-acting member of the PDE-5 inhibitor class.
The extended duration of action distinguishes tadalafil from sildenafil and vardenafil and enables both on-demand use and once-daily low-dose therapy. Tadalafil is also the only PDE-5 inhibitor approved for the treatment of BPH symptoms, making it particularly useful in men who have both ED and lower urinary tract symptoms.
Mechanism of Action
Tadalafil selectively and reversibly inhibits PDE-5, the enzyme that degrades cyclic guanosine monophosphate (cGMP) in smooth muscle cells of the corpus cavernosum, pulmonary vasculature, and bladder neck. By preventing cGMP breakdown, tadalafil prolongs smooth muscle relaxation and vasodilation in response to nitric oxide (NO) released during sexual stimulation or physiological NO tone in the pulmonary circulation.
In the penis, this leads to increased blood flow and sustained erection in response to sexual stimulation. In the prostate and bladder, smooth muscle relaxation reduces urethral resistance and improves urinary flow. In the pulmonary vasculature, the vasodilatory effect lowers pulmonary arterial pressure and reduces right ventricular afterload, improving exercise capacity in PAH.
Tadalafil has greater selectivity for PDE-5 over PDE-6 (found in the retina) than sildenafil, explaining the lower frequency of visual disturbances. It also inhibits PDE-11, found in testicular tissue, though the clinical significance of this remains unclear.
Indications
- Erectile dysfunction: On-demand dosing (10 mg or 20 mg) or once-daily low-dose therapy (2.5 mg or 5 mg)
- Benign prostatic hyperplasia with lower urinary tract symptoms: Once-daily 5 mg; can be combined with the ED indication
- Pulmonary arterial hypertension (WHO functional class II and III): 40 mg once daily (Adcirca)
Dosage and Administration
On-demand ED: 10 mg approximately 30 minutes before sexual activity; increase to 20 mg or reduce to 5 mg based on response. Maximum one dose per 24 hours. Once-daily ED: 2.5 mg to 5 mg at the same time each day, regardless of anticipated sexual activity — allows spontaneous intercourse. BPH: 5 mg once daily. PAH: 40 mg once daily.
Tadalafil can be taken with or without food. Unlike sildenafil, a high-fat meal does not significantly affect absorption or onset of action. Dose reduction is required for patients with severe renal impairment (CrCl below 30 ml/min); once-daily dosing is not recommended in this group. Severe hepatic impairment contraindicates tadalafil use.
Side Effects
Common (over 10 percent): Headache, flushing, dyspepsia, back pain, myalgia, nasal congestion. Back pain and myalgia are more specific to tadalafil compared with other PDE-5 inhibitors and are attributed to PDE-11 inhibition; they typically resolve within 48 hours.
Occasional to rare: Dizziness, hypotension, palpitations, visual disturbances (less common than with sildenafil), priapism (sustained erection over 4 hours, urological emergency), sudden hearing loss (rare, must be reported).
In BPH patients: Dizziness may be more pronounced due to additive effects with alpha-blockers; appropriate dosing intervals should be observed.
Interactions
- Nitrates and NO donors: Absolute contraindication; potentially life-threatening hypotension; minimum interval 48 hours after the last tadalafil dose
- Alpha-1 blockers (tamsulosin, doxazosin): Additive hypotensive effect; tamsulosin combination generally better tolerated than with non-selective alpha-blockers; observe dosing intervals
- Strong CYP3A4 inhibitors (ketoconazole, ritonavir, clarithromycin): Increased tadalafil exposure; reduce to maximum 10 mg every 72 hours for on-demand use
- CYP3A4 inducers (rifampicin, phenytoin, carbamazepine): Reduced tadalafil plasma levels; may reduce efficacy
- Antihypertensives: Additive blood pressure reduction; clinical significance depends on dose and patient profile
- Alcohol: Amplifies vasodilatory and hypotensive effects
Special Notes
Duration of action and nitrate timing: Due to tadalafil's long half-life, a minimum interval of 48 hours after the last dose must be observed before administering nitrates in an emergency. Healthcare providers should always ask about recent tadalafil use in patients presenting with chest pain.
Once-daily dosing: Low-dose once-daily tadalafil maintains sufficient plasma levels for continuous therapeutic effect, allowing spontaneous sexual activity without the need to plan around medication intake. This may improve quality of life compared to on-demand dosing for some patients.
Cardiovascular evaluation: Before prescribing tadalafil, the patient's cardiovascular status should be assessed. Sexual activity is associated with a moderate increase in cardiac workload; in patients with significant cardiac disease, specialist assessment is advisable.
Pregnancy and breastfeeding: Tadalafil is not indicated for use in women for ED. For PAH in women, use during pregnancy requires careful risk-benefit assessment; data in breastfeeding are insufficient.
Related Topics
- Sildenafil — Shorter-acting PDE-5 inhibitor, first of its class
- Vardenafil — PDE-5 inhibitor with rapid onset
- All active ingredients overview
Frequently Asked Questions
Why is tadalafil called the weekend pill?
Tadalafil's duration of action of up to 36 hours means that a single dose taken on Friday evening can still be effective on Sunday morning — hence the colloquial term. This extended window allows greater spontaneity compared with shorter-acting alternatives.
Can tadalafil be taken daily?
Yes. Tadalafil 2.5 mg or 5 mg once daily is an approved treatment strategy for both erectile dysfunction and BPH. Daily low-dose therapy maintains stable plasma levels and eliminates the need to time intercourse around medication intake.
Does tadalafil affect vision like sildenafil?
Visual disturbances such as colour tinge are less common with tadalafil because it has higher selectivity for PDE-5 over PDE-6 in the retina. However, the risk of NAION (non-arteritic anterior ischaemic optic neuropathy) is a class effect shared by all PDE-5 inhibitors and requires vigilance.