Tadalafil

Tadalafil is a phosphodiesterase type 5 (PDE5) inhibitor used to treat erectile dysfunction (ED), benign prostatic hyperplasia (BPH), and pulmonary arterial hypertension (PAH). It is the active ingredient in Cialis, one of the best-known branded ED treatments, and is now widely available as a generic medicine. Tadalafil has earned a reputation for its exceptionally long duration of action - up to 36 hours - which distinguishes it from other PDE5 inhibitors such as sildenafil and vardenafil.

Mechanism of Action

During sexual arousal, nitric oxide is released in the corpus cavernosum of the penis, which activates guanylate cyclase and increases levels of cyclic guanosine monophosphate (cGMP). This causes the smooth muscle in penile blood vessels to relax, allowing blood to flow into the corpora cavernosa and produce an erection. PDE5 is the enzyme responsible for breaking down cGMP, thereby ending the erection. Tadalafil inhibits PDE5, prolonging the presence of cGMP and facilitating erection in response to sexual stimulation. Critically, tadalafil requires sexual arousal to work - it does not cause an erection spontaneously.

Indications and Formulations

For erectile dysfunction, tadalafil is available as 10 mg and 20 mg tablets for on-demand use, and as 2.5 mg and 5 mg tablets for daily use. The daily regimen is particularly beneficial for men who want spontaneity without planning intercourse around a dose schedule. For BPH - where tadalafil relaxes the smooth muscle of the prostate and bladder neck to improve urinary flow - 5 mg once daily is the standard dose. In PAH, tadalafil 40 mg once daily is used to reduce pulmonary vascular resistance and improve exercise capacity.

Duration of Effect

The 36-hour window of effectiveness has led tadalafil to be nicknamed the "weekend pill." Unlike sildenafil, which is usually effective for four to six hours, tadalafil allows greater flexibility in timing sexual activity relative to the dose. Food and alcohol (in moderate amounts) have minimal effect on tadalafil's absorption, making it more convenient than sildenafil for many users.

Tadalafil for erectile dysfunction can be taken either on demand or as a daily low-dose regimen, depending on the individual's preference and frequency of sexual activity.

On-Demand Use

For on-demand use, the recommended starting dose is 10 mg taken at least 30 minutes before anticipated sexual activity. Given its long duration of action, tadalafil does not need to be taken immediately before sex - it can be taken several hours in advance. If 10 mg is not sufficiently effective, the dose may be increased to 20 mg with a doctor's advice. The maximum frequency of on-demand dosing is once per 24 hours. A single dose remains effective for up to 36 hours, which means one tablet can cover an entire weekend.

Daily Low-Dose Use

The daily regimen (2.5 mg or 5 mg once daily) provides a steady state blood level that allows erections in response to sexual stimulation at any time. This approach is recommended for men who have intercourse more than twice per week, those who prefer spontaneity, and men also using tadalafil for BPH symptoms. The tablet should be taken at approximately the same time each day, with or without food. Allow 1 to 2 weeks at the daily dose before fully assessing efficacy.

Erectile dysfunction - on-demand:

• Starting dose: 10 mg at least 30 minutes before sexual activity
• Increased dose if needed: 20 mg
• Maximum: once per 24 hours

Erectile dysfunction - daily:

• 2.5 mg once daily; may increase to 5 mg if needed
• Take at the same time each day

BPH (benign prostatic hyperplasia):

• 5 mg once daily

Pulmonary arterial hypertension:

• 40 mg once daily (specialist-initiated)

Renal/hepatic impairment: Dose reduction required; avoid in severe hepatic impairment. Not recommended in severe renal impairment (creatinine clearance under 30 mL/min) for daily dosing.

Common Side Effects

• Headache (most common, affects up to 1 in 10 users)
• Flushing or facial redness
• Dyspepsia (indigestion or heartburn)
• Back pain and muscle aches (more common with tadalafil than other PDE5 inhibitors, typically 12-24 hours after dosing)
• Nasal congestion or runny nose
• Dizziness
• Limb pain

Serious Side Effects

• Sudden vision loss (non-arteritic anterior ischaemic optic neuropathy, NAION) - rare but reported; seek immediate medical attention
• Sudden hearing loss or tinnitus - stop use and seek urgent care
• Priapism (prolonged painful erection lasting over 4 hours) - requires emergency treatment to prevent permanent damage
• Severe hypotension, especially with nitrates or alpha-blockers
• Hypersensitivity reactions including Stevens-Johnson syndrome (very rare)

Tadalafil is absolutely contraindicated with nitrate medicines, including GTN spray, isosorbide mononitrate, and isosorbide dinitrate, as well as recreational nitrite drugs ("poppers"). The combination can cause a catastrophic, potentially fatal drop in blood pressure. Do not take tadalafil if you use nitrates in any form.

Cardiovascular Considerations

Sexual activity itself places demands on the cardiovascular system. Tadalafil should be used with caution in men with active cardiovascular disease, left ventricular outflow obstruction, autonomic dysfunction, or those for whom sexual activity is inadvisable. A cardiovascular assessment may be appropriate before prescribing. Tadalafil causes a modest reduction in blood pressure; when combined with antihypertensives or alpha-blockers, this effect is additive and can cause symptomatic hypotension.

Vision, Hearing, and Priapism

Any sudden loss of vision in one or both eyes, or sudden hearing loss, should prompt immediate cessation of tadalafil and urgent medical review. Priapism - an erection lasting more than four hours - is a urological emergency requiring prompt treatment to preserve erectile function. Patients should be counselled to seek emergency care immediately if this occurs. Men with anatomical penile deformation (Peyronie's disease) or predisposing conditions for priapism (sickle cell anaemia, multiple myeloma, leukaemia) should use tadalafil with particular caution.

• Concurrent use of nitrate medicines in any form or nitrite recreational drugs ("poppers")
• Known hypersensitivity to tadalafil or any excipient
• Severe hepatic impairment (Child-Pugh Class C)
• Recent myocardial infarction (within 90 days) or stroke (within 6 months)
• Unstable angina or angina occurring during sexual intercourse
• Uncontrolled hypertension (systolic >170 mmHg or diastolic >100 mmHg)
• Severe hypotension (systolic <90 mmHg)
• Loss of vision in one eye due to NAION - risk of second eye involvement
• Concurrent use with riociguat (guanylate cyclase stimulator used in pulmonary hypertension)