Tadalafil

Tadalafil received FDA approval in 2003 for erectile dysfunction. It is the only PDE5 inhibitor approved at a low daily dose (2.5 mg or 5 mg) for ED, and is also approved for benign prostatic hyperplasia at 5 mg daily, including a combined ED+BPH indication.

The molecule selectively inhibits phosphodiesterase type 5, the enzyme that degrades cyclic guanosine monophosphate (cGMP) in penile vascular smooth muscle. By blocking cGMP breakdown, tadalafil enhances the natural vasodilatory response to sexual stimulation.

The defining pharmacokinetic property is the long half-life of approximately 17.5 hours. This produces a clinical window of 24-36 hours after a single dose, distinguishing tadalafil from sildenafil (4-6 hour clinical window). Tadalafil is also unaffected by food intake, unlike sildenafil.

Common side effects include headache, flushing, nasal congestion, dyspepsia, and back pain or muscle aches. Back pain is more commonly reported with tadalafil than with sildenafil. Serious but rare risks include priapism, sudden hearing loss, and non-arteritic anterior ischemic optic neuropathy.

The most important contraindication is concurrent nitrate therapy, which produces dangerous hypotension. Alpha blocker dose-staggering is generally required.

Daily low-dose tadalafil produces a steady-state plasma concentration after 5-7 days and provides continuous PDE5 inhibition without peaks and troughs, which many patients find beneficial for spontaneity.