It has been calculated that 150 million men in the world are unable to achieve and/or maintain an erection adequate for satisfactory sexual performance. The clinical management of these men was transformed in the late 1990s with the introduction of sildenafil (Viagra, Pfizer Inc.), the first oral therapy licensed for treating erectile dysfunction (ED). Sildenafil is a selective phosphodiesterase type-5 (PDE5) inhibitor and has shown good efficacy across a broad spectrum of causes of ED. In February 2003, tadalafil (Cialis, Eli Lilly, USA) was introduced, the first highly selective PDE5 inhibitor to be licensed for the treatment of ED since sildenafil.
The integrated analyses of findings from five randomized, double-blind placebo-controlled trials involving men with ED of varying severity and causes were recently published. Tadalafil therapy at 10 and 20 mg significantly improved erectile function, as assessed by all co-primary efficacy variables. The mean International Index of Erectile Function (IIEF), erectile function domain score, increased marginally on placebo (0.6) compared with changes of 6.5 and 7.9 (both P < 0.001) in the tadalafil 10 and 20 mg treatment groups, respectively. This improvement resulted in 59% of men on tadalafil 20 mg achieving normal erectile function according to IIEF scores at endpoint compared with 11% of controls (P < 0.001).
SAFETY TESTS
Like sildenafil, tadalafil potentiates the hypotensive effects of nitric-oxide donors, and thus co-administration is contraindicated. Further, men with cardiovascular disease sufficient to make sexual intercourse unwise were excluded from the clinical trials, and again tadalafil use in this population is contraindicated. However, as with sildenafil, the incidence of myocardial infarction and cardiac death in the tadalafil clinical trials has so far been low and similar to that seen in patients treated with placebo.
In the integrated analyses of the five phase III studies, all doses of tadalafil were well tolerated. The most frequently reported adverse events were a headache and dyspepsia; other adverse events include back pain, nasal congestion, myalgia and flushing. These events were mostly transient, mild or moderate and decreased in frequency with continued treatment. As with sildenafil, the rate of discontinuation caused by adverse events in the tadalafil group was low, at 2.2% compared with 1.3% in controls. Unlike sildenafil, tadalafil had no clinically significant effect on vision.
CONCLUSIONS
Tadalafil is a novel and highly selective PDE5 inhibitor. It has shown good efficacy in a broad population of men with ED and appears to be safe and well tolerated. It has a relatively rapid onset of action and, more interestingly, has a prolonged duration of action of up to 24 hours. Also, as per the tadalafil reviews too, it is a very safe PDE5 inhibitor and liked by many across the world.
