In all studies published to date, tadalafil has been generally well tolerated, with side effects comparable to those seen with other PDE5 inhibitors. The most common side effects have been dyspepsia and headache. Table 2 shows the rate of side effects reported in the integrated analysis of 1112 men. The side effects tended to occur shortly after initial doses of tadalafil and generally became less frequent and less severe with repeated dosing. The duration of side effects was similar between tadalafil and placebo. No life-threatening or cumulative side effects were seen, and most side effects became less noticeable with ongoing use of tadalafil. Figure 7 illustrates this attenuation of side effects with continued use.
The rates of adverse events in the Spanish study of diabetic men were comparable, with dyspepsia in 11% of men taking tadalafil, headache in 9%, back pain in 3.4%, myalgia in 4.8% and flushing in 3.4%. Of these, only dyspepsia was reported at a rate statistically significantly different from that seen with placebo (P=0.005).
A review of placebo-controlled phase 3 studies found that tadalafil was not associated with an increase in cardiovascular adverse events or an increase in the incidence of potentially clinically significant changes in blood pressure in patients taking antihypertensive agents when compared with those patients not taking antihypertensive agents.
Clinical trial evidence currently available on tadalafil has shown it to be an effective and well-tolerated agent for the oral treatment of ED. Instructions that tadalafil may be taken without regard to food make the therapy simple to administer. Tadalafil’s extended period of responsiveness, with studies demonstrating improved erectile function out to 36 h, may offer clinical benefits to patients. Tadalafil should provide an important new therapeutic option for physicians treating ED and for their patients.
TABLE 2 Summary of most commonly reported adverse events and discontinuations from treatment
|Safety variable||Placebo||All tadalafil||2.5||Tadalafil (mg)5 10||20|
|Overall, n (%)|
|Subjects with at least one treatment-||159||479||38||68||185||188|
|emergent adverse event|
|Discontinuations from adverse events||4 (1.3)||17 (2.1)||3 (4.1)||1 (0.7)||5 (1.6)||8 (3.1)|
|Most common treatment-emergent adverse events,||n (%)|
|Rhinitis (nasal congestion)||12||40||4||6||18||12|