Those with left ventricular out ow obstruction (aortic and subaortic stenosis), recent (<6 months) myocardial infarction, and stroke or life threatening arrhythmias, as well as hypotensive (RR < 90/50) and hypertensive (RR > 170/110) patients, can be particularly sensitive to the systemic actions of PDE5 inhibitors In conditions/drugs with a known risk of priapism, such as sickle cell disease, leukemia and multiple myeloma, PDE-5 inhibitors must be used with special precautions

interactions with nitrates in the sense of symptomatic blood pressure decays if given simultaneously [56 58,68 69] Therefore all three PDE-5 inhibitors are contraindicated for patients with nitrate medications The time interval considered to be safe between the administration of a PDE-5 inhibitor and a nitrate medication is 24 hours for the short-acting sildena l and vardena l, and 48 hours for tadala l [56 58,68]

The ef cacy of the three PDE-5 inhibitors was investigated world wide in large-scale trials, both in mixed ED populations as well as in subpopulations, like patients with diabetes, and after nerve-sparing radical prostatectomy (Table 74) To interpret Table 74 correctly it has to be mentioned that SEP 2 and SEP 3 diary data were available in all the tadala l and vardena l trials, whereas in the early sildena l trials SEP 2 and 3 were not available, the tool successful intercourse was used instead All three PDE-5 inhibitors were remarkably successful in a variety of ED subpopulations including patients with diabetes, patients with neurologic disorders such as spinal cord injuries and multiple sclerosis, patients after radical prostatectomy provided they have undergone a nerve sparing procedure, patients with hypertension or coronary artery disease, as well as patients with renal insuf ciency or after kidney transplant

Sildena l 25 mg simultaneously applied with doxazosin 4 mg resulted in symptomatic postural hypotension, which was also the case with tadala l 20 mg [56,57] After tamsulosin 04 mg, both tadala l 20 mg and vardena l 5 mg did not exert any clinically relevant in uence on blood pressure, whereas vardena l 5 mg, if simultaneously applied with terazosin 10 mg, resulted in symptomatic hypotension, which could not be observed if both drugs were taken six hours apart [57, 58] Tadala l 20 mg applied with alfuzosin 10 mg did not result in clinically signi cant hemodynamic interaction [66]

Table 74 Ef cacy of the three PDE-5 inhibitors in various ED populations Sildena l/Placebo (50/100 mg) ED Population Mixed GAQ(%) SEP/2/3(%) GAQ(%) 81/35 Tadala l/Placebo (10/20 mg) SEP 2(%) Not rep (n = 1112) [70] SEP 3(%) 75/32 GAQ(%) 80/30 85/28 Vardena l/Placebo (10/20 mg) SEP 2(%) Not rep (n = 601) [71] 81/52 (n = 804) [72] 64/36 (n = 452) [75] 48/22 (n = 427) [77] SEP 3(%) 75/39 67/33

82/24 66/20 (n = 1600 1787) [56]

64/25

57/30 (n = 216) [74] 54/32 (n = 303) [76]

48/20

72/13

54/23

62/23

41/19

65/13

37/10

7

Having said that, it has to be stated that all three PDE-5 inhibitors yielded very similar success rates, with only minor differences in the ef cacy endpoints (Table 74)

served in a small portion of patients after tadala l In the overwhelming majority, these drug-related adverse events were mild to moderate and resulted in only 1 2% of early drop-outs in the clinical trials

Long-term studies (two years) were able to prove that, in general there is no loss of ef cacy among the three PDE-5 inhibitors In recent experimental research studies no upregulation of PDE-5 in the penis was observed with the long-acting PDE-5 inhibitor tadala l [78 81] Apart from improvement in ED, improvements in other sexual domains such as orgasmic function, overall satisfaction with the sexual experience, and the quality of life [82] along with improvement of depressive symptoms [83], and increases in partner satisfaction with the sexual life [84,85], were regularly reported with the use of PDE-5 inhibitors