Table 19

Intra-urethral Treatment: Patients with Adverse Events.

Alprostadil versus placebo. Three trials compared the efficacy and harms of IU alprostadil to placebo. ^302–304

Harms. In the first trial, compared with men in placebo group, alprostadil-treated men had an increased frequency of penile pain (3.3 percent versus 32.8 percent) and minor urethral trauma (1.0 percent versus 5.2 percent).³⁰⁴ Urinary tract infection occurred in fewer than 1 percent of participants in both groups. No cases of prolonged erection, priapism or fibrosis were observed in either treatment group.

In the second trial, men randomized to IU alprostadil reported an increased frequency of urogenital burning (6.4 percent versus 0 percent), but statistically nonsignificant increase in risk of penile pain (5.1 percent versus 1.2 percent), dizziness (2.6 percent versus 0 percent), prolonged erection (1.3 percent versus 0 percent), and testicular pain (2.6 percent versus 0 percent).³⁰²

Minor urethral trauma was reported by 1.3 and 1.2 percent of men allocated to IU alprostadil and placebo, respectively.

There were no cases of priapism or fibrosis, or urinary tract infection in either treatment group.

In the third trial, penile pain was reported by 1.7, 23.6, 20.5, 20.9 and 17.0 percent of men allocated to placebo, 1000μ g, 500μ g, 250μ g, and 125μ g IU alprostadil, respectively, ³⁰³ The corresponding proportions for reporting testicular pain were: 0.4, 1.8, 4.4, 4.4, and 2.0 percent.

Urethral pain was reported by 1.7, 9.1, 8.0, 5.1, and 1.0 percent of the men allocated to placebo, 1000μ g, 500μ g, 250μ g, and 125μ g IU alprostadil, respectively.

Efficacy. Men randomized to IU alprostadil reported that 50.4 percent of their sexual intercourse attempts during the 3 month treatment period were successful versus 10.1 percent for men allocated to placebo. Sixty-two percent of men allocated to IU alprostadil reported at least one successful sexual intercourse attempt during the study period versus 18.2 percent of men allocated to placebo.

In the second trial, men randomized to IU alprostadil reported that 51.1 percent of their sexual intercourse attempts during the 3 month treatment period were successful versus 7.5 percent for men allocated to placebo. In the third trial, ³⁰³ 31 percent of men reported erections sufficient for intercourse (grade 4 or 5) with 500μ g IU alprostadil versus 14.1 percent of the men treated with 125μ g IU alprostadil. Results were not provided for 250μ g and 1000μ g alprostadil doses.

Alprostadil (250μ g) versus alprostadil (starting dose: 500μ g). One trial ²⁹⁹ compared the efficacy and harms of initiating IU alprostadil treatment at doses of 250μ g and 500μ g.

Harms. In the 4 weeks prior to IU alprostadil dose titration, 14.5 percent of men allocated to an initial dose of 250μ g reported penile pain versus 27.7 percent of those allocated to an initial dose of 500μ g (p < 0.05). During this period, there was no difference between treatment groups for urethral pain (250μ g: 1.2 percent versus 500μ g: 2.4 percent) or hypotension/dizziness (250μ g: 2.4 percent versus 500μ g: 3.6 percent).

Efficacy. Seventy-seven percent of men allocated to an initial dose of 250μ g versus 69 percent of those allocated to an initial dose of 500μ g elected to increase their dose at 4 weeks. Pooled clinical efficacy results were presented for treatment groups, namely the proportion of men during the study period with at least one successful sexual intercourse attempt (68.1 percent) and the proportion with erections sufficient for intercourse (grade 4 or 5) (73.5 percent).²⁹⁹

Alprostadil (IU) versus alprostadil (IC). Two trials compared the efficacy and harms of IU alprostadil versus IC alprostadil.^{300, 301}

Harms. In the first trial, men allocated to IU alprostadil were less likely to report urogenital pain than those allocated to IC alprostadil (6.7 percent versus 46.7 percent) with statistically nonsignificant differences between the treatment groups for urethral bleeding (3.3 percent versus 0 percent) or dizziness (6.7 percent versus 0 percent). ³⁰¹ In the second trial, there was no statistically significant difference between the two treatment groups with regard to penile pain (25.0 percent versus 33.8 percent), prolonged erections (0 versus 2.9 percent), or local bleeding (2.9 versus 1.5 percent). ³⁰⁰

Efficacy. In one trial, men randomized to IU alprostadil reported 55.0 percent successful intercourse attempts versus 85.1 percent for those allocated to IC alprostadil.³⁰¹ Furthermore, 53.3 percent of men allocated to IU alprostadil reported at least one successful sexual intercourse attempt during the study period versus 86.7 percent of men allocated to IC alprostadil. In the second 3-week trial, 61.8 percent of men randomized to IU alprostadil reported at least one erection sufficient for intercourse during at home use versus 92.6 percent of those allocated to IC alprostadil.³⁰⁰

Alprostadil (IU) versus prazosin (IU). One trial compared the efficacy and harms of IU alprostadil versus IU prazosin.³⁰³

Harms. Penile pain was reported by 23.6, 20.5, 20.9 and 17.0 percent of men allocated to 1000μ g, 500μ g, 250μ g, and 125μ g IUalprostadil, respectively versus 5.5, 0.7, 1.4 and 1.1 percent of men allocated to 2000μ g, 1000μ g, 500μ g, and 250μ g IU prazosin, respectively. ³⁰³ Urethral pain was reported by 9.1, 8.0, 5.1, and 1.0 percent of men allocated to 1000μ g, 500μ g, 250μ g, and 125μ g IU alprostadil, respectively versus 0, 2.0, 2.0, and 2.1 percent of men allocated to 2000μ g, 1000μ g, 500μ g, and 250μ g IU prazosin, respectively.

Efficacy. In this trial, each of 234 participants received single administrations of two of four potential alprostadil doses (125, 250, 500 and 1000μ g) and two of four potential prazosin doses (250, 500, 1000 and 2000μ g). Thirty-one percent of men with 500μ g IU alprostadil reported erections sufficient for intercourse (grade 4 or 5) versus 14.1 percent with 125μ g IU alprostadil versus 3 percent of men with 2000μ g prazosin. Results were not provided for the 250μ g and 1000 μ g alprostadil doses or for the 250μ g, 500μ g, and 1000μ g prazosin doses.

Prazosin (IU) versus placebo. One trial compared the efficacy and harms of prazosin versus placebo.³⁰³

Harms. Penile pain was reported by 5.5, 0.7, 1.4 and 1.1 percent of men allocated to 2000, 1000, 500, and 250μ g IU prazosin, respectively, versus 1.7 percent of those allocated to placebo. Urethral pain was reported by 0, 2.0, 2.0, and 2.1 percent of men allocated to 2000, 1000, 500, and 250μ g IU prazosin, respectively, versus 1.7 percent of those allocated to placebo.

Efficacy. In this trial, 3 percent of men assigned to 2000μ g IU prazosin reported erections sufficient for intercourse versus 0.4 percent of those assigned to treatment with placebo. Results were not provided for the 250, 500, and 1000μ g prazosin doses, though it was stated that 2000μ g was the most efficacious prazosin dose.

Alprostadil (IU) plus IU prazosin versus IU alprostadil versus IU prazosin versus placebo. One trial compared the efficacy and harms of IU alprostadil plus IU prazosin versus IU alprostadil versus IU prazosin versus placebo.³⁰³ All combinations of IU alprostadil plus IU prazosin appeared to improve erections more than IU prazosin or placebo.

Harms. The proportions of patients with penile pain among those allocated to various alprostadil/prazosin combinations were: 23.9(125μ g/250μ g), 23.4 (125μ g/500μ g), 23.4 (250μ g/250μ g), 17.0 (250μ g /500μ g), 27.3 (250μ g /1000μ g), 23.2 (500μ g /500μ g), 23.1 (500μ g/1000μ g), 31.6 (500μ g /2000μ g), and 26.9 percent (1000μ g /1000μ g). The proportions of patients with penile pain who were allocated to various doses of IU alprostadil were: 23.6 (1000μ g), 20.5 (500μ g), 20.9 (250μ g), and 17.0 percent (125μ g). The corresponding proportions for various doses of IU prazosin were: 5.5 (2000μ g), 0.7 (1000μ g), 1.4 (500μ g) and 1.1 percent (250μ g). Of the placebo-treated patients, 1.7 percent experienced penile pain.

The corresponding proportions of patients with urethral pain with respect to various alprostadil/prazosin combinations were: 6.5, 10.6, 8.5, 8.5, 11.4, 7.1, 1.9, 5.3, and 13.5 percent respectively. The corresponding proportions of men with urethral pain for various doses of IU alprostadil were: 9.1, 8.0, 5.1, and 1.0 percent, respectively. The proportions for various doses of IU prazosin were: 0, 2.0, 2.0, and 2.1 percent respectively. Urethral pain was experienced by 1.7 percent of the placebo-treated patients.

Efficacy. Erections sufficient for intercourse were reported by 30.4 percent of men assigned to 125/500μ g alprostadil/prazosinversus 31.9 percent with 250/500μ g alprostadil/prazosin, 35.7 percent with 500/2000μ g alprostadil/prazosin, 31.1 percent with 500μ g alprostadil, 14.1 percent with 125μ g alprostadil, 3 percent with 2000μ g prazosin, and 0.4 percent with placebo. Results were not provided for the other six alprostadil/prazosin combinations tested, for the 250 and 1000μ g alprostadil doses, or for the 250, 500, and 1000μ g prazosin doses. However, it was stated that 500/2000μ g was the most efficacious alprostadil/prazosin dose, 500μ g was most efficacious alprostadil dose, and 2000μ g was the most efficacious prazosin dose.