Erectile Function, Erection Hardness and Tolerability in Men Treated With Sildenafil 100 mg vs. 50 mg for Erectile Dysfunction

M. Kirby; D. L. Creanga; V. J. Stecher

Disclosures

Int J Clin Pract. 2013;67(10):1034-1039. 

In This Article

Discussion

These analyses confirm that men with ED treated with sildenafil 100 mg, compared with those treated with sildenafil 50 mg, may be more likely to achieve a greater improvement in erectile function with little or no greater risk to overall tolerability and, during the first 2 weeks of treatment, completely hard and fully rigid (EHS4) erections. In this analysis, erection hardness outcomes focus on EHS4, which has previously been associated with prolonged erection maintenance [7] and with significant improvements in erectile function and emotional response [scores on the Self-Esteem And Relationship (SEAR) questionnaire] compared with EHS3.[8] Indeed, statistical modelling showed a strong and approximately linear relationship between EHS and scores on several ED-specific patient-reported outcomes, including the IIEF, SEAR, Sexual Experience Questionnaire (SEX-Q) and Quality of Erection Questionnaire.[9]

The current results confirm previously published reports, which also showed superior clinical benefits in men treated with sildenafil 100 mg compared with 50 mg for ED. Previously reported results from one of the DBPC studies of fixed-dose sildenafil that were analysed in this report (A1481239) showed that EHS4 erections were achieved by 25.3% of men in the 50-mg group (95% CI, 18.5–33.4%; n = 94) and 34.6% in the 100-mg group (95% CI, 27.1–42.9%; n = 99).[10] Patient responses to a general efficacy question (… has the medication you have been taking over the past 4 weeks allowed you to have better sex?') indicated better sex in the 100-mg group compared with the 50-mg group (p = 0.0103).[10] In another controlled clinical study, conducted in two 4-week periods, men with ED received 50-mg doses of sildenafil single-blinded for period 1 (completed by 97% of 492 enrolled men), and the completers were randomised to DBPC treatment with sildenafil 50 mg (n = 240) or 100 mg (n = 237) for period 2 (completed by 96% of men).[11] Those who titrated to 100 mg showed improvement in erectile function compared with those who remained at 50 mg (p < 0.001). Also, affirmative patient responses to a general efficacy question ('…has the medication you have been taking over the past 4 weeks improved your ability to have sexual intercourse?') indicated improved ability relative to prerandomisation values (after period 1) in the group titrated to 100 mg (91% of patients) compared with the group that remained fixed at 50 mg [83% of patients; OR = 1.96 (95% CI, 1.12–3.41); p = 0.018]. Furthermore, in the 100-mg group compared with the 50-mg group, the odds were significantly greater that sexual intercourse would be attempted [OR = 1.29 (95% CI, 1.02–1.63); p = 0.035], an erection would be maintained long enough to have successful intercourse [OR = 1.29 (95% CI, 1.00–1.67); p = 0.046], and orgasm would be achieved [OR = 1.30 (95% CI, 1.03–1.64); p = 0.025]. In a post hoc comparison of the results of two DBPC studies of similar design, except for a fixed-dose regimen (including an initial and fixed dose of sildenafil 100 mg) vs. a flexible-dose regimen, improvements in erectile function and hardness were similar. This is not surprising, given that almost 90% of the men in the flexible-dose study titrated to 100 mg after 2 weeks. However, relative to the flexible-dose regimen, approximately one-third more men were satisfied with an initial and fixed dose of 100 mg, with which improvements in emotional response (scores on the SEAR questionnaire) and in the overall sexual experience (scores on the SEX-Q) were also superior.[2] There was no evidence of a dose-related increase in adverse events with the higher dose in any of these earlier published results.

The current analysis showed that men with ED treated with sildenafil 100 mg may be more likely to achieve EHS4 erections than those treated with 50 mg, and that the superiority in erection hardness occurred as early as during the first 2 weeks of treatment. This rapid improvement to EHS4 erections is supported by the results of a recent post hoc analysis of two previously published, DBPC studies of flexible-dose sildenafil, in which an increase in the ability to achieve EHS4 erections occurred as rapidly as the initial attempt at sexual intercourse after increasing from a dose of 50 mg to a dose of 100 mg.[12]

The current analysis also determined that the tolerability profiles of sildenafil 100 mg and 50 mg are generally similar. This confirms a previously published report that established the tolerability and safety of sildenafil 50 and 100 mg in men with ED using collated data from 67 DBPC studies conducted by the manufacturer and using data from the manufacturer's postmarketing safety database.[3]

In the current analyses, there was little or no apparent difference in the incidence of adverse events among those receiving 100 mg as a fixed dose compared with those receiving 50 mg as a fixed dose, other than a slightly higher incidence of ocular events, headache and dyspepsia and a slightly lower incidence of flushing. Transient altered colour vision (chromatopsia and cyanopsia) is a known dose-related effect believed to be attributable to PDE6 inhibition in the retina,[4] and headache, flushing and nasal congestion are common adverse events related to the pharmacology of PDE5 inhibition. Previously reported data collated from 17 randomised, DBPC, flexible-dose studies showed that the rate of these common adverse events decreased markedly over a 16-week treatment period, such that by 8 weeks of treatment, the rate was similar between sildenafil- and placebo-treated patients.[13] Treatment-related adverse events with PDE5 inhibitors such as sildenafil, vardenafil and tadalafil are generally mild-to-moderate, showing minor differences across the PDE5 inhibitor class.[14,15] Headache, facial flushing, nasal congestion, dyspepsia, and back pain (tadalafil) are the most common adverse events.[14,16–18]

With little or no greater tolerability risk, an initial dose of sildenafil 100 mg may be advantageous compared with an initial dose of sildenafil 50 mg, except in men for whom it is inappropriate. The greater likelihood of achieving completely hard and fully rigid erections during the first 2 weeks of treatment with an initial dose of 100 mg would reduce the need for titration and could prevent discouragement and treatment abandonment. Superior improvement in erectile function with an initial dose of 100 mg would increase the likelihood of achieving optimal efficacy.

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