Response to treatment with tadalafil in men with erectile dysfunction who reported no successful intercourse attempts at baseline

Introduction Highly selective inhibitors of phosphodiesterase type 5 (PDE5I) have been commercially available for over a decade. Our knowledge of these drugs continues to expand. Aims To review recent (since 2007) developments on the utilization of PDE5I in clinical practice. The focus of this manuscript is on the use of PDE5I for sexual concerns. Also reviewed are recent reports of rare but potentially serious toxicity. Methods Pubmed search utilizing the search terms “phosphodiesterase type 5 inhibitor,”“PDE5 inhibitor,”“sildenafil,”“vardenafil,” and “tadalafil.” Articles were screened for their relevance to the clinical practice of sexual medicine and/or PDE5I toxicity. Publications on routine dose PDE5I for penile rehabilitation, lower urinary tract symptoms, and stuttering priapism are summarized in a separate manuscript in this series. Main Outcome Measures Peer-reviewed publications since the last major update on PDE5I published in the medical literature. Results Recent investigations have suggested a number of interventions to potentially improve patient compliance with PDE5I therapy. Additionally, the approval in the past year of tadalafil as a daily medication signifies a potential paradigm shift in our concept of this disorder. Daily dosing may be useful in some men; however, the other available PDE5I continue to show excellent efficacy in the management of erectile dysfunction (ED). In addition to direct effects on ED, several recent reports highlight the use of PDE5I for improvement of premature ejaculation, sexual relationship status, and sexual function in women. There have also been several recent reports of rare but serious toxicity, particularly ototoxicity, associated with PDE5I use. Conclusions Recent studies have suggested new ways to optimize utilization of PDE5I not only for the management of ED but also for other sexual concerns in both men and women. Rare but serious toxicities have been reported with PDE5I and, therefore, judicious counseling is indicated before prescribing these medications.

Section: Methodsmentioning

confidence: 99%

Continuing Medical Education: 2009 Update on Phosphodiesterase Type 5 Inhibitor Therapy Part 2: Updates on Optimal Utilization for Sexual Concerns and Rare Toxicities in This Class (CME)

Shindel

2009

“…The reasons that these subjects with normal erectile function had no successful attempts have not been characterized but are likely multifactorial. However, this phenomenon has been reported previously [38]. This finding might also point to the potential for recall bias in the completion of the IIEF questionnaires and SEP diaries.…”

Section: Discussionmentioning

confidence: 51%

Efficacy and Safety of Once-Daily Tadalafil in Men with Erectile Dysfunction Who Reported No Successful Intercourse Attempts at Baseline

Shabsigh¹,

Seftel²,

Kim³

et al. 2013

Introduction Tadalafil is efficacious and well tolerated for erectile dysfunction (ED), but effects in men with “complete ED” are unclear. Aim To investigate effects of once-daily tadalafil in men with no successful intercourse attempts at baseline. Methods Through a post hoc, pooled-data analysis of four randomized, double-blind trials on the effects of tadalafil 2.5 or 5 mg (vs. placebo) in men with ED, we evaluated efficacy and safety in subjects with 0 “yes” responses to Sexual Encounter Profile question 3 (SEP3) during an initial 4-week treatment-free run-in period. Main Outcome Measures Changes from baseline in the SEP diary and the International Index of Erectile Function-erectile function (IIEF-EF) domain were subjected to analysis of covariance models. Results Five hundred ninety-five subjects with no successful attempts at baseline were included in the analysis. The mean (±standard deviation) age was 58.2 ± 10.7 years; and most subjects had ED for ≥1 year (95.0%). ED was severe in 61.5% and moderate in 26.4%. Approximately 45% had diabetes mellitus or hypertension. After 12 weeks, the mean per-patient SEP3 percentage increased from 0% to 32.4% with tadalafil 2.5 mg and to 46.4% with tadalafil 5 mg (each P < 0.001 vs. placebo). Corresponding data for successful penetration (SEP2) were increases from 21.1% to 48.2% with tadalafil 2.5 mg and from 24.4% to 66.2% with 5 mg (each P < 0.001 vs. placebo). Mean IIEF-EF increased from 9.7 to 15.7 with tadalafil 2.5 mg and from 10.7 to 19.2 with 5 mg (each P < 0.001 vs. placebo). Tadalafil also significantly improved the intercourse-satisfaction and overall-satisfaction domains (vs. placebo). Both doses of tadalafil were generally well tolerated, with adverse event rates similar to placebo. Conclusions The posttreatment intercourse success rate was 32% and 46% for tadalafil 2.5 mg and 5 mg, respectively, in men with no successful intercourse attempts at baseline.

Pharmacotherapy for Erectile Dysfunction: Recommendations From the Fourth International Consultation for Sexual Medicine (ICSM 2015)

Hatzimouratidis

Salonia

Adaikan

et al. 2016

184

199

Introduction Treatment of erectile dysfunction is based on pharmacotherapy for most patients. Aim To review the current data on pharmacotherapy for erectile dysfunction based on efficacy, psychosocial outcomes, and safety outcomes. Methods A review of the literature was undertaken by the committee members. All related articles were critically analyzed and discussed. Main Outcome Measures Levels of evidence (LEs) and grades of recommendations (GRs) are provided based on a thorough analysis of the literature and committee consensus. Results Ten recommendations are provided. (i) Phosphodiesterase type 5 (PDE5) inhibitors are effective, safe, and well-tolerated therapies for the treatment of men with erectile dysfunction (LE = 1, GR = A). (ii) There are no significant differences in efficacy, safety, and tolerability among PDE5 inhibitors (LE = 1, GR = A). (iii) PDE5 inhibitors are first-line therapy for most men with erectile dysfunction who do not have a specific contraindication to their use (LE = 3, GR = C). (iv) Intracavernosal injection therapy with alprostadil is an effective and well-tolerated treatment for men with erectile dysfunction (LE = 1, GR = A). (v) Intracavernosal injection therapy with alprostadil should be offered to patients as second-line therapy for erectile dysfunction (LE = 3, GR = C). (vi) Intraurethral and topical alprostadil are effective and well-tolerated treatments for men with erectile dysfunction (LE = 1, GR = A). (vii) Intraurethral and topical alprostadil should be considered second-line therapy for erectile dysfunction if available (LE = 3, GR = C). (viii) Dose titration of PDE5 inhibitors to the maximum tolerated dose is strongly recommended because it increases efficacy and satisfaction from treatment (LE = 2, GR = A). (ix) Treatment selection and follow-up should address the psychosocial profile and the needs and expectations of a patient for his sexual life. Shared decision making with the patient (and his partner) is strongly recommended (LE = 2, GR = A). (x) Counterfeit medicines are potentially dangerous. It is strongly recommended that physicians educate their patients to avoid taking any medication from unauthorized sources (LE = 2, GR = A). The first seven recommendations are the same as those from the Third International Consultation for Sexual Medicine and the last three are new recommendations. Conclusion PDE5 inhibitors remain a first-line treatment option because of their excellent efficacy and safety profile. This class of drugs is continually developed with new molecules and new formulations. Intracavernosal injections continue to be an established treatment modality, and intraurethral and topical alprostadil provide an alternative, less invasive treatment option.