733

OPTIMAL DOSING OF SILDENAFIL CITRATE FOR THE TREATMENT OF ERECTILE DYSFUNCTION: POOLED ANALYSIS OF FLEXIBLE-DOSE, PLACEBO-CONTROLLED, DOUBLE-BLIND STUDIES AND OPEN-LABEL EXTENSION

Ivan P Levinson*, Vera J Stecher, Richard L Siegel, Dana L Creanga, New York, NY

INTRODUCTION AND OBJECTIVE: Sildenafil is an effective and well-tolerated treatment for erectile dysfunction (ED). To determine the optimal dosage, we pooled safety and usage data from flexible-dose, placebo-controlled, double-blind (DB) studies.

METHODS: Data on final sildenafil dosage and, for sildenafil 100 mg, treatment-related adverse events (AE) were pooled from 9 studies with open-label extension. Data on final sildenafil dosage in men with mild or mild to moderate ED at baseline were pooled from 26 phase II/III/IV studies. The Erectile Function domain of the International Index of Erectile Function was used to define ED as mild (score of 22-25) or mild to moderate (score of 17-25).

RESULTS: Most men in the 9 pooled studies titrated sildenafil up to the 100-mg dose. During DB this included 69% (782/1135) of men randomized to sildenafil. During open-label extension, this included 75% (747/994) who were initially randomized to placebo, 89% (621/701) who finished DB on sildenafil 100 mg, and 32% (91/285) who finished DB on sildenafil 50 mg. In these men, the most commonly reported AEs were headache, flushing, gastrointestinal (GI) upset, and vision changes (Table), which were mostly mild or moderate in severity. Most men in the 26 pooled studies titrated sildenafil dosage to 100 mg even when ED was mild (63%, 110/176) or mild to moderate (62%, 457/739).

CONCLUSIONS: Sildenafil 100 mg is well tolerated and most men prefer the efficacy of this dosage, even those with mild or mild to moderate ED. Thus, 100 mg might be the optimal sildenafil dosage for initiating therapy.

*Placebo, 50 mg, and 100 mg refer to the final dosage during the DB phase. Sildenafil open-label dose started at 50 mg and was flexible.

734

CARDIOVASCULAR SAFETY OF THE COMBINATION OF VARDENAFIL AND ALPHA-BLOCKERS: A SUBGROUP ANALYSIS OF THE POST MARKETING SURVEILLANCE STUDY 'REAL LIFE SAFETY AND EFFICACY OF VARDENAFIL (REALISE)

Herman Van Ahlen*, Osnabrueck, Germany; Gerald Faich, Narberth, PA; Joel Morganroth, Philadelphia, PA; Kuno Sprenger, Ernst Weidmann, Elberfeld, Germany; Kathrin Stauch, Harald Landen, Leverkusen, Germany

INTRODUCTION AND OBJECTIVE: From an ongoing large international post-marketing surveillance study in subjects with erectile dysfunction treated with vardenafil in routine medical practice, the German cohort was the first country completed and analyzed. Results from 5032 sites of this prospective, non-interventional study conducted between March-December, 2003, showed that vardenafil (Levitra) 5, 10, and 20mg is effective and safe in a real-world environment.

METHODS: The impact of concomitant use of vardenafil and a-blockers on cardiovascular safety was assessed by subgroup analysis. Special attention was paid to cardiac safety parameters particularly to incidence rates of dizziness, hypotension, syncope, stroke, and myocardial infarction.

RESULTS: Data from a total of 29,358 subjects were analyzed. A high percentage (23.4%) was over 65 years of age. Concomitant a-blocker treatment was reported for 1,239 (4.2%) of subjects. The most frequently used a-blockers were tamsulosin (n=725), alfuzosin (n=223), doxazosin (n=189) and terazosin (n=103). Relevant co-morbidities of patients on a-blockers included presence of cardiac disease (28%), vascular disease (50%), hypertension (42%), and benign prostatic hyperplasia (82%). Adverse events (AEs) were reported by 28 (2.3%) of subjects receiving a-blockers and vardenafil concomitantly. These AEs were typical for these classes of compounds and did not differ in rates between patients using and not using alpha blockers. Out of these, the pattern of AEs of special medical interest were as follows. A total of 5 subjects reported dizziness. Serious AEs were reported in 2 subjects receiving tamsulosin; one subject reported severe fatigue, and one patient reported syncope within 5 to 24 hours of taking the first vardenafil dose. There were no reports of stroke, myocardial infarction, ventricular tachycardia, torsades de pointes, or death. A limitation of the study was that 5 patients using alpha blockers were lost to follow-up.

CONCLUSIONS: In this large, post-marketing surveillance trial, data from 1,239 subjects treated with a-blockers concomitantly with vardenafil showed a favorable cardiovascular safety profile.

735

FIVE-YEAR EFFICACY OF SILDENAFIL CITRATE AFTER RADICAL PROSTATECTOMY

Rupesh Raina*, Kalyana C Nandipati, Ashok Agarwal, Craig D Zippe, Cleveland, OH

INTRODUCTION AND OBJECTIVE: Five-year efficacy and compliance of sildenafil citrate after radical prostatectomy (RP) has not been reported in the literature. In this study, we evaluated the 5-year efficacy and side effects of sildenafil after RP.

METHODS: In this database, we identified 68 patients with erectile dysfunction (ED) who were initial sildenafil responders following RP and had a minimum followup of 5 years. Using a self-administered questionnaire, we surveyed these 68 patients at both one and five years to determine patient response/efficacy, compliance and side effects. Sildenafil citrate was prescribed at a dose of 50 mg and increased to 100 mg if needed. Data were collected from a self-administered questionnaire using the 5 question Sexual Health Inventory of Men (SHIM).

RESULTS: At 5 years, 31/68 (45.6%) were still responding to sildenafil, but 37/68 (54.4%) were not responding satisfactory and either discontinued the drug, switched to another therapy or used sildenafil in combination therapy. Specifically, in the 37 unsatisfied patients, 14/37 (37.8%) found sildenafil nonresponsive, with 8 patients discontinuing the drug and 6 switching to other forms of treatment (3 vacuum compression device (VCD), 3 intracavernosal injections (IC)). Twelve of 37 patients (32.4%) developed a suboptimal response and used combination therapy (VCD, ICI, MUSE ). Eleven of the 37 (29.7%) discontinued the treatment due to side effects (2), change in the personal circumstances (4) , and cardiovasular comorbidities (5). The most common side effects at 5 years were headache (4/25, 16%), flushing (2, 8%), and blurred vision (2, 8%). The vast majority of patients (88.8%) still responding to sildenafil at 5 years had nerve-sparing procedures, 22/25).

CONCLUSIONS: At 5 years, 50% of initial sildenafil responders continue to do well but required bilateral nerve-sparing procedures. Conversely, 50% of the patients become dissatisfied with the response and switched or added other erectaids, or discontinued therapy due to comorbidities, loss of partner, or side effects.

Read Male / Female Sexual Dysfunction Selected Abstracts - Part 3

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