vardenafil-dihydrochloride and Flushing

To assess the efficacy and tolerability of vardenafil in men with erectile dysfunction (ED) due to traumatic spinal cord injury (SCI).. In this multicenter, double-blind, placebo-controlled, parallel-group 12-week study, 418 men aged 18 years and older with ED for more than 6 months consequent to SCI were randomized to vardenafil (n = 207) or placebo (n = 211) (10 mg for 4 weeks, then maintained or titrated to 5 or 20 mg at weeks 4 and 8). Efficacy assessments included the erectile function (EF) domain score of the International Index of Erectile Function questionnaire and diary questions regarding penetration, maintenance of erection to completion of intercourse, and ejaculation.. Baseline patient characteristics were similar in the vardenafil (mean age 40 years) and placebo (mean age 39 years) groups. Mean baseline EF domain scores were 11.6 in the vardenafil group and 12.1 (moderate ED) in the placebo group. EF domain score in the vardenafil group improved to 22.0 (mild ED) at last observation carried forward vs 13.5 in the placebo group (p < 0.001). Over 12 weeks of treatment, mean per-patient penetration (76% vs 41%), maintenance (59% vs 22%), and ejaculation (19% vs 10%) success rates were significantly greater vs placebo (all p < 0.001). The most frequently reported drug-related adverse events were headache (vardenafil 15%, placebo 4%), flushing (vardenafil 6%, placebo 0%), nasal congestion (vardenafil 5%, placebo 0%), and dyspepsia (vardenafil 4%, placebo 0%).. Vardenafil significantly improved erectile and ejaculatory function and was generally well tolerated in men with erectile dysfunction due to spinal cord injury.

Topics: Adult; Coitus; Double-Blind Method; Dyspepsia; Ejaculation; Erectile Dysfunction; Flushing; Headache; Humans; Imidazoles; Male; Medical Records; Nasal Obstruction; Penile Erection; Phosphodiesterase Inhibitors; Piperazines; Spinal Cord Injuries; Sulfones; Surveys and Questionnaires; Treatment Outcome; Triazines; Vardenafil Dihydrochloride

Vardenafil, a potent and selective oral PDE5 inhibitor, is efficacious and generally well-tolerated in men with erectile dysfunction (ED). Of considerable interest to patients and physicians is an understanding of the time required after dosing to attain penile erection sufficient for successful sexual intercourse.. To determine the earliest time to onset of action of vardenafil 10 and 20 mg leading to successful intercourse compared to placebo in men with ED.. A prospective, randomized, double-blind, parallel-group, at-home study of 732 men with ED (mean age 55.5 years) was conducted at 64 sites in North America and Europe. Following a 4-week run-in period, patients were randomized to either vardenafil 10 (N = 237) or 20 mg (N = 248) or placebo (N = 247) to be taken on demand over 4 weeks. Using a stopwatch, patients recorded the elapsed time from dosing to attainment of an erection perceived to be adequate for penetration that led to intercourse completion. Earliest time of onset was defined as the fastest time among the first four doses for each patient. Time points from 25 to 5 minutes were tested for significance (alpha = 0.025) using a backward stepping procedure.. Mean baseline erectile function domain score (13.4) indicated moderate ED. Within 25 minutes after dosing, 50%/53% of men on vardenafil 10/20 mg had at least one erection in the first four doses perceived to be sufficient for penetration with subsequent intercourse completion compared to 26% on placebo (P < 0.0001). A statistically superior response to vardenafil vs. placebo was observed in these responders at all times >or= 10 and >or= 11 minutes (P < 0.025) in the 10 and 20 mg groups, respectively. In a retrospective analysis using time intervals of

Topics: Adult; Coitus; Dose-Response Relationship, Drug; Double-Blind Method; Erectile Dysfunction; Flushing; Headache; Humans; Imidazoles; Male; Middle Aged; Phosphodiesterase Inhibitors; Piperazines; Placebos; Prospective Studies; Sexual Behavior; Sulfones; Time Factors; Treatment Outcome; Triazines; Vardenafil Dihydrochloride

The North American Pivotal Trial was designed to investigate the efficacy and safety of vardenafil in males with erectile dysfunction (ED).. In this randomized, double-blind, placebo-controlled, multicenter, fixed-dose, parallel group, 6-month study, vardenafil at three doses (5 mg, 10 mg, and 20 mg) was compared to placebo with the primary efficacy variables being the International Index of Erectile Function (IIEF) Erectile Function (EF) domain score and per patient diary response success rates for penetration and maintenance of erection through completion of intercourse. Additional efficacy variables included IIEF domain scores measuring intercourse satisfaction, orgasmic function, sexual desire, and overall satisfaction. Diary entries for overall per patient satisfaction rates for hardness and sexual experience were also measured. Improvements in quality of sexual life were assessed using the Fugl-Meyer quality of life (QoL) questionnaire.. Compared to placebo, patients taking 10 mg and 20 mg doses of vardenafil showed statistically significantly greater improvement in IIEF domain scores measuring intercourse satisfaction (10.3 and 10.3 vs. 7.7), orgasmic function (7.1 and 6.9 vs. 5.3), overall satisfaction. (7.1 and 7.1 vs. 5.2) for vardenafil 10 mg and 20 mg vs. placebo, respectively, at last observation carried forward (LOCF). Vardenafil 5 mg was statistically significantly better than placebo for the secondary IIEF domain variables of intercourse satisfaction (8.9 vs. 7.7) and overall satisfaction (6.3 vs. 5.2) for vardenafil vs. placebo, respectively, at LOCF. Per patient satisfaction rates for the secondary diary variables measuring erection hardness (38%, 52%, 58% and 18%) and overall satisfaction (45%, 58%, 62% and 23%) were dose dependent and statistically significantly superior for vardenafil at 5 mg, 10 mg and 20 mg compared with placebo, respectively. Patients' answers to the Fugl-Meyer QoL questionnaire assessing improvement in sexual life also indicated statistically significant superiority for all doses of vardenafil vs. placebo treatment. The most frequent adverse events (AE) in the 5 mg, 10 mg, and 20 mg of vardenafil and placebo groups, respectively, were: headache (10%, 22%, 21% and 4%), flushing (5%, 10%, 13% and 0%), dyspepsia (1%, 4%, 6% and < 1%), and rhinitis (9%, 14%, 17% and 5%). Most AEs were mild or moderate in severity and transient in nature.. Vardenafil was superior to placebo for IIEF domain scores, per patient success rates for diary questions, and assessment of quality of sexual life, in a broad range of patients with ED irrespective of etiology or severity. Vardenafil was generally well tolerated, with most AEs being mild or moderate in severity and transient in nature.

Topics: Adult; Canada; Dose-Response Relationship, Drug; Double-Blind Method; Erectile Dysfunction; Flushing; Headache; Humans; Imidazoles; Male; Patient Satisfaction; Phosphodiesterase Inhibitors; Piperazines; Placebos; Quality of Life; Sexual Behavior; Sulfones; Surveys and Questionnaires; Time Factors; Treatment Outcome; Triazines; United States; Vardenafil Dihydrochloride

Flushing is one of the most common vasodilation-related adverse effects associated with both nitrates and phosphodiesterase type 5 (PDE5) inhibitors. The present study aimed to investigate the effects of orchidectomy and ovariectomy on isosorbide dinitrate-, sildenafil-, vardenafil- and tadalafil-induced flushing of tail-skin in mice. Both orchidectomy and ovariectomy markedly increased the tail-skin temperature, a good parameter of flushing, induced by isosorbide dinitrate (500 microg/kg, i.p.). These observations suggest that both testosterone withdrawal and estrogen withdrawal are risk factors for isosorbide dinitrate-induced flushing. In contrast, sildenafil (100 mg/kg, p.o.)-, vardenafil (10 mg/kg, p.o.)- and tadalafil (40 mg/kg, p.o.)-induced flushing of tail-skin in mice was aggravated by ovariectomy but not by orchidectomy. Orchidectomized male mice, but not ovariectomized female mice, showed significantly lower levels of PDE5 mRNA expression in tail artery compared with those of sham-operated mice. The present findings suggest that estrogen withdrawal, but not testosterone withdrawal, is a risk factor for PDE5 inhibitor-induced flushing. These gender differences in the vascular adverse reactions of PDE5 inhibitors may be interpreted as occurring due to differences in the levels of PDE5 mRNA expression in peripheral arteries.

Topics: Animals; Carbolines; Climacteric; Cyclic Nucleotide Phosphodiesterases, Type 5; Female; Flushing; Gene Expression Regulation; Imidazoles; Male; Mice; Mice, Inbred ICR; Models, Animal; Nitrates; Phosphodiesterase 5 Inhibitors; Phosphodiesterase Inhibitors; Piperazines; Purines; RNA, Messenger; Sex Characteristics; Sildenafil Citrate; Skin; Sulfones; Tadalafil; Tail; Triazines; Vardenafil Dihydrochloride