sildenafil-citrate and Flushing

Erectile dysfunction (ED) is a major care problem worldwide. Tadalafil and sildenafil are the two most common phosphodiesterase 5 inhibitors used to treat ED. This systematic review and meta-analysis were conducted to directly compare tadalafil with sildenafil for the treatment of ED.. We designed a strategy for searching the PubMed, Embase, EBSCO, Web of Science and Cochrane library databases; the reference lists of the retrieved studies were also investigated. A literature review was performed to identify all published randomized or non-randomized controlled trials that compared tadalafil with sildenafil for the treatment of ED and to assess the quality of the studies. Two investigators independently and blindly screened the studies for inclusion. The meta-analysis was performed using RevMan 5.0.. A total of 16 trials that compared tadalafil with sildenafil for the treatment of ED were included in the meta-analysis. In the meta-analysis, tadalafil and sildenafil appeared to have similar efficacies and overall adverse event rates. However, compared with sildenafil, tadalafil significantly improved psychological outcomes. Furthermore, the patients and their partners preferred tadalafil over sildenafil, and no significant difference was found in the adherence and persistence rates between tadalafil and sildenafil. Additionally, the myalgia and back pain rates were higher and the flushing rate was lower with tadalafil than with sildenafil.. Tadalafil shares a similar efficacy and safety with sildenafil and significantly improves patients' sexual confidence. Furthermore, patients and their partners prefer tadalafil to sildenafil. Hence, tadalafil may be a better choice for ED treatment.

Topics: Back Pain; Controlled Clinical Trials as Topic; Erectile Dysfunction; Flushing; Humans; Male; Myalgia; Patient Preference; Phosphodiesterase 5 Inhibitors; Self Efficacy; Sildenafil Citrate; Tadalafil

Clinical studies evaluating the effectiveness and safety of phosphodiesterase type 5 inhibitors (PDE5is) for female sexual dysfunction have reported conflicting results.. To systematically review evidence from studies comparing PDE5is with placebo in the treatment of female sexual dysfunction.. Searches of PubMed, the Cochrane Library, and Embase databases were performed using the MeSH terms "females/female/women", "sexual", and "sildenafil/tadalafil/vardenafil/PDE5/PDE5i".. All randomized controlled trials, available in English, published no later than January 28, 2015 comparing the effectiveness of PDE5is, or PDE5is in combination with other agents, with placebo in improving female sexual function were included.. The inclusion criteria were met by 14 studies, which were analyzed by two reviewers.. The randomized controlled trials included in the present study adopted different questionnaires for measuring sexual function; consequently, most of the data had to be considered separately rather than pooled. Generally, the use of PDE5is resulted in significant improvements in sexual function compared with placebo, with some studies demonstrating negative results. Pooled data regarding adverse events demonstrated significantly higher rates of headache, flushing, and changes in vision in PDE5i-treated patients.. PDE5is could be an effective treatment modality for female sexual dysfunction. Although there were significant increases in adverse events in comparison with placebo, PDE5is were still relatively safe.

Topics: Female; Flushing; Headache; Humans; Nausea; Orgasm; Phosphodiesterase 5 Inhibitors; Randomized Controlled Trials as Topic; Sexual Dysfunction, Physiological; Sildenafil Citrate; Treatment Outcome; Vision Disorders

To determine the efficacy and safety of sildenafil citrate in the treatment of male erectile dysfunction.. The MEDLINE, HealthSTAR, Current Contents, and Cochrane Library databases (January 1, 1995, through December 31, 2000); bibliographies of retrieved articles and review articles; conference proceedings abstracts; the Food and Drug Administration Web site; and the manufacturer.. Trials were eligible if they included men with erectile dysfunction, compared sildenafil with control, were randomized, were of at least 7 days' duration, and assessed clinically relevant outcomes.. Two reviewers independently evaluated study quality and extracted data in a standardized fashion.. Twenty-seven trials (6659 men) met the inclusion criteria. In results pooled from 14 parallel-group, flexible as-needed dosing trials, sildenafil was more likely than placebo to lead to successful sexual intercourse, with a higher percentage of successful intercourse attempts (57% vs 21%; weighted mean difference, 33.7; 95% confidence interval [CI], 29.2-38.2; 2283 men) and a greater percentage of men experiencing at least 1 intercourse success during treatment (83% vs 45%; relative benefit increase, 1.8; 95% CI, 1.7-1.9; 2205 men). In data pooled from 6 parallel-group, fixed-dose trials, efficacy appeared slightly greater at higher doses. Treatment response appeared to vary between patient subgroups, although relative to placebo, sildenafil significantly improved erectile function in all evaluated subgroups. In trials with parallel-group design and flexible dosing, men randomized to receive sildenafil were less likely than those receiving placebo to drop out for any reason and no more likely to drop out due to an adverse event or laboratory abnormality. Specific adverse events with sildenafil included flushing (12%), headache (11%), dyspepsia (5%), and visual disturbances (3%); all adverse events were significantly less likely to occur with placebo. Sildenafil was not significantly associated with serious cardiovascular events or death.. Sildenafil improves erectile function and is generally well tolerated. Treatment response seems to vary between patient subgroups, although sildenafil has greater efficacy than placebo in all evaluated subgroups.

Topics: Age Factors; Aged; Dose-Response Relationship, Drug; Dyspepsia; Erectile Dysfunction; Flushing; Headache; Humans; Male; Middle Aged; Patient Satisfaction; Penile Erection; Phosphodiesterase Inhibitors; Piperazines; Purines; Severity of Illness Index; Sexual Behavior; Sildenafil Citrate; Sulfones; Vasodilator Agents; Vision Disorders

The aim of the present study was to show the efficacy and safety of sublingual sildenafil and to determine whether lower doses cause the same effect with a faster onset of action in this mode of application.. Forty consecutive patients with erectile dysfunction for more than three months were included in the study. The mean age was 55 years (range, 25-65). Serum glucose and testosterone levels, lipid profile and erectile function scores were obtained in all patients. Twenty patients received placebos and the other 20 patients received 20 mg sublingual sildenafil in a double blind randomized design.. The effect of sildenafil on erection was significantly higher than that of placebo. Sixty-five percent of patients (13/20) who received sublingual sildenafil achieved satisfying erections and coitus, whereas the rate was 15% in the placebo group (3/20). The mean onset of action with sublingual sildenafil was 15.5 min and lasted for an average of 40 min. Minimal headaches, sweating and flushing were noted as the side-effects.. 20 mg sublingual sildenafil is safe and effective in the treatment of erectile dysfunction. Sublingual administration has some advantages as it is not effected by food ingestion and quickly appears in the circulation. These advantages provide a faster onset of action with a lower dose when compared to oral sildenafil. Sublingual use of sildenafil may be more cost-effective and possibly provides a more predictable onset of action.

Topics: 3',5'-Cyclic-GMP Phosphodiesterases; Administration, Sublingual; Adult; Aged; Dose-Response Relationship, Drug; Erectile Dysfunction; Flushing; Headache; Humans; Male; Middle Aged; Phosphodiesterase Inhibitors; Piperazines; Purines; Sildenafil Citrate; Sulfones; Sweating; Treatment Outcome

Viagra (sildenafil citrate) has a rapid onset of action for the treatment of erectile dysfunction (ED). However, its duration of action has not been thoroughly investigated. Practical knowledge of the time window available for sexual intercourse would be valuable for couples planning sexual activity.. We investigated the duration of action of sildenafil in men with ED.. This was a double-blind, randomized, placebo-controlled, four-way crossover study of 16 men, mean age of 55 years (range, 36-68 years) with ED of no known organic cause. Participants received oral sildenafil (100 mg) or placebo 1, 8, or 12 hours before visual sexual stimulation (VSS). Measurements included the duration of erections of >or= 60% rigidity, assessed by penile plethysmography (RigiScan), and the proportion of sildenafil responders, defined as patients with erections of >or= 60% rigidity for >or= 4 minutes and >or= 50% improvement over erections achieved in their placebo arm. Self-assessed duration of grade 3 (hard enough for penetration) or grade 4 (fully hard) erections was also recorded.. At 1, 8, and 12 hours after dosing with sildenafil, the mean duration of erections with >or= 60% rigidity was 26, 11, and 8 minutes, respectively, compared with only 3 minutes after placebo dosing (P < 0.05). However, the mean duration of self-assessed erections was 33, 23, and 16 minutes, respectively, compared with 7 minutes after placebo dosing (P < 0.05), and was greater than that assessed by RigiScan. Of the 69% sildenafil responders at 1 hour, 82% responded at 8 hours and 45% responded at 12 hours after sildenafil administration.. Sildenafil improved objective and self-assessed erectile function in men with ED, and the duration of action of sildenafil was longer than that previously reported. These data suggest that sildenafil may be effective in a significant proportion of men with ED up to 12 hours after being taken.

Topics: Adult; Aged; Cross-Over Studies; Double-Blind Method; Drug Administration Schedule; Erectile Dysfunction; Flushing; Headache; Humans; Male; Middle Aged; Phosphodiesterase Inhibitors; Piperazines; Placebos; Plethysmography; Purines; Sexual Behavior; Sildenafil Citrate; Sulfones; Time Factors; Treatment Outcome

Sildenafil citrate (Viagra Pfizer, New York, NY) is indicated for the treatment of erectile dysfunction in men. The nitric oxide-cyclic guanosine monophosphate pathway (NO-cGMP) involved in penile erection and enhanced by sildenafil may also play a role in some components of the female sexual arousal response. The efficacy and safety of sildenafil were evaluated in estrogenized and estrogen-deficient women with sexual dysfunction that included female sexual arousal disorder (FSAD).. Patients were randomized to receive 10-100 mg sildenafil or matching placebo. To assess efficacy, patients completed two global efficacy questions (GEQ), the Life Satisfaction Checklist (LSC), an event log of sexual activity, and a 31-item sexual function questionnaire (SFQ). To assess safety, adverse event (AE) data were recorded.. A total of 577 estrogenized and 204 estrogen-deficient women were randomized to treatment. All were diagnosed with FSAD, but it was the primary presenting symptom in only 46% and 50% of women, respectively. Differences in efficacy between sildenafil and placebo were not significant for any patient or partner end points (e.g., the two GEQ, the sexual event logs, the LSC, and the SFQ). The main AE were headache, flushing, rhinitis, nausea, visual disturbances, and dyspepsia, which were generally mild to moderate in nature.. Any genital physiological effect of sildenafil was not perceived as improving the sexual response in estrogenized or estrogen-deficient women with a broad spectrum of sexual dysfunction that included FSAD. Whether more specific subgroups of women with FSAD could potentially benefit from treatment with sildenafil is an area for future research.

Topics: Adult; Analysis of Variance; Dose-Response Relationship, Drug; Double-Blind Method; Dyspepsia; Estradiol; Estrogen Replacement Therapy; Female; Flushing; Headache; Humans; Middle Aged; Nausea; Piperazines; Purines; Rhinitis; Sexual Behavior; Sexual Dysfunction, Physiological; Sexual Dysfunctions, Psychological; Sildenafil Citrate; Statistics as Topic; Sulfones; Surveys and Questionnaires; Treatment Outcome; Vasodilator Agents; Vision Disorders

We evaluated the safety and side effects of sildenafil in a group of sexually active volunteers younger than 40 years under conditions without sexual stimulation. Single oral dose of 50 mg dildenafil (n = 20) or placebo (n = 20) was randomly administered to 40 sexually active volunteers with the mean age of 26.80 +/- 5.29 in sildenafil group and 25.70 +/- 4.95 in placebo group. All the subjects were informed about the study, but not about the medicine. The following tests were performed immediately before and 90 minutes after the administration of the medicine: resting heart rate, blood pressure, electrocardiogram, visual acuity, color vision. The subjects were also asked to describe any discomfort or difference. Mann Whitney U test was used for statistical analyses. The only statistically significant difference was between heart rates before and after the administration of the sildenafil (p = 0.02). Color vision, visual acuity tests yielded no differences. The decrease in blood pressure was not significant. The most common side effects were flushing (75% and 0%), headache (50% and 5%), dyspepsia (15% and 5%), unintentional incomplete sexual arousal (15% and 0%) and palpitation (15% and 10%) in groups of sildenafil and placebo, respectively. The only serious side effect requiring medical treatment was arthralgia on the knee in one subject. Although these side effects can be acceptable, the likelihood of these side effects needs to be made clear to potential users of this medication.

Topics: 3',5'-Cyclic-GMP Phosphodiesterases; Adult; Arthralgia; Blood Pressure; Double-Blind Method; Erectile Dysfunction; Flushing; Headache; Heart Rate; Humans; Male; Phosphodiesterase Inhibitors; Piperazines; Purines; Sildenafil Citrate; Sulfones

Sildenafil citrate has been shown to be effective in a wide range of patients with erectile dysfunction and has been approved in the United States for this indication. The overall clinical safety of oral sildenafil, a potent inhibitor of phosphodiesterase type 5, in the treatment of erectile dysfunction was evaluated in more than 3700 patients (with a total of 1631 years of exposure worldwide). Safety and tolerability data were analysed from a series of double-blind, placebo-controlled studies and from 10 open-label extension studies of sildenafil in the treatment of erectile dysfunction. A total of 4274 patients (2722 sildenafil, 1552 placebo; age range 19-87 y) received double-blind treatment over a period of up to six months' duration, and 2199 received long-term, open-label sildenafil for up to 1 y. The most commonly reported adverse events (all causes) were headache (16% sildenafil, 4% placebo), flushing (10% sildenafil, 1% placebo), and dyspepsia (7% sildenafil, 2% placebo) and they were predominantly transient and mild or moderate in nature. These adverse events reflect the pharmacology of sildenafil as a phosphodiesterase type 5 inhibitor. No cases of priapism were reported. The rate of discontinuation due to adverse events (all causes) was comparable for patients treated with sildenafil (2.5%) and placebo (2.3%). In open-label extension studies, 90% of patients completed long-term sildenafil treatment, with only 2% withdrawing due to adverse events. Sildenafil is a well-tolerated oral treatment for erectile dysfunction.

Topics: 3',5'-Cyclic-GMP Phosphodiesterases; Adolescent; Adult; Aged; Aged, 80 and over; Cardiovascular Diseases; Double-Blind Method; Dyspepsia; Enzyme Inhibitors; Erectile Dysfunction; Flushing; Headache; Humans; Middle Aged; Piperazines; Placebos; Purines; Sildenafil Citrate; Sulfones

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

Sildenafil citrate is the first FDA-approved oral agent for male erectile dysfunction. Common adverse effects include flushing, headache, and dyspepsia, although more serious side effects have been reported. Because of its specific therapeutic indication, sildenafil toxicity has been limited almost exclusively to adults. We report a symptomatic case of pediatric sildenafil ingestion.. A 2-year-old male ingested 75 mg of sildenafil citrate (Viagra) 2 hours prior to arrival at an emergency room. Ipecac syrup had been given at home with one episode of vomiting. Activated charcoal was considered but withheld due to the delayed presentation to the hospital. The patient was observed in the hospital for 17.5 hours. Observed clinical effects included facial flushing, transient penile engorgement, bilateral rhonchi, and diarrhea. No significant cardiovascular effects were seen. A bronchodilator was given with resolution of rhonchi. No other specific interventions were required. One day after discharge, the patient had one additional bout of diarrhea and complained of pain in the penile region for one day. Two weeks after the exposure, the patient's mother denied any unusual symptoms.. Pediatric ingestion of sildenafil may result in mild symptoms including persistent flushing and penile engorgement with associated pain. Penile pain may persist even after resolution of the erection. It is questionable whether the respiratory symptoms and diarrhea were related since neither has been described following sildenafil exposure. Significant cardiovascular symptoms were not seen. Early administration of ipecac syrup did not prevent symptoms from developing.

Topics: Bronchodilator Agents; Child, Preschool; Diarrhea; Emetics; Flushing; Humans; Hypotension; Ipecac; Male; Piperazines; Poisoning; Priapism; Purines; Respiratory Sounds; Sildenafil Citrate; Sulfones

Sildenafil citrate (Viagra) has been shown to be an effective treatment for erectile dysfunction. Initial studies reported a high tolerability and low incidence of certain characteristic adverse reactions. We sought to evaluate the incidence of side effects of sildenafil citrate, independent of industry support and constraints, utilizing a heterogeneous cohort of patients from a university-based practice.. A prospective, open-label, flexible-dose study of 256 patients treated with sildenafil citrate for erectile dysfunction was performed at a single institution. The patients were questioned explicitly about the occurrence of headache, flushing, dyspepsia, nasal congestion, visual changes, and other side effects.. The adverse reactions most commonly observed were flushing (30.8%), headache (25. 4%), nasal congestion (18.7%), and heartburn (10.5%). All events were short lived and mild in nature. In the present study, 31.6% of patients experienced one or more adverse events. However, no one withdrew from the study because of the severity of these events. There was a significant association between higher doses and the occurrence of side effects.. The incidence of adverse events attributable to sildenafil citrate may be higher than initially reported, but an explanation may be the methodology of data collection and the industry-independent nature of this study. The side-effect profile is dose related and mild. Sildenafil citrate remains a safe and well-tolerated treatment for erectile dysfunction.

Topics: Adult; Aged; Dizziness; Dyspepsia; Erectile Dysfunction; Flushing; Headache; Humans; Incidence; Male; Middle Aged; Nose; Phosphodiesterase Inhibitors; Piperazines; Prospective Studies; Purines; Sildenafil Citrate; Sulfones; Vision, Ocular