Sildenafil generics pharmacy

Adverse events that were serious or led to dosing changes or discontinuation (temporary or permanent) were recorded. Many of the 979 participants (mean age, 58 [range, 27–82] years; mean ED

duration

In the current study, 979 of these men subsequently received up to 4 more years of open-label, flexible-dose (25, 50, and 100 mg) sildenafil.

Preliminary (3-year) results were reported previously (Carson et al 2002; Padma-Nathan et al 2002), and we now present the final data. The population included patients with ED of organic and psychogenic etiology and typical concomitant medical conditions for this population (ie, hypertension, diabetes, hyperlipidemia, and a history of ischemic heart disease).

Our objective was to assess the long-term safety and effectiveness of sildenafil treatment in men with ED.

This was a 4-year, open-label, flexible-dose (25, 50, and 100 mg) study of sildenafil.

Men who previously completed and were compliant with sildenafil or placebo treatment in 1 of 4 double-blind, placebo-controlled trials, and subsequently completed and were compliant with sildenafil treatment in initial open-label extension, were eligible for inclusion in this long-term extension study.

Compliance was assessed by medication diaries and by continued study participation.

A total of 1,545 men were originally enrolled in the double-blind trials, with 1,358 of these men continuing in the initial open-label extension studies.

The current study includes 979 of the original patients, who agreed to participate in the long-term extension ( Figure 1 ). The procedures were in accordance with the ethical standards of the responsible committee on human experimentation (institutional or regional). Number of patients and treatment duration in the original double-blind trials and the initial open-label extensions and disposition throughout 4 years of open-label, flexible-dose (25, 50, and 100 mg) sildenafil long-term extension study.

Of the 979 participants who entered the sildenafil long-term extension study, 584 (60%) completed all 4 years. Reasons for discontinuation, other than insufficient clinical response and treatment-related adverse event (AE), included AE unrelated to treatment, protocol violation, loss to follow-up, and other (eg, loss of interest in participation in a clinical study, loss of sexual partner, and ability to afford sildenafil after approval [thus, no longer needing to participate in a clinical study to obtain the medication]).

N for the satisfaction question (“Are you satisfied with the effect of treatment on your erections?”) is equal to the number of men who answered. *Some of the discontinued subjects supplied satisfaction data. At the time the study started, the FDA stated that there were sufficient routine safety data on sildenafil to make collection of standard adverse event data unnecessary. Therefore, only serious adverse events and adverse events leading to changes in dosing or to temporary or permanent discontinuation were recorded and evaluated by the investigators for relatedness to sildenafil treatment. Because the major focus of this study was safety, and it was designed before the development and validation of patient-reported outcomes to assess satisfaction with the quality of erection (eg, Quality of Erection Questionnaire (Porst et al 2007)) or satisfaction with ED treatment (eg, the Erectile Dysfunction Inventory of Treatment Satisfaction (Althof et al 1999)), effectiveness was assessed by asking, at yearly intervals or at discontinuation, simple, unvalidated general efficacy questions, “Are you satisfied with the effect of treatment on your erections?” and “If yes, has treatment improved your ability to engage in sexual activity?” The second question was based on the ED definition of the National Institutes of Health Consensus Conference: “…inability to attain and/or maintain penile erection sufficient for satisfactory sexual performance.” (NIH Consensus Conference. NIH Consensus Development Panel on Impotence 1993). Overall, 979 men initially agreed to participate in the study, most of whom were white (89%) and whose mean age was 58 years ( Table 1 ).

The duration of the double-blind trials plus initial open-label extension was 0.9 to 1.2 years (48–60 weeks). Median duration of participation in the open-label, long-term extension study was 4 years, the median number of doses taken was 420 (range, 1–1469) ( Figure 2 ), and the preferred dose was 100 mg in more than 88% of the men.

The retention rate was 84% (818/979) the first year, 75% (731/979) the second year, and 66% (648/979) the third year; the entire 4-year extension study was completed by 584 of the initial 979 men (60%) ( Figure 1 ).

Reasons for discontinuation included loss of interest in participation in a clinical study, loss of sexual partner, loss to follow-up, ability to afford sildenafil after approval (thus, no longer needing to participate in a clinical study to obtain the medication), insufficient clinical response, and adverse events. Usage of flexible-dose (25, 50, and 100 mg) sildenafil over 2–1561 days by the 979 participants who entered the study.

Age, mean (range) years 58.2 (27–82) Weight, mean (range) kg 89.2 (53.5–158.8) Race, n (%) White 873 (89.2) Black 68 (6.9) Asian 8 (0.8) Other 30 (3.1) ED duration, mean (range) years 4.5 (0.1–35.8) ED etiology, % organic/mixed/psychogenic 72/17/11 Common concomitant medical conditions, n (%) Hypertension 272 (27.8) Diabetes mellitus 213 (21.8) Hyperlipidemia 139 (14.2) History of ischemic heart disease 83 (8.5) Tolerability.

Over the 4-year study period, 37 (3.8%) of the men had 1 or more adverse events that led to changes in dosing or to temporary or permanent discontinuation and were determined by the investigators to be treatment-related ( Table 2 ).

Of the 47 events, headache and dyspepsia were most common (n = 10 each), followed by rhinitis (n = 6), flushing (n = 5), abnormal vision (n = 4), dizziness (n = 3), and 1 report each of mild palpitations, moderate tachycardia, diarrhea, nausea, myalgia, hypertonia, respiratory disorder, conjunctivitis, and photophobia. Of the few cardiovascular events determined by the investigator to be treatment related (4 cases of mild flushing and 1 each of moderate flushing, mild palpitations, and moderate tachycardia), only 1 led to permanent discontinuation.

In this case the man experienced mild flushing with the first dose of sildenafil 100 mg but continued therapy after a dose reduction. After 629 days of therapy, at which time his dosage was once again 100 mg, he permanently discontinued sildenafil because of the flushing. Two other cardiovascular events led to temporary discontinuation (mild flushing and moderate tachycardia), and the remainder were addressed with a change in dosing.

Of the 149 serious adverse events that occurred during the 4 years of the study, including 18 acute myocardial infarctions, none were considered by the investigator to be treatment related.

Adverse events that led to changes in dosing or to temporary or permanent discontinuation. Adverse events (AEs) in 979 men Treatment-related a All causality Patients with AEs, n (%) 37 (3.8) 210 (21.5) Discontinued because of AEs, n (%) 11 (1.1) 55 (5.6) Most frequent (?0.5%) AEs, n (%) Headache 10 (1.0) 10 (1.0) Dyspepsia 10 (1.0) 12 (1.2) Rhinitis 6 (0.6) 6 (0.6) Flushing 5 (0.5) 5 (0.5) Coronary artery disorder 0 24 (2.5) Prostatic disorder 0 16 (1.6) Carcinoma 0 14 (1.4) Myocardial infarction 0 11 (1.1) b Arthritis 0 9 (0.9) Bone fracture accidental 0 9 (0.9) Accidental injury 0 7 (0.7) Cerebrovascular disorder 0 7 (0.7) Atrial fibrillation 0 6 (0.6) Cholecystitis 0 6 (0.6) Sepsis 0 5 (0.5) Heart failure 0 5 (0.5) Gastrointestinal carcinoma 0 5 (0.5) Bone disorder 0 5 (0.5) Each treatment year, less than 1% of the men who started the year discontinued sildenafil because of treatment-related adverse events, for a total of only 11 (1.1%) of the original 979 participants over the 4 years of the study ( Table 3 ).

Discontinuations were caused by dyspepsia (n = 4), rhinitis (n = 2), abnormal vision plus headache (n = 1), dyspepsia plus rhinitis (n = 1), and flushing, dizziness, and myalgia (n = 1 each).

Percentage of participants who discontinued, (n/N) a Study year Treatment-related adverse event Insufficient response Other reasons (not treatment related) 1 0.5 (5/979) 2.2 (22/979) 13.7 (134/979) 2 0.2 (2/818) 2.3 (19/818) 8.1 (66/818) 3 0.1 (1/731) 1.9 (14/731) 9.3 (68/731) 4 0.5 (3/648) 1.1 (7/648) 8.3 (54/648) Effectiveness. Of the 979 men who participated in the study, 932 (95%) were analyzed for efficacy. At the completion of each year, at least 94% of the annually decreasing number of participants reported satisfaction with the effect of sildenafil treatment on their erections, with only a 3.3 percentage point variation across the 4 yearly assessments ( Table 4 ). Almost all of these men reported improved ability to engage in sexual activity. Percentage of participants (n/N) a Study year Satisfied with treatment effect on erections Improved ability to have sexual activity End of year End of year 1 98.1 (806/822) 99.6 (803/806) 2 96.6 (672/696) 99.9 (671/672) 3 94.8 (551/581) 99.6 (549/551) 4 96.3 (550/571) 100 (550/550) Each treatment year, less than 3% of the men who started the year discontinued sildenafil treatment because of insufficient clinical response. Over the 4 years of the study, only 62 (6.3%) of the original 979 participants discontinued because of insufficient response ( Table 3 ). There are numerous data published on the efficacy and safety of sildenafil treatment for ED. Before approval, sildenafil was evaluated in sildenafil 110 mg troche 18 phase II/III double-blind, placebo-controlled trials, in which men with ED were randomized to receive treatment with sildenafil (n = 2722) or placebo (n = 1552) for up to 6 months (Morales et al 1998). Pooled data from these trials demonstrated that sildenafil is a well-tolerated oral therapy for ED (Morales et al 1998).

Adverse events were mostly transient and mild to moderate in severity and included most commonly headache, flushing, dyspepsia, and rhinitis. The rate of discontinuation because of adverse events was low and comparable between patients who received sildenafil and those who received placebo. A more recent retrospective analysis, in which data were pooled from 35 Pfizer-sponsored double-blind trials involving 4819 patients who received sildenafil and 3296 patients who received placebo, supports the conclusions of the earlier pooled data but also found that sildenafil is well tolerated among patients taking antihypertensive medications, including those on multidrug regimens (Padma-Nathan et al 2002).

Pooled data also support the efficacy of sildenafil; results from 11 double-blind, flexible-dose, placebo-controlled trials that included a total of 2,667 men ages 23 to 89 years with ED of broad-spectrum etiology show significantly improved erectile function for sildenafil compared with placebo as measured by the International Index of Erectile Function, a global efficacy question, and a patient-recorded event log of sexual activity (Carson et al 2002).

More than 300 million men worldwide are expected to experience erectile dysfunction by 2025. More than 300 million men worldwide are expected to experience erectile dysfunction by 2025.

As the last patents on the erectile dysfunction drug run out, interest in finding new treatments has been renewed. A re we witnessing the end of an era for Viagra and Pfizer? Since the famous “little blue pill” exploded on to the market in 1998, becoming the fastest selling drug in history, the American pharmaceutical giant has made vast sums marketing it to erectile dysfunction sufferers all over the world. Within three months of its launch, Viagra had already earned Pfizer $400m, and over the past two decades, it has consistently generated annual sales to the tune of $1.8bn. However, this will soon come to an end, as in 2020, Pfizer’s remaining patents on Viagra expire for good.

A whole host of generic versions have emerged in the past six years, often in quirky forms such as mint strips or breath sprays, as Pfizer’s grip on the rights to the drug has slowly loosened. Soon, these are expected to flood the market, as manufacturers jostle for a slice of the pie.

This will make Viagra more accessible and cheaper, but for the millions of men worldwide with erectile dysfunction, it could also spell good news in the form of much needed treatment innovations.

Since Viagra was launched, few genuinely novel therapies have been developed, and while Viagra and similar drugs like Cialis and Levitra – which all increase blood flow to the penis by blocking an enzyme known as PDE5 – are effective in around 70% of patients, they come with significant downsides.

To start with, there are often prominent side-effects ranging from headaches to stomach pain. In addition, with Viagra taking more than an hour to work, there’s the need to pre-plan intercourse, and in the case of older patients, the drugs can often be unsuitable due to potentially dangerous interactions with medications for high blood pressure, or hypertension.

For patients with the most severe forms of erectile dysfunction, often resulting from nerve damage due to diabetes or prostate cancer surgery, Viagra typically doesn’t work at all.