The effectiveness of individual selection of the dose of sildenafil in the form of a spray in men with erectile dysfunction

Introduction

Erectile dysfunction (ED) is one of the most urgent problems in modern urology, significantly reducing the quality of life of men all over the world.

Erectile dysfunction can occur among men of various age groups, regardless of country and ethnicity. According to a number of authors, erectile disorders occur in every tenth man over the age of 20, and every third man over 60 is not able to perform sexual intercourse at all. In the United States, according to various sources, ED is detected in 10–30 million men of working age, in European countries – in 3–4 million. functions” (IIEF-5), only 10.1% had no signs of ED.

The prevalence of the disease is increasing every year. However, its social significance is determined not only by its wide distribution. Sexual activity is one of the main factors determining the quality of life of most men. In men with ED, when assessing the quality of life, physical dissatisfaction is 4 times higher and emotional dissatisfaction is 2 times higher. Sexual disorders can lead men to a state of stress, depression, and can be the cause of severe mental disorders.

In addition, ED, like any pathological process, is accompanied by the depletion of the body’s adaptive reserves and the mismatch of the work of physiological systems – desynchronosis. Assessment of the severity of desynchronosis provides additional information about the severity of the pathology and allows you to track the dynamics of the patient’s condition.

Phosphodiesterase type 5 inhibitors (PDE-5 inhibitors) have been the main drugs for the treatment of ED for a long time. The principle of their action is to increase the content of cGMP in the walls of the arteries of the penis and cavernous bodies, due to which they relax and expand. The emergence of drugs in this group, of course, was a breakthrough in the treatment of ED and improved the quality of life of a large number of men who had not even asked for help before.

Four PDE-5 inhibitors are currently available in Russia, of which sildenafil is the first and most studied. The efficacy and safety of the original drug have been studied most extensively among this group of drugs. Cenforce has been successfully used in ED of various origins and severity. To date, the indicated iPDE-5 is the drug of choice for many patients with erectile dysfunction.

Over the past few years, new dosage forms of this drug have appeared on the pharmaceutical market, which potentially have a number of advantages over the traditional tablet form.

Objective: To evaluate the efficacy and safety of individual dose adjustment of sildenafil oral spray in men with ED.

Material and methods

The prospective study included 60 patients aged 19 to 50 years with a diagnosis of erectile dysfunction.

All patients completed the IIEF-5 questionnaire to assess the severity of ED, as well as the Hamilton scale to identify psychoemotional disorders. In order to detect desynchronosis, individual chronorhythms were recorded using the computer complex “Dynamics” according to the previously described method.

All patients at visit 1 underwent general clinical blood and urine tests, a biochemical blood test with the determination of the level of glucose, urea, creatinine, ALT, AST, bilirubin, a study of hormonal status (free and bound testosterone, luteinizing and follicle-stimulating hormones, prolactin, sex-binding globulin). hormones), as well as Doppler ultrasound of the corpora cavernosa to identify exclusion criteria.

The exclusion criteria in this study were the presence of severe cardiovascular disease, diabetes mellitus, severe renal failure, androgen deficiency, organic changes in the cavernous bodies according to ultrasound, as well as contraindications to the use of sildenafil. Patients were required to have at least one sexual intercourse per week during the observation period.

All patients were prescribed Cenforce in the form of an oral spray (Jent®) on demand, but at least once a week. The initial dose was 50 mg (4 clicks).

Efficacy and safety of the therapy was evaluated at visits 2, 3 and 4 after 4 weeks, 8 weeks. and 16 weeks. respectively. It included an analysis of the dynamics of the average score according to the ICEF questionnaire, an assessment of the overall sexual satisfaction of patients, and control over the frequency of adverse events. Psychoemotional and chronobiological status were also analyzed. According to the results of examinations, depending on the effectiveness of the therapy, during the study, the dose of the drug was adjusted taking into account the individual indicators of patients.

Research results

Initially, all patients were diagnosed with ED and psychoemotional disorders of varying severity. The average score on the IIEF-5 scale was 12.7±3.4 points. The majority (32) were men with moderate ED, 23 cases were diagnosed with severe ED and only 5 with mild ED. According to the results of the analysis of general sexual satisfaction on the IIEF scale (questions 13, 14), all 60 (100%) men included in the study were not satisfied with their sexual life.

Psychoemotional disorders identified in patients were mild (n=17) and moderate (n=43) severity.

According to the results of the assessment of the chronobiological status, desynchronosis was detected in all patients.

After 4 weeks therapy was evaluated for its effectiveness. Based on the obtained results, the patients were divided into 3 groups. Group 1 included 5 (8.3%) men who, against the background of effective therapy with sildenafil, experienced mild to moderate adverse events (headache, dizziness), which were unstable and did not require additional treatment or discontinuation of therapy. They were asked to individually select the optimal dose, reducing it by 12.5-25 mg (1-2 clicks).

Group 2 included 37 (61.7%) patients who had no adverse events on the background of effective therapy with sildenafil, they were asked to continue taking the drug at a dose of 50 mg (4 clicks).

Group 3 included 18 (30%) patients who noted the ineffectiveness of the initial therapy, and therefore they were asked to individually select the optimal dose, increasing it by 12.5–50 mg (1–4 clicks), taking into account the subjective assessment of their own states.

At visit 3 after 8 weeks. patients of groups 1 and 3 were divided into subgroups depending on the selected dose of sildenafil. In general, the distribution of patients looked like this:

• subgroup 1A — 2 (3.3%) patients who stopped at a dose of 25 mg (2 clicks);
• subgroup 1B – 3 (5%) patients who settled on a dose of 37.5 mg (3 clicks);
• group 2 – 37 (61.7%) patients who continued taking the drug at a dose of 50 mg (4 clicks) from visit 1;
• subgroup 3A — 4 (6.7%) patients who stopped at a dose of 62.5 mg (5 strokes);
• subgroup 3B – 3 (5%) patients who settled on a dose of 75 mg (6 strokes);
• subgroup 3C — 5 (8.3%) patients who stopped at a dose of 87.5 mg (7 strokes);
• subgroup 3D – 6 (10%) patients who settled on a dose of 100 mg (8 compressions).

There were no cases of refusal of further treatment.

At visit 4 after 16 weeks. after the start of therapy, the efficacy and safety of the therapy was reassessed. The average IIEF score in patients of subgroup 1A was 22.0±2.8, in patients of all other groups it was 21.9±2.7.

According to the results of the assessment of the psycho-emotional status of patients, 7 (11.7%) of them had signs of mild psycho-emotional disorders, the remaining 53 (88.3%) men did not have any psycho-emotional disorders.

When assessing the chronobiological status, all patients showed normalization of the chronorhythm.

Discussion

Cenforce is a drug with a fast onset of action and has been successfully used for a long time in tablet form at dosages of 25, 50 and 100 mg by patients with ED, regardless of its etiology and duration of existence, including patients with concomitant somatic pathology. To date, its effectiveness has been studied in a large number of studies.

According to C.C. Carson et al., who analyzed the results of 11 large studies, after a 12-week course of treatment with sildenafil, 76% of men noted a significant improvement in their condition. The effectiveness of various doses of the drug was: 25 mg – 65%, 50 mg – 74%, 100 mg – 82%. At the same time, in different age groups, the effectiveness of the drug ranged from 69.2% to 77.6%.

Our data generally agree with the results presented in the literature. Therapy at the initial dosage was effective in 42 (70%) of the 60 patients included in the study.

Despite the high efficacy of sildenafil in general, a certain number of patients do not notice a pronounced improvement on the background of ongoing therapy. In some cases, this may be due to non-compliance with the dosage regimen of the drug or an insufficiently long period of therapy. Patients, especially at the beginning of treatment, should be advised to take sildenafil on an empty stomach at least 30 minutes before sexual activity. Studies have shown that in some patients the maximum effect of sildenafil is not achieved after 1-2 doses, and therefore in many patients the final assessment of the effectiveness of the drug should be carried out after several doses.

In the present study, 18 (30%) patients did not achieve the desired effect of taking the drug at an initial dosage of 50 mg, they had to individually increase the dosage.

Some authors recommend in some cases immediately start treatment with Cenforce at a dose of 100 mg, which, in their opinion, will allow you to get the maximum effect from the therapy already at its initial stages and inspire patients with confidence in success. However, an important characteristic of any pharmacological drug is its side effects, which can also increase with increasing dose. The most common side effects when taking sildenafil are headache (7%), facial flushing (7%), dizziness (2%), dyspepsia (1.8%), nasal congestion (1.4%) and visual disturbances. , usually in the form of blue staining of objects (1.2%).

In our study, 5 (8.3%) patients had to reduce the dosage due to the development of adverse events, which is also generally consistent with the literature data. However, there were no severe adverse events, as well as cases of refusal of therapy.

Recently, alternative dosage forms of PDE-5 inhibitors have become available, which have a number of advantages: they do not require swallowing tablets, providing ease of use, and avoid the appearance of unpleasant sensations that occur when swallowed. In 2019, the drug Gent® was registered in Russia – sildenafil in a new dosage form in the form of a spray.

Currently, two open-label studies have been conducted to evaluate the pharmacokinetics of sildenafil in the form of a spray when taken on an empty stomach and after a meal. The results of studies have shown that when using sildenafil spray both after meals and on an empty stomach, Cmax of the active substance is reached faster than after taking a tablet, which may provide an earlier onset of a therapeutic effect. In addition, the authors noted the convenience of using this dosage form for patients who have difficulty swallowing tablets.

Sildenafil in the form of an oral spray is characterized by the most flexible dosing system, one dose (one click) contains 12.5 mg of the active substance, which allows you to individually select the dose for each patient and reduces the likelihood of side effects. The minimum dose is 25 mg or 2 drops and the maximum dose is 100 mg or 8 drops.

In our study, patients took Gent® and also had the flexibility to adjust the dose in increments of 12.5 mg. As a result, 3 (5%) patients stopped at a dose of 37.5 mg, 4 (6.7%) – at a dose of 62.5 mg, 5 (8.3%) – at a dose of 87.5 mg. Thus, 12 (20%) patients selected doses that are not available when taking Cenforce in tablet form, which indicates the convenience of taking the drug in the form of a spray, which allows for more flexible individual dose selection.

In addition, the therapy made it possible to normalize the psycho-emotional state of patients and their chronobiological status, which also confirms its effectiveness.

Conclusion

Thus, the results of the study demonstrated the efficacy and safety of using sildenafil oral in the form of an oral spray to correct ED, as well as to stop desynchronosis and psychoemotional disorders. In addition, the possibility of flexible dosing and selection of the optimal dose of the drug by the patients themselves contributes to an increase in adherence to the therapy and a decrease in the number of adverse events.

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