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ORIGINAL ARTICLE
Year : 2021  |  Volume : 34  |  Issue : 1  |  Page : 13-17

Evaluation of avanafil in the treatment of erectile dysfunction


1 Department of Dermatology, Andrology and STIs, Faculty of Medicine, Menoufia University, Menoufia, Egyp
2 Dermatology, Andrology and STIs, General Hospital of Berket-Elsabea, Menoufia University, Menoufia, Egypt

Date of Submission10-Mar-2019
Date of Decision03-Apr-2019
Date of Acceptance08-Apr-2019
Date of Web Publication27-Mar-2021

Correspondence Address:
Sarah M.A. El-Soud
Shebin El-Kom, Menoufia
Egypt
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/mmj.mmj_115_19

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  Abstract 


Objective
To evaluate the post-marketing efficacy of avanafil 100 mg, safety, and the probable adverse events in the treatment of Egyptian men with erectile dysfunction (ED).
Background
ED is one of the most common sexual disorders due to organic, psychogenic, or mixed etiologies. Its prevalence ranges from 6 to 64% increasing with age. Avanafil is a highly selective and potent second-generation phosphodiesterase 5 inhibitor.
Patients and methods
This was a double-blind, placebo-controlled, crossover study including 26 patients with mild to severe ED using the International Index of Erectile Function-Erectile Function. Patients received avanafil 100 mg or placebo for 6 weeks each, with a 2-week washout period in between. It was taken 30 min precoital on-demand twice weekly. Follow-up was at the end of the third and sixth week.
Results
Avanafil 100 mg significantly increased the mean IEEF-EF score when compared with the baseline (P < 0.001) and when compared with the placebo (P = 0.005), while placebo was not significant (P > 0.05). On use of avanafil 100 mg, 45% of patients became normal (no ED, score >25) by the end of the sixth week; 40% showed different grades of improvement; and 15% showed no improvement. The onset of action of avanafil was within 30 min in 85% of responders. The reported adverse events were nasal congestion, headache, facial flushing, tingling of hands and/or feet, heartburn, and diarrhea.
Conclusion
Avanafil 100 mg has a rapid onset of action, is efficient, and a tolerable drug for the treatment of ED.

Keywords: avanafil, erectile dysfunction, phosphodiesterase 5 inhibitors


How to cite this article:
Attia AM, El-Soud SM. Evaluation of avanafil in the treatment of erectile dysfunction. Menoufia Med J 2021;34:13-7

How to cite this URL:
Attia AM, El-Soud SM. Evaluation of avanafil in the treatment of erectile dysfunction. Menoufia Med J [serial online] 2021 [cited 2021 Dec 7];34:13-7. Available from: http://www.mmj.eg.net/text.asp?2021/34/1/13/311988




  Introduction Top


Erectile dysfunction (ED) is defined as the persistent inability to obtain or to maintain penile erection sufficient for satisfactory sexual relations [1]. Several studies have explored the epidemiology of ED by considering the different settings and populations. Massachusetts Male Ageing Study showed a prevalence of mild to moderate ED of 52% in men aged 40–70 years. ED is strongly related to age, health status, and emotions [2]. Conversely, the European Male Aging Study which is the largest European multicenter population-based study of aging men (40–79 years) reported a prevalence of ED ranging from 6 to 64% depending on the different age subgroups with an average prevalence of 30% [3]. The recent advances in the diagnostic procedures have shown that the ED may be caused by organic factors in up to 50% of patients while the other 50% of them have psychogenic causes [4]. However, most of the patients demonstrate a combination of both organic and psychogenic components [5]. Organic causes include vasculogenic, neurogenic, anatomic, and endocrine causes. Diabetes mellitus (DM), coronary artery disease, and systemic hypertension are systemic problems that could affect penile erection and should be ruled out clinically [6]. ED is a common complication of DM which may affect more than half of diabetic men and the incidence of ED is three times higher in diabetic men than in the age-matched nondiabetic men [2].

Oral phosphodiesterase 5 (PDE5) inhibitors created a sexual revolution as considered in the first-line therapy for ED. The first-generation PDE5 inhibitors including sildenafil, vardenafil, and tadalafil are widely used for the treatment of ED, but a recent meta-analysis study showed a mean discontinuation rate of 4% per month for this group of drugs mostly due to adverse events (AEs) [7].

Avanafil is a highly selective and potent second-generation PDE5 inhibitor that was approved by the FDA in 2012 followed by the European Medicines Agency in 2013 for the treatment of ED [8]. It is characterized by its faster onset and shorter duration of action, and fewer drug interactions than the other PDE5 inhibitors due to its high selectivity on PDE5 isoenzyme compared with first-generation PDE5 inhibitors making it a favorable option for the treatment of ED [7],[8],[9].

We aimed by this work to evaluate the post-marketing efficacy of avanafil 100 mg, its safety, and the probable AEs in the treatment of Egyptian men with ED.


  Patients and methods Top


This study was conducted in the Andrology Unit, Dermatology, Andrology, and STI Department, Faculty of Medicine, Menoufia University during the period from October 2017 to August 2018. It was a prospective, double-blind, placebo-controlled crossover study. It included 26 men in stable continuous marriage with no marital conflict C/O mild to severe ED according to International Index of Erectile Function-Erectile Function (IIEF-EF) scoring in which severe ED (score 1–10), moderate (11–16), mild to moderate (17–21), mild (22–25), and no ED (26–30) [10]. Full history taking, general, local examination and HBA1c, serum prolactin, total testosterone, free testosterone, ICI test, and penile duplex were done for some cases. The patients received avanafil 100 mg and placebo for 6 weeks each, with 2 weeks in between as a washout period. The drug and placebo were received 30 min precoital on demand. The patients were instructed to have sexual intercourse twice/week. Evaluation of efficacy, safety, tolerability, and probable AEs were done by the end of the third and the sixth week.

Inclusion criteria

ED patients having stable marital relationship and IIEF-EF scoring from 1 to 25 (i.e., mild to severe ED) were included and did not use any drug for the treatment of ED 2 weeks prior to inclusion in this study.

Exclusion criteria

Include any contraindication for avanafil that include: (a) patients taking nitrates, (b) patients having unstable angina during sexual activity, severe heart failure, or uncontrolled blood pressure, (c) patients who had a heart attack, stroke, life-threatening irregular heartbeats, or heart surgery within the past 6 months, (d) patients having eye problems (e.g., hereditary degenerative retinal disorder, including retinitis pigmentosa), (e) sensitivity to avanafil, and (f) patients with severe impairment of the liver or kidney functions.

Data analysis

All data were collected, tabulated, and statistically analyzed using SPSS 19.0 for Windows (SPSS Inc., Chicago, Illinois, USA) and MedCalc 13 for windows (MedCalc Software BVBA, Ostend, Belgium).

The Wilcoxon test was performed for continuous, quantitative, parametric variables and the Mann–Whitney for nonparametric variables. Partial correlation coefficient for testing the association between variables was also applied. A P value of less than 0.05 was considered statistically significant.


  Results Top


We successfully consented 26 patients with mild and moderate to severe. ED of organic and psychogenic causes according to the IIEF-EF domain scoring from 1 to 25 (i.e., mild to severe ED). Their ages ranged from 26 to 61 years (mean ± SD 47.58 ± 10.35). All were in stable marriage for periods varied from 1 to 40 years (mean ± SD 21.92 ± 12.27). The onset of ED ranged from 4 to 90 months (mean ± SD 31.50 ± 23.86).

Six (23.07%) patients out of the 26 patients included in this study did not complete the study due to various reasons: two (7.69%) patients were lost during follow-up, two (7.69%) patients due to lack of effect of treatment, and two (7.69%) patients due to marital conflict. These six patients were excluded from the final analysis.

According to history taking, general examination, HBA1c, total testosterone, free testosterone, serum prolactin, Intracorporal injection (ICI), and penile duplex examination which were done for some cases, the patients were distributed etiologically into nine (45%) patients who had organic causes and 11 (55%) patients who had psychogenic cause of ED.

Concerning the onset of action of the drug, the results of this study showed that 85% of the responders achieved successful sexual intercourse within ∼30 min and 15% reported within 30–45 min after drug administration.

The results showed that placebo had no significant change in the IIEF-EF score in the percentage of responders by the end of the study compared with the baseline score, while avanafil 100 mg showed significant improvement by the end of the study as 45% became normal (no ED, score > 25), 40% showed different grades of improvement, and 15% showed no improvement [Table 1].
Table 1: Distribution of patients according to the severity of erectile dysfunction, measured by International Index of Erectile Function-Erectile Function score at baseline and by the end the study (sixth week) after treatment by placebo and avanafil 100 mg

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There was no significant changes on the use of placebo compared with the baseline neither by the third nor by the sixth week (P > 0.05), while after treatment by 100 mg avanafil, the IIEF-EF score showed significant improvement from 14.50 ± 7.32 at the baseline to 21.85 ± 8.34 by the third week (P < 0.001). This improvement continued without further rise (P < 0.001) by the sixth week [Figure 1].
Figure 1: International Index of Erectile Function-Erectile Function (IIEF-EF) score changes by avanafil 100 mg and placebo after the third and the sixth week of treatment compared with the baseline.

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In addition, there was significant improvement on the use of avanafil 100 mg compared with placebo by the end of the third and sixth week treatment (P = 0.005) for both [Figure 2].
Figure 2: International Index of Erectile Function-Erectile Function (IIEF-EF) score changes by avanafil 100 mg compared with placebo after the third and the sixth week of treatment.

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The most common drug-related AE reported was nasal congestion (20%), followed by headache (15%), facial flushing (10%) and tingling of hand and/or feet, heartburn, and diarrhea by the same degree (5%). Most of these AEs were mild to moderate in severity and none of the patients stopped the drug due to these AEs. No AEs were reported due to placebo intake [Figure 3].
Figure 3: Frequency of adverse events reported by avanafil 100 mg compared with placebo.

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  Discussion Top


PDE5 inhibitors are recommended in the guidelines as the standard treatment for ED [11]. First-generation PDE5 inhibitors including sildenafil, vardenafil, and tadalafil showed high efficacy and safety profile in the treatment of ED in many comparative studies. They are generally similar, but differ in the efficacy time period of action and their AEs. They also differ in their pharmacokinetic properties and in their effect on the different PDE isoenzymes [12].

Avanafil presents the second-generation of PDE5 inhibitors with the advantage of its rapid onset of efficacy with less AEs than the first-generation of PDE5 inhibitors due to its high selectivity for PDE5 [13].

It was approved by the FDA in 2012 followed by the European Medicines Agency in 2013 for the treatment of ED [8]. It is available in many countries in three doses of 50, 100, and 200 mg and in Egypt as 100 mg tablet only at the time of the study.

In this study, we evaluated the post-marketing efficacy using IIEF-EF scoring, safety, tolerability, and the probable AEs of avanafil 100 mg in Egyptian men with ED.

To approach our goal, we designed this study to be a double-blinded, placebo-controlled cross-over study which included 26 patients with mild, mild to moderate, moderate, and severe ED according to the IIEF-EF domain scoring from 1 to 25 due to different etiologies. Their ages ranged from 26 to 61 years (mean ± SD 47.58 ± 10.35). All were in stable marriage for periods that varied from 1 to 40 years (mean ± SD 21.92 ± 12.27). The onset of ED ranged from 4 to 90 months (mean ± SD 31.50 ± 23.86).

The results showed that six (23.07%) patients out of the 26 patients included were dropped out due to various reasons: two (7.69%) patients were lost during follow-up, two (7.69%) patients due to lack of efficacy of treatment, and two (7.69%) patients due to marital conflict. These six patients were excluded from the final analysis and discussion of the results.

History taking and investigations showed that 11 (55%) patients had psychogenic ED while the remaining nine (45%) patients had organic ED. Five (25%) patients were diabetic with HBA1c more than 7 (i.e., uncontrolled DM); three patients out of these diabetic patients were found to have venous leakage proved by the penile duplex study; two patients showed hyperprolactinemia; one patient had low free and total testosterone levels; and one patient had neurogenic ED from a previous neural surgery.

Regarding the severity of ED, IIEF-EF scoring showed that eight (40%) patients had severe ED (score ≤10), four (20%) had moderate ED (score 11–16), three (15%) had mild to moderate ED (score 17–21), and five (25%) had mild ED (score 22–25).

The results showed that avanafil 100 mg is effective in the treatment of ED of different etiologies as nine (45%) patients by the end of the sixth week became normal and their IIEF-EF score is more than 25. These patients reported successful intercourse on using the drug. The remaining eight (40%) patients showed different grades of improvement in the severity of ED, while three (15%) patients showed no improvement of their score. On using the placebo, none of the patients showed any improvement in their ED. These results go with that reported by Mulhall et al. [14], who reported a 40% success rate on the use of the same dose and Zhao et al. [15], who reported a 45.6% success rate, but less than that reported by Belkoff et al. [16], who reported a higher success rate (66.4%). On the other hand, Park et al. [17] reported a much less (20%) success rate. The differences in success rate may be explained by the difference in culture, design, and methodology of each study.

Compared with the baseline score, the results showed that placebo showed no effect (P > 0.05), while avanafil 100 mg is highly significantly efficient in improving ED by the end of the third and the sixth week as the score elevated from 14.50 ± 7.32 at baseline to 21.85 ± 8.34 by the end of third week and this rise continued by the same degree at the sixth week treatment (P < 0.001) for both. These results agreed with that reported by Goldstein et al. [18], who found that avanafil 100 mg significantly increased the IIEF-EF score from 12.6 at baseline to 20.9 after treatment (P < 0.001) and Belkoff et al. [16], who found that avanafil 100 mg on demand raised the score from 13.6 at baseline to 22.2 after avanafil 100 mg treatment (P < 0.001).

When compared with the placebo; avanafil 100 mg was highly significantly superior in improving the IIEF-EF score as it rose from 15.75 ± 6.96 (for placebo) to 21.85 ± 8.34 (for avanafil) at the end of the third week and from 15.75 ± 6.99 (for placebo) to 21.85 ± 8.34 (for avanafil) by the end of the sixth week (P = 0.005 for both). The same was reported by Goldstein et al. [18], Zhao et al. [15], Mulhall et al. [14], Hellstrom et al. [13], and Park et al. [17].

The results showed that 85% of the responders achieved successful intercourse within ∼30 min and the remaining 15% reported after 30–45 min Reviewing of the literature in this regard, we have found different figures as the onset of response was found to be after 15 min reported by Goldstein et al. [18], Belkoff et al. [16], Mulhall et al. [14], and Hellstrom et al. [13], after 20 min reported by Hellstrom et al. [19], and after 30–60 min reported by Belkoff et al. [16], and Park et al. [17].

Regarding the tolerability and AEs of avanafil 100 mg, the results showed that it is highly tolerable and AEs were mild to moderate in severity. None of the patients stopped the drug due to AEs. No serious AEs in vision, hearing, or cardiac functions were recorded. The most reported AEs – in frequency of order – were nasal congestion (20%), headache (15%), facial flushing (10%) and 5% for tingling of hands and/or feet, heartburn, and diarrhea. Most of these AEs disappeared on continuation of the drug use. No AEs were reported with placebo intake. Reviewing of the literature in this regard, we have found controversial results. Goldstein et al. [18] reported headache as the most common AE but occurred only in 7.5% of patients followed by flushing (6.2%), nasal congestion (4.3%), back pain (2.5%) nasopharyngitis (1.2%), and bronchitis (0.6%). Hellstrom et al. [19] and Zhao et al. [15] reported flushing as the most common AE (7.4 and 11.43%, respectively) while Belkoff et al. [16] and Mulhall et al. [14] found that the most common AE was headache (2.7 and 8.1%, respectively). On the other hand, Hellstrom et al. [13] found that upper respiratory tract infection was the most common AE. We have no explanation for this diversity in the reported AEs of the drug. but we think that it may be due to the differences in the culture and habits. It can also be due to the small number of patients included in this study.


  Conclusion Top


Although this study is defective in being done on a small number of ED patients we can conclude that avanafil 100 mg has a rapid onset of action, is efficient, and a highly tolerable drug for the treatment of ED.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

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