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Role of avanafil in management of erectile dysfunction

Dr. Hip Wo Yeung
Specialist in Urology
Private practice
10 Oct 2019
Effective phosphodiesterase 5 (PDE5) inhibitors are the backbone of personalized management of erectile dysfunction (ED). Avanafil, a newer PDE5 inhibitor for the treatment of ED, has the advantage of rapid onset of action with effects lasting over 6 hours. At an interview with MIMS Doctor, Dr Victor Hip-Wo Yeung, Specialist in Urology in private practice in Hong Kong, discussed study findings supporting the use of avanafil (Spedra®, Menarini) in the management of ED. 

ED management: Diagnosis and treatment options

ED affects about half of men older than 40 years of age and often causes emotional distress with an impact on quality of life. According to the Canadian Urological Association’s practice guidelines, curable causes of ED, such as endocrine conditions, should be identified by physical examination and laboratory testing and treated if possible. Possible contributing causes, including diabetes mellitus (DM) and vascular diseases, should be addressed. It is also important to differentiate between ED and other sexual disorders, such as premature ejaculation, which can often be misdiagnosed. [Can Urol Assoc J 2015;9:23-29]

“Lifestyle changes and risk factor modification should be encouraged in some patients to improve erectile function. Cigarette smoking, for instance, contributes to a large proportion of ED cases in Hong Kong and patients should be encouraged to stop smoking,” advised Yeung. “ED could also be related to psychological and emotional problems, whereby stress and low libido may hinder sexual functioning. Counselling is helpful for these patients and their partners.”

“In terms of treatment options, although injected, implanted or topically applied medications are available, oral PDE5 inhibitors remain the treatment of choice for patients with ED in Hong Kong,” said Yeung.

Role of PDE5 inhibitors

Oral PDE5 inhibitors are important drugs that inhibit the PDE5 receptor, allowing the release of nitric oxide (NO) from nerve endings, which subsequently helps in restoration of penile blood flow and relaxation of corporal smooth muscle cells, causing erection in response to sexual stimulation. [P T 2013;38:414-419]

A previous in vivo study showed that avanafil strongly inhibited PDE5, with an inhibitory concentration resulting in a 50 percent reduction in PDE activity (IC50) of 5.2 nmol/L. Some PDE5 inhibitors also inhibit PDE1, PDE6 and PDE11, causing undesirable effects, such as visual disturbances, or haemodynamic or musculoskeletal adverse events (AEs). Avanafil, however, has demonstrated high selectivity for PDE5 over other PDE isozymes, confirming its safety and improved tolerability. [J Sex Med 2012;9:2122-2129]

Efficacy and safety of avanafil

“The choice of PDE5 inhibitor should be personalized because different drugs within the same class may have different onset,” commented Yeung.

On average, most couples take only 15 minutes from first deciding to then engaging in intercourse. It is therefore important to consider the time from dosing to onset of action when selecting an appropriate ED therapy. [J Urol 2015;194:485-492]

“Avanafil has the fastest onset of action among PDE5 inhibitors. Its onset of action is within 15 minutes, compared with 30–60 minutes for other PDE5 inhibitors. Avanafil therefore has an advantage for ad hoc sexual intercourse,” said Yeung. [J Urol 2015;194:485-492]

The benefit of avanafil’s fast onset of action was demonstrated in a randomized, double-blind study in men with mild to severe ED who were randomized to receive avanafil (100 mg or 200 mg) or placebo. In the study, a statistically significant difference between avanafil and placebo was found in the average per subject proportion of successful intercourse attempts. “This occurred as early as 10 minutes after dosing with avanafil 200 mg,” noted the authors. [J Urol 2015;194:485-492]

During the 8-week treatment period, avanafil 200 mg showed an up to 2-fold increase vs placebo in the mean per subject proportion of successful intercourse attempts, in which erection sufficient for vaginal penetration was achieved within 15 minutes of dosing and maintained for successful intercourse (Sexual Encounter Profile question 3 [SEP 3]). (Table)

As mentioned in the European Association of Urology (EAU) guidelines, the most common treatment-emergent AEs (TEAEs) of avanafil 200 mg were headache (9.3 percent) and flushing (3.7 percent). The rates of these TEAEs are lower with avanafil 200 mg other PED5 inhibitors. (Table) [Eur Urol 2006;49:806-815]

HK-PLI-047md

Avanafil in ED patients with comorbidities

Similar findings on the efficacy of avanafil were reported in a multicentre, randomized, double-blind study among patients with DM and mild to severe ED. Patients were randomized (1:1:1) to receive avanafil (100 mg or 200 mg) or placebo. [Mayo Clin Proc 2012;87:843-852]

Treatment with avanafil led to a significant improvement in the percentage of successful sexual attempts in which patients were able to insert their penis into the partner’s vagina (21.5 percent increase with avanafil 100 mg and 25.9 percent increase with avanafil 200 mg vs 7.5 percent increase with placebo; p<0.01).

The mean change in mean International Index of Erectile Function erectile function (IIEF-EF) domain score between baseline and end of treatment averaged 4.5 for avanafil 100 mg and 5.4 for avanafil 200 mg vs 1.8 for placebo (p=0.002 and p<0.001, respectively).

Furthermore, exploratory analysis revealed higher rates of successful intercourse attempts (SEP 3) for each interval tested in the avanafil treatment groups vs placebo. At 15 minutes or less after dosing, 62.3 percent and 35.6 percent of intercourse attempts were successful in men treated with avanafil 100 and 200 mg, respectively, compared with 26.1 percent in the placebo group. At more than 6 hours after dosing, 50.0 percent and 67.7 percent of the intercourse attempts were successful after treatment with avanafil 100 and 200 mg, respectively, compared with 4.8 percent in the placebo group.

Managing ED in the clinic

“The topic of ED is sensitive, and patients’ confidentiality should be protected. It is important to ensure that patients are comfortable during the consultation and have their history taken alone, if possible. Through detailed history taking, a full understanding of patients’ concerns and expectations can be gained,” suggested Yeung.

Management of ED is done through a shared decision-making approach, whereby patients are educated about the condition, its possible causes and treatment options.

“Avanafil showed significant improvements in rates of successful intercourse vs placebo, and is relatively safe with few AEs,” said Yeung.  “Its fast onset of action and 6-hour half-life make it suitable for most patients with ED in Hong Kong.”

“Doses of avanafil are up-titrated gradually, depending on erectile response, side effects and treatment satisfaction. Patients should be advised to take avanafil 30 minutes prior to sexual attempts, and be made aware that avanafil has no effect on sexual performance per se. They should also be informed of the possible side effects of treatment as well as when to stop and seek medical review,” he advised. “Contraindicated medications, such as alpha-blockers and psychotropic drugs, should be withheld for as long as possible when patients are on PDE5 inhibitor therapy.”

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Most Read Articles
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