New ED Treatment Newly Approved Vitaros Topical Cream for the Treatment of Erectile Dysfunction (ED)

Approximately 50% of men over 40 years old live with a consistent inability to achieve or maintain a satisfactory erection. The prevalence dramatically increases with age and with the rapidly ageing population, erectile dysfunction (ED) has become a prominent problem. ED is strongly linked to common comorbidities of the elderly generation, such as cardiovascular disease and depression, in addition to anti-hypertensive agents and alpha-blockers. Treating ED has been shown to have a profound effect on patients’ quality of life and overall satisfaction.1

Nitric oxide (NO) is the primary neurotransmitter involved in achieving and maintaining an erection, which is released on stimulation. NO relaxes the corpora cavernosa, compressing the veins within the penis and preventing venous return, which results in an erection. This is caused by NO utilising the guanosine triphosphate and cyclic guanosine monophosphate (cGMP) pathway by stimulating cGMP to decrease intracellular calcium. Phosphodiesterase type 5 (PDE5) is an enzyme that counteracts the relaxation of smooth muscle by aiding the degradation of cGMP.1

Men with erectile dysfunction may suffer from anxiety, depression, low self-esteem, and a decrease in quality of life. They may also emotionally and physically withdraw from their partners. There is a strong association between erectile dysfunction and depression. However, successful treatment of the condition can improve depression.2

Any disruption to the psychological, endocrine, vascular and neurological systems that coordinate to maintain normal sexual function can result in ED, see table 1 for full list of ED origins. The most commonly encountered form of ED is vasculogenic, which correlates with studies that suggest 49% of coronary artery disease patients also have ED.1

Current treatments

Increased understanding of ED has allowed the development of multiple medical treatment options, which can also alleviate the psychological burden associated with ED. Currently, first-line treatment for ED is oral PDE5 inhibitors, which block the enzyme responsible for cGMP degradation. The average response rate from the approved PDE5 inhibitors for the treatment of ED is ~70% within 12-24 weeks. However, as seen in table 2, there are a number of limiting factors in the use of PDE5 inhibitors for ED.1

Second-line treatment for ED involves intracavernous injections with phentolamine, papaverine, and alprostadil, which are as effective as PDE5 inhibitors, but have a more rapid onset. However, intracavernosal therapy is highly invasive and associated with dropout rates up to 40-50% due to pain, priaprism, penile fibrosis, haematoma, ecchymosis or fear of needles. Alprostadil can also be administered intraurethrally, by inserting a pellet into the urethral meatus where the drug is absorped into the corposa cavernosa. This method is significantly less invasive, but it results in a lower response and is associated with high discontinuation rates due to urethral pain and bleeding.1

American and European Urologist associations have reported that there is a significant number of ED patients unable to use the conventional PDE5 inhibitors, creating a large patient population with an unmet need. In Arab countries, this counts for 49% of all ED patients, approximately 8 million men across the region (Iraq, Saudi Arabia, Yemen, Syria, UAE, Jordan, Lebanon, Oman, Kuwait, Qatar and Bahrain).

Vitaros

Vitaros contains the active ingredient alprostadil, which is a synthetic analogue of prostaglandin E1. Vitaros’ mechanism of action involves binding to G proteins coupled to PGE1 receptors on the surface of smooth muscle cells, activating cyclic adenosine monophosphate (cAMP) pathway and thus inducing vascular smooth muscle relaxation and erection. Vitaros’ mechanism of action does not utilise the NO pathway, unlike other medications, and is a direct agonist, meaning an erection can be produced independent of a stimulus.1

Vitaros topical cream also includes patented novel ‘NexACT’, a multi-route drug delivery platform consisting of more than 100 different skin permeation enhancer molecules. These molecules are able to loosen the tight junctions in skin epithelial cells, allowing enhanced skin permeation at the site of application to radically improve drug absorption and bioavailability.1

Benefits of using alprostadil

Vitaros has a favourable pharmacodynamic profile, and in one study, full rigidity was observed within 10-12 minutes of application lasting for over one hour. Clinical trials have demonstrated that Vitaros is an effective alternative to conventional first-line treatments. One trial found that, use of alprostadil gel led to an erectile response in 67-75% of patients at varying doses, compared to 17% of controls, with no serious adverse events. Various studies have shown that Vitaros is a safe treatment for ED.1

Vitaros topical cream also has a superior side effects profile compared to other alprostadil delivery methods. This comparison can be seen in the Urology Update for Primary Care Physicians 2013, published in the Canadian Journal of Urology (table 3).3

In another study, 52% of men who used alprostadil cream over 12 weeks reported an improved erection, compared to 20% using placebo. This improvement was also similar in patients with comorbidities such as diabetes mellitus, cardiovascular disease, hypertension, a prostatectomy, and severe ED, compared to the general population.4,5

In addition to the superior efficacy and safety, using a topical cream is much more simple and discreet for patients. Application is simple and non-invasive compared to injections and suppositories.4

References

1. Anaissie J, Hellstrom WJG. Clinical use of alprostadil topical cream in patients with erectile dysfunction: a review. Res Rep Urol 2016; 8: 123-131

2. Medscape. http://www.medscape.com/viewarticle/551562_4. Accessed October 25, 2016.

3. Urology Update for Primary Care Physicians for 2013. Can J Urol 2012; 19(Suppl 1)

4. Vitaros. http://www.vitaros.co.uk/hcp/vitaros-information/. Accessed October 17, 2016.

5. Rooney M, Pfister W, Mahoney M, et al. Long-term, multicentre study of the safety and efficacy of topical alprostadil cream in male patients with erectile dysfunction