Treatment Options
Second-line therapy
For patients not responding to oral drugs may be offered intracavernous injections with high success rates of 85%.
Intracavernous injections
Alprostadil
Intracavernous administration of vasoactive drugs was the first medical treatment for erectile dysfunction more than 20 years ago1. Alprostadil (CaverjectTM, Edex/ViridalTM) is the first and only drug approved for intracavernous ED treatment2. The erection appears after 5-15 minutes and lasts according to the dose injected. Efficacy rates for intracavernous alprostadil of more than 70% have been found in general ED populations, as well as in patient subgroups (e.g. diabetes or cardiovascular disease), with reported sexual activity after 94% of the injections and satisfaction rates of 87-93.5% in patients and 86-90.3% in partners3,4.
Complications of intracavernous alprostadil include penile pain (50% of patients, after 11% of injections), prolonged erections (5%), priapism (1%) and fibrosis (2%)2,6. Pain is usually self-limited after prolonged use. It can be alleviated with the addition of sodium bicarbonate or local anaesthetics7,8. Fibrosis requires temporary discontinuation of the injection programme for several months. Systemic side effects are uncommon. The most common is mild hypotension especially when using higher doses. Contraindications include men with a history of hypersensitivity to alprostadil, men at risk of priapism and men with bleeding disorders. Despite these favourable data, intracavernous pharmacotherapy is associated with high drop-out rates and limited compliance. Patients not responding to oral drugs may be offered intracavernous injections with high success rates of 85% 5,9.
Intraurethral alprostadil
A specific formulation of alprostadil (125-1000 μg) in a medicated pellet (MUSETM) has been approved for use in erectile dysfunction patients10. Vascular interaction exist between the urethra and the corpora cavernosa that permits drug transfer between these structures11. Erections sufficient for intercourse were achieved in 30-65.9% of patients10,12,13. In clinical practice, only the higher doses (500 and 1000 μg) were encountered and consistency rates were low14. The application of a constriction ring at the root of the penis (ACTISTM) may improve efficacy15.
The most common adverse events are local pain (29-41%) and dizziness (1.9-14%). Penile fibrosis and priapism are very rare (< 1%). Urethral bleeding (5%) and urinary tract infections (0.2%) are adverse events related to the mode of administration1.
Efficacy rates are significantly lower than intracavernous pharmacotherapy16. Intraurethral pharmacotherapy is a second-line therapy, providing an alternative to intracavernous injections in patients who prefer a less invasive, but less efficacious, treatment.
References:
1. Leungwattanakij S, Flynn V, Jr., Hellstrom WJ. Intracavernosal injection and intraurethral therapy for erectile dysfunction. Urol Clin North Am 2001;28:343-354. http:/anti-infectives/Paris-Event/Live-Webcast.cfmwww.ncbi.nlm.nih.gov/entrez/query
2. Linet OI, Ogrinc FG. Efficacy and Safety of Intracavernosal Alprostadil in Men with Erectile Dysfunction. N Engl J Med 1996;334:873-877. http:/anti-infectives/Paris-Event/Live-Webcast.cfmwww.ncbi.nlm.nih.gov/entrez/query
3. Porst H. The rationale for prostaglandin E1 in erectile failure: a survey of worldwide experience. J Urol 1996;155:802-815. http:/anti-infectives/Paris-Event/Live-Webcast.cfmwww.ncbi.nlm.nih.gov/entrez/query UPDATE MARCH 2005 23
4. Heaton JP, Lording D, Liu SN, Litonjua AD, Guangwei L, Kim SC, Kim JJ, Zhi-Zhou S, Israr D, Niazi D, Rajatanavin R, Suyono S, Benard F, Casey R, Brock G, Belanger A. Intracavernosal alprostadil is effective for the treatment of erectile dysfunction in diabetic men. Int J Impot Res 2001;13:317-321.http:/anti-infectives/Paris-Event/Live-Webcast.cfmwww.ncbi.nlm.nih.gov/entrez/query
5. Shabsigh R, Padma-Nathan H, Gittleman M, McMurray J, Kaufman J, Goldstein I. Intracavernous alprostadil alfadex (EDEX/VIRIDAL) is effective and safe in patients with erectile dysfunction after failing sildenafil (Viagra). Urology 2000;55:477-480. http:/anti-infectives/Paris-Event/Live-Webcast.cfmwww.ncbi.nlm.nih.gov
6. Lakin MM, Montague DK, VanderBrug Medendorp S, Tesar L, Schover LR. Intracavernous injection therapy: analysis of results and complications. J Urol 1990;143:1138-1141. http:/anti-infectives/Paris-Event/Live-Webcast.cfmwww.ncbi.nlm.nih.gov/entrez/query
7. Kattan S. Double-blind randomized crossover study comparing intracorporeal prostaglandin E1 with combination of prostaglandin E1 and lidocaine in the treatment of organic impotence. Urology 1995;45:1032-1036. http:/anti-infectives/Paris-Event/Live-Webcast.cfmwww.ncbi.nlm.nih.gov/entrez/query
8. Mulhall JP, Daller M, Traish AM, Gupta S, Park K, Salimpour P, Payton TR, Krane RJ, Goldstein I. Intracavernosal forskolin: role in management of vasculogenic impotence resistant to standard 3-agent pharmacotherapy [see comments]. J Urol 1997;158:1752-1758; discussion 1758-1759.http:/anti-infectives/Paris-Event/Live-Webcast.cfmwww.ncbi.nlm.nih.gov/entrez/query
9. Baniel J, Israilov S, Segenreich E, Livne PM. Comparative evaluation of treatments for erectile dysfunction in patients with prostate cancer after radical retropubic prostatectomy. BJU Int 2001;88:58-62. http:/anti-infectives/Paris-Event/Live-Webcast.cfmwww.ncbi.nlm.nih.gov/entrez/query
10. Padma-Nathan H, Hellstrom WJ, Kaiser FE, Labasky RF, Lue TF, Nolten WE, Norwood PC, Peterson CA, Shabsigh R, Tam PY. Treatment of men with erectile dysfunction with transurethral alprostadil. Medicated Urethral System for Erection (MUSE) Study Group [see comments]. N Engl J Med 1997;336:1-7. http:/anti-infectives/Paris-Event/Live-Webcast.cfmwww.ncbi.nlm.nih.gov/entrez/query.fcgi
11. Vardi Y, Saenz de Tejada I. Functional and radiologic evidence of vascular communication between the spongiosal and cavernosal compartments of the penis. Urology 1997;49:749-752. http:/anti-infectives/Paris-Event/Live-Webcast.cfmwww.ncbi.nlm.nih.gov/entrez/query
12. Guay AT, Perez JB, Velasquez E, Newton RA, Jacobson JP. Clinical experience with intraurethral alprostadil (MUSE) in the treatment of men with erectile dysfunction. A retrospective study. Medicated urethral system for erection. Eur Urol 2000;38:671-676. http:/anti-infectives/Paris-Event/Live-Webcast.cfmwww.ncbi.nlm.nih.gov/entrez/query
13. Fulgham PF, Cochran JS, Denman JL, Feagins BA, Gross MB, Kadesky KT, Kadesky MC, Clark AR, Roehrborn CG. Disappointing initial results with transurethral alprostadil for erectile dysfunction in a urology practice setting. J Urol 1998;160:2041-2046. http:/anti-infectives/Paris-Event/Live-Webcast.cfmwww.ncbi.nlm.nih.gov/entrez/query
14. Mulhall JP, Jahoda AE, Ahmed A, Parker M. Analysis of the consistency of intraurethral prostaglandin E(1) (MUSE) during at-home use. Urology 2001;58:262-266. http:/anti-infectives/Paris-Event/Live-Webcast.cfmwww.ncbi.nlm.nih.gov/entrez/query
15. Lewis RW, Weldon K, Nemo K, the MUSE-ACTIS Study Group. Combined use of transurethral alprostadil and an adjustable penile constriction band in men with erectile dysfunction: results from a multicentre trial. Int J Impot Res 1998;10:S49 (365). UPDATE MARCH 2005 25
16. Shabsigh R, Padma-Nathan H, Gittleman M, McMurray J, Kaufman J, Goldstein I. Intracavernous alprostadil alfadex is more efficacious, better tolerated, and preferred over intraurethral alprostadil plus optional actis: a comparative, randomized, crossover, multicentre study. Urology 2000;55:109-113. http:/anti-infectives/Paris-Event/Live-Webcast.cfmwww.ncbi.nlm.nih.gov/entrez/query
