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Men's Health Blog - February 2019

The Art of Titrating and Optimizing Penile Injection Therapy for Patients with Erectile Dysfunction

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Stanton Honig, MD
Professor of Urology
Director of Men’s Health
Yale Urology
330 Orchard Street, Suite 164
New Haven, CT 06511


For patients that do not respond to medication for erectile dysfunction (ED), called PDE 5 inhibitors, or have significant side effects, there are multiple other options for therapy. One option is penile injection therapy or intracavernosal injection therapy (ICI). This is one of the standard second line options for treatment of erectile dysfunction. Finding an experienced urologist who can provide optimal dosing and treatment for intracavernosal therapy is critical for a timely and good long-term result.

This treatment usually involves a combination of two or three medications named papaverine, phentolamine, and prostaglandin E1, referred to as a bimix or trimix. These medications have been used for over 20 years as the standard of care for treatment of erectile dysfunction. Since the combination is an “off label” use of the medication, you will not see advertising for this and therefore many patients are not aware of the excellent success rates with this treatment.

However, dropout rates can be quite high if medication use is not taught properly to patients and their dosing regimens are not appropriately optimized. Patients are often worried about injecting themselves. It is critical to relieve this fear for patients. One needs to explain that this is a virtually painless experience and well tolerated with minimal long-term risks.

Patients are also unfamiliar with self-injections. Having a team both at the office as well as a compounding pharmacy that is extremely compassionate and understanding for patients is paramount to achieving an excellent result.

Yale urologists spend a considerable amount of time with patients in the office to achieve optimal outcomes on the first visit. Our first decision is dosing patients appropriately during the first “in office” injection. This is an art, not a science, and requires experience and understanding of the cause of ED and interpretation of the results of the IIEF (international index of erectile function) questionnaire.

In my experience, certain patients should be started at a lower strength of medication and others should begin at a much higher strength. Despite this, we are only accurate in getting the appropriate dose on the first visit about 60% of the time. During the “in office” injection, three things may happen. 1) the patient may get a full erection and come down in a reasonable time frame. This is the ideal result.
2) the patient gets a full erection but his erection does not come down in a timely fashion and will require reversal of the erection with an antidote medication – this means that the treatment will work, but the dosing is too high.
3) the patient may get a ½ or ¾ erection that may require either a second dose or may require increasing the dose of medication at home.

In situations 1 and 3, the patient can be sent home after the first visit with the appropriate dose of medication. In the case where the patient had a prolonged erection (2), I recommend a follow-up appointment and re-dose the patient with a lower dose or strength of medication. This will relieve any of his fears of ending up in the emergency room with a prolonged erection.

In my practice, the following groups are dosed at a very low level.
1) Men 18- 40 with no risk factors and significant situational anxiety.
2) Nerve injury related ED from spinal cord injury or non-nerve or partial nerve sparing pelvic operations, such as radical prostatectomy or radical cystectomy. In these cases, I will start off with a small dose of a low concentration of trimix.

At the other end of the spectrum, is the older gentleman (greater than 75 years old) with significant vascular risk factors who has an IIEF score that is quite low and who has failed PDE5 inhibitors. In this group, I typically start with a much higher dose of trimix. Most other patients between the ages of 40 and 70 with more severe ED (low to moderate IIEF score) despite taking oral pills, I begin on a moderate strength trimix.

I feel that it is important to show the patient that the medication works on the first one or two visits or he will lose confidence in my ability to help him. Therefore, redosing with a higher dose on the first or second visit is paramount to see if the medication will work.

If the patients in group 3 do not have a full erection with penile injection therapy, I increase the amount of medication and I bring them back within a short period of time to make sure they are increasing their dose appropriately and do not lose confidence in our treatment plan.

Of course, there are patients who will not respond to penile injection therapy or will not be happy with self-injection therapy. Certainly, these patients are then excellent candidates for placement of penile prothesis.

In summary, there is an art as well as a science to intracavernosal injections. It is important to optimize patients early and have close follow up care and conversations to achieve a vigorous long-term result with this therapy. Finding a urologist with sexual medicine training will optimize your results. Overall, success rates are high.