The Art of Optimizing Injection Therapy for ED

There are many treatment solutions for erectile dysfunction including oral medications, injections, intraurethral gels, hormone replacement therapy, vacuum therapy, and implants. Your healthcare provider will prescribe a treatment plan based on your situation.

Men with ED who do not respond to oral medications, i.e. Viagra (sildenafil), Cialis (tadalafil) or experience significant side effects should consider penile injection therapy. Intracavernosal Injection (ICI) therapy is one of the standard second line ED treatment options after oral medications fail. Finding a urologist who can optimize you for the appropriate dosing and train you on the proper injection technique is critical to a timely and successful long-term result.

The Medicine

The injection liquid is most commonly a mixture of two or three medications in a sterile vial. The possible medications are alprostadil (sometimes called prostaglandin E1, or PGE1), papaverine, and phentolamine. Mixtures of all three ingredients are commonly referred to as trimix, while mixtures of just papaverine and phentolamine are commonly referred to as bimix. Injection therapy has been used in the standard of care for treatment of erectile dysfunction for over 25 years. However, since trimix and bimix are ‘off label’ sterile compounds, you won’t see them advertised and therefore many patients are not aware of this treatment option or its very high success rate.

Having an experienced team at the office, supported by a compounding pharmacy that is knowledgeable and compassionate is paramount to excellent patient outcomes

Patients are scared of injecting themselves, so it’s critical to relieve them of this fear. I explain to my patients that this is a virtually painless experience and well tolerated with minimal long-term risks. Since most patients aren’t familiar with injecting themselves, having an experienced team at the office, supported by a compounding pharmacy that is knowledgeable and extremely compassionate is paramount to excellent patient outcomes. Dropout rates for this therapy can be quite high if medications are not taught properly to patients and their dosing regimens are not optimized appropriately.


We spend a considerable amount of time with patients in the office optimizing them on the first visit. Our first decision is dosing patients appropriately for the first in office injection. This is an art and a science and requires experience, an understanding of the cause of the problem, and interpretation of the results of the International Index of Erectile Function (IIEF) questionnaire.

The patient gets a full erection and comes down in a reasonable time. This is the ideal result

It has been my experience that certain patients should be started at a lower strength of medication and others started at a much higher strength. Regardless, 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 gets a full erection and comes 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 partial erection and require a second dose at the office, or increasing the dose of medication at home.

In situations 1 & 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’ll bring him back at a later date and re-dose him 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.
The following groups are dosed at a very low level:

1. Men 18- 40 with no risk factors or significant situational anxiety.

2. Men with nerve injury-related ED. These may be spinal cord injuries or non-nerve or partial nerve sparing pelvic operations such as radical prostatectomy or radical cystectomy. In these cases, I start with a low-dose, low-strength trimix or bimix.

At the other end of the spectrum are men 75 or older with significant vascular risk factors, very low IIEF scores, who have failed oral medications. I typically start this group on a much higher dose of trimix. Most other patients between the ages of 40 and 70 with more severe ED, and low to moderate IIEF scores, despite taking oral meds, I’ll start on a moderate strength trimix.

For patients who experience penile pain from the medication, I typically switch them to a bimix formulation without prostaglandin E1. Prostaglandin E1 may cause pain after injection and typically occurs more often in neurogenic erectile dysfunction cases after radical prostatectomy and with diabetics who have significant neuropathy (nerve damage).

It is important to optimize patients early and have close follow up to get a vigorous, long-term result with this therapy

It is important to show the patient that the medication works on the first or second visit or he may lose confidence in our ability to help him. Therefore, if initial results are poor, I will re-dose with a higher dose on the first or second visit to instill confidence that the medication will work.

For the patients in group 3 who do not get a full erection, I’ll increase the amount of medication, and then bring them back within a short period of time to make sure they are increasing their dose appropriately.
Of course, there are patients who will not respond to penile injection therapy or can’t tolerate self-injections. Certainly these patients are excellent candidates for placement of penile prosthesis.

Potential Side effects

ICI treatments should not be used more than once in a 24-hour period. The most common adverse effect is priapism. Priapism is defined as a prolonged erection lasting for more than four hours. If you experience priapism seek immediate medical attention at an emergency room. Other reported side effects include hematomas, burning pain after injection, local infections, and scar tissue formation. Scar tissue formation may result in penile curvature, but this occurs in less than 5% of patients. If it does occur, bring it to the attention of your healthcare provider. To reduce the likelihood of scar tissue formation, I recommend changing the injection site location within the injection target areas of the penis.

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 to get a vigorous, long-term result with this therapy. Finding a urologist with sexual medicine training will optimize your results. Overall, injection therapy success rates are high.


Stanton Honig

Stanton C. Honig M.D.

Clinical Professor of Urology
Director, Men’s Health

Yale School of Medicine
Department of Urology
330 Orchard St. Suite 164
New Haven, CT 06511
Phone: (203) 785-2815