Intracavernous injection therapy is the process whereby a small amount of a chemical is injected directly into the corpora cavernosa. These chemicals are smooth muscle relaxants and thus help increase blood flow into the penis. The advantage of injection therapy is that it does not depend on oral absorption, as pills do, and does not depend on absorption through the tissues, as with MUSE. The disadvantage is that it requires a small injection. Most men are anxious when they initially start with injection therapy but find that the procedure itself is usually not that uncomfortable. In most patients who do not respond to first-line, oral therapy or who are not candidates for oral therapy, injection therapy provides satisfactory erections.
The only FDA-approved chemicals for intracavernous injection therapy are Caverject (Pharmacia and Upjohn, Kalamazoo, MI) and Edex (Schwarz Pharma, Monheim, Germany). Both of these agents are prostaglandin E1. Other agents used alone or in combination are papaverine and phentolamine. All three – prostaglandin E1, papaverine, and phentolamine – may be used in combination, and the combination is referred to as “triple P” or “trimix.” Prostaglandin E1 and triple P are the two most common forms of injection therapy used, and they each have unique advantages and disadvantages.
Who is a candidate for penile injection therapy?
Because the injection requires manual dexterity, it is important that the man be able to perform self-injection. In some men for whom giving an injection may be difficult or who are anxious about pushing the needle into the side of their penis, an autoinjector is available that makes this easier. Another option is to have the man’s partner perform the injection. Similarly, if the man is obese and has trouble seeing his penis, self-injection may be difficult, and he would need to enlist the aid of his partner.
If a man has tried MUSE in the past and has had significant discomfort with it, then using Caverject/Edex will only cause further discomfort. In this situation, it would be more appropriate to try triple P. In addition, if the man has a known hypersensitivity or has had a prior reaction to prostaglandins, then Caverject/Edex would not be appropriate, and depending on the severity of the reaction, he could consider using bimix (papaverine and phentolamine only).
There are a number of conditions for which injection therapy might cause additional side effects. Men who are prone to priapism, such as those with sickle cell disease or trait, multiple myeloma, and leukemia, are at increased risk for priapism if they use this therapy. Men with Peyronie’s disease should be aware that during the process of injection, there is local trauma to the tunica albuginea, which could theoretically cause new plaques to form. Men taking blood thinners, such as warfarin (Coumadin) can use injection therapy, but should apply pressure to the injection site for a minute or so to prevent a bruise. Men taking an older type of antidepressant, a monoamine oxidase inhibitor such as Marplan, Nardil, Phenelzine, or Parnate, should not use this therapy.
How does one perform penile injection therapy?
Before you start to use intracavernous injection therapy at home, you are test dosed in the office. Of all of the therapies available, intracavernous injection therapy carries the highest risk of priapism, up to 2%. Most cases of priapism occur with first use, during the test dosing, which is important because if you return to your urologist’s office within 3 to 4 hours, the erection can easily be brought back down with just an injection of another chemical. If your urologist is concerned about priapism, he or she may choose to terminate your erection by injecting you with a chemical to stop the erection before you head home. Thus, test dosing minimizes your risk of having a case of priapism at an inopportune time. Secondly, your urologist can use the test dosing as a time for hands-on instruction, and you can be shown how to inject and actually perform your first self-injection with guidance in the office. This is very important because the first time you perform the injection therapy at home, you will be nervous, and remembering that you performed the injection in the office may help you relax.
The needle that you use to inject is quite small and short. It does not need to pierce deeply into the penis, just into the corpora on one side, for it to be effective (Figure 8). The syringe used is small also because the volume that you will be injecting is usually 1 cc or less. After your initial test dose, your urologist will decide on a dose that you will try initially at home. Do not get discouraged if this initial dose is not adequate. Most of us would prefer to prescribe a dose that is too small and then increase it as needed in order to avoid priapism.
Dosage and Volume Calculations for Injection Therapy
Using Prostaglandin E1 (Caverject, Edex)
|10 μg/mL vial||20 μg/mL vial||40 μg/mL vial|
|1.0 μg/0.10 mL||2.5 μg/0.125 mL||10 μg/0.25 mL|
|2.0 μg/0.20 mL||5.0 μg/0.25 mL||16 μg/0.40 mL|
|2.5 μg/0.25 mL||7.5 μg/0.375 mL||20 μg/0.50 mL|
|5.0 μg/0.50 mL||10.0 μg/0.50 mL||24 μg/0.6 mL|
|7.5 μg/0.75 mL||15.0 μg/0.75 mL||30 μg/0.75 mL|
|10.0 μg/1.0 mL||20 μg/1.0 mL||40 μg/1.0 mL|
When using injection therapy at home, you should keep several points in mind:
- Look where you are going to inject to make sure that no superficial veins are in the area.
- Gently wipe the area with an alcohol swab.
- Always inject on the side of the penis toward the base. The needle should be inserted straight into the penis at a 90-degree angle to the penis.
- Apply pressure to the injection site for a minute or two. If there is any bleeding from the injection site, hold the pressure for about 5 minutes. Men taking blood thinners should apply pressure to the injection site for about 5 minutes.
- Never reinject once you have injected, even if you fear that you have not injected properly.
- Alternate sides with each injection.
- Do not inject more frequently than every 48 to 72 hours.
- If your erection lasts longer than 3 hours, call the urologist on call. Don’t wait, it will only make it more difficult to treat the prolonged erection.
- If you are having troubles with performing the injections, talk with your urologist; perhaps getting more instructions or the autoinjector (PenInject 2.25 autoinjector) or teaching your partner would be helpful.
- Remember that with Edex and Caverject, once the medication has been reconstituted (i.e., once the powder is dissolved in the sterile water), it must be refrigerated. The solutions tend to lose their efficacy after 7 days.
- Make sure that the volume of the medication and the dose of medication that you are injecting are consistent (see calculation tables below).
- Do not reuse needles, and carefully dispose of used needles.
- Remember that your erection may persist after you climax and ejaculate and will go down when the medication wears out of your system.
What is the success rate of penile injection therapy?
Intracavernous injection therapy has a success rate ranging from 70% to 94%. It is helpful in erectile dysfunction of all causes. Injection therapy does not interfere with orgasm or ejaculation. However, its long-term success requires that the individual be comfortable with the injection therapy. Besides its overall success rate, another advantage of injection therapy is its quick onset of action, within 5 to 20 minutes of injection.
The dose required to achieve a successful erection varies greatly with the cause of the erectile dysfunction. Young men with spinal cord injury may only require 1 μg of Caverject/Edex, whereas older men with vascular disease and diabetes may require 40 μg of Caverject/Edex.
When compared with other therapies, injection therapy has been shown to be more effective than MUSE (alprostadil inserted into the urethra) in patients with erectile dysfunction. In addition, patients preferred injection therapy to MUSE, despite the need for injection, which most likely reflects the superior efficacy of injection therapy.
Injection therapy does appear to be efficacious in men who have not responded to Viagra therapy. Because it is not dependent on intact nerves, patients with a neurologic component to their erectile dysfunction (i.e., those who have undergone non-nerve-sparing radical prostatectomies) often respond to injection therapy.
What are the risks of penile injection therapy?
Despite the high efficacy and relatively low side effect profile of injection therapy, there is a high discontinuation rate. A recent review demonstrated that 15% of men who are offered injection therapy do not even try it, 40% will discontinue treatment within 3 months, and only 20% to 30% of men will continue with injection therapy for more than 3 years. Reasons for discontinuation include fear of needles, the injected volume, adverse effects, partner discontent with therapy, loss of partner °r relationship issues, problems with ability to administer the medication, and return of spontaneous erections.
Approximately 30% of men have pain with injection therapy. This pain may be injection site pain or, with Caverject/Edex, it may be a diffuse penile pain. Men who experience penile pain with Caverject/Edex can be switched to triple P (prostaglandin E1 phentolamine, and papaverine), which has a much lower incidence of penile pain.
If one does not look closely where one is injecting, it is possible to injure a superficial vein in the penis, causing a bruise, and, less frequently, a hematoma (a collection of blood). If this occurs, gentle pressure on the injection site will prevent further bleeding. The bruise or hematoma will resolve with time. Men taking blood thinners should be cautious when injecting and should always apply pressure after injecting. If there is significant penile swelling, you should contact your urologist.
The risk of priapism with injection therapy is about 2%, and most of these cases occur during the initial test dosing. Triple P carries a higher risk of priapism than Caverject/Edex. If your erection lasts longer than 3 hours, you should contact your urologist or the urologist on call. Never re-inject after you have injected, no matter how little you think you received with the first injection. Do not combine therapies for erectile dysfunction without the prior approval and guidance of your urologist.
The development of scar tissue within the corpora is a risk of injection therapy, and this risk is higher with triple P than with Caverject/Edex. Over time, this may be manifested by the need to use a higher dose of medication to achieve an adequate erection.
One of the concerns with injection therapy is that each time the small needle pierces the tunica albuginea to enter the corpora, it causes minor trauma to the area. Theoretically, this trauma may cause plaques to form, as occurs in Peyronie’s disease. Given this potential risk, men should not inject any more frequently than every 48 hours and should alternate sides. This will evenly distribute the trauma and keep the man’s penis from curving to one side.
The risk of liver injury with injection therapy is low and does not appear to be a concern for men taking Caverject and Edex. Liver function tests (blood tests obtained to assess how the liver is working) have shown elevated liver enzyme levels in men with a history of alcohol abuse or liver damage who were using intracavernous papaverine or papaverine in combination with phentolamine (bimix). Periodic liver function tests should be considered only in this select patient population.
Intracavernous Injection Therapy
In a study comparing Viagra with injection therapy, of the men who had satisfactory erections with both Viagra and injection therapy, 73% preferred to use Viagra. In a study of men who had satisfactory erections using < 20 μg of alprostadil injection therapy (Caverject or Edex), 69% of them successfully changed from injection therapy to Viagra and decided to continue with the Viagra. Although success with injection therapy was higher in this study, the satisfaction rate was higher for Viagra. In another study looking at use of triple P injection therapy, the dose of triple P needed to obtain an erection correlated with the likelihood of response to Viagra. If the dose of triple P was between 0.35 and 0.6 cc, the success rate with Viagra was 55%; however, if the dose of triple P was >= 0.7 cc, then the success rate with Viagra was 20%. Other studies have demonstrated that the patient’s response to prior treatments for erectile dysfunction was not a predictor of response to Viagra.