BIMIX, TRIMIX, QUADMIX: Penile Injection Therapy for Erectile Dysfunction

A patient guide to Penile injection therapy, formulations, dosages, and unique injection techniques.

Keywords: Impotence, Atropine Sulfate, Penile injection, Trimix, Bimix, Edex, Alprostadil, Priapism, Alprostadil, Papaverine, Quad Mix, Caverject, Muse, Intracavernosal Injection, ICI,

Introduction

Penile injections have long been used for the diagnosis and treatment of erectile dysfunction (ED). Before the dawn of Viagra, the primary treatment methods for ED were microvascular surgeries, penile prosthesis implantation, psychosocial interventions and penile injection therapies. For patients who fail oral ED medication such as Viagra or Cialis the next line therapy can be 1) change the type of oral ED medication or 2) proceed to penile injections. While penile shockwave therapy is gaining much attraction as a therapy that can fit nicely between patients who fail to respond to ED meds penile injection therapy remains the next step in therapy and has high satisfaction rates.

Penile injection therapies remain a mainstay of therapy in the field Urology and have several benefits:

Benefits of Penile Injection Therapy for Men.

1) Provides a rapid and natural erection to occur within 5-10 minutes of injection

2) Dosage can be titrated to promote erection duration and hardness of erection.

3) No sexual stimulation or erotic thoughts are required for an erection to occur.

4) Maintains full penile sensation and orgasmic function.

Side effects of Penile Injection Therapy for Men

1) Risk of priapism

2) Reduces ability of spontaneity

3) Requires a small, painless injection into the penis

4) Medication does require refrigeration

Benefits of TRIMIX compared to Viagra and Cialis

In some men, Viagra, Cialis and other ED meds are contraindicated. In men who have a history of heart attack or who use nitrates for chest pain may not be able to used oral ED medication. Some men cannot tolerate the systemic side effects that can occur with oral ED meds such as stuffy nose, headaches, muscle pain, back pain, or blurry vision. In these particular situations, penile injections can be an option. Unique to penile injection therapy is the mechanism of action and localization of the medication. Penile injections do not exert an effect on the entire body unlike oral ED meds. Penile injections are localized within the penile cavernosal tissue. Furthermore, the mechanism of action of penile injection is significantly different than the normal pathway utilized by ED meds to assist in achieving an erection. This can owe to the lower side effect profile of penile injections and can be a safer, better and more efficacious treatment option for men with contraindication to oral ED medication usage.

Much of the barrier to penile injection therapy is the anxiety surrounding an injection into the penis. It is known that men who consistently used penile injections, also known as intracavernosal injections or ICI, have high satisfaction rates. Many patients can attest that the injections can be made virtually painless.

How to Properly Administer Penile Injections

According to the American Urologic Association (AUA) guidelines an in-office test injection should be performed to ascertain the following by the urologist:

1) the length of duration of penile erection

2) injection response

3) penile rigidity after injection

4) penile injection technique (how to give injection/location on penis)

5) observe for priapism

6) observe for pain on erection

7) evaluate penile anatomy

8) provide men the confidence to perform their own injection

9) educating the patients partner about the injection technique and site for injection.

TRIMIX Penile Injection Components

Trimix is a non-FDA approved product for the treatment of erectile dysfunction. The only FDA approved penile injection therapy for the treatment of ED is Alprostadil, also known as Caverject, Edex or Muse. Trimix, on the other hand, is a combination of three vasoactive ingredients. The components of Trimix include Papaverine, Phentolamine, and Alprostadil. The three components together are commonly called combination therapy. Together Trimix utilizes several different mechanisms to achieve an erection, such as:

1) Increasing corporal smooth muscle relaxation

2) Decreasing smooth muscle and blood vessel contraction

3) Increasing blood vessel dilation

Papaverine

A vasodilating agent that promotes the widening of the blood vessels and influx of blood volume into the penis. Mechanism of action is by relaxing the smooth muscle contained within the walls of blood vessels.

Phentolamine

An alpha blocker that prevents the excitatory signals to blood vessels that normally keeps blood vessel constricted, thereby leading to muscle relaxation.

Alprostadil

Alprostadil is the only FDA approved mono therapy penile injection for the treatment for ED. Alprostadil was introduced in the early 1980’s and approved by the FDA in 1994. Alprostadil acts by stimulating the production of cAMP (Cyclic adenosine monophosphate) in both penile smooth muscle and blood vessels. A cascade of events leads to muscle relaxation, penile hardness and a rigid erection.

Alprostadil is unique compared to oral ED medication , it does not rely on the Nitric Oxide pathway utilized by oral ED meds to encourage an erection. Most men who fail to respond to oral ED meds have an underlying neurogenic injury or history of radical prostatectomy (removal of the prostate for prostate cancer). For men with neurogenic ED who use Alprostadil mono-therapy a lower dose should be utilized.

Bimix Penile Injection

Bimix is composed of two components, Papaverine and Phentolamine Mesylate.

Men who are candidates for Bimix injection, compared to Trimix, are those men who are very sensitive to low doses of Trimix. Often times, men who have a neurologic injury require a very low dose of penile injection medication. The dosage of Trimix can be so low, on the magnitude of 0.1 or 0.05 micrograms, that the patient will have difficulty drawing this dosage into a syringe. In this particular clinical scenario, Bimix is great candidate medication to utilize.

Quad Mix for Penile Injection

Quad Mix has the same components as Trimix with the addition of atropine sulfate.

Atropine sulfate inhibits nervous system receptors responsible for smooth muscle control. In effect, atropine sulfate provides further smooth muscle relaxation in combination with the other three components of trimix. Quad Mix is a great option for men who fail Trimix and have achieved the maximum dosage.

Combining Trimix and Oral ED Meds

There are several studies that report a high satisfaction rate in men who utilized a combination of both ED meds with penile injection therapy. In effort to improve penile function and penile rehabilitation, men post radical prostatectomy, have performed the following: Intracavernosal injection of alprostadil 2-3x times per week in addition to use of the Viagra ™ during sexual activity. It is important to note that Alprostadil was injected 2-3x per week on a scheduled basis and not during sexual activity. Satisfaction scores my men who use this therapy were high, especially in men who had failed oral ED meds and did not want to perform penile injection just before activity.

Another study treated 35 men post non nerve sparing radical prostatectomy with Quad Mix (papaverine hydrochloride, prostaglandin E1, phentolamine mesylate, and atropine) three times weekly combined with Cialis ( Tadalafil) 20mg given 2 hours prior to sexual activity ( on days penile injection was not used). This unique protocol conveyed an acceptable level of patient satisfaction with limited adverse events.

How to improve Spontaneity with Penile Injection Therapy

Trimix has to be refrigerated at all times and this makes it difficult to be spontaneous with a partner. Also, trimix has to be injected, reducing spontaneity. One easy way patients have improved their spontaneity is by pre-fill the syringes with the prescribed dosage of trimix. Keep the pre-filled syringes in the refrigerator as opposed to the trimix bottle. This will provide the individual a quick and easy opportunity to excuse himself, inject with a pre-filled syringed and enjoy the moment. Having to draw up TRIMIX every time during an intimate time can be difficult and time consuming.

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Sources

Mydlo JH, Volpe MA, Macchia RJ. Initial results utilizing combination therapy for patients with a suboptimal response to either alprostadil or sildenafil monotherapy. Eur Urol. 2000;38:30-34. 2

Raina R, Nandipati KC, Agarwal A, et al. Combination therapy: medicated urethral system for erection enhances sexual satisfaction in sildenafil citrate failure following nerve-sparing radical prostatectomy. J Androl. 2005;26:757-760.

Nehra A, Blute ML, Barrett DM, Moreland RB. Rationale for combination therapy of intraurethral prostaglandin E(1) and sildenafil in the salvage of erectile dysfunction patients desiring noninvasive therapy. Int J Impot Res. 2002;14 (1 suppl):S38-S42.

McMahon CG, Samali R, Johnson H. Treatment of intracorporeal injection nonresponse with sildenafil alone or in combination with triple agent intracorporeal injection therapy. J Urol. 1999;162:1992-1997

E. Ventimiglia et.al. 679 Proposal of new rehabilitation protocol based on the use of intracavernous injections and Tadalafil. Preliminary results from a pilot study. The Journal of Sexual Medicine, Vol. 15, Issue 7, S390. Published in issue: July 2018