For men with erectile dysfunction who are not able to use the oral drugs for ED like sildenafil, tadalafil, and other phosphodiesterase Type 5 inhibitors, another option is the penile injection most commonly known as Tri-Mix. Tri-Mix is, as the name implies, a combination of 3 separate medications in one injection, which is very effective in producing an erection within a few minutes.
The typical Tri-Mix formula contains papaverine, phentolamine, and prostaglandin E1 (PGE1 or also known as alprostadil). There are related formulas like Quad-Mix which has those ingredients combined with atropine, and Bi-Mix which is typically papaverine and phentolamine without the alprostadil.
Since these formulations are not available from drug manufacturers, they must be made at a compounding pharmacy that is certified for sterile products. The highest standards for cleanroom operation and sterile technique are required to make these products accurately and consistently.
Since these formulations are compounded by the pharmacy, the options for dosing are much greater than for typical drug company formulations. Each of the 3 active components can be varied (within limits) so that the patient has many options to reach the best effects. The response is a function of both the concentrations of the components and the injection volume. Most men will use an injection volume between 0.2ml and 0.5ml per injection, with a maximum of 1ml per use, with no more than once per day or 3 times per week. If the injection volume required for a lower concentration formula becomes excessive, the concentration of one or more components can be increased.
The primary limiting factor for Tri-Mix formulas is typically the concentration of the alprostadil. Pain on injection is commonly reported with higher doses of this component, assuming the patient is using proper injection technique. If this is reported by the patient, the usual response is to reduce the injection volume until either the pain is gone or the injection is not effective. If the injection becomes ineffective and there is still pain on injection, a trial of a higher amount of papaverine or phentolamine while lowering the alprostadil is appropriate. Some men are sensitive enough to the alprostadil that they have to leave it out altogether, which would be Bi-Mix. Some men start out with Bi-Mix because it works for them without alprostadil.
Quad-Mix is occasionally used when the patient has gotten unsatisfactory results with optimum concentration and injection volume of Tri-Mix. The additional atropine (a parasympatholytic drug) inhibits receptors that control smooth muscle relaxation which can increase firmness during the erection.
The primary side effects of therapy include: pain on injection, either from injection technique or alprostadil; fibrosis from poor technique or high levels of papaverine; and priapism. Certain hematologic conditions such as Sickle Cell Anemia, Multiple Myeloma, and Leukemia are known to increase the incidence of priapism.
For those men for whom oral therapy has failed, these penile injections are an accessible option for erectile dysfunction. The therapy is generally well-tolerated and effective for these men.