Intracavernous Injection Combinations

July 4, 2014 admin Intracavernous Injection

Combination therapy for intracavernous injections was conceived to improve efficacy as a result of the synergistic effects of the drugs, and later, to reduce side effects as a result of using lower dosages of each agent.

One difficulty encountered with the use of combination agents is the need for the pharmacy to com-pound these agents since there are no combination intracavernous injection drugs currently approved by the FDA. In Europe, bimix is approved in several countries. Besides the obvious logistical difficulties

in obtaining the medications, it also then becomes necessary for the patient to use combinations containing alprostadil with some degree of expediency. This is due to the degradation of alprostadil in solution which occurs at a rate of approximately 30% over the course of 2 months.

Bimix (Papaverine, Phentolamine)

The combination of papaverine/phentolamine is attractive since it is highly effective. No FDA approved combination exists. In Europe, a papaverine/phentolamine combination is marketed as Androskat. It is distributed as a 2 mL ampule of papaverine 15 mg/mL and phen-tolamine 0.5 mg/mL.

The combination of papaverine and phentolamine is seen as an alternative to alprostadil monotherapy when significant pain results from alprostadil injection. Unfortunately, bimix also results in significant pain in a large percentage of patients using it, though the populations experiencing pain from the two regimens do not necessarily overlap.

It should be noted that bimix and alprostadil have nearly equivocal efficacies at 68.5% and 73% respectively. The approximate dose equivalency of 10 mg of alprostadil has similar efficacy to 30 mg papaverine + 1 mg phentolamine.

Trimix (PGE1, Papaverine, Phentolamine)

No standardized mixture is approved by the FDA or any European regulatory agencies and so these must be compounded by the pharmacy based on physician instructions. Concentrations of each component vary widely in the literature, but ratios of 12–30 mg papaverine: 10–20 mg alprostadil:1 mg phentolamine are fairly standard. Albaugh recommends a mixture of 30 mg papaverine + 10 mg alprostadil + 1 mg phentolamine per 1 mL with a starting dose of 0.1–0.5 mL.

Bechara et al. reported a crossover study of alprostadil versus trimix in a group of 32 men who had failed high dose bimix therapy. In this study, 50% responded to trimix compared to only 22% responding to alprostadil. Rates of pain for alprostadil were significantly higher than for trimix (41% vs. 12.5%).

Seyam et al. studied multiple combinations of trimix ingredients versus alprostadil in 180 men with erectile dysfunction. They found that all tested mixtures were highly effective and produce erections that are of equal frequency and quality to those produced by alprostadil. Sixtyeight percent of men using alprostadil and 67% of men using trimix achieved a rigid erection. However, duration of erections is longer than alprostadil and a larger number of episodes of priapism (5% vs. 0.6%) were produced. Interestingly, rates of pain were similar between the combined trimix group and the alprostadil group (14.5% vs. 17.9%, respectively). Viagra pills online

Combining trimix with sildenafil increases efficacy even in patients who are recalcitrant to many other pharmaceutical therapies. McMahon et al. found that of 62 patients who failed high dose sildenafil, high dose alprostadil, and high dose trimix separately, 29 (47.5%) achieved erections sufficient for intercourse by combining trimix with oral sildenafil citrate australia. Trimix concentration used in this study was 24 mg papaverine + 20 mg alprostadil + 1.6 mg phentolamine per 1 mL with a mean dose of 0.6 mL and a dose range from 0.15 mL to 1 mL.

Limited data exists about the potential for trimix to cause fibrosis. One study reported 2 (3.8%) episodes of clinically evident fibrosis of 53 patients using trimix. Few studies report data on fibrosis. While it is important to know that fibrosis can occur on trimix, stated rates of occurrence are misleading as there is no standard ratio, dose, or recommended frequency of trimix administration, and fibrosis is likely a phenomenon related to dose of phentolamine.