Penile Injectable Medications for ED
Injection therapy has been an efficacious treatment option for patients since it was introduced in 1983 (Brindley, 1986). Efficacy for this treatment option is as high as 87% to 93% (Linet & Ogring, 1996; Porst, Buvat, Meuleman, Michal, & Wagner, 1998).
Injection therapy can be given as a single agent (monotherapy) with prostaglandin E-1 or a multiagent mixture such as a trimixture of phentolamine, papaverine, and prostaglandin E1; a quadmixture of phentolamine, papaverine, prostaglandin E1 and atropine; or a bimixture of phentolamine and papaverine. Prostaglandin E1 can be compounded generically or is also dispensed as injectable alprostadil either as Caverject Impulse® or Edex®. While the Caverject Impulse or Edex systems are the FDA-approved drugs, some clinicians may use other forms of alprostadil. For example, some Veteran's Administration hospitals still use individual bottles of powder and teach the patient to reconstitute with bacteriostatic water for injection.
FDA-approved medications (Caverject Impulse, Edex) are utilized first, unless otherwise specified by the referring health care professional (although some clinics may not follow this practice related to cost factors). FDA-approved medications (Edex, Caverject Impulse) are more likely to be approved for insurance reimbursement than off-label compounded agents.
Seyam, Mohamed, Akhras, and Rashwan (2005) described the reasons for switching from monotherapy with prostaglandin to combination therapy with multiple vasoactive agents as pain, a lack of efficacy, and cost. These are the same reasons that I and the physicians I work with would switch a patient from prostaglandin E1 treatment. The main reason for switching from prostaglandin E1 to bimix, trimix, or quadmix is pain. Pain is the most common side effect for both Edex (Schwarz Pharma, 2004) and Caverject Impulse (Pharmacia, 2002) for men with ED.
Patients in my clinic who were post radical prostatectomy frequently reported pain in the penis as the injected Edex or Caverject Impulse began to work (about 10 to 20 minutes after injection). This complaint of pain in these patients fits with the hypothesis that pain is caused by activation of pain receptors via the prostaglandin in the time frame following prostatectomy when surgical incisions are still vulnerable to activation of local pain receptors. Trimix has been associated with decreased incidence of pain than with alprostadil alone (Baniel et al., 2000). If pain occurs with prostaglandin E1/alprostadil, the patient can be switched to trimix, quadmix, or bimix to decrease that side effect. The triple synergistic action of the three agents in trimix, which include prostaglandin E1, provides an erection utilizing much lower doses of the prostaglandin. Baniel et al. (2000) described the incidence of pain with monotherapy of prostaglandin E1 as 48.5%, while incidence of pain with trimix was 2.9%, and 0 for quadmix and bimix. Pain increased with increased doses of prostaglandin. Bimix does not contain prostaglandin and therefore may be the ultimate choice for patients who complain of pain from the injected medications that contain prostaglandin. Patients for whom pain is a problem are switched to trimix, quadmix, or bimix in the algorithm.
Patients may also be switched to trimix or quadmix if the prostaglandin E1 injection is not effective. The synergistic effects of combination therapy with trimix and quadmix are typically utilized when monotherapy is not effective (Baniel et al., 2000; Kuan & Brock, 2001; Seyam et al., 2005). The trimix may be increased to a super trimix combination of the same papaverine 30 mg, while doubling both the phentolamine (to 2 mg) and the prostaglandin E1 (to 20 mg) in doses up to 1 ml maximum. Finally, if a single-agent prostaglandin and trimix are ineffective, atropine 0.15mg/ml can be added to the trimix combination to create a quad mixture (Baniel et al., 2000; Montorsi et al., 2002).
The final reason for a change from Edex or Caverject Impulse to either generic prostaglandin E1 or multiagent therapy is cost. Edex and Caverject cost an average of $33 to $38 per injection for doses of 20 mcg. The same dose of generic compounded prostaglandin E1 is approximately $8 to $10 per injection from a compounding pharmacy. A 1 ml dose (which is actually a maximal dose) of trimix or quadmix costs about $12 to $15 per dose. Most patients utilize lower doses of 0.2 to 0.5 mls, which reduces the cost further. Patients for whom insurance will not cover medication and who can not afford the cost of medication may be switched to generic prostaglandin E1 or multi-agent mixtures. Costs for intracavernosal injections are shown in Table 1 .
Unrelated surgery January 2008 delayed incontinence recovery, which is now showing good signs of improvement (fraction of a pad a day as of late April 2008)