In Part 1, we introduced what Trimix is — a compounded injectable therapy for erectile dysfunction (ED) consisting of alprostadil, papaverine, and phentolamine. In Part 2, we take a deeper educational look into:
- Who Trimix may be appropriate for, based on clinical experience and literature.
- How to Inject Trimix safely and most effectively.
- Real-world candidate scenarios and administration tips from pharmacy and patient perspectives.
Who Trimix May Be For
Trimix may be prescribed to men experiencing ED, particularly when other first-line options have failed. It combines three agents that work via different mechanisms to relax smooth muscle and improve penile blood flow.
According to peer-reviewed literature and clinical experience, Trimix may be considered in patients who:
- Do not respond to oral PDE-5 inhibitors (like sildenafil or tadalafil), which occurs in approximately 30–40% of ED cases.
- Cannot tolerate oral ED medications due to side effects (e.g., headache, flushing, nasal congestion) or contraindications like nitrate use or certain heart conditions.
- Have underlying conditions affecting nerves or blood vessels, such as post-prostatectomy nerve injury, diabetes-induced vascular disease, or post-radiation fibrosis.
- Require customized therapy: Because it is compounded, Trimix allows physicians to select specific concentrations of each agent to suit a patient’s unique needs.
The combination of alprostadil (a prostaglandin E1), papaverine (a nonspecific PDE inhibitor), and phentolamine (an alpha-blocker) may help address multiple contributors to ED.
Read Part 1 of this Trimix Blog Series to learn about the 3 active ingredients in Trimix and what they do.
Trimix May Not Be Appropriate For:
- Individuals with a history of priapism or blood disorders like sickle cell anemia or leukemia.
- Those with penile anatomical deformities, scarring (Peyronie’s disease), or prior penile implant surgery.
- Patients with uncontrolled cardiovascular conditions or those on medications that increase bleeding risk, unless medically cleared.
A thorough clinical assessment is necessary before starting therapy.
How to Inject Trimix
Trimix is administered via intracavernosal injection (ICI) using a small, fine-gauge insulin syringe. Despite initial hesitation, most patients report the process is relatively painless when done correctly.
Steps of Administration:
- Draw Up the Dose: Medication is drawn into the syringe under sterile conditions.
- Select Injection Site: The injection is typically placed at the 10 or 2 o’clock position on the shaft of the penis, avoiding visible veins.
- Injection Technique: The needle is inserted directly into the corpus cavernosum. Injection should be slow and steady.
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4. Post-Injection: Apply gentle pressure to the site with gauze to prevent bleeding. An erection usually develops within 5–15 minutes.
Onset & Duration:
- Onset: Typically within 10–15 minutes.
- Duration: 30 to 60 minutes, depending on dose and individual response.
Safety Considerations
Side Effects May Include:
- Minor pain at the injection site.
- Bruising or hematoma formation.
- Penile fibrosis with frequent use in the same area.
- Priapism (erection lasting >4 hours) — this is a medical emergency. Patients are trained to recognize and respond if this occurs.
Proper dose titration under physician supervision and adherence to protocols significantly reduce risks.
Real-World Candidate Examples
Example 1: Post-Prostatectomy Patient
Background: 58-year-old male with ED following radical prostatectomy for cancer. Tried tadalafil without improvement.
Why Trimix?: Nerve injury during surgery often impairs response to oral meds. Trimix may bypass this by directly stimulating smooth muscle vasodilation.
Example 2: Patient with Diabetes and Vascular Disease
Background: 64-year-old with long-standing diabetes, hypertension, and poor response to PDE-5 inhibitors.
Why Trimix?: Microvascular damage may limit blood flow despite intact nerve signaling. The multimodal mechanism of Trimix may improve penile perfusion.
Example 3: Patient on Nitrates for Angina
Background: 71-year-old male using nitroglycerin patches for cardiac angina. Unable to use sildenafil due to drug interaction risk.
Why Trimix?: As a local therapy, Trimix does not carry the same systemic interaction profile, making it a viable alternative under cardiology clearance.
Example 4: Healthy Male in His 40s With Performance Anxiety
Background:
A 45-year-old man in good physical health reports inconsistent erections during partnered sex, particularly in new relationships. He does not have a history of diabetes, cardiovascular disease, or surgery. PDE-5 inhibitors provided only partial results, and he dislikes the unpredictability of timing and onset.
Why Trimix?
In cases where psychological factors like performance anxiety contribute to ED, oral medications may not be enough to overcome the brain’s inhibition of arousal. Trimix works directly on the penile tissue, bypassing the need for sexual stimulation or central arousal signals. This can provide reassurance and a sense of control, helping break the anxiety-performance cycle. Trimix is sometimes used as a “second-line” approach in these cases when behavioral therapies and oral agents are not sufficient.
Pro Tips for Successful Administration of Trimix
Here are some tips from providers and pharmacists for maximizing comfort and safety:
Rotate Injection Sites: Alternate between sides and avoid injecting in the same spot more than once every 7 days to minimize fibrosis risk.
Titrate Dose: Start low (as instructed) and increase slowly based on physician guidance. Many men find that minimal dosing works well.
Store Properly: Depending on the formulation, some Trimix must be kept refrigerated or frozen. Ask your pharmacy for exact handling instructions.
Keep an Emergency Plan: Know when to seek medical care for priapism, and ensure your partner (if applicable) is informed.
Don’t Inject More Than 3 Times a Week: This reduces long-term tissue risk and gives recovery time.
Watch Step-by-Step Guide: Our expert pharmacist, Tony Buchta, RPh guides you through every step of the way in this informational video. Watch it a couple of times before you administer.
Searching for the Best Trimix Compounding Pharmacy in Ohio?
Trimix may be an option for men with ED who have not found success or are unable to use oral medications. As a compounded medication, it allows for physician-directed dosing that aligns with individual needs. With proper training, most patients can safely and confidently self-administer Trimix at home.
At Central Ohio Compounding Pharmacy, we support providers and patients with precise formulations, pharmacist support, and in-depth education to ensure safe use. If you think you might be a candidate, speak to your healthcare provider to learn more.
If you’re an Ohio physician, PA or NP interested in offering your patients Trimix, connect with our team. We’ve heard our patients and doctors describe us as the best trimix compounding pharmacy in Ohio, and we work hard to keep them satisfied with the quality of the medication, as well as our top-notch customer service.
References
- Hua, V., Roth, B., Shumaker, A., Bole, R., & Bajic, P. (2024). What are options for my patients with erectile dysfunction who have an unsatisfactory response to PDE5 inhibitors? Cleveland Clinic Journal of Medicine, 91(11), 667–670. Link
- Heaton, J. P. W., Lording, D., Liu, S.-N., Litonjua, A. D., Guangwei, L., Kim, S.-C., … Bélanger, A. (2001). Intracavernosal alprostadil is effective for the treatment of erectile dysfunction in diabetic men. International Journal of Impotence Research, 13, 317–321. Link
- Belew, D., Klaassen, Z., & Lewis, R. W. (2015). Intracavernosal injection for the diagnosis, evaluation, and treatment of erectile dysfunction: A review. Sexual Medicine Reviews, 3(2), 115–128. Link
- Burnett, A. L., Nehra, A., Breau, R. H., Culkin, D. J., Faraday, M. M., Hakim, L. S., … Shindel, A. W. (2018). Erectile dysfunction: AUA guideline. The Journal of Urology, 200(3), 633–641. Link
- Bechara, A., Casabé, A., Chéliz, G., Romano, S., & Fredotovich, N. (1996). Prostaglandin E1 versus mixture of prostaglandin E1, papaverine and phentolamine in nonresponders to high papaverine plus phentolamine doses. The Journal of Urology, 155(3), 913–914. Link
- Kulkarni, A., Ikedionwu, I., Singh, A., Penukonda, S., Bloom, D., & Raheem, O. (2024). History of priapism treatment in the 20th century. The Journal of Sexual Medicine, 21(Suppl 1), qdae001.309. Link
- Sokolakis, I., & Hatzichristodoulou, G. (2020). Current trends in the surgical treatment of congenital penile curvature. International Journal of Impotence Research, 32, 64–74. Link
- Köhler, T. S., Kloner, R. A., Rosen, R. C., Burnett, A. L., Blaha, M. J., Ganz, P., Goldstein, I., Kim, N. N., Lue, T., McVary, K. T., Mulhall, J. P., Parish, S. J., Sadeghi-Nejad, H., Sadovsky, R., Sharlip, I. D., & Miner, M. (2024). The Princeton IV consensus recommendations for the management of erectile dysfunction and cardiovascular disease. Mayo Clinic Proceedings, 99(9). Link