What Is Trimix?
Trimix injections are a sterile, compounded medication that is administered directly into the corpus cavernosum of the penis.
This is part one of our Trimix FAQ Series.
It is used in men with erectile dysfunction who have not achieved satisfactory results with oral medications or who are unable to take them due to medical concerns or side effects.
Research supports the effectiveness of intracavernosal injection therapy for erectile dysfunction. A large-scale study found that
“ICI therapy is associated with very high success rates even in men with high comorbidity profiles” and demonstrated that “89% of Trimix users were capable of having sexual intercourse.”
What makes Trimix unique is its combination of three active pharmaceutical ingredients:
- Alprostadil
- Papaverine
- Phentolamine
Each of these medications on its own may help support penile blood flow, but in combination, they work synergistically to improve the chances of achieving and maintaining an erection firm enough for sexual activity.
This formulation is prepared by compounding pharmacies, meaning it’s not commercially mass-produced or FDA-approved, but is created specifically to meet a prescribing physician’s directions and the patient’s unique needs.
How Do Trimix Injections Work?
To understand how Trimix injections potentially work, it’s helpful to first understand the mechanics of an erection.
A Quick Overview of Erections and Blood Flow
An erection is largely a vascular event, meaning it depends on healthy blood vessels. When a man is sexually stimulated, signals from the brain trigger the relaxation of smooth muscle in the penis and an increase in blood flow into the corpora cavernosa, the two sponge-like regions of erectile tissue.
The blood gets trapped in these tissues as the outflow is restricted, resulting in a firm erection.
Now, let’s explore how Trimix supports this process.
The Three Ingredients in Trimix and What They Do
Each component of Trimix contributes to the overall effect in its own way:
1. Alprostadil
- Function: Alprostadil is a prostaglandin (PGE1) that works by directly relaxing smooth muscle and dilating blood vessels, increasing blood flow into the penis.
- Pearl: Alprostadil is the same active ingredient found in the brand-name single-drug injection Caverject, but using it alone often requires higher doses that may cause more discomfort or side effects.
2. Papaverine
- Function: Papaverine is a vasodilator that works by inhibiting phosphodiesterase enzymes, resulting in smooth muscle relaxation and vessel dilation.
- Pearl: Papaverine isn’t used orally for ED, but is quite effective in intracavernosal use because it relaxes the penile blood vessels directly.
3. Phentolamine
- Function: Phentolamine is an alpha-adrenergic blocker that works by preventing the constriction of blood vessels. This helps to sustain the erection by allowing the blood to stay trapped in the penis longer.
- Pearl: It acts more as a support agent, reducing the chance of premature detumescence (loss of erection).
Together, these three agents form a well-balanced formulation designed to address multiple points of dysfunction in the erection process.
Why Trimix May Be Prescribed
Medical professional often consider trimix injections as a second-line or third-line therapy for ED after oral medications have failed or caused unwanted side effects. Some common scenarios where Trimix may be considered:
- Ineffective oral PDE5 inhibitors (like Viagra or Cialis)
- Intolerable side effects from oral medications
- Contraindicated PDE5s in patients with certain cardiovascular conditions
- Men with diabetes, post-prostatectomy ED, or neurological causes of ED
Important Note:
Since Trimix is a compounded medication, it’s essential to get it from a licensed compounding pharmacy that adheres to USP <797> sterile compounding standards. This ensures the preparation is safe, sterile, and meets quality expectations.
Administration: A Needle, Yes — but Not as Scary as It Sounds
The idea of an injection into the penis understandably causes concern for many men. However, most patients report that, with proper training and technique, the process is far less uncomfortable than expected.
Key points about administration:
- Trimix is injected with a very fine needle into the lateral side of the penis.
- The injection should be done while seated or lying down.
- Injections are usually limited to no more than 2–3 times per week.
- Providers carefully titrate the dose to avoid complications such as prolonged erections.
Providers will typically start patients on a low dose and adjust as needed.
Approach to Using Trimix: What to Expect
- Consultation & Evaluation: Providers review ED causes and assess oral medication history.
- Initial Prescription: Expert pharmacists compound a low-dose formula based on the provider’s judgment.
- Patient Training: In-office training on proper injection technique is often provided.
4. Trial at Home: Patients try the dose and report effectiveness and any side effects.
5. Dose Adjustment: The provider may adjust the concentration or volume based on the patient’s response.
6. Ongoing Monitoring: Periodic check-ins to reassess effectiveness, tolerability, and satisfaction.
Clinical Pearls for Patients and Providers
- Storage Matters: Trimix must be stored in the refrigerator or freezer, depending on the formulation. Improper storage may affect potency.
- Don’t Double-Dose: If the medication doesn’t work the first time, never re-inject on the same day. Follow up with your provider.
- Communication is Key: Open communication between patient and provider is crucial, especially when fine-tuning the dose.
- Priapism is Rare — but Serious: If an erection lasts longer than 4 hours, seek medical attention immediately to avoid permanent damage.
Wrapping Up Part 1
Trimix may offer a promising option for men seeking alternatives to oral ED medications. While the concept of self-injection can feel daunting, many find that the outcomes are well worth the learning curve. With its unique combination of three vasodilators, Trimix works at multiple levels to support healthy erectile function.
In Part 2 of this blog series, we’ll answer common questions like:
- How long does Trimix last?
- What are the potential side effects?
- What should you do if it doesn’t work?
- How do you properly store and travel with Trimix?
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References
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- Coombs, P., Heck, M., Guhring, P., Narus, J., & Mulhall, J. P. (2012). A review of outcomes of an intracavernosal injection therapy programme. BJU International, 110(11), 1787–1791. Link
- Duncan, C., Omran, G. J., Teh, J., Davis, N. F., Bolton, D. M., & Lawrentschuk, N. (2019). Erectile dysfunction: A global review of intracavernosal injectables. World Journal of Urology, 37(7), 1495–1503. Link
- Kim, N., Vardi, Y., Padma-Nathan, H., Daley, J., Goldstein, I., & Saenz de Tejada, I. (1993). Oxygen tension regulates the nitric oxide pathway: Physiological role in penile erection. The Journal of Clinical Investigation, 91(2), 437–442. Link
- Linet, O. I., & Neff, L. L. (1994). Intracavernous prostaglandin E1 in erectile dysfunction. Journal of Molecular Medicine, 72(2), 139–149. Link
- Selvin, E., Burnett, A. L., & Platz, E. A. (2007). Prevalence and risk factors for erectile dysfunction in the U.S. The American Journal of Medicine, 120(2), 151–157. Link
- Seyam, R. M., Mohamed, K. R., Akhras, A. A., & Rashwan, H. M. (2005). A prospective randomized study to optimize the dosage of Trimix ingredients and compare its efficacy and safety with prostaglandin E1. International Journal of Impotence Research, 17(4), 346–353. Link
- Shmueli, J., Israilov, S., Segenreich, E., Baniel, J., & Livne, P. (1999). Progressive treatment of erectile dysfunction with intracorporeal injections of different combinations of vasoactive agents. International Journal of Impotence Research, 11, 15–19. Link
- Traish, A., Gupta, S., Gallant, C., Huang, Y-C., & Goldstein, I. (1999). Phentolamine mesylate relaxes penile corpus cavernosum tissue by α1- and α2-adrenergic receptor blockade. International Journal of Impotence Research, 11(1), 7–14. Link
- Virag, R. (1982). Intracavernous injection of papaverine for erectile failure. The Lancet, 320(8299), 938–939. Link