- Trimix is a compounded drug comprised of papaverine, phentolamine, and alprostadil.
- Trimix penile injection therapy is often used as a second-line alternative to PDE5 inhibitors (oral drugs, such as Viagra, Cialis, or Levitra) for the treatment of erectile dysfunction (ED).
- When injected into the penis, the three drugs in Trimix work together to dilate blood vessels, allowing increased blood flow that can trigger an erection in 5 minutes or less.
- Trimix injections are easy to use and often self-administered by the patient at home after receiving instructions from a physician.
- Each patient’s Trimix dosage is customized according to their needs and response to the treatment, and the medication is filled in a sterile environment by a compounding pharmacy.
Trimix Injections for Erectile Dysfunction:
A Guide
Trimix At a Glance
Table of Contents
- • What is Trimix?
- • Trimix’s 3 Components
- • Trimix Dosage Recommendations
- • How Trimix Works
- • Who Should Use Trimix?
- • How to Self-Administer Trimix Injections
- • Potential Trimix Side Effects
- • Frequently Asked Questions
- • Meet Our Trimix Expert
- • How to Get Trimix Online
What is Trimix?
Trimix is an injectable medication comprised of papaverine, phentolamine, and alprostadil used as a treatment for erectile dysfunction (ED). Trimix injections can trigger an erection within 5 minutes and result in longer and firmer erections that last through climax. Since Trimix dosages are customized to each patient’s needs, the drug must be prescribed by a healthcare provider.
Erectile dysfunction (ED), a sexual health condition characterized by the inability to achieve or maintain an erection, affects an estimated 15-30 million men in the U.S., with over 600,000 new cases arising each year.[1] While ED can occur in younger men, it becomes more prevalent after age 40. Additionally, large multinational studies have estimated the prevalence of ED in young men to be as high as 30%. It’s predicted that by 2025, 322 million men worldwide will have ED.
Trimix aims to provide a reliable, easy, safe way for men with ED to achieve and sustain erections firm enough for sex. Its main benefits include:
- • Efficacy
- • Simple storage
- • Long duration
- • Easy self-administration
Trimix was developed in 1983 when scientists discovered that adding phentolamine and alprostadil to papaverine, at the time a standalone ED treatment, created a more effective compound.[4] Today, Trimix injections are an accepted second-line ED medication when oral PDE5 inhibitors, like Viagra, Levitra, or Cialis, are ineffective or create side effects.[3] Since Trimix works locally where it is injected, rather than circulating throughout the bloodstream like oral drugs, it tends to have a lower risk of side effects.
At Olympia Compounding Pharmacy, we specialize in Trimix medication. In this Trimix guide for patients as well as physicians, we’ll explain the components of Trimix, dosage recommendations, potential side effects, as well as how to get Trimix online for yourself or your patients. Learn more about our compounding pharmacy or use our contact form to reach us for additional help.
* Olympia Pharmacy is the official Trimix supplier to Memorial Sloan Kettering Cancer Center. *
What Are Trimix’s Components?
Trimix medication contains papaverine, phentolamine, and alprostadil. These three drugs are compounded into a customized formula tailored to each patient’s requirements. Before using Trimix, it is recommended that you consult a healthcare provider to confirm you are not allergic to any of these three components.
Papaverine
Papaverine aids men with ED by enhancing blood flow to the penis, allowing patients to achieve and sustain a firm erection for sexual intercourse. When used alone, papaverine is often prescribed for patients with circulatory disorders to improve blood flow.[5] As a vasodilator, papaverine relaxes and widens blood vessels, facilitating blood circulation to the heart and body. Furthermore, papaverine relaxes smooth muscle inside large blood vessels, particularly the coronary, systemic peripheral, and pulmonary arteries, with minimal effects on the central nervous system.
Phentolamine
Phentolamine is a long-acting adrenergic alpha-receptor blocker that increases blood flow to the skin, mucous membranes, abdominal organs, and reduces blood pressure.[6] Phentolamine works by obstructing alpha receptors in the body, which are present in the smooth muscle lining blood vessel walls. When these alpha receptors are blocked by phentolamine, the muscles relax and blood vessels dilate, producing a significant boost in circulation.
Alprostadil
As a vasodilator, alprostadil relaxes the muscles and widens the blood vessels in the penis, enabling continuous blood flow to achieve and sustain an erection. Three separate studies on the efficacy and safety of alprostadil found it is an effective ED treatment with manageable side effects.[7][8]
Additional ED Treatment Options
Atropine
Recent clinical interest has highlighted atropine’s potential in ED treatment, particularly through its ability to block muscarinic receptors at low doses and induce the release of endothelium-derived relaxing factor (EDR) at higher doses. This dual action suggests atropine could play a role in enhancing erectile function.
Prostaglandin E1 (PGE-1)
Another notable component is PGE-1, recommended in doses ranging from 10-60 micrograms (mcg) for ED treatment. It’s a vasoactive agent that, like the other components of Trimix, helps in achieving erections by dilating blood vessels.
Reversal
Phenylephrine (Erection Reversal)
In cases of prolonged erections, phenylephrine offers a solution. It should be injected using the same method as Trimix, but only after about 4 hours of sustained erection to prevent negative outcomes. Dosing with 0.5 ml and repeating every 5-10 minutes until the erection subsides is advised, but frequent use for erection “knock down” is not recommended due to potential risks.
Trimix Dosages
Trimix dosages are customized based on each patient’s needs. At Olympia Pharmaceuticals, we recommend starting with a lower dosage to avoid prolonged erections. After the first dose, your doctor may adjust the dosage. Don’t be discouraged by a poor result with the first few injections, as the initial dose is kept low to prevent prolonged erections during dosage titration.
Typically, the starting Trimix dosage should be 0.05-0.2 cc. We recommend waiting 48 hours before increasing the dose, then going up by 0.025-0.05 cc until optimal results are achieved.
Key points to remember about Trimix dosages:
- • The starting Trimix dose is typically 0.05-0.1 cc.
- • Wait 2-3 days between dose increases when beginning the drug.
- • Increase by 0.025-0.05 cc until you’re experiencing optimal results.
- • Phenylephrine is commonly used to reverse prolonged erections during dosage titration.
- • Typically, .25-.6 cc of 1 mg/ml phenylephrine reverses the effects of Trimix adequately.
How Does Trimix Work?
Once Trimix is injected directly into the shaft of the penis, the compounded mixture of papaverine, phentolamine, and alprostadil triggers a vasodilation effect that causes the relaxation and expansion of blood vessels, allowing for the increased blood flow needed to achieve and sustain an erection.
Trimix can work quickly, triggering an erection within 5-10 minutes or less. Some men respond after foreplay begins. Erections typically last 1-2 hours with Trimix, often persisting through climax. Trimix is not designed to enlarge the size of the penis. However, it can help men with ED obtain and maintain a firm erection for longer periods.
With appropriate administration, Trimix can assist men in regaining their lost sexual function due to ED, enhancing their overall quality of life. Remember, erections lasting over 4 hours are a medical emergency requiring immediate care.
Who Should Use Trimix?
Trimix may be suggested for men with erectile dysfunction as an alternative to PDE5 inhibitors if they have proven ineffective or resulted in side effects.
Some common risk factors and conditions associated with ED include:
- • Low testosterone
- • Cardiovascular disease
- • Diabetes
- • Prostate issues
- • Depression
- • Anxiety
- • Neurological/spinal cord injury
Trimix may also be appropriate for patients with medical conditions that preclude taking oral ED drugs, such as men who’ve had prostate surgery or certain cardiovascular diseases, or for patients who cannot take PDE5 inhibitors due to concurrent nitrate therapy or certain beta-blockers.
If you’re a patient, contact your physician to find out if Trimix is right for you. Here are questions to ask your doctor about ED to help start the conversation.
Trimix Benefits
Tri-mix injections offer several advantages over alternative medications for erectile dysfunction (ED) treatment, such as:
- • Swift onset with prolonged duration
- • Straightforward and minimally invasive administration
- • Demonstrated high efficacy in clinical evaluations
How to Self-Administer Trimix Injections
After receiving a physician’s instructions, Trimix injections are typically self-administered at home. While this may sound daunting, it’s actually an easy procedure that many patients find painless with practice. (See our injection instructions below.) However, it’s important to use proper injection technique with a 29-30 gauge x 1/2″ needle inserted fully into the shaft of the penis for intracavernosal administration.
Below are the general step-by-step instructions for self-administering Trimix. Be sure to follow the specific instructions of your medical provider. Always consult a healthcare provider before starting any new medication.
1. Getting Set Up:
- • Proper hygiene is important. Wash your hands and keep the penis clean to prevent infection.
- • Assemble the following: bottle of Trimix, alcohol pad, syringe.
- • Keep the Trimix cold by returning the bottle to the refrigerator or placing the bottle in a cup of ice.
2. Prepare the Syringe:
- • Wipe the rubber top of the vial with an alcohol pad to sanitize it.
- • After removing the cap of the needle, pull the plunger back to the desired dosage, filling this volume with air. Use a new needle
and syringe each time. - • Insert the needle through the rubber top and inject the air into the vial.
- • Turn the vial with the needle and syringe inserted upside down. Pull back on the syringe plunger in a slow and steady motion until the desired dosage is achieved.
- • Tap the side of the syringe (1cc tuberculin syringe with a 29 gauge needle) to allow any air bubbles to float towards the needle.
Avoid having these air bubbles in the syringe when self-injecting by first injecting out the collected bubbles that may form. - • Remove the needle from the bottle and replace the protective cap on the needle.
3. Select and Prepare the Site for Injection:
- • The proper location for injection is at the 9-11 and 1-3 o’clock positions, between the base and mid-portion of the penis. (See the diagram in Step 3 of our Trimix Self-Injection Instructions PDF.) Avoid the midline because of the potential for injury to the urethra (6 o’clock for urinary passage) and the penile arteries and nerves (near 12 o’clock). Avoid any visible veins or arteries on the surface.
- • Grasp and pull the head of the penis toward the side of your leg with the index finger and thumb (use the left hand, if right handed). While maintaining light tension, select a site for injection.
- • Clean the site with an alcohol pad.
4. Inject Trimix and Apply Compression:
- • With a steady and continuous motion, penetrate the skin with the needle at a 90-degree angle. The needle should then be advanced to the hub. Slight resistance is encountered as the needle passes into the proper position within the erectile tissue (corporeal body).
- • Inject the Trimix over approximately 4 seconds. Withdraw the needle from the penis and apply compression to the injection site
for approximately 1 minute. Several minutes of compression may be required to avoid bleeding, especially if you are an aspirin
user. - • Replace the cap on the needle and dispose of it properly.
For additional information, please contact us or refer to the video or PDF instructions below.
How to Inject Trimix Medication Video
See our instructional video for guidance on self-administering Trimix injections.
Trimix Self-Injection Instructions PDF
Download our PDF for step-by-step instructions and a visual diagram of how to self-administer Trimix.
*Remember, these Trimix self-injection instructions are meant to serve as a general guide only. Always follow the specific instructions provided by your healthcare provider.
Potential Side Effects of Trimix
While Trimix injections tend to cause fewer side effects than systemic ED medications, some adverse reactions may still occur. Trimix side effects can vary significantly between individuals.
A serious but rare side effect of Trimix is priapism, an erection lasting over 4 hours. This is also a potential risk with other ED drugs like Viagra, Levitra, and Cialis. An erection persisting longer than 4 hours requires prompt medical care.
Other possible Trimix side effects include:
- • Mild to moderate penile pain
- • Priapism (prolonged erections)
- • Penile scarring
- • Bruising or hematoma
- • Low blood pressure or dizziness
- • Allergic reactions
Note that this list is not comprehensive, and patients may experience other uncommon or individual-specific side effects. It’s vital to discuss treatment with a healthcare provider who can monitor response, address concerns, and manage any side effects from Trimix injections.
Trimix is not recommended for men with:
- • Known allergies to Trimix ingredients
- • Sickle cell anemia
- • Bleeding disorders
- • Conditions increasing priapism risk
- • Leukemia
- • Penile abnormalities
- • Penile implants
- • Explicit medical advice to refrain from sexual activity
It’s important to inform your provider of all medications, over-the-counter drugs, herbal products, and other substances you take. Trimix components can interact with some medications, potentially making them less effective or causing adverse reactions.
Frequently Asked Questions
Is Trimix Safe?
According to the American Urological Association, intracavernous injections like Trimix are the most potent non-surgical ED treatment currently available. Trimix injections themselves have been an accepted ED treatment since the 1980s.[2] As a localized ED therapy, Trimix has few to no systemic side effects and is usually unaffected by alcohol when used responsibly. At Olympia Compounding Pharmacy, our Trimix formulas undergo third-party testing before they are released to patients.
How Effective Is Trimix Compared to Oral ED Drugs?
Trimix is an accepted second-line drug for ED treatment when oral PDE5 inhibitors aren’t effective or cause side effects. Compared to PDE5 inhibitors like Viagra, Cialis, or Levitra, studies show Trimix is often more effective for patients with diabetes or those unresponsive to oral meds. Clinical trial results indicate patients using Trimix achieved erections firm enough for sex 82-90% of the time, versus 62-72% with PDE5 inhibitors alone. Trimix may also work faster since it is injected directly into the penis.
Multiple studies demonstrate Trimix outperforms PDE5 inhibitors in efficacy and safety. A 2016 Baylor College study found Trimix yielded 61% greater improvement in penile rigidity compared to 18% with PDE5 inhibitors in men with mild to severe ED. Another trial in The Canadian Urological Association Journal showed significantly fewer adverse events with Trimix versus sildenafil or vardenafil.
Because Trimix is injected locally into the penis, there are typically few to no systemic side effects, unlike oral medications that circulate through the bloodstream and can sometimes cause headaches, nausea, or vomiting.
How Should You Store Trimix?
After receiving a physician’s instructions, Trimix injections are typically self-administered at home. While this may sound daunting, it’s actually an easy procedure (see our injection instructions below). However, it’s important to use proper injection technique with a 29-30 gauge x 1/2″ needle inserted fully into the shaft of the penis for intracavernosal administration.
For storage, all Trimix vials should be frozen at 0-31°F, except for the active vial currently in use, which should be refrigerated at 32-39°F. When the active vial starts running low, remove a frozen vial to refrigerate to replace the active vial. Frozen Trimix can be stored for up to 1 year. For travel, use ice packs to maintain temperature. You can view our Trimix storage guide here.
Meet Our Trimix Expert: Dr. Jonathan Ramnauth
Dr. Jonathan Ramnauth is a distinguished Sterile Compounding Pharmacist at Olympia Pharmaceuticals, holding a Doctor of Pharmacy degree from the University of Florida, earned in 2018. His academic and professional journey is marked by a relentless pursuit of excellence, culminating in his recognition as a leading expert in TriMix injections, a specialized area of pharmacy that requires precision and deep knowledge of compounded medications.
Since obtaining his Pharm.D., Dr. Ramnauth has dedicated himself to setting the highest standards in patient care and medication management. He is adept at collaborating with interdisciplinary healthcare teams, including physicians and nurses, to ensure the safe and effective dispensing and administration of medications. His expertise is not just limited to the technical aspects of pharmacy; he is equally committed to patient education. Dr. Ramnauth excels in communicating complex medication information to clients, ensuring they have a comprehensive understanding of their treatments, including potential drug interactions and side effects. This dedication to patient care ensures continuity and coherence in treatment plans prescribed by their healthcare providers.
Dr. Ramnauth’s commitment to excellence extends beyond patient interaction to the operational aspects of pharmacy practice. He is vigilant in monitoring the daily operations of his practice environment, ensuring strict adherence to organizational standards, industry regulations, and compliance with local, state, and federal laws. His proactive approach to maintaining operational excellence is critical in the highly regulated field of sterile compounding, where precision and adherence to strict protocols are paramount.
Through his expertise in TriMix formulations and his unwavering commitment to patient care and operational excellence, Dr. Jonathan Ramnauth embodies the ideals of the pharmacy profession. His contributions not only enhance patient outcomes but also elevate the standards of practice in the field of sterile compounding pharmacy.
Dr. Jonathan Ramnauth has medically reviewed and approved the content on this page.
How to Get Trimix Online
Trimix is available online from Olympia Pharmaceuticals. Follow the instructions below for patients and providers to get Trimix. Alternatively, you can view our guide on how to get Trimix.
Instructions for Patients:
Though Trimix requires a doctor’s prescription, getting it through our compounding pharmacy is simple:
- 1. Download and print our Trimix Prescription Form.
- 2. Bring the form to your physician (usually your family doctor or urologist).
- 3. Your doctor faxes the completed form to Olympia Compounding Pharmacy. We’ll then ship your medication directly.
Trimix is also available online for those without a physician or who prefer not to involve their doctor. Just complete our quick online intake. Our staff will contact you to schedule a telemedicine evaluation with a licensed provider.
Instructions for Physicians:
With over 35 years of compounding expertise, we aim to support physicians in caring for their patients. Our custom formulations and dosing fit your prescribing needs.
To prescribe Trimix for your patients:
- 1. Download and print our Trimix Prescription Form.
- 2. Complete and fax the signed form to Olympia Compounding Pharmacy at 877-359-3990
- 3. We’ll ship the patient’s Trimix injections directly.
Trimix Medical Study for Physician Reference
To better understand Trimix and its efficacy, refer to this summarized International Journal of Impotence Research study.[9]
Objective
The study evaluated Trimix (Tx) injections for patients unable to use prostaglandin E1 (PgE1) due to poor response, discomfort, or cost. Researchers systematically increased Tx drug doses to analyze penile hemodynamic response.
Key Findings
180 ED patients were prospectively randomized into 9 equal groups receiving varying Tx doses. Post-injection, cavernous artery ultrasound and axial rigidometry were performed. Patients rated erection quality, satisfaction, time to detumescence, and side effects.
Significant results included:
• Many patients unresponsive to oral ED drugs or with PDE5 inhibitor contraindications were candidates for self-injection therapy.
• Some patients preferred injection rigidity, with 36.2% choosing injections over sildenafil.
• The Tx combination led to full erection response in over 90% of patients.
• In those unresponsive to 40μg PGE1, Tx evoked a response in 31%.
• TTx offered a cost advantage.
References
1. Sooriyamoorthy, T., & Leslie, S. W. (2023). Erectile Dysfunction. In StatPearls [Internet]. Treasure Island, FL: StatPearls Publishing. Available: https://www.ncbi.nlm.nih.gov/books/NBK562253/
2. Burnett, Arthur, et al. (2018) Erectile dysfunction: AUA guideline. American Urological Association. Available: www.auanet.org/guidelines-and-quality/guidelines/erectile-dysfunction-(ed)-guideline.
3. Huang, S. A., & Lie, J. D. (2013). Phosphodiesterase-5 (PDE5) Inhibitors In the Management of Erectile Dysfunction. P & T : a peer-reviewed journal for formulary management, 38(7), 407–419. Available: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3776492/
4. Dinsmore, W., & Evans, C. (1999). ABC of sexual health: erectile dysfunction. BMJ (Clinical research ed.), 318(7180), 387–390. Available: https://doi.org/10.1136/bmj.318.7180.387
5. National Center for Biotechnology Information (2023). PubChem Compound Summary for CID 4680, Papaverine. Available: https://pubchem.ncbi.nlm.nih.gov/compound/Papaverine.
6. National Center for Biotechnology Information (2023). PubChem Compound Summary for CID 5775, Phentolamine. Available: https://pubchem.ncbi.nlm.nih.gov/compound/Phentolamine.
7. Jain, A., & Iqbal, O. A. (2023). Alprostadil. In StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing. Available: https://www.ncbi.nlm.nih.gov/books/NBK542217/
8. Linet, O. I., & Ogrinc, F. G. (1996). Efficacy and safety of intracavernosal alprostadil in men with erectile dysfunction. The Alprostadil Study Group. The New England journal of medicine, 334(14), 873–877. Available: https://doi.org/10.1056/NEJM199604043341401
9. Seyam, R., Mohamed, K., Akhras, A. A., & Rashwan, H. (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. Available: https://doi.org/10.1038/sj.ijir.3901313