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Intracavernosal Injection
An intracavernous injection, according to the American Urologic Association, is the most effective non-surgical treatment for ED. Injections into the penis, unlike oral medications, trigger an automatic erection. Injection can be done by the individual 5 minutes prior to sexual activity and should last for no more than 1 hour. Injection is considered second line to be used if oral therapy fails. Compounds that can be injected include alprostadil, papaverine, and phentolamine. Alprostadil and phentolamine are the most common agents used as monotherapy. However, combination therapies are used to increase efficacy and decrease side effects. Combination therapy includes Tri-Mix and Bi-Mix. Both products are not commercially available and must be compounded by specialty pharmacies. Below is a description of the medications that are in Tri-Mix and Bi-Mix including mechanism, dose and side effects of each agent.

-       Commercially available for monotherapy as Caverject® and Edex®
-       Mechanism: a prostaglandin E1 that stimulates the relaxation of the smooth muscle and dilates arteries in the penis increasing blood flow
-       Studies have shown efficacy in 75% of men when injected into the penis
-       Usual dose: start at 10-15 mcg in patients who have failed oral therapy or 2.5-5 mcg in patients who have neurogenic or psychogenic ED and have failed or declined oral therapy
-       Median dose is 12-15 mcg. Benefit is not seen at doses greater than 40mcg. It is recommended to try a drug combination that includes papaverine, phentolamine or both.
-       Side Effects
o   Priapism: prolonged erection lasting more than 4 hours- must seek medical attention
o   Penile pain- during or immediately after injection, occurs in up to 31%, may be reduced if mixed with other agents
o   Bruising at injection site- can be minimized with a 30G needle, should be minimal with proper injection technique
o   Hypotension- occurs when drug leaks out of injected area into general circulation. Rare with alprostadil.
o   Fibrosis- scaring of penile tissue is lower with alprostadil, may result after long term use of injection therapy
o   Occasional increase in liver function tests
-       Commercially available as Regitine®
-       Mechanism: alpha-adrenergic antagonist that produces a direct vasodilation in the arteries increasing blood flow to the penis.
-       Usual Dose: 1 to 2 mg
-       Side Effects
o   Painful prolonged erection lasting more than 4 hours
o   Fibrosis- penile scaring
o   Systemic hypotension (low blood pressure)
o   Reflex tachycardia (increase in heart rate)
o   Nasal congestion
o   Gastrointestinal upset
-       Not commercially available and must be used with phentolamine to produce hard erections.
-       Mechanism: Phosphodiesterase inhibitor that results in smooth muscle relaxation allowing for an increase in blood flow to the penis. It’s used mainly in combination with alprostadil and/or phentolamine. Although it has been used since the early 1980’s, it is not approved for ED.
-       Usual dose ranges from 5 to 30mg
-       Side effects
o   Priapism- high rate of 1-6%
o   Fibrosis-  highest rate and can present as a lump within the penis
o   Hypotension

Combination Therapy
Bi-Mix: Papaverine + Phentolamine

Bi-Mix was first introduced by a study in 1985 that showed a success rate of 71% amongst 250 patients that were given 1mg of phentolamine mixed with 30mg of papaverine. In 1987, 2 more studies were published. One study showed that phentolamine mixed with papaverine had a 72.9% success rate verse 20% with papaverine alone. In another study, papaverine mixed with phentolamine was examined for a follow up of 26 months. Only 13% of the patients failed to respond to therapy.

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-       Usual prescribed strength: Papaverine 6-25mg + Phentolamine 0.05-2.0mg/ml

Tri-Mix: Papaverine, Phentolamine, Alprostadil
Tri-Mix is a compounded medication the combine’s papaverine, phentolamine and alprostadil in one vial to achieve maximum efficacy, lower incidence of pain, and lower cost per dose. Studies have been done that have shown the efficacy of all three agents combined into one formulation. Combination therapy was first introduced in 1991 by Bennett and his colleagues who demonstrated a success rate of TriMix of 92% in 116 patients. Tri-Mix is often reserved for patients who fail alprostadil (PGE-1), fail Bi-Mix or for patients with severe penile pain from prostaglandin E1. Since Tri-Mix uses lower doses of alprostadil, penile pain often subsides.

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-       Usual prescribed strength: Papaverine 18-25mg + Phentolamine 1.0-2.0mg + Prostaglandin E1 10-25mcg/ml

Quad-Mix: Papaverine, Phentolamine, Alprostadil, Atropine
Quad-Mix includes the addition of atropine which may work synergistically to cause smooth muscle relaxation in the penis. In a study conducted by Israilov and colleagues, 13 patients that failed tri-mix had a positive response to quad-mix. Seven (53.8%) of the patients responded successfully with the addition of atropine.

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-       Usual prescribed strength: Papaverine 20-25mg + Phentolamine 1.5-2.0mg + Prostaglandin E1 20-25mcg + Atropine 0.02-0.08mg/ml



The information on this website if purely informational and should not be used to diagnose, cure or treat any patient without the direction and supervision of a physician. If you are intersted in using Tri-Mix or any other treatment for erectile dysfunction make sure to check with your physician first. This and any therapy should be individualized for you by a prescribing physician that knows you, your medical history, and any current and prior medication history. Tri-Mix is not approved by the FDA for the treatment of Erectile Dysfunction and does require a prescription that can only be filled at a compounding pharmacy.

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