Intracavernosal Injection An Introduction to the main drugs used By Matthew Dubrow, DO and Jason Arbogast An intracavernous injection, according

g to the American Urologic Association, is the most effective non-surgical treatment for ED1. Injections into the penis, unlike oral medications, trigger an automatic erection. Injection can be administered by the individual five minutes prior to sexual activity and should last for sixty to ninety minutes. Injection is considered second line to be used if oral therapy fails. Medications that can be injected include prostaglandin E1, papaverine, phentolamine, and atropine. Prostaglandin E1 and phentolamine are the most common single agents used as monotherapies. However, combination therapies are used to increase efficacy and decrease side effects. Combination therapy includes but is not limited to Quad-Mix, Tri-Mix and BiMix. These products are not commercially available and must be compounded by specialty pharmacies. Below are descriptions, including the mechanisms, dosages and side effects, of the medications that are in Quad-Mix, Tri-Mix and Bi-Mix. Prostaglandin E1 Availability - Commercially available for injection as Alprostadil and marketed as monotherapies in Caverject and Edex Mechanisms: a prostaglandin E1 that stimulates the relaxation of the smooth muscle and dilates the arteries in the penis increasing the blood flow to the penis Studies have shown effective action in 75% of men when injected into the penis Dosages: common dosages begin at 10-15 mcg in patients with vasculogenic ED and 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 Average dosing is 5-30 mcg. Using combination therapies that include papaverine, phentolamine or both has been recommended. Side Effects: Priapism Prolonged erection lasting more than 4 hours Requires immediate medical attention Penile pain During or immediately after injection can occur in up to 31% of individuals May be reduced when used in combination therapy Bruising Can occur at the site of injection Can be minimized with a 30G needle
1 AUA Guideline on the Management of Erectile Dysfunction: Diagnosis and Treatment Recommendations, Chapter 1-16, 2005, rev. 2007.

Rev. 5/10/2011

Should be mitigated with proper injection technique Fibrosis Thickening of the internal penile tissue This is less common with prostaglandin E1 but can occur after long term use Certain medical conditions can allow intracavernosal medications to leak from the injection site into systemic circulation. Although the dosages are small some systemic side effects may be experienced under such circumstances. They can include: Hypotension - low blood pressure Decreased liver function

Phentolamine Availability: Commercially available as Regitine Mechanisms: Alpha-adrenergic antagonist that produces a direct vasodilation in the arteries increasing blood flow to the penis. Dosages: 1 to 3 mg, but can be used outside of that range Side Effects: Priapism Prolonged erection lasting more than 4 hours Requires immediate medical attention Fibrosis Thickening of the internal penile tissues Certain medical conditions can allow intracavernosal medications to leak from the injection site into systemic circulation. Although the dosages are small some systemic side effects may be experienced under such circumstances. They can include: Systemic hypotension - low blood pressure Reflex tachycardia - increase in heart rate Nasal congestion Gastrointestinal upset Papaverine Availability: Not commercially produced for monotherapy. Typically used with phentolamine to produce firm erections Mechanisms: Phosphodiesterase inhibitor that results in smooth muscle relaxation allowing for an increase in blood flow to the penis. Its used mainly in combination with prostaglandin E1 and/or phentolamine. Although it was not specifically indicated for ED, it has been FDA approved and used since the early 1980s as an injectable medication. Dosages:

Usual dose ranges from 3 to 30 mg, but can be used outside of that range Side effects: Priapism - higher rates than other injectable medications varying from 16% Prolonged erection lasting more than 4 hours Requires immediate medical attention Fibrosis Thickening of the internal penile tissues Highest rates among the injectable medications and can present as a lump or thickening within the penis Certain medical conditions can allow intracavernosal medications to leak from the injection site into systemic circulation. Although the dosages are small, some systemic side effects may be experienced under such circumstances. They can include: Systemic hypotension - low blood pressure

Atropine Availability: Atropine Sulfate Injection, USP is a sterile, nonpyrogenic isotonic solution of atropine sulfate monohydrate in water for injection with sodium chloride sufficient to render the solution isotonic. It is administered parenterally by subcutaneous, intramuscular or intravenous injection. Mechanisms: It is believed the addition of atropine sulfate increases the synergism of the pharmacological combination, leading to a relaxation of the smooth muscles of the cavernous sinusoids and helicine arteries and thereby improving the hemodynamics of arterial dilation, venous compression and sinusoidal relaxation during erection. Dosages: Usual doses range from 0.02 to 0.2 mg Side Effects: The most common side effect of Atropine when used intracavernosally is dry mouth. Combination Therapies Bi-Mix: Papaverine + Phentolamine Bi-Mix, a compounded medication, 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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Study Information: Dosages: Usual prescribed strength: Papaverine 6-25mg + Phentolamine 0.052.0mg/ml

Tri-Mix: Papaverine, Phentolamine, Prostaglandin E1 Tri-Mix, a compounded medication, combines papaverine, phentolamine and prostaglandin E1 to achieve maximum efficacy, lower the incidence of side effects, and lower the cost per dose. Studies of Tri-Mix have shown definitive efficacy when used as an injectable therapy. First introduced in 1991 by Bennett and his colleagues, they demonstrated a success rate of 92% in 116 patients. Tri-Mix is often reserved for patients who fail prostaglandin E1 monotherapy, fail Bi-Mix therapy or have severe side effects from prostaglandin E1. Using lower doses of prostaglandin E1 in Tri-Mix often resolve the side effects experienced with prostaglandin E1 monotherapy. often subsides. Study Information: Dosages: Usual prescribed strength: Papaverine 18-25mg + Phentolamine 1.02.0mg + Prostaglandin E1 10-25mcg/ml Quad-Mix: Papaverine, Phentolamine, Prostaglandin E1, Atropine Quad-Mix includes the addition of atropine which may work synergistically to cause smooth muscle relaxation in the penis. Study Information: 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. Dosages: Usual prescribed strength: Papaverine 20-25mg + Phentolamine 1.52.0mg + Prostaglandin E1 20-25mcg + Atropine 0.02-0.08mg/ml