An intra-cavernous 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 papaverine, prostaglandin 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.
Prostaglandin
- 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
- Priapism: prolonged erection lasting more than 4 hours- must seek medical attention
- Penile pain- during or immediately after injection, occurs in up to 31%, may be reduced if mixed with other agents. Lidocaine maybe added to prescription to aid in discomfort,
- Bruising at injection site- can be minimized with a 30G needle, should be minimal with proper injection technique
- Hypotension- occurs when drug leaks out of injected area into general circulation. Rare with prostaglandin.
- Fibrosis- scaring of penile tissue is lower with alprostadil, may result after long term use of injection therapy if instructions received at the clinic are not followed. Such as rotating injections sites or using it more then once in a 24 hour period.
- Occasional increase in liver function tests
Phentolamine
- Commercially available as Regitine®
- Mechanism: alpha-adrenergic antagonist that produces a direct vasodilation in the arteries increasing blood flow to the penis.
Side Effects
- Painful prolonged erection lasting more than 4 hours
- Fibrosis- penile scaring if instructions received at the clinic are not followed. Such as rotating injections sites or using it more then once in a 24 hour period
- Systemic hypotension (low blood pressure)
- Reflex tachycardia (increase in heart rate)
- Nasal congestion
- Gastrointestinal upset
Papaverine
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.
Side effects
Priapism- high rate of 1-6%
Fibrosis- highest rate and can present as a lump within the penis
Hypotension
Tri-Mix: Papaverine, Phentolamine, Prostaglandin Tri-Mix is a compounded medication the combine’s papaverine, phentolamine and prostaglandin in one vial to achieve maximum efficacy. 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 prostaglandin (PGE-1), fail Bi-Mix or for patients with severe penile pain from prostaglandin E1. Since Tri-Mix uses lower doses of prostaglandin , penile pain often subsides.
Usual prescribed strength: Papaverine 18-25mg + Phentolamine 1.0-2.0mg + Prostaglandin E1 10-25mcg/ml
Compounding Pharmacies can customize therapies to meet patient specific needs per the physician prescription. Compounding Pharmacists are medication problem solvers that work within the triad of care, the relationship between the Patient, Physician and Pharmacist. Several compounds, such as Tri-Mix Injection have been formulated to help bring about excellent results for patients with Erectile Dysfunction
