Alprostadil for Injection (Intracavernosal Use)
(Caverject Dual Chamber System)
Manufacturer: Pharmacia and Upjohn, Kalamazoo, MI
Indications: Used for the treatment of erectile dysfunction
caused by neurogenic, vasculogenic, or mixed-etiology disorders.
Drug Class: Alprostadil is the naturally occurring form of
prostaglandin E1 (PGE1).
Uniqueness of Drug: Alprostadil (dose range 2.5–60 mcg) is
injected in smaller doses directly into the corpus cavernosum
of the penis, where erections form. Injection therapy produces
erections in about five to 20 minutes by relaxing the penile muscle
tissue and allowing blood to become trapped in the shaft of
the penis in a natural way. Generally, the erection lasts about one
hour. The drug is known to cause an erection by relaxing the
smooth muscle within the penis, and this action allows blood to
enter and to become trapped in the penis.
Warnings: Prolonged erection, lasting more than four hours
and up to six hours in duration, occurred in 4% of 1,861 patients
treated up to 18 months with alprostadil sterile powder. The incidence
of priapism (erections lasting more than six hours in duration)
was 0.4% with the same length of use. Pharmacologic inter
vention and/or aspiration of blood from the corpus
cavernosum were performed in two of seven patients with priapism.
To minimize the chances of prolonged erection or priapism,
alprostadil for injection should be titrated slowly to the
lowest effective dose (see Dosage). The patient must be instructed
to immediately report to his prescribing physician or,
if he or she is unavailable, to seek immediate medical attention
for any erection persisting longer than four hours. If priapism
is not treated immediately, penile tissue damage and permanent
loss of potency can result.Vol. 27 No. 9 • September 2002 • P&T® 431
The following precautions should be heeded with alprostadil
for injection: possible penile fibrosis, increased peripheral blood
concentrations of PGE1, and excess bleeding in patients receiving
warfarin. Alprostadil should not be used in combination
with other vasoactive drugs, and patients should not reuse or
share needles.
Dosage and Administration: The dosage of alprostadil for injection
should be individualized for each patient by careful titration
under supervision of a physician. In patients with erectile
dysfunction of vasculogenic, psychogenic, or mixed etiology,
dosage titration should be initiated at 2.5 mcg of alprostadil. If
there is a partial response, the dose may be increased by 2.5 mcg
to a dose of 5 mcg and then in increments of 5 to 10 mcg, depending
on erectile response, until the dose that produces an
erection suitable for intercourse and not exceeding a duration
of one hour is reached. If there is no response to the initial dose
of 2.5 mcg, the second dose may be increased to 7.5 mcg, followed
by increments of 5 to10 mcg. The patient must stay in the
physician’s office until complete detumescence has occurred. If
there is no response, the next higher dose may be given within
one hour. If there is a response, there should be at least a oneday
interval before the next dose is given.
In patients with erectile dysfunction of pure neurogenic origin
(spinal cord injury), the initial dose titration should be 1.25
mcg of alprostadil. The dose may be increased by 1.25 mcg to
a dose of 2.5 mcg and then in 5-mcg increments until the dose
that produces an erection suitable for intercourse, and not exceeding
one hour, is reached. If there is no response, the next
higher dose may be given within the next hour. If there is a response,
there should be at least a one-day interval before the
next dose is given.
For maintenance use, self-injection therapy by the patient can
be started only after the patient is properly trained in the selfinjection
technique. The dose of alprostadil for injection that is
selected for self-injection treatment should provide the patient
with an erection that is suitable for intercourse and that is maintained
for no longer than one hour. If the duration of erection is
longer than one hour, the dose should be reduced.
P&T Committee Considerations: Sildenafil citrate was the
first drug approved by the FDA for the treatment of male erectile
dysfunction. Although the drug is effective, there are many
instances of erectile failure, so that another pharmaceutical
might be useful to treat vasculogenic, psychogenic, or mixed
erectile dysfunctions. A clinical study has provided evidence that
alprostadil for injection can produce erections in male patients
who failed to respond to sildenafil citrate therapy. Therefore, it
is recommended that alprostadil for injection be placed on the
hospital formulary to treat patients who do not respond to the
orally administered sildenafil citrate. The patient must be closely
supervised by the physician in obtaining the effective and safe
dose necessary to achieve erection for intercourse. Alprostadil
for injection will be supplied as a Dual Chamber Impulse syringe
system, 10 mcg powder and diluent, with the price of $39.02 as
a single product. The Dual Chamber Impulse syringe system,
20 mcg powder and diluent, costs $50.25 as a single product. The
system includes a glass cartridge, which contains sterile, freezedried
alprostadil in the front chamber and sterile bacteriostatic
water for injection in the rear chamber.
also:
Penile Injection Therapy
Highlights of Injection Therapy
First FDA-approved medication for the treatment of E.D.
80 percent of men in clinical trials achieved firm erections-
Individualized dosage determined for each patient's needs-
Works for men with a broad range of medical conditions
Produces a safe predictable erection
The only medication that will initiate an erection
What is Injection Therapy
CaverjectTM or EdexTM (Alprostadil) is injected directly into the side of the penis and produces an erection. The medication dilates the arteries of the penis and allows blood to flow in. An erection occurs anywhere from 5 to 15 minutes after injection. A patient must learn to perform a penile self-injection each time he wishes to engage in sexual activity. The erection will last 30 minutes to an hour or up to orgasm.
Learning to Inject
The first injection is performed by Dr. Eid, and is used both for diagnosis and to decide how much medication will be required in the future for that specific patient to have sexual activity. In other words, the medication dose for each individual is tailored to the erectile response to the first injection. After that, the patient learns to inject under Dr. Eid's watchful eye and coaching. With a little practice and familiarity, the patient gains confidence with the injection technique such that he is able to perform it at home. Most patients find that they get used to the needle sensation over time. The number of injections is not to exceed 12 each month, and should be spaced as evenly as possible. The site of injection should alternate between left and right side of the penis.
Injection Therapy Side Effects
The most common side effect reported (37%) is a mild to moderate dull ache, which occurs 5 to 20 minutes after injection. This ache is increased by standing, and subsides when the erection is gone. It is believed that the ache is due to the potassium present in the medication. The alternative for men who cannot tolerate this ache is to use off label a mixture of Papaverine, Phentolamine, and Alprostadil, which is very effective and painless (approved by the FDA for use in the human body but never tested for use in the penis).
Whenever a needle is stuck into one's body, a small bruise may develop at the site of the injection over time. Sometimes, a small nodule or lump may develop if the same site is injected again and again. Rarely, scarring or a plaque of the penis can occur.
Occasionally, the medication may produce a painful, sustained, prolonged erection, known as priapism. Priapism (a rigid erection for more than 4 to 8 hours) requires immediate medical attention, but is easily reversed when treated early.
Frequently Asked Questions
How was it discovered?
In 1977, a surgeon accidentally injected the drug Papaverine in the area near the penis while performing a bypass procedure. This produced a prolonged, fully rigid erection of two hour’s duration in an impotent patient. In laboratory tests, medications such as Phentolamine (Regitine) were administered intravenously to produce erections in cats. However, it wasn’t until 1982 that Dr. Virag, a surgeon in France, formally noted that the pressure inside the penis increased after an injection of Papaverine. In 1983, Dr. Brindley, professor of Physiology at the Institute of Psychiatry in London, first reported that 11 impotent men were able to have intercourse following the injection.
For more than twenty years, the injection of medication into the penis for the evaluation and treatment of erectile dysfunction has been one of the most popular and controversial subjects in the field of urology. Although there has been a rapid and widespread acceptance of medically induced erections over the last seven years, many questions remain to be answered.
What are the medications that are being used?
After having experimented with over forty different types of medications, we presently use the most effective three: Papaverine, Phentolamine, and Prostaglandin E1.
Papaverine hydrochloride was initially the most often used medication. Papaverine injections relax the muscle cells present in the arterial wall, causing dilation and increased blood flow in the penis. Several researchers have also noted that a second Papaverine injection reduces the blood flow out of the penis, so that the blood is trapped and the erection is maintained.
Phentolamine (Regitine) blocks the nerves that signal the arterial muscle wall contraction. Thus, the muscle cells in the arterial wall relax and the artery dilates when the nerves are blocked. This action compliments the action of Papaverine, and the two drugs are usually mixed together prior to injection.
Prostaglandin E-1 is a chemical that occurs naturally in the human body. Discovered approximately 30 years ago, it as a very potent vasodilator. Similar to the effect of Papaverine, Prostaglandin E-1 causes the relaxation of the muscle cells of the arteries in the penis, resulting in an erection.
Are there any side effects?
We can divide the side effects into two categories:
First, whenever a needle is stuck into the body, a small bruise or hematoma may develop on the site of injection. A small nodule or lump may develop if the same site is injected over a long period of time. Rarely, scarring or fibrosis in the inner body of the penis may occur, or hardened area called plaque can develop at the site of injection.
The second category of side effects is produced by the medications themselves. Papaverine and Phentolamine may produce a painful, prolonged erection known as priapism. This side effect generally occurs while the doctor is attempting to adjust the dosage of medication. Once the dosage of medication is established, priapism is rare. Very often with injections, a man may develop erections lasting two to three hours. We consider priapism to be an erection lasting longer than four hours and we request that you seek medical attention immediately if this should occur. Priapism is easily reversed when treated early.
Other rare side effects include dizziness and headache. Even less frequently is an increase in the liver enzymes usually associated with the Papaverine injection. In comparison, Prostaglandin E1 is safer as it rarely produces priapism or liver enzyme abnormalities. Since it is a natural product of the body, Prostaglandin E1 can be broken down by the enzymes locally present in the penis. However, one of the possible side effects of Prostaglandin E1 is the development of a slight dull ache in the penis, which will usually subside when lying down.
How safe is it?
These medications are safe for use in men. However, like any other medication, they do have their side effects.
Papaverine is a very safe medication that has been used for more than twenty years. In addition to dilating the arteries in the heart, Papaverine has also been used to treat Alzheimer’s disease and Multiple Sclerosis. Vascular surgeons and radiologists have used Papaverine for procedures involving the arteries.
One of the toxic effects reported of Papaverine is a skipped heartbeat or abnormal conduction in the heart, which usually only occurs with a large dosage. Cardiologists and surgeons have used up to 120 mg of Papaverine intravenously every three hours without toxic effects. The usual dosage used in the penis is 30 mg twice a week. Therefore, the amount of Papaverine is well below dangerous toxic levels.
Phentolamine, when used in higher dosages, has the ability to lower the blood pressure of the body. Side effects include heart beat irregularities, diarrhea, and abdominal discomfort.
This medication was originally used to uncover tumors of the adrenal glands. This test was described as the “pheochromocytoma test,” and involved the intravenous injection of 5 mg of Phentolamine. The dose used in the penis is only 0.5 mg to 1 mg, well below any toxic levels.
How long have these medications been used for this purpose?
Papaverine and Phentolamine have been used for the purpose of stimulating an erection since 1983. However, Prostaglandin E1 has only been used for the past 2-3 years.
Is it painful?
The needle utilized for this injection is a 30 gauge ultra-fine needle. Over ninety percent of the patients claim that although they could feel the needle, they were surprised how painless it felt. Also, since the needle hole is very tiny, very little bruising or bleeding occurs. It is safe for patients who are taking Aspirin, Persantine, and Coumadin.
When injected, Papaverine and Phentolamine do not produce any pain. On the other hand, Prostaglandin E1 may result in a transient dull ache at the base of the penis. This is generally well tolerated by the patient and does not interfere with intercourse. If present, the pain usually subsides in 15 minutes.
How often can I use it?
The number of injections is not to exceed ten per month and we recommend that injections be spaced evenly. Also, the site of the injection should alternate between the left and right side of the penis.
Does it work?
The pharmacological treatment has been successful in producing an erection in over 80% of the patients in the Erectile Dysfunction Unit. This erection is more than adequate to perform intercourse. The rest of the patients in whom the injection has no effect are candidates for other forms of treatment.
How long must I wait for the medication to work?
An erection will occur anywhere from 10 to 20 minutes following the injection. In general, Prostaglandin E1 works slightly faster than Papaverine and Phentolamine. We recommend that the site of injection be held for three to five minutes after the injection. A better erection is usually obtained with the addition of foreplay. Some men may require a 30 minute wait before a fully rigid erection is obtained. In general, the amount of time that it takes to obtain an erection is a correlate to the extent of arterial blockage.
How long will the erection be maintained?
Anywhere from 20 minutes to an hour and a half is a considered a successful result.
How long before the medication expires?
The Papaverine and Phentolamine mixture is effective for sixty days. Dr. Lloyd Allen of the University of Oklahoma College of Pharmacy studied the stability of the mixture. He showed that when stored in a refrigerated temperature of 5 degrees Centigrade, Papaverine lost less the 3% of its activity and Phentolamine lost less than 7%. Stored at about room temperature, 25 degrees Centigrade, Papaverine lost less than 3% of activity and Phentolamine less than 9% over a sixty day period. Prostaglandin E1, on the other hand, must be kept refrigerated at 5 degrees Centigrade, and it will last for four months.
Do pharmacological erections cure the arterial blockage?
Erection by the injection method is not treatment. It does not cure or reverse the blockage of the arteries. It simply allows one to obtain an erection without the need for surgery or a penile prosthesis. Furthermore, the injections may not continue to work, especially in the conditions (high cholesterol, high blood pressure, etc.) continue to affect the penile arteries. Tobacco smoking will also affect erectile function and may worsen the atherosclerosis of the penile arteries to the point where the injections will not work.
Can I still have an orgasm?
Erections produced by the injection method will not interfere with capacity to obtain an orgasm. Generally, men who are able to achieve orgasm without an erection continue to do so when having an erection with the injection method.
What happens if I inject myself in the wrong place?
There are only four possible locations for the injection. The first target is the body of the penis, which will produce an erection. If the injection occurs in one of the penis veins, a bruise may result. If the tube that drains the bladder and the urethra is injected, the medication may leak out of the tip of the penis. Injection into the urethra will not result in an erection. It is very unlikely that injection in the wrong place or into the urethra will cause a problem. Finally, the last possible mishap that may occur is injection underneath the skin and this will result in a temporary swelling of the skin. Also, an erection will not occur.
In case of a problem, is there someone available?
It’s always possible to reach a doctor if a problem should occur.
Who uses this type of treatment?
A wide range of men use the injection method to obtain erections. In general, these men are active in life and would like to remain sexually active. Men who are reluctant to have surgery find the injection method to be a good alternative to penile prosthesis. For this reason, pharmacological erections are gaining popularity.
Who is a candidate for the pharmacological erection program?
In general, men who suffer from erectile dysfunction and who respond positively to test injections are candidates for this treatment. Contraindications to penile injections include: problems with the veins in the penis, Sickle Cell disease, poor manual dexterity or poor vision, unreliability with a potential for misuse and abuse, and abnormal liver enzymes.
In summary, the long term effects of intracavernous injections are unknown. However, this treatment is effective and it another option for patients who suffer from erectile dysfunction.
Thank you.
J. Francois Eid, M.D.