Caverject (Alprostadil) contains alprostadil as the naturally occurring form of prostaglandin E (PGE) and is designated chemically as (11α,13E,15S)-11,15-dihydroxy-9-oxoprost-13-en-1-oic acid. The molecular weight is 354.49.

Alprostadil is a white to off-white crystalline powder with a melting point between 115° and 116°C. Its solubility at 35°C is 8000 micrograms (mcg) per 100 milliliter double distilled water.

The structural formula of alprostadil is represented below:

Caverject (Alprostadil) IMPULSE is available as a disposable, single-dose, dual chamber syringe system. The system includes a glass cartridge which contains sterile, freeze-dried alprostadil in the front chamber and sterile bacteriostatic water for injection in the rear chamber. The alprostadil is reconstituted with the sterile bacteriostatic water just before injection. Caverject (Alprostadil) IMPULSE is available in two strengths for intracavernosal administration:

When necessary, the pH of the alprostadil for injection was adjusted with hydrochloric acid and/or sodium hydroxide before lyophilization.

Alprostadil has a wide variety of pharmacological actions; vasodilation and inhibition of platelet aggregation are among the most notable of these effects. In most animal species tested, alprostadil relaxed retractor penis and corpus cavernosum urethrae . Alprostadil also relaxed isolated preparations of human corpus cavernosum and spongiosum, as well as cavernous arterial segments contracted by either noradrenaline or PGF . In pigtail monkeys (), alprostadil increased cavernous arterial blood flow . The degree and duration of cavernous smooth muscle relaxation in this animal model was dose-dependent.

Alprostadil induces erection by relaxation of trabecular smooth muscle and by dilation of cavernosal arteries. This leads to expansion of lacunar spaces and entrapment of blood by compressing the venules against the tunica albuginea, a process referred to as the corporal veno-occlusive mechanism.

The safety and efficacy of Caverject (Alprostadil) Sterile Powder was investigated in men with a diagnosis of erectile dysfunction due to psychogenic, vasculogenic, neurogenic, and/or mixed etiology in two well-controlled studies (Study 1 and Study 2) and in one 6-month open-label study (Study 3).

Study 1: One hundred fifty-three men with a mean age of 53 years (range 23–69 years) were enrolled. The study had three phases: a 2.5 week double-blind, in-office randomized crossover phase in which each man received placebo or 2.5 mcg, 5 mcg, 7.5 mcg, or 10 mcg of Caverject (Alprostadil) Sterile Powder; a 2 week open-label, in-office dose-titration phase to identify the optimum home-use dose (the latter dose was defined as a dose inducing an erection sufficient for penetration and lasting ≤ 60 minutes); and a 4-week open-label, self-injection phase. In the double-blind phase, each dose of Caverject (Alprostadil) was significantly more effective than placebo by clinical evaluation ("full penile rigidity") and by RigiScan criteria (≥ 70% rigidity for at least 10 minutes); there was no response to placebo. The percentage of responders increased with increasing doses of Caverject (Alprostadil) . The overall response in the dose-ranging phases was 76% (117/153) by clinical evaluation and 51% (78/152) by RigiScan criteria. The optimum dose for self-injection ranged from 1.25 to 65 mcg (median 20 mcg). Seventy-three percent of the injections in 102 men who self-injected Caverject (Alprostadil) resulted in satisfactory intercourse. Seventy-five percent of the patients remained on the dose identified during the dose-ranging phase; 17% and 8% of the patients slightly decreased or increased the dose, respectively. The mean duration of erection per injection was 70.8 minutes.

Study 2: Two hundred ninety-six men with a mean age of 53.8 years (range 21–74 years) were enrolled in this parallel-design, double-blind study. The men were randomly assigned to one of five groups and received either a single dose of placebo, 2.5 mcg, 5 mcg, 10 mcg, or 20 mcg of Caverject (Alprostadil) Sterile Powder. No patient responded to placebo. The differences in the response rates in both the clinical and the RigiScan evaluations between each of the doses of Caverject (Alprostadil) and placebo were statistically significant. There was also a statistically significant dose-response relationship with higher clinical response rates and higher RigiScan response rates with increasing doses of Caverject (Alprostadil) (with exception of the 10-mcg dose). The mean duration of erection after injection ranged from 12 minutes after the 2.5-mcg dose to 44 minutes after the 20-mcg dose and the relationship was linear ( = .025, linear regression analysis).

Study 3: The safety and efficacy of Caverject (Alprostadil) Sterile Powder was evaluated in a 6-month, open-label study in 683 men with a mean age of 58 years (range 20–79 years). The optimum dose of Caverject (Alprostadil) was established by titration in 89% of men (606/683). Four hundred seventy-one men (69%) completed the 6-month study. At the start of the study, the mean dose was 17.7 mcg of Caverject (Alprostadil) and at the end of the study it was 20.7 mcg. Eighty-seven percent of the 13,762 injections of Caverject (Alprostadil) , administered by self-injection by the men in the study, resulted in satisfactory sexual activity. The mean duration of erection was 67.5 minutes.

The formulation of alprostadil contained in Caverject (Alprostadil) IMPULSE includes the inactive excipient alpha cyclodextrin. This formulation was compared with Caverject (Alprostadil) Sterile Powder in 87 men in a single-blind, crossover study designed to evaluate efficacy and safety. The doses used by the patients in the study ranged from 2.5 mcg to 20 mcg and were the same for both formulations. The efficacy of the two formulations was shown to be comparable, as assessed by the 30-point erectile function (EF) domain score from the International Index of Erectile Function (IIEF) and by a physician-assessment score for erectile response. The mean EF domain scores for Caverject (Alprostadil) Sterile Powder and the formulation contained in Caverject (Alprostadil) IMPULSE were 26.6 (SD=5.3) and 27.6 (SD=3.8), respectively. The mean physician's assessment scores for Caverject (Alprostadil) Sterile Powder and the formulation contained in Caverject (Alprostadil) IMPULSE were 2.6 (SD=0.6) and 2.7 (SD=0.5), respectively, based on a scale of 0 (no tumescence) to 3 (full rigidity).

Caverject (Alprostadil) (Caverject (Alprostadil) IMPULSE, Caverject (Alprostadil) Sterile Powder, and Caverject (Alprostadil) Injection) is indicated for the treatment of erectile dysfunction due to neurogenic, vasculogenic, psychogenic, or mixed etiology.

Intracavernosal Caverject (Alprostadil) is also indicated as an adjunct to other diagnostic tests in the diagnosis of erectile dysfunction.

Caverject (Alprostadil) should not be used in patients who have a known hypersensitivity to the drug, in patients who have conditions that might predispose them to priapism, such as sickle cell anemia or trait, multiple myeloma, or leukemia, or in patients with anatomical deformation of the penis, such as angulation, cavernosal fibrosis, or Peyronie's disease. Patients with penile implants should not be treated with Caverject (Alprostadil) .

Caverject (Alprostadil) is intended for use in adult men only.

Caverject (Alprostadil) is not indicated for use in children or newborns.

Caverject (Alprostadil) should not be used in men for whom sexual activity is inadvisable or contraindicated.

Prolonged erection defined as erection lasting > 4 to ≤ 6 hours in duration occurred in 4% of 1,861 patients treated up to 18 months in studies of Caverject (Alprostadil) Sterile Powder. The incidence of priapism (erections lasting > 6 hours in duration) was 0.4% with the same length of use. Pharmacologic intervention and/or aspiration of blood from the corpora cavernosum was performed in 2 of the 7 patients with priapism. To minimize the chances of prolonged erection or priapism, Caverject (Alprostadil) should be titrated slowly to the lowest effective dose (see ). The patient must be instructed to immediately report to his prescribing physician, or, if unavailable, to seek immediate medical assistance for any erection that persists longer than 4 hours. If priapism is not treated immediately, penile tissue damage and permanent loss of potency may result.

To ensure safe and effective use of Caverject (Alprostadil) , the patient should be thoroughly instructed and trained in the self-injection technique before he begins intracavernosal treatment with Caverject (Alprostadil) at home. The desirable dose should be established in the physician's office.

Any reconstituted solution with precipitates or discoloration should be discarded. The Caverject (Alprostadil) IMPULSE syringe system is designed for one use only and should be discarded after use. The device and the needle must be properly discarded after use. Needles must not be re-used or shared with other persons. Patient instructions for administration are included in each package of Caverject (Alprostadil) IMPULSE.

The dose of Caverject (Alprostadil) that is established in the physician's office should not be changed by the patient without consulting the physician. The patient may expect an erection to occur within 5 to 20 minutes. A standard treatment goal is to produce an erection lasting no longer than 1 hour. Generally, Caverject (Alprostadil) should be used no more than 3 times per week, with at least 24 hours between each use.

Patients should be aware of possible side effects of therapy with Caverject (Alprostadil) ; the most frequently occurring is penile pain after injection, usually mild to moderate in severity. A potentially serious adverse reaction with intracavernosal therapy is priapism. Accordingly, the patient should be instructed to contact the physician's office immediately or, if unavailable, to seek immediate medical assistance if an erection persists for longer than 4 hours.

The patient should report any penile pain that was not present before or that increased in intensity, as well as the occurrence of nodules or hard tissue in the penis to his physician as soon as possible. As with any injection, an infection is a possibility. Patients should be instructed to report to the physician any penile redness, swelling, tenderness or curvature of the erect penis. The patient must visit the physician's office for regular check-ups for assessment of the therapeutic benefit and safety of treatment with Caverject (Alprostadil) .

Note: Use of intracavernosal Caverject (Alprostadil) offers no protection from the transmission of sexually transmitted diseases. Individuals who use Caverject (Alprostadil) should be counseled about the protective measures that are necessary to guard against the spread of sexually transmitted diseases, including the human immunodeficiency virus (HIV).

The injection of Caverject (Alprostadil) can induce a small amount of bleeding at the site of injection (see section hematoma, ecchymosis, hemorrhage at the site of injection). In patients infected with blood-borne diseases, this could increase the risk of transmission of blood-borne diseases between partners.

In clinical trials, concomitant use of agents such as antihypertensive drugs, diuretics, antidiabetic agents (including insulin), or non-steroidal anti-inflammatory drugs had no effect on the efficacy or safety of Caverject (Alprostadil) .

Long-term carcinogenicity studies have not been conducted. Rat reproductive studies indicate that alprostadil at doses of up to 0.2 mg/kg/day does not adversely affect or alter rat spermatogenesis, providing a 200-fold margin of safety compared with the usual human doses. The following battery of mutagenicity assays revealed no potential for mutagenesis: bacterial mutation (Ames), alkaline elution, rat micronucleus, sister chromatid exchange, CHO/HGPRT mammalian cell forward gene mutation, and unscheduled DNA synthesis (UDS).

A 1-year irritancy study was conducted in three groups of 5 male Cynomolgus monkeys injected intracavernosally twice weekly with either vehicle or 3 or 8.25 mcg of alprostadil/ injection. An additional two groups of 6 monkeys each were injected with vehicle or with 8.25 mcg/injection twice weekly as described previously plus they received multiple doses during weeks 44, 48, and 52. Three monkeys from each group were retained for a 4-week recovery period. There was no evidence of drug-related penile irritancy or nonpenile tissue lesions, which could be directly related to alprostadil. The irritancy, which was noted for control and treated monkeys, was considered to be a result of the injection procedure itself, and any lesions noted were shown to be reversible. At the end of the 4-week recovery period, the histological changes in the penis had regressed.

The frequency of hematoma and ecchymosis was 3% and 2%, respectively. In most cases, hematoma/ecchymosis was judged to be a complication of a faulty injection technique. Accordingly, proper instruction of the patient in self-injection is of importance to minimize the potential of hematoma/ecchymosis (see ).

The following local adverse reactions were reported by fewer than 1% of patients after injection of Caverject (Alprostadil) : balanitis, injection site hemorrhage, injection site inflammation, injection site itching, injection site swelling, injection site edema, urethral bleeding, penile warmth, numbness, yeast infection, irritation, sensitivity, phimosis, pruritus, erythema, venous leak, painful erection, and abnormal ejaculation.

The following systemic adverse event information was derived from controlled and uncontrolled studies of Caverject (Alprostadil) Sterile Powder, including an uncontrolled 18-month safety study.

The following systemic events, which were reported for
Hemodynamic changes, manifested as decreases in blood pressure and increases in pulse rate, were observed during clinical studies, principally at doses above 20 mcg and above 30 mcg of alprostadil, respectively, and appeared to be dose-dependent. However, these changes were usually clinically unimportant; only three patients discontinued the treatment because of symptomatic hypotension.

Caverject (Alprostadil) had no clinically important effect on serum or urine laboratory tests.

The safety of Caverject (Alprostadil) IMPULSE was evaluated in a study that compared the formulation of alprostadil for injection contained in Caverject (Alprostadil) IMPULSE with the formulation contained in Caverject (Alprostadil) Sterile Powder. The doses used by the 87 patients in this crossover study were the same for both formulations. The number and type of events reported for Caverject (Alprostadil) IMPULSE were consistent between formulations in this study and in other controlled and uncontrolled studies with Caverject (Alprostadil) Sterile Powder.

Overdosage was not observed in clinical trials with Caverject (Alprostadil) . If intracavernous overdose of Caverject (Alprostadil) occurs, the patient should be under medical supervision until any systemic effects have resolved and/or until penile detumescence has occurred. Symptomatic treatment of any systemic symptoms would be appropriate.

The dose of Caverject (Alprostadil) should be individualized for each patient by careful titration under supervision by the physician. In clinical studies, patients were treated with Caverject (Alprostadil) Sterile Powder in doses ranging from 0.2 to 140 mcg; however, since 99% of patients received doses of 60 mcg or less, doses of greater than 60 mcg are not recommended. In general, the lowest possible effective dose should always be employed. In clinical studies, over 80% of patients experienced an erection sufficient for sexual intercourse after intracavernosal injection of Caverject (Alprostadil) .

The first injections of Caverject (Alprostadil) must be done at the physician's office by medically trained personnel. Self-injection therapy by the patient should be started only after the patient is properly instructed and well trained in the self-injection technique. The physician should make a careful assessment of the patient's skills and competence with this procedure. The intracavernosal injection must be done under sterile conditions. The site of injection is usually along the dorso-lateral aspect of the proximal third of the penis. Visible veins should be avoided. The side of the penis that is injected and the site of injection must be alternated; the injection site must be cleansed with an alcohol swab.

The dose of Caverject (Alprostadil) that is selected for self-injection treatment should provide the patient with an erection that is satisfactory for sexual intercourse and that is maintained for no longer than 1 hour. If the duration of erection is longer than 1 hour, the dose of Caverject (Alprostadil) should be reduced. Self-injection therapy for use at home should be initiated at the dose that was determined in the physician's office; however, dose adjustment, if required (up to 57% of patients in one clinical study), should be made only after consultation with the physician. The dose should be adjusted in accordance with the titration guidelines described above. The effectiveness of Caverject (Alprostadil) for long-term use of up to 6 months has been documented in an uncontrolled, self-injection study. The mean dose of Caverject (Alprostadil) Sterile Powder at the end of 6 months was 20.7 mcg in this study. Caverject (Alprostadil) IMPULSE in the 10 mcg strength is designed to deliver a minimum dose of 2.5 mcg and a maximum dose of 10 mcg. Caverject (Alprostadil) IMPULSE in the 20 mcg strength is designed to deliver a minimum dose of 5 mcg and a maximum dose of 20 mcg. The physician should determine the most suitable formulation of Caverject (Alprostadil) for the individual patient (Caverject (Alprostadil) IMPULSE, Caverject (Alprostadil) Sterile Powder, or Caverject (Alprostadil) Injection).

Careful and continuous follow-up of the patient while in the self-injection program must be exercised. This is especially true for the initial self-injections, since adjustments in the dose of Caverject (Alprostadil) may be needed. The recommended frequency of injection is no more than 3 times weekly, with at least 24 hours between each dose. All formulations of Caverject (Alprostadil) are intended for single use only and should be discarded after use. The user should be instructed in the proper disposal of the injection materials (e.g., device, needles).

While on self-injection treatment, it is recommended that the patient visit the prescribing physician's office every 3 months. At that time, the efficacy and safety of the therapy should be assessed, and the dose of Caverject (Alprostadil) should be adjusted, if needed.

Caverject (Alprostadil) IMPULSE consists of a disposable, single-dose, dual chamber syringe system. The system includes a glass cartridge, which contains sterile, freeze-dried alprostadil in the front chamber and sterile bacteriostatic water for injection in the rear chamber. Following proper reconstitution instructions, the 10 mcg strength syringe can deliver up to 0.5 mL of solution. Each 0.5 mL of solution contains 10 mcg of alprostadil, 324.7 mcg of alpha cyclodextrin, 45.4 mg of lactose, 23.5 mcg of sodium citrate, and 4.45 mg of benzyl alcohol. The delivery device can be set to deliver a solution volume of 0.125, 0.25, 0.375, or 0.50 mL to enable administration of 2.5, 5, 7.5, or 10 mcg of alprostadil. Following proper reconstitution instructions, the 20 mcg strength syringe can deliver up to 0.5 mL of solution. Each 0.5 mL of solution contains 20 mcg of alprostadil, 649.3 mcg of alpha cyclodextrin, 45.4 mg of lactose, 23.5 mcg of sodium citrate, and 4.45 mg of benzyl alcohol. The delivery device can be set to deliver a solution volume of 0.125, 0.25, 0.375, or 0.50 mL to enable administration of 5, 10, 15, or 20 mcg of alprostadil. After reconstitution, the solution of Caverject (Alprostadil) should be used within 24 hours when stored at or below 25°C (77°F). Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration whenever the solution and container permit. The product should not be used if particulate matter or discoloration are present. Following a single use, the injection device and any remaining solution should be properly discarded.

Caution: Caverject (Alprostadil) IMPULSE is for single use only.

Caverject (Alprostadil) IMPULSE is supplied as a disposable, single-dose, dual chamber syringe system. The system includes a glass cartridge, which contains sterile, freeze-dried alprostadil in the front chamber and sterile bacteriostatic water for reconstitution in the rear chamber. The syringes contain either 12.8 or 25.6 mcg of alprostadil to allow delivery of a maximum of 10 or 20 mcg/0.5mL. Store the unreconstituted product at 25°C (77°F); excursions permitted to 15° to 30°C (59° to 86°F) [see USP Controlled Room Temperature].

When reconstituted and used as directed, the deliverable amount for the 10 mcg strength is 10 mcg/0.5 mL or an increment of 10 mcg/0.5 mL, 2.5 mcg/0.125 mL, 5 mcg/0.25 mL, or 7.5 mcg/0.375 mL of alprostadil and the deliverable amount for the 20 microgram strength is 20 mcg/0.5 mL or an increment of 20 mcg/0.5 mL, 5 mcg/0.125 mL, 10 mcg/0.250 mL, or 15 mcg/0.375 mL of alprostadil. The reconstituted solution should be used within 24 hours when stored at or below 25°C (77°F).

Caverject (Alprostadil) IMPULSE is supplied in a carton containing 2 blister trays. Each blister tray contains one dual chamber syringe system, one needle and 2 alcohol swabs. It is available in the following strengths:

Caverject (Alprostadil) is also available as follows:

Caverject (Alprostadil) Sterile Powder (alprostadil for injection) packaged in vials, 6 vials per carton

Caverject (Alprostadil) Sterile Powder (alprostadil for injection) vials with diluent syringe, 6 syringe systems per carton

Caverject (Alprostadil) Injection ([alprostadil injection] aqueous), 5 ampoules per carton

Read this information carefully before using Caverject (Alprostadil) [KAV-er-jeckt]. Read the information you get each time you renew your prescription, in case anything has changed. This is a summary and does not replace talking with your doctor when you start this medication and at check-ups. If you have any questions or concerns, talk to your doctor about them.

Caverject (Alprostadil) is a medicine to treat male impotence (erectile dysfunction). Caverject (Alprostadil) is injected into a specific area of the penis and should produce an erection in 5 to 20 minutes. The erection should last for no longer than 1 hour.

Caverject (Alprostadil) IMPULSE is for one use only and should be thrown away properly after a single use.

Caverject (Alprostadil) does not protect you from sexually transmitted diseases (STDs), such as HIV (the virus that causes AIDS). In addition, small amounts of bleeding at the injection site can increase the risk of passing diseases carried by the blood, such as HIV.

There are several causes of impotence. These include medications that you may be taking for other conditions, poor blood circulation in the penis, nerve damage, emotional problems, too much smoking or alcohol use, use of street drugs, and hormonal problems. Often, impotence is due to more than one cause.

Treatments for impotence include switching medications if you are taking a medication that causes impotence, prescription medications, medical devices that produce an erection, surgical procedures to correct blood flow in the penis, penile implants, and psychological counseling.

You should not stop taking any prescription medications, unless told to do so by your doctor.

The use of other medical treatments for impotence in combination with Caverject (Alprostadil) is not recommended. Discuss any concerns you may have about combination treatment with your doctor.

Do not use Caverject (Alprostadil) if you have certain conditions that might cause long-lasting erections (lasting more than 4 hours). Long-lasting erections may cause penis damage. These conditions include:

Do not use Caverject (Alprostadil) if you

Women and children should not use Caverject (Alprostadil) .

You will be treated with Caverject (Alprostadil) in your doctor's office to find out what dose is best for you. After that, you can inject it yourself at home. Do not use it more than 3 times a week. There should be at least 24 hours between doses. See your doctor for regular check-ups to be sure Caverject (Alprostadil) is not causing damage and that it is working as well as possible.

See the section at the end of this leaflet for details about how to use Caverject (Alprostadil) .

About 4 in 100 men who use Caverject (Alprostadil) may get erections that last more than 4 hours. These can cause serious and permanent damage.

The most common side effect of Caverject (Alprostadil) is mild to moderate pain after injection. About one-third of patients report this effect.

You may get a small amount of bleeding at the injection site. This is more likely if you have a medical condition or are taking a medicine that interferes with blood clotting.

Call your doctor if you notice any redness, lumps, swelling, tenderness, or curving of the erect penis. Also, tell your doctor about any penis pain you did not have before or other penis problems you have.

There is a possibility of needle breakage with use of Caverject (Alprostadil) IMPULSE. To best avoid breaking the needle, you should pay careful attention to your doctor's instructions and try to handle the device properly. If the needle breaks during injection and you are able to see and grasp the broken end, you should remove it and contact your doctor. If you cannot see or cannot grasp the broken end, you should promptly contact your doctor.

Medicines are sometimes prescribed for purposes other than those listed in a Patient Information Leaflet. If you have any concerns about Caverject (Alprostadil) , ask your doctor. Your doctor or pharmacist can give you information about Caverject (Alprostadil) that was written for health care professionals. Do not use Caverject (Alprostadil) for a condition for which it was not prescribed. Do not share Caverject (Alprostadil) with other people.

You can get more information about impotence (erectile dysfunction) and its treatment from the National Institutes of Health (Washington, DC), the American Foundation for Urological Diseases (Baltimore, MD), or the Impotence Institute of America (Washington, DC).

Before using Caverject (Alprostadil) , talk to your doctor about what to expect when using it, possible side effects, and what to do if side effects occur. Your dose has been selected for your individual needs. Do not change your dose without consulting your doctor. If you are not sure of the volume or dose to be used, talk to your doctor or pharmacist.

Follow these instructions exactly to prepare and inject a sterile (germ-free) dose of Caverject (Alprostadil) .

Caverject (Alprostadil) IMPULSE is packaged with a needle for injection (Figure A) and alcohol swab.

Caverject (Alprostadil) IMPULSE is available in 10 and 20 mcg strengths.

After use, dispose of all injection materials safely. Your pharmacist may be able to supply a disposal box especially for disposable injection devices.

Contains 2 single doseinjection systems

Diluent Contains Benzyl Alcohol

For intracavernosal use only

Dual Chamber System

NDC 0009518101

Contains 2 single doseinjection systems

Diluent Contains Benzyl Alcohol

For intracavernosal use only

Dual Chamber System

NDC 0009518201