Caverject alprostadil for injection
Caverject Information
Company Name Pharmacia and Upjohn Company
Caverject (Alprostadil)
Caverject (Alprostadil) Description
Caverject (Alprostadil) Sterile Powder 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 per 100 milliliter double distilled water. Caverject (Alprostadil) is available as a sterile freeze-dried powder for intracavernosal use in four sizes: 5, 10, 20 and 40 micrograms per vial — When reconstituted as directed with 1 milliliter of bacteriostatic water for injection or sterile water, both preserved with benzyl alcohol 0.945% w/v, gives 1.13 milliliters of reconstituted solution. Each milliliter of Caverject (Alprostadil) contains 5.4, 10.5, 20.5 or 41.1 micrograms of alprostadil depending on vial strength, 172 milligrams of lactose, 47 micrograms of sodium citrate and 8.4 milligrams of benzyl alcohol. The deliverable amount of alprostadil is 5, 10, 20 or 40 micrograms per milliliter because approximately 0.4 microgram for the 5 microgram strength, 0.5 microgram for the 10 and 20 microgram strengths and 1.1 microgram for the 40 microgram strength is lost due to adsorption to the vial and syringe. When necessary, the pH of alprostadil for injection was adjusted with hydrochloric acid and/or sodium hydroxide before lyophilization.
The structural formula of alprostadil is represented below:
Caverject (Alprostadil) Clinical Pharmacology
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.
Caverject (Alprostadil) Indication And Usage
Caverject (Alprostadil) is indicated for the treatment of erectile dysfunction due to neurogenic, vasculogenic, psychogenic, or mixed etiology.
Intracavernosal Caverject (Alprostadil) may be a useful adjunct to other diagnostic tests in the diagnosis of erectile dysfunction.
Caverject (Alprostadil) Contraindications
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) should not be used in women or children and is not for use in newborns.
Caverject (Alprostadil) should not be used in men for whom sexual activity is inadvisable or contraindicated.
Caverject (Alprostadil) Precautions
Prolonged erection (erection lasting 4 to 6 hours) and priapism (erection lasting over 6 hours) are known to occur following intracavernosal administration of vasoactive substances, including Caverject (Alprostadil) . The patient should be instructed to immediately report to his physician or, if unavailable, to seek immediate medical assistance for any erection that persists for longer than 4 hours. Treatment of priapism should be according to established medical practice.
The overall incidence of penile fibrosis, including Peyronie's disease, reported in clinical studies with Caverject (Alprostadil) was 3%. In one self-injection clinical study where duration of use was up to 18 months, the incidence of fibrosis was 7.8%. Regular follow-up of patients, with careful examination of the penis, is strongly recommended to detect signs of penile fibrosis. Treatment with Caverject (Alprostadil) should be discontinued in patients who develop penile angulation, cavernosal fibrosis, or Peyronie's disease.
Patients on anticoagulants, such as warfarin or heparin, may have increased propensity for bleeding after intracavernosal injection.
Underlying treatable medical causes of erectile dysfunction should be diagnosed and treated prior to initiation of therapy with Caverject (Alprostadil) .
The safety and efficacy of combinations of Caverject (Alprostadil) and other vasoactive agents have not been systematically studied. Therefore, the use of such combinations is not recommended.
The patient should be instructed not to re-use or to share needles or syringes. As with all prescription medicines, the patient should not allow anyone else to use his medicine.
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. The instructions for preparation of the solution of Caverject (Alprostadil) should be carefully followed. Vials with precipitates or discoloration should be discarded. The reconstituted vial is designed for one use only and should be discarded after withdrawal of proper volume of the solution. The content of the reconstituted vial should not be shaken. The needle must be properly discarded after use; it must not be re-used or shared with other persons. Patient instructions for administration are included in each package of Caverject (Alprostadil) .
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 intravenous 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 checkups 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 milligram/kilogram/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 micrograms of alprostadil per injection. An additional two groups of 6 monkeys each were injected with vehicle or with 8.25 micrograms/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.
Caverject (Alprostadil) Adverse Reactions
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, 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 micrograms and above 30 micrograms 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.
Caverject (Alprostadil) Overdosage
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.
Caverject (Alprostadil) Dosage And Administration
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) in doses ranging from 0.2 to 140 micrograms; however, since 99% of patients received doses of 60 micrograms or less, doses of greater than 60 micrograms 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) . A 1/2-inch, 27- to 30-gauge needle is generally recommended.
The first injections of Caverject (Alprostadil) must be done at the physician's office by medically trained personnel. Self-injection therapy by the patient can 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) at the end of 6 months was 20.7 micrograms in this study.
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. The reconstituted vial of Caverject (Alprostadil) is intended for single use only and should be discarded after use. The user should be instructed in the proper disposal of the syringe, needle, and vial.
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) How Supplied
Caverject (Alprostadil) is a dry lyophilized powder and is supplied in vials containing 6.15, 11.9, 23.2 or 46.4 micrograms of alprostadil for intracavernosal administration. Store the 5, 10 and 20 microgram strengths at or below 25°C (77°F).
When reconstituted and used as directed, the deliverable amount of alprostadil is 5, 10, 20 or 40 micrograms, respectively. The reconstituted solution should be used within 24 hours when stored at or below 25°C (77°F) and not refrigerated or frozen. Only the accompanying diluent or bacteriostatic water for injection with benzyl alcohol should be used when reconstituting Caverject (Alprostadil) .
Caverject (Alprostadil) is available in the following packages: 6–5 microgram vials NDC 0009-5131-02 6–10 microgram vials NDC 0009-3778-05 6–20 microgram vials NDC 0009-3701-05 6–40 microgram vials NDC 0009-7686-04
Other available packages: 6–20 microgram vials with diluent syringes NDC 0009-3701-01
Caverject (Alprostadil) Patient Instructions Forcaverject Alprostadil For Injection
There are several causes of impotence, a condition known medically as erectile dysfunction. These include: medications that you may be taking for other conditions, impaired blood circulation in the penis, nerve damage, emotional problems, excessive smoking or alcohol use, use of street drugs, and hormonal imbalances. Often, impotence is due to more than one cause.
Treatments for impotence include: switching medications (if you are taking a medication that causes impotence), administration of hormones, penile injections, use of medical devices that produce an erection, surgical procedures to correct blood flow in the penis, penile implants, and psychological counseling. Your doctor has selected Caverject (Alprostadil) for injection to treat your impotence. Your doctor can also discuss other available treatments. You should not stop taking any prescription medications, unless told to do so by your doctor.
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 about 1 hour. Generally, you should not use Caverject (Alprostadil) more than 3 times a week, with at least 24 hours between uses.
Men who have conditions that might result in long-lasting erections should not use Caverject (Alprostadil) . Some of these conditions include: sickle cell anemia or trait, leukemia, and tumor of the bone marrow (multiple myeloma). Men with penile implants, or an abnormally formed penis, or who have been advised not to engage in sexual activity should not use Caverject (Alprostadil) . Caverject (Alprostadil) should not be used by women or children.
Erections that last more than 4 hours 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.
Call your doctor if you notice any redness, lumps, swelling, tenderness, or curving of the erect penis.
A small amount of bleeding at the injection site may occur. Tell your doctor if you have a condition or are taking a medicine that interferes with blood clotting.
NOTE: Caverject (Alprostadil) offers no protection from the transmission of sexually transmitted diseases such as HIV (the virus that causes AIDS). Small amounts of bleeding at the injection site can increase the risk of transmission of blood-borne diseases between partners.
There is no approved injectable treatment using multiple drug components or "cocktails" for erectile dysfunction. Moreover, there are no data on the efficacy and safety of these combinations.
There is a technical leaflet discussion of Caverject (Alprostadil) written for health-care professionals that your pharmacist can let you read.
More information about erectile dysfunction and its treatment is available 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 dose of Caverject (Alprostadil) .
If the needle is severely bent at any time, do not use it for injecting Caverject (Alprostadil) and do not attempt to straighten it prior to injecting Caverject (Alprostadil) . A severely bent and restraightened needle may be predisposed to breakage. Needle breakage, with a portion of the needle remaining in the penis, has been reported and, in some cases, required hospitalization and surgical removal. If the needle is severely bent while preparing the injection, remove it from the syringe, discard, and attach a new, unused sterile needle to the syringe as described under "Prepare the Dose" below.
Use the needle, syringe, alcohol swabs, and vials then safely discard the supplies and any unused solution. Discard your needle/syringe, and alcohol swabs in a special container for disposal of sharp medical supplies. Ask your doctor or pharmacist where you can get these special containers.
To prepare and inject Caverject (Alprostadil) you will need a vial of Caverject (Alprostadil) Sterile Powder, a vial of diluent (bacteriostatic water for injection or sterile water, both preserved with benzyl alcohol 0.945% w/v), a disposable sterile 3-milliliter (3-cc) syringe, a 1/2-inch 27-gauge sterile needle, and two alcohol swabs (Figure A).
Caverject (Alprostadil) comes in 5, 10, 20 or 40 microgram strengths.
Caverject (Alprostadil)
Caverject (Alprostadil) Principal Display Panel - Mcg Vial
NDC 0009-5133-08
For Intracavernosal Use Only
Caverject (Alprostadil) Principal Display Panel - Mcg Vial Carton
NDC 0009-3701-05Contains 6 of NDC 0009-5133-08
For Intracavernosal Use Only
Diluent to be Used With This ProductContains Benzyl Alcohol as a Preservative
This Package Does NOT Contain Diluent
Caverject (Alprostadil) Principal Display Panel - Mcg Vial
NDC 0009-7686-01
For Intracavernosal Use Only
Caverject (Alprostadil) Principal Display Panel - Mcg Vial Carton
NDC 0009-7686-04Contains 6 of NDC 0009-7686-01
For Intracavernosal Use Only
Diluent to be Used With This ProductContains Benzyl Alcohol as a Preservative
This Package Does NOT Contain Diluent
