PRECAUTIONS
General 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. 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 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 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.
The safety and efficacy of combinations of CAVERJECT 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.
Information for the Patient
To ensure safe and effective use of CAVERJECT, the patient should be thoroughly instructed and trained in the self-injection technique before he begins intracavernosal treatment with CAVERJECT at home. The desirable dose should be established in the physician's office. The instructions for preparation of the solution of CAVERJECT 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.
The dose of CAVERJECT 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 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; 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.
Note: Use of intracavernosal CAVERJECT offers no protection from the transmission of sexually transmitted diseases. Individuals who use CAVERJECT 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 can induce a small amount of bleeding at the site of injection (see ADVERSE REACTIONS 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.
Carcinogenesis, Mutagenesis, and Impairment of Fertility
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.
Pregnancy, Nursing Mothers, and Pediatric Use
CAVERJECT is not indicated for use in newborns, children, or women.
Geriatric Use
A total of 341 subjects included in clinical studies were 65 and over. No overall differences in safety and effectiveness were observed between these subjects and younger subjects, and the other reported clinical experience has not identified differences in responses between elderly and younger patients, but decreased sensitivity of some older individuals cannot be ruled out.
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