EDEX Powder for solution Ref.[28058] Active ingredients: Alprostadil

Prolonged erections greater than four hours in duration occurred in 4% of all patients treated up to 24 months. The incidence of priapism (erections greater than 6 hours in duration) was <1% with long-term use for up to 24 months. In the majority of cases, spontaneous detumescence occurred. Pharmacologic intervention and/or aspiration of blood from the corpora was necessary in 1.6% of 311 patients with prolonged erections/priapism. To minimize the chances of prolonged erection or priapism, Edex should be titrated slowly to the lowest effective dose (see DOSAGE AND ADMINISTRATION). 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 six hours. If priapism is not treated immediately, penile tissue damage and permanent loss of potency may result.

Edex, administered by intracavernous injection in doses ranging from 1 to 40 mcg per injection for periods up to 24 months, has been evaluated in clinical trials for safety in over 1,065 patients with erectile dysfunction. Discontinuation of therapy due to a side effect in clinical trials was required in approximately 9% of patients treated with Edex and in <1% of patients treated with placebo.

Local Adverse Reactions

The following local adverse reactions were reported in studies including 1,065 patients treated with Edex for up to two years.

Penile Pain

With use of up to 24 months, penile pain was reported at least once by 29% of patients during injection, 35% of patients during erection, and by 30% of patients after erection. On a per injection basis, 15% of injections were associated with penile pain. Penile pain was judged by patients to be mild in intensity for 80% of painful injections, moderate in intensity for 16% of painful injections, and severe in intensity for 4% of painful injections. The frequency of penile pain reports decreased over time; 41% of the patients experienced pain during the first 2 months and 3% of the patients experienced pain during months 21-24. In placebo-controlled studies, penile pain was reported by 31% of patients after Edex and by 9% of patients after placebo injection.

Prolonged Erection / Priapism

Prolonged erections greater than four hours in duration occurred in 4% of all patients treated up to 24 months. In placebo-controlled studies, 3% of patients treated with Edex and <1% of patients treated with placebo reported prolonged erections greater than four hours. The incidence of priapism (erections greater than 6 hours in duration) was <1% with long-term use for up to 24 months. In the majority of cases, spontaneous detumescence occurred. A higher incidence of prolonged erections was found in younger patients (<40 years), non-diabetic patients, and patients with psychogenic etiology of erectile dysfunction (See WARNINGS).

Hematoma / Ecchymosis

In patients treated with Edex for up to 24 months, local bleeding, hematoma, and ecchymosis were observed in 15%, 5%, and 4% of patients, respectively. In placebo-controlled studies, the frequency of local bleeding was 6% with injection of Edex and 3% with injection of placebo. In most cases, these reactions were attributed to faulty injection technique.

Local Adverse Reactions Reported by ≥1% of Patients All Study Periods*:

^* Protocol Numbers KU-620-001, KU-620-002, KU-620-003, F-8653.
^† Penile pain reported without an association to injection site or erection, such as pain in penis and scrotum, pain in glans penis, and burning penile pain.
^‡ Examples include injection into glans penis, urethra or subcutaneously.

Systemic Adverse Experiences

The following systemic adverse experiences were reported in controlled and uncontrolled studies in ≥1% of patients treated for up to 24 months with Edex.

Systemic Adverse Experiences Reported by ≥1% of Patients*:

Hemodynamic changes, manifested as increases or decreases in blood pressure and pulse rate, were observed during clinical studies but did not appear to be dose-dependent. Four patients (<1%) reported clinical symptoms of hypotension such as dizziness or syncope.

Edex had no clinically important effect on serum or urine laboratory tests.

Post-Marketing Adverse Experiences

Needle breakage.

1. Intracavernous injections of Edex can lead to increased peripheral blood levels of PGE₁ and its metabolites, especially in those patients with significant corpora cavernosa venous leakage. Increased peripheral blood levels of PGE₁ and its metabolites may lead to hypotension and/or dizziness.
2. Regular follow-up of patients, with careful examination of the penis at the start of therapy and at regular intervals (e.g. 3 months), is strongly recommended to identify any penile changes. The overall incidence of penile fibrosis, including Peyronie’s disease, reported in clinical studies up to 24 months with Edex was 7.8%. Treatment with Edex should be discontinued in patients who develop penile angulation, cavernosal fibrosis, or Peyronie’s disease. Treatment can be resumed if the penile abnormality subsides.
3. The safety and efficacy of combinations of Edex and other vasoactive agents have not been systematically studied. Therefore, the use of such combinations is not recommended.
4. After injection of the Edex solution, compression of the injection site for five minutes, or until bleeding stops, is necessary. Patients on anticoagulants, such as warfarin or heparin, may have increased propensity for bleeding after intracavernous injection.
5. Underlying treatable medical causes of erectile dysfunction should be diagnosed and treated prior to initiation of therapy with Edex.
6. Edex uses a superfine (29 gauge) needle. As with all superfine needles, the possibility of needle breakage exists. Careful instruction in proper patient handling and injection techniques may minimize the potential for needle breakage.
7. The patient should be instructed not to reuse or to share needles or cartridges. As with all prescription medicines, the patient should not allow anyone else to use his medicine.
8. Cardiovascular Risk Related to Underlying Medical Conditions

There is a potential for cardiac risk of sexual activity in patients with preexisting cardiovascular disease. Therefore, treatments for erectile dysfunction, including Edex, generally should not be used in men for whom sexual activity is inadvisable because of their underlying cardiovascular status. In addition, the evaluation of erectile dysfunction should include a determination of potential underlying causes and the identification of appropriate treatment following a complete medical assessment.

To ensure safe and effective use of Edex, the patient should be thoroughly instructed and trained in the self-injection technique before he begins intracavernous treatment with Edex at home. The desirable dose should be established in the physician’s office. The instructions for preparation of the Edex solution should be carefully followed. The reconstituted solution may initially appear cloudy due to small air bubbles. Do not use the solution if it remains cloudy, contains precipitates, or is discolored. The reconstituted solution should be gently mixed, not shaken. A patient information pamphlet is included in each package of Edex cartridges.

Edex should be used immediately after reconstitution. The patient should follow the instructions in the patient information pamphlet to limit the possibility of bacterial contamination. The reconstituted cartridge is designed for one use only and should be discarded after use. The Edex cartridge contains a solid layer or Iyophilized cake of dry white powder approximately 3/8" in thickness. A normal cake may appear cracked or crumbled. If the cartridge is damaged, the cake may shrink in size. Do not use the cartridge if it appears damaged or the cake is substantially reduced in size.

If the dosage prescribed is less than 1 mL of Edex solution, excess solution will be expelled through the needle as the plunger is pushed and the upper rim of the top stopper reaches the correct volume mark for the prescribed dose. The needle must be properly discarded after use; it must not be reused or shared with other persons.

The dose of Edex 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. Edex 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 Edex; the most frequently occurring is penile pain during and/or after injection, usually mild to moderate in severity. A potentially serious adverse reaction with intracavernous 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 6 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, infection is possible. 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 Edex.

Note: Individuals who are sexually active 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). Use of intracavernous Edex offers no protection from the transmission of sexually transmitted or blood-borne diseases. The injection of Edex can induce a small amount of bleeding 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.

The pharmacodynamic interaction between heparin (5,000 units) and alprostadil intravenous infusion (90 mcg over 3 hours) was investigated. The results indicate significant changes in partial thromboplastin time (140% increase) and thrombin time (120% increase). Therefore, caution should be exercised with concomitant administration of heparin and Edex.

(Also, see Drug-Drug Interactions in CLINICAL PHARMACOLOGY, Pharmacokinetics).

Edex is not indicated for use in women.

Edex is not indicated for use in women.

Edex is not indicated for use in pediatric patients.

Of the approximately 1,065 patients who entered the in-office dose-titration period in clinical studies, 25% were 65 years or older. In clinical studies, geriatric patients required, on average, higher minimally effective doses and had a higher rate of lack of effect (optimum dose not determined). Overall differences in safety were not observed between these geriatric patients and younger patients. Geriatric patients should be dosed and titrated according to the same DOSAGE AND ADMINISTRATION recommendations as younger patients, and the lowest possible effective dose should always be used.

This drug is known to be substantially excreted by the kidney, and the risk of toxic reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function.