Edex Drug Information

Edex ® is indicated for the treatment of erectile dysfunction due to neurogenic, vasculogenic, psychogenic, or mixed etiology.

Edex ® in the Treatment of Erectile Dysfunction The dosage range of edex ® for the treatment of erectile dysfunction is 1 to 40 mcg. The intracavernous injection should be given over a 5 to 10 second interval. In a study with a dose range of 1 to 20 mcg of edex ®, the mean dose was 10.7 mcg at the end of the dose titration period.

In two studies with a dose range of 1 to 40 mcg of edex ®, the mean dose was 21.9 mcg at the end of the dose titration period. Doses greater than 40 mcg have not been studied. A ½-inch, 27- to 30-gauge needle is generally recommended for the intracavernous injection.

The patient is advised not to exceed the optimum edex ® dose which was determined in the doctor's office. The lowest possible effective dose should always be used. Initial Titration in Physician's Office 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 upon erectile response, until the dose that produces an erection suitable for intercourse and not exceeding a duration of 1 hour is reached. If there is no response to the initial 2.5-mcg dose, the second dose may be increased to 7.5 mcg, followed by increments of 5 to 10 mcg. The patient must stay in the physician's office until complete detumescence occurs.

If there is no response, then the next higher dose may be given within 1 hour. If there is a response, then there should be at least a 1-day interval before the next dose is given. Erectile Dysfunction of Pure Neurogenic Etiology (Spinal Cord Injury): Dosage titration should be initiated at 1.25 mcg of alprostadil.

At-Home (Maintenance Therapy) Dosing Instructions The first injections of edex ® 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 instruct the patient to discard any needles which become bent during the self-injection procedure as these needles may break.

The physician should make a careful assessment of the patient's skills and competence with the self-injection procedure. The intracavernous injection must be done under sterile conditions. The site of injection is usually along the 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 before injection.

The dose of edex ® 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 edex ® should be reduced. The lowest effective dose should be used at home.

Self-injection therapy for use at home should be initiated at the dose that was determined in the physician's office. Dose adjustment may be required and should be made only after consultation with the physician. 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 edex ® 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 edex ® cartridge and needle are intended for single use only and should be discarded after use.

The user should be instructed in the proper disposal of the needles and cartridges. 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 edex ® should be adjusted, if needed.

The patient is instructed to follow the enclosed patient information pamphlet. Preparation of Solution The edex ® injection device is used to reconstitute the single-dose, dual-chamber cartridge. The plunger is used to force the sterile 0.9% sodium chloride (1.075 mL) in one chamber into the chamber containing alprostadil.

After reconstitution, the edex ® injection device is used to administer the intracavernous injection of alprostadil. The reusable edex ® injection device is for use only with the cartridges and needles included in the edex ® Cartridge Packs. Prepare the edex ® solution immediately before use.

Do not administer unless solution is clear. Do not add any drugs or solutions to the edex ® solution. Discard any unused solution remaining in the cartridge.

The reconstituted solution should not be stored. The edex ® cartridge contains a solid layer or lyophilized 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. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration.

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. CAUTION: Do not reuse any solution remaining in the cartridge due to the possibility of bacterial contamination.

Administration edex ® is given as an intracavernous injection over a 5- to 10-second interval. See patient information for edex ®. Stability The single-dose, dual-chamber cartridge should be reconstituted only when it is certain that the patient is ready to administer the drug.

The reconstituted drug solution should be used immediately after reconstitution. Any solution remaining in the cartridge should be discarded.

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.

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 ).

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

Drug Interactions 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.)

Pregnancy, Nursing Mothers and Pediatric Use edex ® is not indicated for use in women or pediatric patients.

Edex ® should not be used: in men who have conditions that predispose them to priapism, such as sickle cell anemia or sickle cell trait, multiple myeloma, or leukemia (see WARNINGS ). for the treatment of erectile dysfunction in men with fibrotic conditions of the penis, such as cavernosal fibrosis or Peyronie’s disease (see PRECAUTIONS ). in men with penile implants

Limited data are available in regard to edex ® overdose in humans. Systemic reactions are uncommon with intracavernous injection of edex ®. Hypotension occurred in less than 1% of patients treated with edex ®.

A single dose rising tolerance study in healthy volunteers indicated that single intravenous doses of alprostadil from 1 to 120 mcg were well tolerated. Beginning with a 40 mcg bolus intravenous dose, the frequency of drug-related systemic adverse events increased in a dose-dependent manner, characterized mainly by facial flushing. The primary symptom of an edex ® overdose is a prolonged erection or priapism.

Because of the potential for tissue hypoxia and possible necrosis, it is strongly recommended to treat an erection lasting more than 6 hours. The patient is strongly encouraged to go to the nearest emergency room if his personal physician is not available. In the event of an overdose, supportive therapy according to the presence of other symptoms is recommended.