Endo USA, Inc.

Edex alprostadil ALPROSTADIL ALPROSTADIL ALFADEX LACTOSE, UNSPECIFIED FORM SODIUM CHLORIDE WATER Edex alprostadil ALPROSTADIL ALPROSTADIL ALFADEX LACTOSE, UNSPECIFIED FORM SODIUM CHLORIDE WATER Edex alprostadil ALPROSTADIL ALPROSTADIL ALFADEX LACTOSE, UNSPECIFIED FORM SODIUM CHLORIDE WATER

edex® (alprostadil for injection) is a sterile, pyrogen-free powder containing alprostadil in an alfadex (α-cyclodextrin) inclusion complex. Alprostadil is an endogenous substance known as prostaglandin E1 (PGE1). edex® is supplied in single-dose, dual-chamber cartridges. edex® is lyophilized in single-dose, dual-chamber cartridges intended for use with the reusable edex® injection device. One chamber of the cartridge contains alprostadil, alfadex and lactose as a sterile, pyrogen-free powder. The other chamber contains 1.075 mL of sterile 0.9% sodium chloride. The edex® cartridges are supplied in three strengths: 10-mcg cartridge (10.75 mcg alprostadil, 347.55 mcg α-cyclodextrin, 51.06 mg lactose); 20-mcg cartridge (21.5 mcg alprostadil, 695.2 mcg α-cyclodextrin, 51.06 mg lactose); 40-mcg cartridge (43 mcg alprostadil, 1,390.3 mcg α-cyclodextrin, 51.06 mg lactose). The edex® injection device is used to reconstitute the sterile powder in one chamber with the sterile 0.9% sodium chloride in the other chamber. After reconstitution, the edex® injection device is used to administer the intracavernous injection of alprostadil. The chemical name for alprostadil is (1R,2R,3R)-3-Hydroxy-2-[(E)-(3S)-3-hydroxy-1-octenyl]-5-oxocyclopentane heptanoic acid. The empirical formula is C20H34O5 and the molecular weight is 354.49. The chemical structure is: The α-cyclodextrin inclusion complex improves the water solubility of alprostadil. The empirical formula of α-cyclodextrin is C36H60O30 and the molecular weight is 972.85. The chemical structure is: Alprostadil alfadex is a white, odorless, hygroscopic powder. It is freely soluble in water and practically insoluble in ethanol, ethyl acetate and ether. After reconstitution, the active ingredient, alprostadil, immediately dissociates from the α-cyclodextrin inclusion complex. The reconstituted solution is clear and colorless and has a pH between 4.0 and 8.0. When the single-dose, dual-chamber cartridge containing either 10.75, 21.5, or 43 mcg of alprostadil is placed into the edex® injection device and reconstituted, the deliverable amount of alprostadil in each milliliter is 10, 20 or 40 mcg, respectively. alprostadil chemical structure α-cyclodextrin chemical structure

Alprostadil (PGE₁) is one of the prostaglandins, a family of naturally occurring acidic lipids with various pharmacological effects. Endogenous PGE₁ is derived from dihomo-gamma-linolenic acid, a fatty acid found within the phospholipids of cellular membranes. As an endogenous substance, PGE₁ exerts its biological effects either directly or indirectly by regulating and modifying the synthesis and effects of other hormones and mediators.

After reconstitution, PGE1 immediately dissociates from the α-cyclodextrin inclusion complex; the in vivo disposition of both components occurs independently after administration. After intravenous infusion of radiolabeled α-cyclodextrin to healthy volunteers, the radiolabeled components were rapidly eliminated within 24-hours, urine accounting for 81% to 83% of radioactivity and feces for 0.1%. There was no evidence of significant accumulation of radiolabeled α-cyclodextrin in the body even after 7 days of repeated intravenous injection. After intracavernous administration in monkeys, radiolabeled α-cyclodextrin was rapidly distributed from the injection site with less than 0.1% of the dose remaining in the penis 1 hour after administration. There was no evidence of tissue retention of radiolabeled α-cyclodextrin in monkeys.

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

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

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.

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.

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.

edex® is given as an intracavernous injection over a 5- to 10-second interval. See patient information for edex®.

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^® (alprostadil for injection) is available in single-dose, dual-chamber cartridges intended for use with the reusable edex^® injection device. One chamber of the cartridge contains 10.75, 21.5, or 43 mcg of alprostadil as a white, sterile, lyophilized powder. The other chamber contains 1.075 mL of sterile 0.9% sodium chloride. When the cartridge is placed into the edex^® injection device and reconstituted, the deliverable amount of alprostadil in each milliliter is 10, 20, or 40 mcg, respectively. edex^® Cartridge 2 Pack contains one reusable edex^® injection device, two single-dose, dual-chamber cartridges, two ½-inch, 29-gauge (0.33 mm × 12.7 mm) needles, and four alcohol swabs. edex^® Cartridge 6 Pack contains one reusable edex^® injection device, six single-dose, dual-chamber cartridges, six ½-inch, 29-gauge (0.33 mm × 12.7 mm) needles, and twelve alcohol swabs. The edex^® cartridges are supplied in the following packages:

edex® Cartridge 2 Pack (includes one injection device, two cartridges, two needles and four alcohol swabs)
10 mcg	1 × 2 Pack	NDC 52244-010-02
20 mcg	1 × 2 Pack	NDC 52244-020-02
40 mcg	1 × 2 Pack	NDC 52244-040-02

edex® Cartridge 6 Pack (includes one injection device, six cartridges, six needles and twelve alcohol swabs)
10 mcg	1 × 6 Pack	NDC 52244-010-06
20 mcg	1 × 6 Pack	NDC 52244-020-06
40 mcg	1 × 6 Pack	NDC 52244-040-06

10 mcg 2 pk

10 mcg 6 pk

20 mcg 2pk

20 mcg 6pk

40 mcg 2pk

40 mcg 2pk