ELIGARD® 7.5 mg, 22.5 mg, 30 mg, 45 mg (leuprolide acetate for injectable suspension)
ELIGARD® is a sterile polymeric matrix formulation of leuprolide acetate for subcutaneous injection. It is designed to deliver leuprolide acetate at a controlled rate over a one-, three-, four- or six-month therapeutic period.

Leuprolide acetate is a synthetic nonapeptide analog of naturally occurring gonadotropin releasing hormone (GnRH or LH-RH) that, when given continuously, inhibits pituitary gonadotropin secretion and suppresses testicular and ovarian steroidogenesis. The analog possesses greater potency than the natural hormone. The chemical name is 5-oxo-L-prolyl-L-histidyl-L-tryptophyl-L-seryl-L-tyrosyl-D-leucyl-L-leucyl-L-arginyl-N-ethyl-L-prolinamide acetate (salt) with the following structural formula:

ELIGARD® is prefilled and supplied in two separate, sterile syringes whose contents are mixed immediately prior to administration. The two syringes are joined and the single dose product is mixed until it is homogenous. ELIGARD® is administered subcutaneously, where it forms a solid drug delivery depot.

One syringe contains the ATRIGEL® Delivery System and the other contains leuprolide acetate. ATRIGEL® is a polymeric (non-gelatin containing) delivery system consisting of a biodegradable poly (DL-lactide-co-glycolide) (PLGH or PLG) polymer formulation dissolved in a biocompatible solvent, N-methyl-2-pyrrolidone (NMP).

Refer to Table 1 for the delivery system composition and constituted product formulation for each ELIGARD® product.

Table 1. ELIGARD® Delivery System Composition and Constituted Product Formulation  ELIGARD®
7.5 mg ELIGARD®
22.5 mg ELIGARD®
30 mg ELIGARD®
45 mg
ATRIGEL® Delivery System Syringe Polymer PLGH PLG PLG PLG
Polymer description Copolymer containing carboxyl endgroups Copolymer with hexanediol Copolymer with hexanediol Copolymer with hexanediol
Polymer DL-lactide to Glycolide Molar Ratio 50:50 75:25 75:25 85:15
Constituted Product  Polymer delivered 82.5 mg 158.6 mg 211.5 mg 165 mg
NMP delivered 160.0 mg 193.9 mg 258.5 mg 165 mg
Leuprolide acetate delivered 7.5 mg 22.5 mg 30 mg 45 mg
Approximate Leuprolide free base equivalent 7.0 mg 21 mg 28 mg 42 mg
Approximate administered formulation weight 250 mg 375 mg 500 mg 375 mg
 Approximate injection volume 0.25 mL 0.375 mL 0.5 mL 0.375 mL

Leuprolide acetate, an LH-RH agonist, acts as a potent inhibitor of gonadotropin secretion when given continuously in therapeutic doses. Animal and human studies indicate that after an initial stimulation, chronic administration of leuprolide acetate results in suppression of testicular and ovarian steroidogenesis. This effect is reversible upon discontinuation of drug therapy.

In humans, administration of leuprolide acetate results in an initial increase in circulating levels of luteinizing hormone (LH) and follicle stimulating hormone (FSH), leading to a transient increase in levels of the gonadal steroids (testosterone and dihydrotestosterone in males, and estrone and estradiol in premenopausal females). However, continuous administration of leuprolide acetate results in decreased levels of LH and FSH. In males, testosterone is reduced to below castrate threshold (≤ 50 ng/dL). These decreases occur within two to four weeks after initiation of treatmen