No excretion studies have been conducted with ELIGARD.

No drug metabolism study was conducted with ELIGARD.

5.3 Preclinical safety data

 Preclinical studies with leuprorelin acetate, revealed in both sexes effects on the reproductive system, which were expected from the known pharmacological properties. These effects were shown to be reversible after discontinuation of the treatment and an appropriate period of regeneration. Leuprorelin acetate did not show teratogenicity. Embryotoxicity/lethality was observed in rabbits, in line with the pharmacological effects of leuprorelin acetate on the reproductive system.

Carcinogenicity studies were performed in rats and mice over 24 months. In rats, a dose-related increase in pituitary apoplexy was observed after subcutaneous administration at doses of 0.6 to 4 mg/kg/day. No such effect was observed in mice.

Leuprorelin acetate and related one-month product ELIGARD 7.5 mg were not mutagenic in a set of in vitro and in vivo assays.

6. PHARMACEUTICAL PARTICULARS

6.1 List of excipients

 Solvent (syringe A):
 Poly (DL-lactic-co-glycolic-acid) (50:50)

 - N-Methylpyrrolidone
 
Powder (syringe B):
 None

6.2 Incompatibilities

 The leuprorelin present in syringe B must only be mixed with the solvent in syringe A and must not be mixed with other medicinal products.

6.3 Shelf life

 2 years

After first opening of the tray or the large outer aluminium pouch, the powder and solvent for solution for injection are to be immediately reconstituted and administered to the patient.

Once reconstituted: use immediately, as the viscosity of the solution increases with time.

6.4 Special precautions for storage

 Store in a refrigerator (2°C – 8°C); in the original package in order to protect from moisture.

6.5 Nature and contents of container

 Two pre-filled cyclic olefin copolymer /polypropylene syringes, one containing powder (Syringe B), and one containing solvent (Syringe A). Together the two syringes comprise a mixing system.

Syringe A has a plunger tip of thermoplastic rubber and is capped with a polyethylene or polypropylene Luer-Lok cover. The syringe tip cap and the two plunger tips of Syringe B are composed of chlorobutyl rubber.

The following pack sizes are available:

• A kit consisting of one large aluminium outer pouch which contains 2 aluminium pouches, a 20-gauge sterile needle and a silicone desiccant pouch. One pouch contains one pre-filled polypropylene syringe A and a plunger. The other pouch contains one pre-filled cyclic olefin copolymer syringe B.

• A kit consisting of two thermoformed trays in a cardboard carton. One tray contains one pre-filled polypropylene syringe A, a large plunger rod and a desiccant pouch. The other tray contains pre-filled cyclic olefin copolymer syringe B, a 20-gauge sterile needle and a silicone desiccant pouch.

• A bundle pack containing kits of 3 x 2 pre-filled polypropylene/ cyclic olefin copolymer syringes (1 x Syringe A; 1 x Syringe B)

Not all pack sizes may be marketed.

6.6 Special precautions for disposal and other handling

7. MARKETING AUTHORISATION HOLDER

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