Administration of other concentrations is not recommended. See “ Instructions for Proper Use ” below. Instructions for Proper Use • Gloves should be worn during preparation and administration. • Reconstituted drug must be admini stered within one hour after addition of sterile water for injection, USP. • Keep the v ial vertical at all times • Do not shake the vials • Follow aseptic technique Preparation • Draw up 2 mL of sterile water for injection , USP (WFI) using a reconstitution needle (21G/2 in) • Inject the WFI slowly into the degarelix 80 mg vial. To keep the product and syringe sterile, do not remove the syringe and the needle. • Keeping the vial in an upright position, swirl it very gently until the liquid l ooks clear and without undissolved powder or particles. If the powder adheres to the vial over the liquid surface, the vial can be tilted slightly to dissolve powder. Avoid shaking to prevent foam formation. A ring of small air bubbles on the surface of th e liquid is acceptable. The reconstitution procedure may take up to 15 minutes. • Tilt the vial slightly and keep the needle in the lowest part of the vial. Withdraw 3 mL of degarelix 80 mg without turning the vial upside down. • Exchange the reconstitutio n needle with the administration needle for d eep subcutaneous injection (27G/1.25 in). Remove any air bubbles. • Inject 2 mL of degarelix 80 mg subcutaneously immediately after reconstitution. Grasp the skin of the abdomen, elevate the subcutaneous tissue. Insert the needle deeply at an angle of not less than 45 degrees. Gently pull back the plunger to check if blood is aspirated. If blood appears in the syringe, the reconstituted product can no longer be used. Discontinue the procedure and discard the syri nge and the needle (reconstitute a new dose for the patient). • Repeat reconstitution procedure for the second dose. Choose a different injection site and inject 3 mL. 6.3.4 Potential Toxicities The most commonly observed adverse reactions with degarelix therapy include injection site reactions ( e.g. pain, erythema, swelling or induration), hot flashes, increased weight, Androgen suppression with prostate GVAX and cyclophosphamide J1265 Johns Hopkins University 35 of 68 J1265 PROT (Vers) 1.4 113012 fatigue, and increases in serum levels of transaminases and glutamyltransferase (GGT). The majori ty of the adverse reactions are grade 1 or 2, with g rade 3/4 adverse reaction s occurring at incidences of ≤1% . The most frequently reported adverse reactions at the injection sites are pain (28%), erythema (17%), swelling (6%), induration (4%) and nodule (3%). These adverse reactions are mostly transient, of mild to moderate intensity, occur primarily with the starting dose and lead to few discontinuations (<1%). Grade 3 injection site reactions occur in ≤2% of patients receiving degarelix. Hepatic laboratory abnormalities are primarily grade 1 o r 2 and are generally reversible. Grade 3 hepatic laboratory abnormalities occur in <1% of patients. Other potential toxicities of degarelix include fatigue, asthenia, chills, night sweats, hypertension, arthralgias, back pain, diarrhea, constipation, erec tile dysfunction, gynecomastia, hyperhidrosis, headache, dizziness, and insomnia. 6.3.5 Treatment Modifications and Dosing Delays Since only a single dose of degarelix acetate will be administered to each patient, dose modifications or treatment delays wil l not be permitted. 6.3.6 Concomitant Medications Degarelix is not a substrate for the human CYP450 enzyme system. Degarelix is not an inducer or inhibitor of the CYP450 system in vitro. Therefore, clinically significant CYP450 pharmacokinetic drug -drug i nteractions are unlikely. 6.4 Concomitant Medications and Supportive Care Because of the potential for drug -drug int eraction s, the concurrent use of all other drugs, over -the- counter medications, and alternative therapies must be documented on the case report form (CRF) . Concurrent use of other therapies (including other experimental modalities) intended for the treatment of prostate cancer is not permitted. Patients may not currently be taking any other form of androgen deprivation therapies, antiandrogens , 5α-reductase inhibitors, chemotherapy, radiation therapy, biologic therapy, or immunosuppressive drugs. Because glucocorticoids ( e.g. dexamethasone) may contribute to immunosuppression, patients should gen erally not initiate steroid therapy while on study. Accordingly, intermittent use of dexamethasone as an antiemetic agent is discouraged. The Principal Investigator must be no tified if steroid use is being considered. Subjects may receive other forms of no n-cancer -directed endocrine replacement therapy (e.g.