Firmagon Drug Information

FIRMAGON ® is indicated for treatment of patients with advanced prostate cancer.

Dosing information FIRMAGON is administered as a subcutaneous injection in the abdominal region only at the dosages in Table 1 below. Before administering FIRMAGON read the Instructions for reconstitution and administration carefully. As with other drugs administered by subcutaneous injection, the injection site should vary periodically.

Injections should be given only in areas of the abdomen that will not be exposed to pressure, e.g., not close to waistband or belt nor close to the ribs. FIRMAGON is supplied as a powder to be reconstituted with Sterile Water for Injection, USP. Starting dose (240 mg): Two single-dose vials each delivering 120 mg of degarelix in a white to off-white lyophilized powder for reconstitution supplied with diluent in two prefilled syringes.

Maintenance dose (80 mg): One single-dose vial delivering 80 mg of degarelix in a white to off-white lyophilized powder for reconstitution supplied with diluent in one prefilled syringe. Follow the instructions for reconstitution closely and read the complete instructions before performing the subcutaneous injection. Reconstituted drug must be administered within one hour after addition of Sterile Water for Injection, USP.

Do not shake the vials. Follow aseptic technique. The drug product must be prepared using the following instructions: NOTE: The mixing process must be repeated for the two injections of the Starting Dose prior to injecting the product into the patient's abdomen.

Disposing used needles and syringes Put used alcohol swabs, needles and syringes in an FDA-cleared sharps disposal container right away after use. Do not throw away loose needles and syringes in the trash. For more information about safe sharps disposal, go to the FDA's website at: http://www.fda.gov/safesharpsdisposal.

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Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. FIRMAGON was studied in a randomized, open-label trial in which patients with prostate cancer were randomized to receive FIRMAGON (subcutaneous) or leuprolide (intramuscular) monthly for 12 months. The most common adverse reactions (≥10%) during FIRMAGON therapy are injection site reactions (e.g., pain, erythema, swelling or induration), hot flashes, and increases in serum levels of transaminases and gamma-glutamyltransferase (GGT).

Table 2: Adverse Reactions Reported in ≥ The following adverse reactions occurred in 1 to < 5% of patients treated with FIRMAGON: Body as a whole: Asthenia, fatigue, fever, night sweats Digestive system: Nausea Nervous system: Dizziness, headache, insomnia The following adverse reactions, not already listed, occurred in ≥ 1% of patients treated in any study with FIRMAGON: Reproductive System: Erectile dysfunction, testicular atrophy Endocrine Disorders: Gynecomastia General: Hyperhidrosis Gastrointestinal: Diarrhea Injection Site Reactions The most frequently reported adverse reactions at the injection sites were pain (28%), erythema (17%), swelling (6%), induration (4%) and nodule (3%). These adverse reactions were mostly transient, of mild to moderate intensity, occurred primarily with the starting dose and led to few discontinuations (<1%). Grade 3 injection site reactions occurred in 2% or less of patients receiving FIRMAGON.

Hepatic Laboratory Abnormalities Hepatic laboratory abnormalities were primarily Grade 1 or 2 and were generally reversible. Grade 3 hepatic laboratory abnormalities occurred in less than 1% of patients. FIRMAGON Extension Study The safety of FIRMAGON administered once every 28 days was evaluated further in an extension study (NCT00451958) in 385 patients who completed the above active-controlled trial.

Of the 385 patients, 251 patients continued treatment with FIRMAGON and 135 patients crossed over treatment from leuprolide to FIRMAGON. The median treatment duration on the extension study was approximately 43 months (range 1 to 58 months). The most common adverse reactions reported in ≥10% of the patients were injection site reactions (e.g., pain, erythema, swelling, induration or inflammation), pyrexia, hot flush, weight loss or gain, fatigue, increases in serum levels of hepatic transaminases and GGT.

One percent of patients had injection site infections including abscess. The detection of antibody formation is highly dependent on the sensitivity and specificity of the assay. Additionally, the observed incidence of antibody (including neutralizing antibody) positivity in an assay may be influenced by several factors including assay methodology, sample handling, timing of sample collection, concomitant medications, and underlying disease.

Anti-Degarelix Antibodies Anti-degarelix antibody development has been observed in 10% of patients after treatment with FIRMAGON for 1 year. There is no indication that the efficacy or safety of FIRMAGON treatment is affected by antibody formation.

Postmarketing Experience

The following adverse reactions have been identified during post-approval use of FIRMAGON. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Changes in bone density Decreased bone density has been reported in the medical literature in men who have had orchiectomy or who have been treated with a GnRH agonist.

It can be anticipated that long periods of medical castration in men will result in decreased bone density.

No drug-drug interaction studies were conducted. Degarelix is not a substrate for the human CYP450 system. Degarelix is not an inducer or inhibitor of the CYP450 system in vitro.

Therefore, clinically significant CYP450 pharmacokinetic drug-drug interactions are unlikely.

Pregnancy Risk Summary The safety and efficacy of FIRMAGON have not been established in women. Based on findings in animal studies and mechanism of action, FIRMAGON can cause fetal harm and loss of pregnancy when administered to a pregnant woman. There are no human data on the use of FIRMAGON in pregnant women to inform the drug-associated risk.

In animal developmental and reproductive toxicity studies in rats and rabbits, oral administration of degarelix during organogenesis caused embryo-fetal lethality and abortion as well as increased post-implantation loss and decreased the number of live fetuses in animals at doses less than the clinical loading dose based on body surface area ( see Data ). Advise pregnant patients and females of reproductive potential of the potential risk to the fetus. Data Animal Data When degarelix was given to rabbits during early organogenesis at doses of 0.002 mg/kg/day (about 0.02% of the clinical loading dose based on body surface area), there was an increase in early post-implantation loss.

Degarelix given to rabbits during mid and late organogenesis at doses of 0.006 mg/kg/day (about 0.05% of the clinical loading dose based on body surface area) caused embryo/fetal lethality and abortion. When degarelix was given to female rats during early organogenesis, at doses of 0.0045 mg/kg/day (about 0.036% of the clinical loading dose based on body surface area), there was an increase in early post-implantation loss. When degarelix was given to female rats during mid and late organogenesis, at doses of 0.045 mg/kg/day (about 0.36% of the clinical loading dose based on body surface area), there was an increase in the number of minor skeletal abnormalities and variants.

Pediatric Use Safety and effectiveness in pediatric patients have not been established.

FIRMAGON is contraindicated in patients with history of severe hypersensitivity to degarelix or to any of the product components.

There have been no reports of overdose with FIRMAGON. In the case of overdose, however, discontinue FIRMAGON, treat the patient symptomatically, and institute supportive measures.