Firmagon (Degarelix)

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

• FIRMAGON is for subcutaneous use only
• Starting Dosage: 240 mg given as two injections of 120 mg each (
  2.1 Dosing information

  FIRMAGON is administered as a subcutaneous injection in the abdominal region only at the dosages in Table 1 below.

  Table 1: FIRMAGON Recommended Dosages

  Starting Dosage	Maintenance Dosage – Administered once every 28 days
  240 mg given as two subcutaneous injections of 120 mg at a concentration of 40 mg/mL	The first maintenance dose should be given 28 days after the starting dose. 80 mg given as one subcutaneous injection at a concentration of 20 mg/mL
  )
• Maintenance Dosage: 80 mg administered as a single injection every 28 days (
  2.1 Dosing information

  FIRMAGON is administered as a subcutaneous injection in the abdominal region only at the dosages in Table 1 below.

  Table 1: FIRMAGON Recommended Dosages

  Starting Dosage	Maintenance Dosage – Administered once every 28 days
  240 mg given as two subcutaneous injections of 120 mg at a concentration of 40 mg/mL	The first maintenance dose should be given 28 days after the starting dose. 80 mg given as one subcutaneous injection at a concentration of 20 mg/mL
  )

For injection:

• FIRMAGON (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.
• FIRMAGON (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.

• Females and males of reproductive potential: FIRMAGON may impair fertility (
  8.3 Females and Males of Reproductive Potential

  Infertility

  Based on findings in animals and mechanism of action, degarelix may impair fertility in males and females of reproductive potential

  [see Nonclinical Toxicology (13.1)].
  )
• Patients with severe liver or kidney dysfunction have not been studied and caution is therefore warranted (
  8 USE IN SPECIFIC POPULATIONS

  • Females and males of reproductive potential: FIRMAGON may impair fertility
  • Patients with severe liver or kidney dysfunction have not been studied and caution is therefore warranted

  8.1 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 [

  see Clinical Pharmacology (12.1)

  ]. 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.

  8.2 Lactation

  The safety and efficacy of FIRMAGON have not been established in females. There are no data on the presence of degarelix in human milk, the effects on the breastfed child, or the effects on milk production. Because many drugs are present in human milk and because of the potential for serious adverse reactions in a breastfed child from degarelix, a decision should be made whether to discontinue nursing or discontinue the drug taking into account the importance of the drug to the mother.

  8.3 Females and Males of Reproductive Potential

  Infertility

  Based on findings in animals and mechanism of action, degarelix may impair fertility in males and females of reproductive potential

  [see Nonclinical Toxicology (13.1)].

  8.4 Pediatric Use

  Safety and effectiveness in pediatric patients have not been established.

  8.5 Geriatric Use

  Of the total number of subjects in clinical studies of FIRMAGON, 82% were age 65 and over, while 42% were age 75 and over. No overall differences in safety or effectiveness were observed between these subjects and younger subjects, but greater sensitivity of some older individuals cannot be ruled out.

  8.6 Renal Impairment

  No pharmacokinetic studies in renally impaired patients have been conducted. At least 20-30% of a given dose of degarelix is excreted unchanged in the urine. A population pharmacokinetic analysis of data from the randomized study demonstrated that there is no significant effect of mild renal impairment [creatinine clearance (CrCL) 50-80 mL/min] on either the degarelix concentration or testosterone concentration. Data on patients with moderate or severe renal impairment is limited and therefore degarelix should be used with caution in patients with CrCL < 50 mL/min.

  8.7 Hepatic Impairment

  Patients with hepatic impairment were excluded from the randomized trial.

  A single dose of 1 mg degarelix administered as an intravenous infusion over 1 hour was studied in 16 non-prostate cancer patients with either mild (Child Pugh A) or moderate (Child Pugh B) hepatic impairment. Compared to non-prostate cancer patients with normal liver function, the exposure of degarelix decreased by 10% and 18% in patients with mild and moderate hepatic impairment, respectively. Therefore, dose adjustment is not necessary in patients with mild or moderate hepatic impairment. However, since hepatic impairment can lower degarelix exposure, it is recommended that in patients with hepatic impairment testosterone concentrations should be monitored on a monthly basis until medical castration is achieved. Once medical castration is achieved, an every-other-month testosterone monitoring approach could be considered.

  Patients with severe hepatic dysfunction have not been studied and caution is therefore warranted in this group.
  )