Firmagon 120 mg/ 80 mg Powder for solution for injection.

FIRMAGON u00ae is a gonadotrophin releasing hormone (GnRH) receptor blocker indicated for treatment of patients with prostate cancer in whom androgen deprivation is warranted.

Posology

Dosage for adult males:

• Starting dose 240 mg administered as two subcutaneous (s.c.) injections of 120 mg each
• Maintenance dose u2013 monthly administration 80 mg administered as one subcutaneous (s.c.) injection

The first maintenance dose should be given one month after the starting dose. The therapeutic effect of FIRMAGON u00ae should be monitored by clinical parameters and by measuring prostate specific antigen (PSA) serum levels. Testosterone (T) suppression occurs immediately after administration of the starting dose and 96 % of the patients would have plasma testosterone at medical castration levels (T u2264 0,5 ng/ml) after three days and 100 % after one month with long term treatment with the maintenance dose up to 1 year shows that 97 % of the patients would have sustained suppressed testosterone levels (T u2264 0,5 ng/ml). In case the patient's clinical response appears to be sub-optimal, it should be confirmed that serum testosterone levels are remaining sufficiently suppressed.

Since FIRMAGON u00ae does not induce a testosterone surge it is not necessary to add an anti-androgen as surge protection at initiation of therapy.

Special populations

Elderly, hepatically or renally impaired: There is no need to adjust the dose for the elderly or in patients with mild or moderate liver or kidney function impairment (see section 5.2). Safety and efficacy in patients with severe liver or kidney dysfunction have not been established (see section 4.4).

Women: There is no relevant indication for FIRMAGON u00ae in women.

Paediatric population: There is no relevant indication for FIRMAGON u00ae in children and adolescents.

Method of administration

FIRMAGON u00ae must be reconstituted prior to administration. For instructions on reconstitution and administration, please see section 6.6. FIRMAGON u00ae is for subcutaneous use ONLY, not to be administered intravenously. FIRMAGON u00ae is administered as a subcutaneous injection in the abdominal region. The injection site should vary periodically. Injections should be given in areas where the patient will not be exposed to pressure e.g., not close to waistband or belt and not close to the ribs. The reconstituted solution should be a clear liquid, free of undissolved matter.

• Hypersensitivity to degarelix, or to any of the excipients listed in section 6.1.
• FIRMAGON u00ae is not indicated in women or paediatric patients. In addition, due to its pharmacological effects FIRMAGON u00ae may cause foetal harm if administered to a pregnant woman (see section 4.6).
• A QTc duration of > 450 msec (e.g., congenital QT prolongation).
• Concomitant use with medicines known to prolong the QT time e.g., class I (e.g., procainamide, quinidine) or class III (amiodarone, sotalol) antidysrhythmic medicines (see section 4.4 and 4.5).

Effect on QT/QTc interval

Long-term androgen deprivation therapy may prolong the QT interval (see section 5.1). In the confirmatory study where monthly ECGs were performed, FIRMAGON u00ae showed QT/QTc intervals exceeding 450 msec in approximately 20 % of the patients, and 500 msec in 1 % of the patients. Degarelix has not been studied in patients with a history of a corrected QT interval over 450 msec, in patients with a history of or risk factors for torsades de pointes and in patients receiving concomitant medicines that might prolong the QT interval (see section 4.3 and 4.5). A thorough QT study in healthy men showed that there was no intrinsic effect of degarelix QT/QTc interval (see section 4.8).

Hepatic impairment

Patients with known or suspected hepatic disorder have not been included in long-term clinical trials with FIRMAGON u00ae. Mild, transient increases in Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) have been seen, these were not accompanied by a rise in bilirubin or clinical symptoms. Monitoring of liver function in patients with known or suspected hepatic disorder is advised during treatment. The pharmacokinetics of FIRMAGON u00ae has been investigated after single intravenous administration in subjects with mild to moderate hepatic impairment (see section 5.2).

Renal impairment

FIRMAGON u00ae has not been studied in patients with severe renal impairment and caution is therefore warranted.

Hypersensitivity

FIRMAGON u00ae has not been studied in patients with a history of severe untreated asthma, anaphylactic reactions or severe urticaria or angioedema.

Changes in bone mineral density

Decreased bone mineral 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 term treatment with FIRMAGON u00ae will have effects on bone mineral density (see section 5.1).

Glucose tolerance

A reduction in glucose tolerance has been observed in men who have had orchiectomy or who have been treated with a GnRH agonist. Development or aggravation of diabetes may occur; therefore, diabetic patients may require more frequent monitoring of blood glucose when receiving androgen deprivation therapy. The effect of FIRMAGON u00ae on insulin and glucose levels has not been studied.

Cardiovascular disease

Cardiovascular disease such as stroke and myocardial infarction has been reported in the medical literature in patients with androgen deprivation therapy. Therefore, all cardiovascular risk factors should be taken into account.

No interaction studies have been performed.

Since androgen deprivation treatment may prolong the QTc interval, the concomitant use of degarelix, such as contained in FIRMAGON u00ae, with medicine known to prolong the QTc interval or medicine able to induce torsades de pointes such as class IA (e.g. quinidine, disopyramide) or class III (e.g. amiodarone, sotalol, dofetilide, ibutilide) antidysrhythmic medicine, methadone, moxifloxacin, antipsychotics, etc., is contraindicated (see section 4.3 and 4.4). Degarelix is not a substrate for the human CYP450 system and has not been shown to induce or inhibit CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP2E1, or CYP3A4/5 to any great extent in vitro. Further, degarelix did not interact with any of the relevant efflux and uptake drug transporters tested. Therefore, clinically significant pharmacokinetic interactions are unlikely.

Pregnancy

FIRMAGON u00ae must not be used in pregnant women. See section 4.3.

Lactation

There is no relevant indication for use of FIRMAGON u00ae in women.

Fertility

FIRMAGON u00ae may inhibit male fertility as long as the testosterone is suppressed.

FIRMAGON u00ae has no or negligible influence on the ability to drive and use machines. Fatigue and dizziness are common adverse reactions that might influence the ability to drive and use machines (see section 4.8).

a. Summary of the safety profile

The most commonly observed adverse reactions during FIRMAGON u00ae therapy in the confirmatory Phase 3 study were due to the expected physiological effects of testosterone suppression, including hot flushes and weight increase (reported in 25 % and 7 %, respectively, of patients receiving treatment for one year) or injection site adverse events. Transient chills, fever or influenza like illness were reported to occur hours after dosing (in 3 %, 2 % and 1 % of patients, respectively). The injection site adverse events reported were mainly pain and erythema, reported in 28 % and 17 % of patients, respectively, less frequently reported were swelling (6 %), induration (4 %) and nodule (3 %). These events occurred primarily with the starting dose whereas during maintenance therapy the incidence of these events per 100 injections was: 3 for pain and < 1 for erythema, swelling, nodule and induration. The reported events were mostly transient, of mild to moderate intensity and led to very few discontinuations (< 1 %). Serious injection site reactions were very rarely reported such as injection site infection, injection site abscess or injection site necrosis that could require surgical treatment/drainage.

b. Tabulated list of adverse reactions

Information is presented by system organ class and frequency. The frequency of undesirable effects listed below is defined using the following convention: very common ( u2265 1/10); common ( u2265 1/100 to < 1/10); uncommon ( u2265 1/1 000 to < 1/100); rare ( u2265 1/10 000 to < 1/1 000) and very rare (< 1/10 000). Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness.

There is no clinical experience with the effects of an acute overdose with FIRMAGON u00ae. In the event of an overdose, treatment is symptomatic and supportive.