DEGARELIX

Posology Table 1. Starting dose and maintenance dose of Degarelix Starting dose Maintenance dose – monthly administration 240 mg administered as two consecutive subcutaneous injections of 120 mg each 80 mg administered as one subcutaneous injection The first maintenance dose should be given one month after the starting dose.

Degarelix may be used as neo-adjuvant or adjuvant therapy in combination with radiotherapy in high-risk localised and locally advanced prostate cancer. The therapeutic effect of degarelix should be monitored by clinical parameters and prostate specific antigen (PSA) serum levels.

5 ng/ml) after three days and 100% after one month. 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 degarelix does not induce a testosterone surge it is not necessary to add an anti- androgen as surge protection at initiation of therapy.

2). 4). Paediatric population There is no relevant use of Degarelix in children and adolescents in the treatment of adult male patients with advanced hormone-dependent prostate cancer. Method of administration Degarelix must be reconstituted prior to administration.

6. Degarelix is for subcutaneous use ONLY, not to be administered intravenously. Intramuscular administration is not recommended as it has not been studied. Degarelix is administered as a subcutaneous injection in the abdominal region.

The injection site should vary periodically. g. not close to waistband or belt and not close to the ribs.

Summary of the safety profile The most commonly observed adverse reactions during degarelix therapy in the confirmatory phase III study (N=409) 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 reactions.

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 reactions 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 with the 80 mg dose, 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. Tabulated list of adverse reactions The frequency of undesirable effects listed below is defined using the following convention: very common (≥ 1/10); common (≥ 1/100 to < 1/10); uncommon (≥ 1/1,000 to < 1/100), rare (≥ 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.

Table 2:

Frequency of adverse drug reactions reported in 1,259 patients treated for a total of 1781 patient years (phase II and III studies) and from post- marketing reports MedDRA System Organ Class (SOC) Very common Common Uncommon Rare Blood and lymphatic system disorders Anaemia* Neutropenic fever Immune system disorders Hypersensitivity Anaphylactic reactions Metabolism and nutrition disorders Weight increase* Hyperglycaemia/Diabetes mellitus, cholesterol increased, weight decreased, appetite decreased, changes in blood calcium Psychiatric disorders Insomnia Depression, libido decreased* Nervous system disorders Dizziness, headache Mental impairment, hypoaesthesia Eye disorders Vision blurred Cardiac disorders Cardiac arrhythmia (incl.

Effect on QT/QTc interval Long-term androgen deprivation therapy may prolong the QT interval. 1). 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 medicinal products that might prolong the QT interval.

8). 8). Hepatic impairment Patients with known or suspected hepatic disorder have not been included in long- term clinical trials with degarelix. Mild, transient increases in ALT and 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. 2). Renal impairment Degarelix has not been studied in patients with severe renal impairment and caution is therefore warranted.

Hypersensitivity Degarelix has not been studied in patients with a history of severe untreated asthma, anaphylactic reactions or severe urticaria or angioedema. 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 testosterone suppression in men will have effects on bone density. Bone density has not been measured during treatment with degarelix. 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 degarelix 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.

1.