FIRMAGON 80 mg powder and solvent for solution for injection

Change of marketing authorisation holder address

Minor typographical updates

Addition of Rhabdomyolysis as a rare adverse reaction in Section 4.8 of the SmPC

Section 3:

Text deleted: … (powder for injection and solvent).

Section 4.2

Word deleted: Special patient populations

New text deleted/added: There is no relevant use indication for use of FIRMAGON in children and adolescents in the treatment of adult male patients with advanced hormone-dependent prostate cancer.

Text removed:

As with other medicinal products administered by subcutaneous injection,

There is no relevant indication for use of FIRMAGON in women, children and adolescents.

Section 4.4:

ECG expanded – electrocardiograms

Text added:

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.

Section 4.5:

Deleted:  Cisapride

Section 4.7:

Text deleted: No studies on the effects of degarelix on the ability to drive and use machines have been performed. However,….

Text added: FIRMAGON has no or negligible influence on the ability to drive and use machines

Section 4.8:

Adverse events replaced by adverse reactions throughout

Table 1 heading is updated to reflect that the table now includes reports from post-marketing experience

Additional column in Table 1 added: Rare events listing ‘neutropenic fever’, ‘anaphylactic reactions’, ‘myocardial infarction’, ‘cardiac failure’.

Text deleted: The following reactions have been reported as being related to treatment in single patients: Febrile neutropenia, myocardial infarction and congestive heart failure. Rare reports of anaphylactic reactions have been received from post-marketing use of FIRMAGON.

Text added:

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions preferably through the online reporting option accessible from the IMB homepage. A downloadable report form is also accessible from the IMB website, which may be completed manually and submitted to the IMB via ‘freepost’. Alternatively, the traditional post-paid ‘yellow card’ option may also continue to be used.

FREEPOST

Pharmacovigilance Section

Irish Medicines Board

Kevin O’Malley House

Earlsfort Centre

Earlsfort Terrace

Dublin 2

Tel: +353 1 6764971

Fax: +353 1 6762517

Website: www.imb.ie

e-mail: imbpharmacovigilance@imb.ie

Section 5.1:

Title added: Mechanism of action

Text added:

Paediatric population

The European Medicines Agency has waived the obligation to submit the results of studies with FIRMAGON in all subsets of the paediatric population (see section 4.2 for information on paediatric use).

 Section 6.5:

Text deleted:

Pack sizes

1 pack containing 1 powder vial, 1 solvent pre-filled syringe, 1 plunger rod, 1 vial adapter and 1 needle. Multipack containing 3 x 1 (1 powder vial, 1 solvent pre-filled syringe, 1 plunger rod, 1 vial adapter and 1 needle). Not all pack sizes may be marketed.

Text added:

Pack sizes

FIRMAGON is available in 2 pack-sizes:

Pack-size of 1 tray containing: 1 powder vial, 1 solvent pre-filled syringe, 1 plunger rod, 1 vial adapter and 1 needle.

Pack-size of 3 trays containing: 3 powder vials, 3 solvent pre-filled syringes, 3 plunger rods, 3 vial adapters and 3 needles.

Section 6.6:

Repeated paragraph deleted (see section 6.3):

Chemical and physical in-use stability has been demonstrated for 2 hours at 25ºC. From a microbiological point of view, unless the method of reconstitution precludes the risk of microbial contamination, the product should be used immediately. If not used immediately, in-use storage times and conditions are the responsibility of the user.

Section 3:

Text deleted: … (powder for injection and solvent).

Section 4.2

Word deleted: Special patient populations

New text deleted/added: There is no relevant use indication for use of FIRMAGON in children and adolescents in the treatment of adult male patients with advanced hormone-dependent prostate cancer.

Text removed:

As with other medicinal products administered by subcutaneous injection,

There is no relevant indication for use of FIRMAGON in women, children and adolescents.

Section 4.4:

ECG expanded – electrocardiograms

Text added:

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.

Section 4.5:

Deleted:  Cisapride

Section 4.7:

Text deleted: No studies on the effects of degarelix on the ability to drive and use machines have been performed. However,….

Text added: FIRMAGON has no or negligible influence on the ability to drive and use machines

Section 4.8:

Adverse events replaced by adverse reactions throughout

Table 1 heading is updated to reflect that the table now includes reports from post-marketing experience

Additional column in Table 1 added: Rare events listing ‘neutropenic fever’, ‘anaphylactic reactions’, ‘myocardial infarction’, ‘cardiac failure’.

Text deleted: The following reactions have been reported as being related to treatment in single patients: Febrile neutropenia, myocardial infarction and congestive heart failure. Rare reports of anaphylactic reactions have been received from post-marketing use of FIRMAGON.

Text added:

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions preferably through the online reporting option accessible from the IMB homepage. A downloadable report form is also accessible from the IMB website, which may be completed manually and submitted to the IMB via ‘freepost’. Alternatively, the traditional post-paid ‘yellow card’ option may also continue to be used.

FREEPOST

Pharmacovigilance Section

Irish Medicines Board

Kevin O’Malley House

Earlsfort Centre

Earlsfort Terrace

Dublin 2

Tel: +353 1 6764971

Fax: +353 1 6762517

Website: www.imb.ie

e-mail: imbpharmacovigilance@imb.ie

Section 5.1:

Title added: Mechanism of action

Text added:

Paediatric population

The European Medicines Agency has waived the obligation to submit the results of studies with FIRMAGON in all subsets of the paediatric population (see section 4.2 for information on paediatric use).

 Section 6.5:

Text deleted:

Pack sizes

1 pack containing 1 powder vial, 1 solvent pre-filled syringe, 1 plunger rod, 1 vial adapter and 1 needle. Multipack containing 3 x 1 (1 powder vial, 1 solvent pre-filled syringe, 1 plunger rod, 1 vial adapter and 1 needle). Not all pack sizes may be marketed.

Text added:

Pack sizes

FIRMAGON is available in 2 pack-sizes:

Pack-size of 1 tray containing: 1 powder vial, 1 solvent pre-filled syringe, 1 plunger rod, 1 vial adapter and 1 needle.

Pack-size of 3 trays containing: 3 powder vials, 3 solvent pre-filled syringes, 3 plunger rods, 3 vial adapters and 3 needles.

Section 6.6:

Repeated paragraph deleted (see section 6.3):

Chemical and physical in-use stability has been demonstrated for 2 hours at 25ºC. From a microbiological point of view, unless the method of reconstitution precludes the risk of microbial contamination, the product should be used immediately. If not used immediately, in-use storage times and conditions are the responsibility of the user.

New sentence added: “No testosterone microsurges were observed after re-injection during degarelix treatment. “

New sections added:

“Testosterone Reversibility

In a study involving patients with rising PSA after localised therapy (mainly radical prostatectomy and radiation) were administered FIRMAGON for seven months followed by a seven months monitoring period. The median time to testosterone recovery (>0.5 ng/mL, above castrate level) after discontinuation of treatment was 112 days (counted from start of monitoring period, i.e 28 days after last injection). The median time to testosterone >1.5 ng/mL (above lower limit of normal range) was 168 days.”

“Effect on prostate volume

Three months therapy with degarelix (240/80 mg dose regimen) resulted in a 37% reduction in prostate volume as measured by trans-rectal ultrasound scan (TRUS) in patients requiring hormonal therapy prior to radiotherapy and in patients who were candidates for medical castration. The prostate volume reduction was similar to that attained with goserelin plus anti-androgen protection. “

Text update:

“Anti-degarelix antibodies

Anti-degarelix antibody development has been observed in 10% of patients after treatment with FIRMAGON for one year and 29% of patients after treatment with FIRMAGON for up to 5.5 years. There is no indication that the efficacy or safety of FIRMAGON treatment is affected by antibody formation after up to 5.5 years of treatment.”

New sentence added: “No testosterone microsurges were observed after re-injection during degarelix treatment. “

New sections added:

“Testosterone Reversibility

In a study involving patients with rising PSA after localised therapy (mainly radical prostatectomy and radiation) were administered FIRMAGON for seven months followed by a seven months monitoring period. The median time to testosterone recovery (>0.5 ng/mL, above castrate level) after discontinuation of treatment was 112 days (counted from start of monitoring period, i.e 28 days after last injection). The median time to testosterone >1.5 ng/mL (above lower limit of normal range) was 168 days.”

“Effect on prostate volume

Three months therapy with degarelix (240/80 mg dose regimen) resulted in a 37% reduction in prostate volume as measured by trans-rectal ultrasound scan (TRUS) in patients requiring hormonal therapy prior to radiotherapy and in patients who were candidates for medical castration. The prostate volume reduction was similar to that attained with goserelin plus anti-androgen protection. “

Text update:

“Anti-degarelix antibodies

Anti-degarelix antibody development has been observed in 10% of patients after treatment with FIRMAGON for one year and 29% of patients after treatment with FIRMAGON for up to 5.5 years. There is no indication that the efficacy or safety of FIRMAGON treatment is affected by antibody formation after up to 5.5 years of treatment.”

Section 4.2:

-          ‘Elderly’ is changed to ‘Older’

Section 4.4:

-          Sentence deleted: The data available on efficacy and safety experience with degarelix is limited to a one year treatment.

-          Sentence inserted: A thorough QT study showed that there was no intrinsic effect of degarelix on QT/QTc interval (see section 4.8).

Section 4.6:

-          Sentence inserted: FIRMAGON may inhibit male fertility as long as the testosterone is suppressed.

Section 4.8:

-          Sentence inserted:  Rare reports of anaphylactic reactions have been received from post-marketing use of FIRMAGON.

-          Additional information inserted under ‘Changes in ECG measurement’: The lack of intrinsic effect of degarelix on cardiac repolarisation (QTcF), heart rate, AV conduction, cardiac depolarisation, or T or U wave morphology was confirmed in a thorough QT study in healthy subjects (N=80) receiving an i.v. infusion of degarelix over 60 min, reaching a mean Cmax of 222 ng/mL, approx. 3-4-fold the Cmax obtained during prostate cancer treatment.

-          New section in relation to adverse event reporting:

                Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via via the national reporting system as follows:

                Pharmacovigilance Section, Irish Medicines Board, Kevin O’Malley House, Earlsfort Centre, Earlsfort Terrace,  Dublin 2

                Tel: +353 1 6764971; Fax: +353 1 6767836; Website: www.imb.ie; e-mail: imbpharmacovigilance@imb.ie

Section 5.2:

-          Sentence updated to: C_max degarelix plasma concentration decreases in a biphasic fashion, with a mean terminal half-life (t_½) of 29 days for the maintenance dose.

Section 4.2:

-          ‘Elderly’ is changed to ‘Older’

Section 4.4:

-          Sentence deleted: The data available on efficacy and safety experience with degarelix is limited to a one year treatment.

-          Sentence inserted: A thorough QT study showed that there was no intrinsic effect of degarelix on QT/QTc interval (see section 4.8).

Section 4.6:

-          Sentence inserted: FIRMAGON may inhibit male fertility as long as the testosterone is suppressed.

Section 4.8:

-          Sentence inserted:  Rare reports of anaphylactic reactions have been received from post-marketing use of FIRMAGON.

-          Additional information inserted under ‘Changes in ECG measurement’: The lack of intrinsic effect of degarelix on cardiac repolarisation (QTcF), heart rate, AV conduction, cardiac depolarisation, or T or U wave morphology was confirmed in a thorough QT study in healthy subjects (N=80) receiving an i.v. infusion of degarelix over 60 min, reaching a mean Cmax of 222 ng/mL, approx. 3-4-fold the Cmax obtained during prostate cancer treatment.

-          New section in relation to adverse event reporting:

                Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via via the national reporting system as follows:

                Pharmacovigilance Section, Irish Medicines Board, Kevin O’Malley House, Earlsfort Centre, Earlsfort Terrace,  Dublin 2

                Tel: +353 1 6764971; Fax: +353 1 6767836; Website: www.imb.ie; e-mail: imbpharmacovigilance@imb.ie

Section 5.2:

-          Sentence updated to: C_max degarelix plasma concentration decreases in a biphasic fashion, with a mean terminal half-life (t_½) of 29 days for the maintenance dose.