4.8       Undesirable effects

 New side effect:

not know:  interstitial lung disease

10.     DATE OF REVISION OF THE TEXT

Revision date: 16 July 2018

(bold– text added, strikethrough – text deleted)

6.5       Nature and contents of container

Two pre-filled cyclic olefin copolymer/polypropylene syringes, one cyclic olefin copolymer syringe containing powder (Syringe B), and one polypropylene syringe containing solvent (Syringe A). Together the two syringes comprise a mixing system.

·                A bundle pack containing kits of 2 x 2 pre-filled polypropylene/cyclic olefin copolymer syringes (1 x Syringe A; 1 x Syringe B)

6.6       Special precautions for disposal and other handling

Step 11:

·         Hold Syringe B upright and hold back the white plunger to prevent loss of the product.

·         Open pack of the safety needle by peeling back paper tab and take out safety needle.

·         Secure the safety needle to Syringe B by holding the syringe and twisting gently turning the needle clockwise with approximately a three-quarter turn until the needle is secure to fully seat the needle (Figure 11).

Do not over tighten as this may cause cracking of the needle hub resulting in leakage of the product during injection.

Should the needle hub crack, appear to be damaged, or have any leakage, the product should not be used. The damaged needle should not be substituted/replaced and the product should not be injected. The entire product should be disposed of securely

In the event of damage to the needle hub, a new replacement product should be used.

10.       DATE OF REVISION OF THE TEXT

24 November 2017

 4.2    Posology and method of administration (underlined text added)

In patients with metastatic castration resistant prostate cancer not surgically castrated receiving a GnRH agonist, such as leuprorelin, and eligible for treatment with androgen biosynthesis inhibitors or androgen receptor inhibitors, treatment with a GnRH agonist may be continued.

4.4       Special warnings and special precautions for use (underlined text added, strikethrough text deleted)

Convulsions: Post marketing reports of convulsions have been observed in patients on leuprorelin acetate therapy with or without a history of predisposing factors. Convulsions are to be managed according to the current clinical practice.

A proportion of patients will have tumors which are not sensitive to hormone manipulation. Absence of clinical improvement despite adequate testosterone suppression is diagnostic of this condition, which will not benefit from further therapy with ELIGARD 7.5 mg.

4.8       Undesirable effects

Section 4.2, the following has been added:
As lack of efficacy may result from incorrect preparation, reconstitution, or administration, testosterone levels should be evaluated in cases of suspected or known handling errors (see section 4.4).

 ELIGARD 22.5 mg should be prepared, reconstituted and administered only by healthcare professionals who are familiar with these procedures.  See section 6.6: Special precautions for disposal and other handling. If the product is not prepared appropriately, it should not be administered.

Section 4.4, the following text has been added:
See section 4.2 and section 6.6 for the instructions for preparation and administration of the product and for evaluation of testosterone levels in cases of suspected or known handling errors.

Section 6.6, the underlined text has been added:
If the product is not prepared using the proper technique, it should not be administered, as lack of clinical efficacy may occur due to incorrect reconstitution of the product.

 The date of revision is updated to May 2015

Section 4.2 & 4.3:
Administrative updates to comply with QrD template
Section 4.4:
The following text has been added:

Androgen deprivation therapy may prolong the QT interval.

In patients with a history of or risk factors for QT prolongation and in patients receiving concomitant medicinal products that might prolong the QT interval (see section 4.5) physicians should assess the benefit risk ratio including the potential for Torsade de pointes prior to initiating ELIGARD 22.5 mg.
Section 4.5:
The following text has been added:

Since androgen deprivation treatment may prolong the QT interval, the concomitant use of ELIGARD 22.5 mg with medicinal products known to prolong the QT interval or medicinal products able to induce Torsade de pointes such as class IA (e.g. quinidine, disopyramide) or class III (e.g. amiodarone, sotalol, dofetilide, ibutilide) antiarrhythmic medicinal products, methadone, moxifloxacin, antipsychotics, etc. should be carefully evaluated (see section 4.4).
Section 4.8:
Administrative & wording updates to comply with QrD template and the following added to the tabulated list of adverse events:

Section 4.4 Special warnings and special precautions for use, the following warning has been added: 
Lack of clinical efficacy may occur due to incorrect reconstitution of the product (see section 4.2).

Section 4.8:
Details on reporting suspected adverse reactions added

Section 6.3 Shelf life, the following text has been added:

Once the product has been removed from the refrigerator, it may be stored in the original packaging at room temperature (below 25°C) for up to four weeks

Section 6.4 Special precautions for storage, the following text has been added:

This product must be at room temperature prior to injection. Remove from the refrigerator approximately 30 minutes before use. Once outside the refrigerator this product may be stored in its original packaging at room temperature (below 25°C) for up to four weeks.

Section 6.6 Special precautions for disposal and other handling, underlined text added: 

Allow the product to come to room temperature by removing from the refrigerator approximately 30 minutes prior to use.

Please prepare the patient for injection first, followed by the preparation of the product, using the instructions below. Lack of clinical efficacy may occur due to incorrect reconstitution of the product.

Section 10:
Date of revision revised to January 2015

4.1     Therapeutic indications (underlined text added)

ELIGARD 22.5 mg is indicated for the treatment of hormone dependent advanced prostate cancer and for the treatment of high-risk localized and locally advanced hormone dependent prostate cancer in combination with radiotherapy.

4.2     Posology and method of administration (underlined text added)

ELIGARD 22.5 mg may be used as neoadjuvant or adjuvant therapy in combination with radiotherapy in high-risk localised and locally advanced prostate cancer.

Administration (underlined text added, strikethrough text deleted)

Children and adolescentsPaediatric population

Safety and efficacy in children aged 0 to 18 years have not been established There is no experience in children (under the age of 18 years) (see also section 4.3).

5.1     Pharmacodynamic properties (underlined text added)

In a phase III randomized clinical trial including 970 patients with locally advanced prostate cancer (mainly T2c-T4 with some T1c to T2b patients with pathological regional nodal disease) of whom 483 were assigned to short-term androgen suppression (6 months) in combination with radiation therapy and 487 to long-term therapy (3 years), a non-inferiority analysis compared the short-term to long-term concomitant and adjuvant hormonal treatment with GnRH agonist (triptorelin or goserelin). The 5-year overall mortality was 19.0% and 15.2%, in the short-term and long-term groups, respectively. The observed Hazard Ratio of 1.42 with an upper one-sided 95.71% CI of 1.79 or two-sided 95.71% CI of 1.09; 1.85 (p = 0.65 for non inferiority), demonstrate that the combination of radiotherapy plus 6 months of androgen deprivation therapy provides inferior survival as compared with radiotherapy plus 3 years of androgen deprivation therapy. Overall survival at 5 years of long-term treatment and short-term treatment shows 84.8% survival and 81.0%, respectively. Overall quality of life using QLQ-C30 did not differ significantly between the two groups (P= 0.37). Results are dominated by the population of patients with locally advanced tumours.

4.4     Special warnings and precautions for use

Precautions

Changes in glucose tolerance have been reported in some patients receiving GnRH agonist therapy. It is advised that diabetic patients are monitored more frequently during treatment with ELIGARD 45 mg.

7     Marketing authorisation holder

Astellas Pharma Co. Ltd.

5 Waterside

Citywest Business Campus

Naas Road

Dublin 24

Ireland

4.8     Undesirable effects

Other adverse events which have been reported in general to occur with leuprorelin acetate treatment

include peripheral oedema, pulmonary embolism, palpitations, myalgia, muscle weakness, an

alteration in the skin sensation, chills, peripheral vertigo, rash, amnesia and visual disturbances.

6.5     Nature and contents of container

Two pre-filled polypropylene syringes, one containing powder (Syringe B), and one containing solvent (Syringe A). Together the two syringes comprise a mixing system.

Syringe A has a plunger tip of thermoplastic rubber and is capped with a polyethylene or polypropylene Luer-Lok cover. The syringe tip cap and the two plunger tips of Syringe B are composed of chlorobutyl bromobutyl rubber.

The following pack sizes are available:

·                A kit consisting of one large aluminium outer pouch which contains 2 aluminium pouches, a 18-gauge sterile needle and a desiccant pouch. One pouch contains one pre-filled polypropylene syringe A and a large plunger rod for syringe B. The other pouch contains one pre-filled cyclic olefin copolymer/polypropylene  syringe B.

·                A kit consisting of two thermoformed trays in a cardboard carton. One tray contains pre-filled polypropylene syringe A, a large plunger rod for syringe B and a desiccant pouch. The other tray contains pre-filled cyclic olefin copolymer /polypropylene syringe B, a sterile 18-gauge needle and a desiccant pouch.

·                A bundle pack containing kits of 2 x 2 pre-filled polypropylene/cyclic olefin copolymer syringes (1 x Syringe A; 1 x Syringe B)

In section 6.5 Nature and contents of container

The syringe material is being changed from Polypropylene to cyclic olefin copolymer

The syringe tip cap and plunger tips material is being changed from Bromobutyl to chorobutyl.

Change detail

Eligard 22.5mg SPC

December 2006 in comparison to May 2009

2.       QUALITATIVE AND QUANTITATIVE COMPOSITION

One pre-filled syringe with powder for solution for injection contains 26.9 mg leuprorelin (as acetate). The deliverable amount after reconstitution is 22.5mg leuprorelin acetate.

For excipients, see section 6.1.

Changed to read

One prefilled syringe with powder for solution for injection contains 22.5 mg leuprorelin acetate, equivalent to 20.87 mg leuprorelin.

For a full list of excipients, see section 6.1.

3.       PHARMACEUTICAL form

Changes Document

Eligard 7.5mg and 22.5mg SPCs

Version October 2005 v December 2006

Main change is that reference is now made to the new tray packs.

Section 4.8

Table 1: Vascular disorders:

Hot flushes changed to hot flashes

Section 6.3 Shelf life

Added in reference to the new tray pack.

Section 6.5 Nature and contents of container

New text inserted describing the new tray pack which may be available:

·         “A kit consisting of two thermoformed trays in a cardboard carton. One tray contains one pre-filled polypropylene syringe A, a large plunger rod and a desiccant pouch. The other tray contains pre-filled polypropylene syringe B, a sterile 20-gauge 12.5 mm sterile cannula and a silicone desiccant pouch.”

Section 6.6 Instructions for use and handling and disposal

Points 1 and 2 now include reference to the tray pack.

Section 10. DATE OF REVISION OF THE TEXT

Updated to December 2006