Update of instructions regarding the safety needle that is not to overtighten.

Adding information as mentioned in the SmPC that testosterone levels should be evaluated in case of suspected or known handling errors.

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 45 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 45 mg.
Section 4.5:
The following text has been added:

Since androgen deprivation treatment may prolong the QT interval, the concomitant use of ELIGARD 45 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 45 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 45 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.

Evidence for the indication of high-risk localized prostate cancer is based on published studies of radiotherapy combined with GnRH analogues, including leuprorelin acetate. Clinical data from five published studies were analyzed (EORTC 22863, RTOG 85-31, RTOG 92-02, RTOG 8610, and D’Amico et al., JAMA, 2004), which all demonstrate a benefit for the combination of GnRH analogue with radiotherapy. Clear differentiation of the respective study populations for the indications locally advanced prostate cancer and high-risk localized prostate cancer was not possible in the published studies.

Clinical data have shown that radiotherapy followed by 3 years of androgen deprivation therapy is preferable to radiotherapy followed by 6 months of androgen deprivation therapy.

The recommended duration of androgen deprivation therapy in medical guidelines for T3-T4 patients receiving radiotherapy is 2-3 years.

10.     DATE OF REVISION OF THE TEXT

August 2014 October 2014

 

 

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

Adverse reactions seen with ELIGARD are mainly subject to the specific pharmacological action of leuprorelin, namely increases and decreases in certain hormone levels. The most commonly reported adverse reactions are hot flashes, nausea, malaise and fatigue and transient local irritation at the site of injection. Mild or moderate hot flashes occur in approximately 58 % of patients.

Other adverse events which have been reported in general to occur with leuprorelin acetate treatment include peripheral oedema, pulmonary embolism, palpitations, myalgia, an alteration in the skin sensation, muscle weakness, chills, peripheral vertigo, rash, amnesia, and visual disturbances.

6.5     Nature and contents of container

Two pre-filled cyclic olefin copolymer / 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)

Please note that the following sections have changed:

6.5 Nature and contents of container (inclusion of cyclic olefin copolymer and the replacement of bromobutyl with clorobutyl)

10. Date of revision of the text (March 2010)

Change detail

Eligard 45mg SPC

October 2007 in comparison to May 2009

4.2     Posology and method of administration

Administration

Heading changed form Children to Children and adolescents

4.8     Undesirable effects

hot flushes, reworded as hot flashes

Adverse reactions seen with ELIGARD 45 mg are mainly subject to the specific pharmacological action of leuprorelin acetate, namely increases and decreases in certain hormone levels.

Updated to read:

Adverse reactions seen with ELIGARD are mainly subject to the specific pharmacological action of leuprorelin, namely increases and decreases in certain hormone levels.

Undesirable effects in clinical studies with Eligard updated

General Disorders and Administration Site Reaction

Changed from

To

The following has been removed:

Other adverse events which have been reported in general to occur with leuprorelin acetate treatment include impotence, decrease in libido (both pharmacological consequences of testosterone deprivation), peripheral oedema, pulmonary embolism, palpitations, muscle weakness, chills, peripheral vertigo, rash, amnesia, visual disturbances and skin sensation. Infarction of pre-existing pituitary adenoma has been reported rarely after administration of both short and long acting GnRH agonists. There have been rare reports of thrombocytopenia and leucopenia. Changes in glucose tolerance have been reported.

Local adverse events reported after injection of ELIGARD 45 mg are typical of those frequently associated with similar subcutaneously injected products. Mild transient burning following injection is very common. Pain,bruising and “injection site reaction NOS’ are common.

And replaced by:

Other adverse events which have been reported in general to occur with leuprorelin acetate treatment include peripheral oedema, pulmonary embolism, palpitations, muscle weakness, chills, peripheral vertigo, rash, amnesia, and visual disturbances. Infarction of pre-existing pituitary apoplexy has been reported rarely after administration of both short and long acting GnRH agonists. There have been rare reports of thrombocytopenia and leucopenia. Changes in glucose tolerance have been reported.

Local adverse events reported after injection of ELIGARD are similar to the local adverse events associated with similar subcutaneously injected products.

5.3     Preclinical safety data

Sentence updated from:

 

No such effect was observed in mice, which allows to regard the effect in rats as species-specific, having no relevance for humans.

 

To

 

No such effect was observed in mice.

 

 

 

 

 

 

6.1     List of excipients

 

(15:85) changed to (85:15)

 

 

6.3     Shelf life

 

Below paragraph was removed

Chemical and physical in-use stability has been demonstrated for 30 minutes at 25°C. From a microbiological point of view, once reconstituted with sterile vehicle, the product should be administered immediately. If not used immediately, in-use storage times and conditions prior to use are the responsibility of the user.

 

And replaced by:

 

After first opening of the tray or the large outer aluminium pouch, the powder and solvent for solution for injection are to be immediately reconstituted and administered to the patient.

 

Once reconstituted: use immediately, as the viscosity of the solution increases with time.

 

 

6.6     Instructions for use and handling and disposal

 

Inserted:

 

Allow the product to come to room temperature

 

Please prepare the patient for injection first, followed by the preparation of the product, using the instructions below:

 

Mixing instruction and diagrams updated for clarification.

 

 

9.                  DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

 

Changed from: Date of first authorisation: 26^th October 2007 to 26^th October 2007

 

 

 

10.     DATE OF REVISION OF THE TEXT

Updated from     October 2007 to May 2009