Prostap 3 DCS

  • Name:

    Prostap 3 DCS

  • Company:
    info
  • Active Ingredients:

    Leuprorelin Acetate

  • Legal Category:

    Product subject to medical prescription which may be renewed (B)

Patient Information Leaflet Patient Information Leaflet last updated on medicines.ie: 06/07/20

files-icon(Click to Download)
Summary of Product Characteristics last updated on medicines.ie: 6/7/2020

Click on this link to Download PDF directly

Takeda Products Ireland Ltd

Takeda Products Ireland Ltd

Company Products

Medicine NameActive Ingredients
Medicine Name Actos tablets Active Ingredients pioglitazone hydrochloride
Medicine Name Adcetris 50 mg powder for concentrate for solution for infusion Active Ingredients Brentuximab vedotin
Medicine Name Alofisel 5 million cells/mL suspension for injection Active Ingredients Human Allogeneic Mesenchymal Adult Stem Cells
Medicine Name Alunbrig Active Ingredients Brigatinib
Medicine Name Blopress Plus Tablets Active Ingredients Candesartan Cilexetil, Hydrochlorothiazide
Medicine Name Blopress tablets Active Ingredients Candesartan Cilexetil
Medicine Name Calcichew 500mg Chewable Tablets Active Ingredients Calcium Carbonate
Medicine Name Calcichew-D3 Forte Chewable Tablets Active Ingredients Calcium Carbonate, Colecalciferol (Vitamin D3)
Medicine Name Calcichew-D3 Forte Double Strength 1000 mg/800 IU chewable tablets Active Ingredients Calcium Carbonate, Colecalciferol (Vitamin D3)
Medicine Name Competact 15 mg/850 mg film-coated Tablets Active Ingredients Metformin Hydrochloride, pioglitazone hydrochloride
Medicine Name Condyline Cutaneous Solution 5 mg/ml Active Ingredients Podophyllotoxin
Medicine Name Edarbi Tablets Active Ingredients Azilsartan medoxomil potassium
Medicine Name Entyvio 108 mg solution for injection in pre-filled syringe/pre-filled pen Active Ingredients Vedolizumab
Medicine Name Entyvio 300 mg powder for concentrate for solution for infusion Active Ingredients Vedolizumab
Medicine Name Instanyl 50, 100 and 200 mcg nasal spray, solution in single-dose container Active Ingredients fentanyl citrate
Medicine Name Matrifen Transdermal patch Active Ingredients Fentanyl
Medicine Name Mepact 4mg powder for suspension for infusion Active Ingredients Mifamurtide
Medicine Name Midon 2.5 mg Tablets Active Ingredients Midodrine Hydrochloride
Medicine Name Midon 5 mg Tablets Active Ingredients Midodrine Hydrochloride
Medicine Name NINLARO 2.3 mg, 3 mg, 4 mg hard capsules Active Ingredients Ixazomib Citrate
Medicine Name Prostap 3 DCS Active Ingredients Leuprorelin Acetate
Medicine Name Prostap 6 DCS Active Ingredients Leuprorelin Acetate
Medicine Name Prostap SR DCS Active Ingredients Leuprorelin Acetate
Medicine Name Protium 20mg Active Ingredients Pantoprazole sodium sesquihydrate
Medicine Name Protium 40mg Active Ingredients Pantoprazole sodium sesquihydrate
1 - 0 of 27 items.Total: Infinity pages

When a pharmaceutical company changes any document, a new version is published on medicines.ie. For each version, we show the dates it was published on medicines.ie and the reasons for change.

Updated on 6 July 2020 PIL

Reasons for updating

  • Change to Section 1 - what the product is
  • Change to section 1 - what the product is used for
  • Change to section 2 - what you need to know - contraindications
  • Change to section 2 - use in children and adolescents
  • Change to section 2 - interactions with other medicines, food or drink
  • Change to section 3 - dose and frequency
  • Change to section 4 - possible side effects
  • Change to section 4 - how to report a side effect
  • Change to section 6 - date of revision

Free text change information supplied by the pharmaceutical company

The PIL has been aligned with the Company Core Data Sheet (CCCD). 

Updated on 6 July 2020 SmPC

Reasons for updating

  • Change to section 2 - Qualitative and quantitative composition
  • Change to section 3 - Pharmaceutical form
  • Change to section 4.2 - Posology and method of administration
  • Change to section 4.3 - Contraindications
  • Change to section 4.4 - Special warnings and precautions for use
  • Change to section 4.5 - Interaction with other medicinal products and other forms of interaction
  • Change to section 4.6 - Pregnancy and lactation
  • Change to section 4.8 - Undesirable effects
  • Change to section 5.1 - Pharmacodynamic properties
  • Change to section 5.2 - Pharmacokinetic properties
  • Change to section 5.3 - Preclinical safety data
  • Change to section 6.2 - Incompatibilities
  • Change to section 6.6 - Special precautions for disposal and other handling
  • Change to section 10 - Date of revision of the text

Legal category: Product subject to medical prescription which may be renewed (B)

Free text change information supplied by the pharmaceutical company

The SmPC has been aligned with the Company Core Data Sheet (CCCD) and the following changes have been made:

 

Section

Change

2 QUALITATIVE AND QUANTITATIVE COMPOSITION

Updated/deleted:

Powder: Each single-dose syringe contains 11.25mg leuprorelin acetate.

Solvent: Solvent contains approximately 0.4 mg (<1mmol) sodium (as carmellose sodium). 

3 PHARMACEUTICAL FORM

Solvent: A colourless, odourless, slightly viscous, aqueous sterile solvent.

4.2 Posology and method of administration

Updated:

Male Adults: The usual recommended dose is 11.25mg presented as a 3 month depot injection and administered as a single subcutaneous or intramuscular injection at intervals of 3 months.

Response to PROSTAP 3 therapy should be monitored by clinical parameters and by measuring prostate-specific antigen (PSA) and testosterone serum levels. Clinical studies have shown that testosterone levels increased during the first 4 days of treatment in the majority of non-orchidectomised patients.  They then decreased and reached castrate levels in 2-4 weeks.  Once attained, castrate levels were maintained as long as drug therapy continued.  Transient increases in PSA levels sometimes occur early in the treatment period but usually return to normal or near normal values by the 4th week of treatment.

Female Adults:

Treatment options for vasomotor symptoms and bone mineral density loss should be considered.

 

Endometriosis

The recommended dose is 11.25mg administered as a single subcutaneous or intramuscular injection every 3 months for a period of up to 6 months.  Treatment should be initiated during the first 5 days of the menstrual cycle.

 

Preoperative management of uterine fibroids

The recommended dose is 11.25mg administered as a single subcutaneous or intramuscular injection every 3 months for a maximum of 6 months.

4.2 Posology and method of administration

Depending on the activity of the central precocious puberty, it may be necessary to increase the dosage in the presence of inadequate suppression (clinical evidence e.g. spotting or inadequate gonadotropin suppression in the LHRH GnRH test). The minimal effective 3-monthly dose to be administered should then be determined by means of the LHRH GnRH test.

4.3 Contraindications

Hypersensitivity to the leuprorelin, any of the excipients (listed in section 6.1) or to other synthetic gonadotrophin releasing hormone (Gn-RH) analogues or Gn-RH derivatives.

In girls with central precocious puberty:

-Pregnancy and breastfeeding

-Undiagnosed vaginal bleeding.

4.4 Special warnings and precautions for use

Added:

PROSTAP 3 injectable suspension must be prepared at the time of use and, after reconstitution, used immediately.

Updated:

Depression: There is an increased risk of incident depression (which may be severe) in patients undergoing treatment with GnRH agonists, such as leuprorelin. Patients should be informed and monitored accordingly and treated as appropriate if symptoms occur.

 

Seizures: Postmarketing reports of seizures have been observed in patients treated with leuprorelin acetate and these events have been reported in both children and adults, and in those with or without a history of epilepsy, seizure disorders or risk disorders for seizures.

Added and updated:

Adults:

Epidemiological data have shown that androgen deprivation therapy in males and estrogen deprivation therapy in females, is associated with metabolic changes (e.g. reduction in glucose tolerance or aggravation of pre-existing diabetes) as well as an increased risk for cardiovascular diseases. However, prospective data did not confirm a link between treatment with GnRH analogues and an increase in cardiovascular mortality. Patients at high risk for metabolic or cardiovascular diseases should be appropriately monitored. Diabetic patients may require more frequent monitoring of blood glucose during treatment with PROSTAP 3.

Hepatic dysfunction and jaundice with elevated liver enzyme levels have been reported. Therefore, close observation should be made and appropriate measures taken if necessary.

Spinal fracture, paralysis and hypotension have been reported.

Bone mineral loss: Long-term estrogen deprivation either by bilateral oophorectomy, ovarian ablation or administration of GnRH analogues, or long-term androgen deprivation either by bilateral orchiectomy or administration of GnRH analogues is associated with increased risk of bone mineral loss which, in patients with additional risk factors, may lead to osteoporosis and an increased risk of bone fracture (see section 4.8). 

The induced hypo-estrogenic state results in a clinically significant loss in bone density over the course of treatment, some of which may not be reversible.  The extent of bone demineralisation due to hypo-estrogenaemia is proportional to time. The level of bone loss seen with GnRH analogues such as PROSTAP 3 is of the order of 5%. In clinical studies the levels varied between 2.3% and 15.7% depending on the method of measurement.

In patients with major risk factors for decreased bone mineral content such as chronic alcohol and/or tobacco use, strong family history of osteoporosis, or chronic use of drugs that can reduce bone mass such as anticonvulsants or corticosteroids, PROSTAP 3 therapy may pose an additional risk.  In these patients, the risks and benefits must be weighed carefully before therapy with PROSTAP 3 is instituted. This is particularly important in women with uterine fibroids where age related bone loss may have already begun to occur.

Treatment options for vasomotor symptoms and bone mineral density loss should be considered

In the initial stages of therapy, a transient rise in levels of testosterone, dihydro-testosterone and acid phosphatase may occur.  In some cases, this may be associated with a "flare" or exacerbation of the tumour growth resulting in temporary deterioration of the patient's condition. This may lead to neurological or systemic effects. For instance, in patients with vertebral metastases, neurological problems such as weakness and/or paraesthesia of the lower limbs may occur. In patients with urinary obstruction or haematuria, worsening of urinary symptoms may occur.  These symptoms usually subside on continuation of therapy.

 

Patients at risk of or with ureteric obstruction or spinal cord compression due to metastasis should be considered carefully and closely supervised in the first few weeks of treatment as bone pain, weakness of lower extremities and parasthesia (as neurologic symptoms) may occur.

Deleted text (updated and moved to section above):

Long-term androgen deprivation either by bilateral orchiectomy or administration of GnRH analogues is associated with increased risk of bone loss which, in patients with additional risk factors, may lead to osteoporosis and increased risk of bone fracture.

Epidemiological data have shown that during androgen deprivation therapy changes in the metabolic condition (e.g. reduction in glucose tolerance or aggravation of pre-existing diabetes) as well as an increased risk for cardiovascular diseases may occur. However, prospective data did not confirm the link between treatment with GnRH analogues and an increase in cardiovascular mortality. Patients at high risk for metabolic or cardiovascular diseases should be appropriately monitored.

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 risks and benefits including the potential for Torsade de pointes prior to initiating treatment with PROSTAP 3.

4.4

Added:

Women:  

Before starting treatment with leuprorelin acetate, pregnancy must be excluded (see section 4.3).

Since menstruation should stop with effective doses of PROSTAP 3, the patient should notify her physician if regular menstruation persists. Spotting/breakthrough bleeding may occur with PROSTAP 3 treatment.

During treatment with PROSTAP 3, patients should be instructed to prevent conception e.g. with the use of non-hormonal methods until return of menses.

Abnormal bleeding

Prior to administration of PROSTAP 3 undiagnosed abnormal vaginal bleeding must be investigated, diagnosis confirmed and relevant management initiated. 

Initial increase in sex steroids

During the early phase of therapy, sex steroids temporarily rise above baseline because of the physiological effect of the drug.  Therefore, an increase in clinical signs and symptoms may be observed during the initial days of therapy, but these will dissipate with continued therapy.

Uterine fibroids diagnosis

In the case of uterine fibroids, it is mandatory to confirm the diagnosis of fibroids and exclude ovarian mass, either visually by laparoscopy or by ultrasonography or other investigative techniques as appropriate, before PROSTAP 3 therapy is instituted.

Uterine fibroids

In women receiving GnRH analogues for the treatment of uterine fibroids, the duration of administration of PROSTAP 3 should be limited to 6 months as its use is associated with an increased risk of bone mineral loss (see Bone mineral loss, section 4.4). If it is necessary to resume administration of leuprorelin acetate changes in bone parameters should be closely followed.

In women with submucous fibroids there have been reports of severe vaginal bleeding following administration of leuprorelin as a consequence of the acute degeneration of the fibroids.  Patients should be warned of the possibility of abnormal bleeding or pain in case earlier surgical intervention is required.

Cervical resistance

PROSTAP 3 may cause an increase in uterine cervical resistance, which may result in difficulty in dilating the cervix for intrauterine surgical procedures.

Endometriosis

In women receiving GnRH analogues for the treatment of endometriosis, the duration of administration of leuprorelin acetate should be limited to 6 months, as its use is associated with an increased risk of bone mineral loss (see Bone mineral loss, section 4.4).  

Children with central precocious puberty:  Before starting the therapy, a precise diagnosis of idiopathic and/or neurogenic central precocious puberty is necessary and, in girls, pregnancy must be excluded (see section 4.3).

4.6 Fertility, pregnancy and lactation

Added:

Contraception is not ensured, however, by taking PROSTAP 3 and therefore, patients should use non-hormonal methods of contraception during treatment and after cessation of treatment until the return of menses.

4.8 Undesirable effects

Added:

The following tables list adverse reactions with leuprorelin based on experience from clinical trials as well as from post-marketing experience. Adverse reactions are grouped by MedDRA System Organ Classes and frequency classification. Frequencies are defined as follows: 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), very rare (< 1/10,000), not known (cannot be estimated from the available data)).

Men : In cases where a "tumour flare" occurs after PROSTAP 3 therapy, an exacerbation may occur in any symptoms or signs due to disease.  Adverse events, which may occur particularly at the beginning of treatment include urinary tract obstruction (as urinary symptoms).  In patients with spinal cord compression, bone pain, weakness of lower extremities and paresthesia (as neurologic symptoms) may also occur (see section 4.4). These symptoms subside on continuation of therapy.

Updated and formatting change:

In women with early breast cancer treated with a GnRH agonist, in combination with tamoxifen or an aromatase inhibitor, the following side effects have been seen:

Very common:  Nausea, fatigue, musculoskeletal disorders, osteoporosis, hot flushes, hyperhidrosis, insomnia, depression, libido decreased, vulvovaginal dryness, dyspareunia, urinary incontinence, hypertension.

Common: Diabetes mellitus, hyperglycaemia, injection site reaction, hypersensitivity fracture, embolism.

Uncommon: myocardial ischaemia, cerebral ischaemia, central nervous system haemorrhage.

Rare: QT prolongation.

** In general, the occurrence of vaginal spotting with continued treatment (subsequent to possible withdrawal bleeding in the first month of treatment) should be assessed as a sign of potential underdosage. Pituitary suppression should then be determined by a gonadotropin releasing hormone (GnRH) stimulation test.

5.1 Pharmacodynamic properties

Added:

Men (prostate cancer):

A randomised, open-label, comparative multi-centre study was performed to compare the efficacy and safety of the 3.75 mg and 11.25 mg depots of leuprorelin acetate. 48% of patients included had locally advanced disease (T3N0M0), and 52% of patients had metastatic disease. Mean serum testosterone level fell below the threshold for chemical castration (0.5 ng/ml) at one month of treatment, continuing to decrease thereafter and stabilising at a value below the castration threshold. The decline in serum prostate-specific antigen (PSA) mirrored that of serum testosterone in both groups.

In an open-label, prospective clinical trial involving 205 patients receiving 3.75 mg leuprorelin acetate on a monthly basis as treatment for metastatic prostate cancer, the long-term efficacy and safety of leuprorelin acetate was assessed. Testosterone levels were maintained below the castrate threshold over the 63-month follow up period. Median survival time exceeded 42.5 months for those receiving monotherapy and 30.9 months for those receiving leuprorelin acetate in combination with anti-androgens (this difference relating to baseline differences between groups).

In a meta-analysis involving primarily patients with metastatic disease, no statistically significant difference in survival was found for patients treated with luteinising hormone-releasing hormone (LHRH) analogues compared with patients treated with orchidectomy.

In another randomised, open-label, multi-centre comparative trial, leuprorelin acetate in combination with flutamide has been shown to significantly improve disease-free survival and overall survival when used as an adjuvant therapy to radiotherapy in 88 patients with high-risk localised (T1-T2 and PSA of at least 10 ng/mL or a Gleason score of at least 7), or locally advanced (T3-T4) prostate cancer. The optimum duration of adjuvant therapy has not been established. This US study used a higher dose of leuprorelin acetate (7.5 mg/month) which is therapeutically equivalent to the European licensed dose.

The use of a LHRH agonist may be considered after prostatectomy in selected patients considered at high risk of disease progression. There are no disease-free survival data or survival data with leuprorelin acetate in this setting.

Neoadjuvant leuprorelin acetate prior to radiotherapy has been shown to reduce prostate volume.

5.2 Pharmacokinetic properties

Updated:

PROSTAP 3 is well absorbed after subcutaneous injection.  It binds to the GnRH receptors and is rapidly degraded.

5.3 Preclinical safety data

Added:

Animal studies have shown that leuprorelin acetate has a high acute safety factor. No major overt toxicological problems have been seen during repeated administration. Whilst the development of pituitary adenomas has been noted in chronic toxicity studies at high doses in some animal species, this has not been observed in long-term clinical studies. No evidence of mutagenicity or teratogenicity has been shown. Animal reproductive studies showed increased foetal mortality and decreased foetal weights reflecting the pharmacological effects of this GnRH agonist.

6.2 Incompatibilities

Added:

In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal products.

6.6 Special precautions for disposal and other handling

Added:

Prepare the injectable suspension at the time of use and, after reconstituting, use immediately. Always ensure the safety device to prevent needle-stick injury is deployed after injection.  For single use only. Discard any unused content. Any unused product or waste material should be disposed of in accordance with local requirements.

10 Date of revision of the text

28th May 2020

 

Updated on 29 May 2020 PIL

Reasons for updating

  • Change to section 6 - marketing authorisation holder
  • Change to section 6 - date of revision

Free text change information supplied by the pharmaceutical company

The MAH (Takeda Products Ireland Limited) address has been changed to:

6th Floor, South Bank House, Barrow Street, Dublin 4, Ireland.

This is the legally registered office.

Also, the local representative/’trading as’ address has been added to the PIL:

5 Riverwalk, Citywest Business Campus, Dublin 24, Ireland. 

The date of revision of the SmPC is February 2020.

Updated on 29 May 2020 SmPC

Reasons for updating

  • Change to section 7 - Marketing authorisation holder
  • Change to section 10 - Date of revision of the text

Legal category: Product subject to medical prescription which may be renewed (B)

Free text change information supplied by the pharmaceutical company

In section 11, the MAH (Takeda Products Ireland Limited) address has been changed to:

6th Floor, South Bank House, Barrow Street, Dublin 4, Ireland.

This is the legally registered office.

In section 10, the date of revision of the SmPC is 12th May 2020.

Updated on 22 August 2019 PIL

Reasons for updating

  • Change to section 1 - what the product is used for
  • Change to section 2 - what you need to know - contraindications
  • Change to section 2 - what you need to know - warnings and precautions
  • Change to section 3 - dose and frequency
  • Change to section 3 - overdose, missed or forgotten doses
  • Change to section 4 - possible side effects
  • Change to section 6 - date of revision

Updated on 22 August 2019 SmPC

Reasons for updating

  • Change to section 4.1 - Therapeutic indications
  • Change to section 4.2 - Posology and method of administration
  • Change to section 4.4 - Special warnings and precautions for use
  • Change to section 4.8 - Undesirable effects
  • Change to section 10 - Date of revision of the text

Legal category: Product subject to medical prescription which may be renewed (B)

Free text change information supplied by the pharmaceutical company

There has been an update to the Prostap 3 and Prostap SR SmPCs to add new indications of early and advanced breast cancer. Information has been added to sections 4.1, 4,2, 4.4 and 4.8 of both SmPCs.

Updated on 12 July 2019 PIL

Reasons for updating

  • Change to section 4 - possible side effects
  • Change to section 6 - date of revision

Updated on 28 June 2018 SmPC

Reasons for updating

  • Change to section 4.8 - Undesirable effects
  • Change to section 10 - Date of revision of the text

Legal category: Product subject to medical prescription which may be renewed (B)

Free text change information supplied by the pharmaceutical company

The updated Prostap DCS SmPCs contain additional information in the following section(s):

  • In section 4.8 (undesirable effects), interstitial lung disease has been added as a side effect with unknown frequency.
  • The date of revision is 09/06/2018.

Updated on 24 May 2018 SmPC

Reasons for updating

  • Change to section 9 - Date of first authorisation/renewal of the authorisation
  • Change to section 10 - Date of revision of the text

Legal category: Product subject to medical prescription which may be renewed (B)

Free text change information supplied by the pharmaceutical company

The HPRA has renewed the licence for Prostap DCS.

Updated on 2 November 2016 PIL

Reasons for updating

  • New PIL for new product

Updated on 2 November 2016 PIL

Reasons for updating

  • Change to section 6 - manufacturer

Updated on 7 March 2016 SmPC

Reasons for updating

  • Change to section 4.4 - Special warnings and precautions for use
  • Change to section 4.8 - Undesirable effects
  • Change to section 10 - Date of revision of the text

Legal category: Product subject to medical prescription which may be renewed (B)

Free text change information supplied by the pharmaceutical company

Change to section

Details of change

4.4 Special warnings and precautions for use

Text in red added:

Postmarketing reports of seizures have been observed in patients treated with leuprorelin acetate and these events have been reported in both children and adults, and in those with or without a history of epilepsy, seizure disorders or risk disorders for seizures.

 

4.8 Undesirable effects

Text in red added

Nervous system disorders:

Common:  headache (occasionally severe)

Rare: dizziness

Very rare: pituitary apoplexy has been reported after administration of both short-and long acting GnRH agonists

Not known: paralysis, seizure

 

 

Nervous system disorders:          

Common: headache

Not known: seizure

 

10. Date of revision of the text

Updated text in red:

 

23 February 2016

Updated on 7 March 2016 SmPC

Reasons for updating

  • New SmPC for new product

Legal category: Product subject to medical prescription which may be renewed (B)

Updated on 3 March 2016 PIL

Reasons for updating

  • Change to side-effects
  • Change to date of revision

Updated on 19 November 2015 SmPC

Reasons for updating

  • Change to section 4.2 - Posology and method of administration

Legal category: Product subject to medical prescription which may be renewed (B)

Free text change information supplied by the pharmaceutical company

In section 4.2, posology and method of administration, the text highlighted in red has been added in the male adults sections:

Male Adults: The usual recommended dose is 11.25mg presented as a 3 month depot injection and administered as a single subcutaneous or intramuscular injection at intervals of 3 months.  The majority of patients will respond to this dosage.  PROSTAP 3 therapy should not be discontinued when remission or improvement occurs. 

 

Response to PROSTAP 3 therapy may be monitored by clinical parameters and by measuring serum levels of testosterone and acid phosphatase.  Clinical studies have shown that testosterone levels increased during the first 4 days of treatment in the majority of non-orchidectomised patients.  They then decreased and reached castrate levels in 2-4 weeks.  Once attained, castrate levels were maintained as long as drug therapy continued.  Transient increases in acid phosphatase levels sometimes occur early in the treatment period but usually return to normal or near normal values by the 4th week of treatment.

 

In patients treated with GnRH analogues for prostate cancer, treatment is usually continued upon development of castrate-resistant prostate cancer. Reference should be made to relevant guidelines.

Updated on 9 October 2015 SmPC

Reasons for updating

  • Change to section 4.1 - Therapeutic indications
  • Change to section 4.2 - Posology and method of administration
  • Change to section 4.3 - Contraindications
  • Change to section 4.4 - Special warnings and precautions for use
  • Change to section 4.8 - Undesirable effects
  • Change to section 5.1 - Pharmacodynamic properties
  • Change to section 5.2 - Pharmacokinetic properties
  • Change to section 10 - Date of revision of the text

Legal category: Product subject to medical prescription which may be renewed (B)

Free text change information supplied by the pharmaceutical company

Change to section

Details of change

4.1. Therapeutic indications

Added:

In children:

Treatment of central precocious puberty (girls under 9 years of age, boys under 10 years of age).

4.2. Posology and method of administration

Added:

Posology

 

Paediatric population:

The treatment of children with leuprorelin acetate should be under the overall supervision of the paediatric endocrinologist.

The dosing scheme needs to be adapted individually.

The recommended starting dose is dependent on the body weight.

 

Children with a body weight ≥ 20 kg

1 ml (11.25 mg leuprorelin acetate) suspension of 130.0 mg sustained-release microcapsules in 1 ml vehicle solution are administered every 3 months as a single subcutaneous injection.

           

Children with a body weight < 20 kg

In these rare cases the following dosage should be administered according to the clinical activity of the central precocious puberty:

0.5 ml (5.625 mg leuprorelin acetate) suspension of 130.0 mg sustained-release microcapsules in 1 ml vehicle solution are administered every 3 months as a single subcutaneous injection.

The remainder of the suspension should be discarded. The child’s weight gain should be monitored.

Depending on the activity of the central precocious puberty, it may be necessary to increase the dosage in the presence of inadequate suppression (clinical evidence e.g. spotting or inadequate gonadotropin suppression in the LHRH test). The minimal effective 3-monthly dose to be administered should then be determined by means of the LHRH test.

Sterile abscesses at the injection site often occurred when leuprorelin acetate was administered intramuscularly at higher than the recommended dosages. Therefore, in such cases, the medicinal product should be administered subcutaneously (see 4.4).

 

It is recommended to use the lowest volumes possible for injections in children in order to decrease the inconvenience which is associated with the intramuscular/subcutaneous injection.

 

The duration of treatment depends on the clinical parameters at the start of treatment or during the course of treatment (final height prognosis, growth velocity, bone age and/or bone age acceleration) and is decided by the treating paediatrician together with the legal guardian and, if appropriate, the treated child. The bone age should be monitored during treatment at 6-12 month intervals.

In girls with bone maturation of older than 12 years and boys with bone maturation of older than 13 years discontinuation of treatment should be considered taking into account the clinical parameters.

In girls, pregnancy should be excluded before the start of treatment. The occurrence of pregnancy during treatment cannot be generally excluded. In such cases, medical advice should be sought.

 

Note:

The administration interval should be 90 ± 2 days in order to prevent the recurrence of precocious puberty symptoms.

Removed:

Children: Safety and effectiveness in children have not been established.

4.3. Contraindications

Added:

In girls with central precocious puberty:

- Pregnancy and lactation

- Undiagnosed vaginal bleeding.

4.4.  Special warnings and precautions for use

 

Added:

In girls with central precocious puberty

Before starting the therapy, a precise diagnosis of idiopathic and/or neurogenic central precocious puberty is necessary.

 

The therapy is a long-term treatment, adjusted individually. PROSTAP 3 should be administered as precisely as possible in regular 3-monthly periods. An exceptional delay of the injection date for a few days (90 ± 2 days) does not influence the results of the therapy.

 

In the event of a sterile abscess at the injection site (mostly reported after i.m. injection of higher than the recommended dosage) the absorption of leuprorelin acetate from the depot can be decreased. In this case the hormonal parameters (testosterone, oestradiol) should be monitored at 2-week intervals (see 4.2).

 

The treatment of children with progressive brain tumours should follow a careful individual appraisal of the risks and benefits.

 

The occurrence of vaginal bleeding, spotting and discharge after the first injection may occur as a sign of hormone withdrawal in girls. Vaginal bleeding beyond the first/second month of treatment needs to be investigated.

 

Bone mineral density (BMD) may decrease during GnRH therapy for central precocious puberty. However, after cessation of treatment subsequent bone mass accrual is preserved and peak bone mass in late adolescence does not seem to be affected by treatment.

 

Slipped femoral epiphysis can be seen after withdrawal of GnRH treatment. The suggested theory is that the low concentrations of estrogen during treatment with GnRH agonists weakens the epiphysial plate. The increase in growth velocity after stopping the treatment subsequently results in a reduction of the shearing force needed for displacement of the epiphysis.

4.8. Undesirable Effects

Added:

In Children:  In the initial phase of therapy, a short-term increase as flare-up of the sex hormone level occurs, followed by a decrease to values within the pre-pubertal range. Due to this pharmacological effect, adverse events may occur particularly at the beginning of treatment.

Immune system disorders:

Very rare: general allergic reactions (fever, rash, e.g. itching, anaphylactic reactions)

Psychiatric disorders:

Common: emotional lability

Nervous system disorders:

Common: headache

As with other medicinal products of this class, very rare cases of pituitary apoplexy have been reported following initial administration in patients with pituitary adenoma.

Gastrointestinal disorders:

Common: abdominal pain / abdominal cramps, nausea/vomiting

Skin and subcutaneous tissue disorders:

Common: acne

Reproductive system and breast disorders:

Common: vaginal bleeding, spotting, discharge

Note:

In general, the occurrence of vaginal spotting with continued treatment (subsequent to possible withdrawal bleeding in the first month of treatment) should be assessed as a sign of potential underdosage. The pituitary suppression should then be determined by an LHRH test.

General disorders and administration site conditions:

Common: injection site reactions.

5.1. Pharmacodynamic properties

Added:

In children:

Reversible suppression of pituitary gonadotropin release occurs, with a subsequent decrease in oestradiol (E2) or testosterone levels to values in the pre-pubertal range. 

Initial gonadal stimulation (flare-up) may cause vaginal bleeding in girls who are already post-menarchal at start of treatment. Withdrawal bleeding may occur at the start of treatment. The bleeding normally stops as treatment continues.

The following therapeutic effects can be demonstrated:

-           Suppression of basal and stimulated gonadotropin levels to pre-pubertal levels.

-           Suppression of prematurely increased sexual hormone levels to pre-pubertal levels and arrest of premature menstruation;

-           Arrest/involution of somatic pubertal development (Tanner stages);

-           Improvement/normalisation of the ratio of chronological age to bone age;

-           Prevention of progressive bone age acceleration;

-           Decrease of growth velocity and its normalization;

-           Increase in final height.

 

Treatment result is the suppression of the pathologically, prematurely activated hypothalamic-pituitary-gonadal axis according to pre-pubertal age.

 

In a long-term clinical trial in children treated with leuprorelin at doses up to 15mg monthly for > 4 years resumption of pubertal progression were observed after cessation of treatment. Follow up of 20 female subjects to adulthood showed normal menstrual cycles in 80% and 12 pregnancies in 7 of the 20 subjects including multiple pregnancies for 4 subjects.

5.2.  Pharmacokinetic properties

Added:

In children:

Figure 1 presents the leuprorelin serum levels in children during the first 6 months of treatment following s.c. administration of leuprorelin acetate 3-month depot (two injections). 

 

From the first injection, the leuprorelin serum levels increase reaching maximal serum levels at month 4 (294.79 pg/ml ± 105.42) and slightly decrease until month 6 (229.02 pg/ml ± 103.33).

 


Figure 1: Leuprorelin serum levels during the first six months of treatment with the leuprorelin acetate 3-month depot formulation (two s.c. injections) (n=42-43)

10. DATE OF REVISION OF THE TEXT

 

Changed to:

29th September 2015

Updated on 9 October 2015 PIL

Reasons for updating

  • Change to, or new use for medicine
  • Change to warnings or special precautions for use
  • Change to side-effects
  • Change to information about pregnancy or lactation
  • Change to date of revision

Updated on 3 July 2015 SmPC

Reasons for updating

  • Change to section 4.2 - Posology and method of administration
  • Change to section 5.1 - Pharmacodynamic properties
  • Change to section 10 - Date of revision of the text

Legal category: Product subject to medical prescription which may be renewed (B)

Free text change information supplied by the pharmaceutical company

4.2       Posology and method of administration

 

In patients treated with GnRH analogues for prostate cancer, treatment is usually continued upon development of castrate-resistant prostate cancer. Reference should be made to relevant guidelines.

 

5.1       Pharmacodynamic properties

Leuprorelin acetate is inactive when given orally.

In patients with metastatic castration resistant prostate cancer, clinical studies have shown benefit from the addition of secondary agents to treatment with LHRH agonists such as leuprorelin. Androgen deprivation therapy (ADT) is generally continued in conjunction with secondary therapies after progression on the initial ADT regimen.

10      DATE OF REVISION OF THE TEXT

                23 June 2015

Updated on 17 November 2014 SmPC

Reasons for updating

  • Change to section 4.4 - Special warnings and precautions for use
  • Change to section 4.5 - Interaction with other medicinal products and other forms of interaction
  • Change to section 4.8 - Undesirable effects
  • Change to section 10 - Date of revision of the text

Legal category: Product subject to medical prescription which may be renewed (B)

Free text change information supplied by the pharmaceutical company

Change to section

Details of change

4.4 Special warnings and precautions for use

Addition of text:

 

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 PROSTAP 3.

 

4.5       Interaction with other medicinal products and other forms of interaction

Addition of text:

 

Since androgen deprivation treatment may prolong the QT interval, the concomitant use of PROSTAP 3 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).

 

4.8       Undesirable effects

 

Addition of text:

 

under “Men”:

 

Frequency unknown:, QT prolongation (see sections 4.4 and 4.5)

  

10        DATE OF REVISION OF THE TEXT

 

 

31/10/2014

 

Updated on 17 November 2014 PIL

Reasons for updating

  • Change to warnings or special precautions for use
  • Change to side-effects
  • Change to drug interactions
  • Change to date of revision

Updated on 2 October 2014 PIL

Reasons for updating

  • Change to MA holder contact details

Updated on 2 October 2014 SmPC

Reasons for updating

  • Change to section 7 - Marketing authorisation holder
  • Change to section 10 - Date of revision of the text
  • Change to MA holder contact details

Legal category: Product subject to medical prescription which may be renewed (B)

Free text change information supplied by the pharmaceutical company



SECTION 7. MARKETING AUTHORISATION HOLDER


Change of address of Marketing Authorisation Holder to: 
 

Takeda UK Limited

Building 3, Glory Park,

Glory Park Avenue,

Wooburn Green,

BUCKS,

HP10 0DF

 

SECTION 10. DATE OF REVISION OF THE TEXT

 

26/09/2014

Updated on 4 June 2014 PIL

Reasons for updating

  • Change to warnings or special precautions for use
  • Change to improve clarity and readability
  • Addition of information on reporting a side effect.

Updated on 4 June 2014 SmPC

Reasons for updating

  • Change to section 2 - Qualitative and quantitative composition
  • Change to section 4.2 - Posology and method of administration
  • Change to section 4.3 - Contraindications
  • Change to section 4.4 - Special warnings and precautions for use
  • Change to section 4.6 - Pregnancy and lactation
  • Change to Section 4.8 – Undesirable effects - how to report a side effect
  • Change to section 6.6 - Special precautions for disposal and other handling
  • Change to section 10 - Date of revision of the text

Legal category: Product subject to medical prescription which may be renewed (B)

Free text change information supplied by the pharmaceutical company

The following highlighted text has been added 

Change to Section 2 an additional word "the" has been added: "For the full list of excipients, see section 6.1"

 

Change to Section 4.2 Additional highlighted text has been added: the word "posology" and the words "Method of"


4.2       Posology and method of administration

Posology

and 

Method of Administration

Change to section 4.3       Contraindications Addition of text “(listed in section 6.1)”

Hypersensitivity to the active substance, any of the excipients (listed in section 6.1) or to synthetic gonadotrophin releasing homone (Gn-RH) or Gn-RH derivatives.


Change to Section 4.4
additional paragraphs have been added to 4.4 Special warnings and precautions for use, under the subheading "Men"

 

Long-term androgen deprivation either by bilateral orchiectomy or administration of GnRH analogues is associated with increased risk of bone loss which, in patients with additional risk factors, may lead to osteoporosis and increased risk of bone fracture.

 

Epidemiological data have shown that during androgen deprivation therapy changes in the metabolic condition (e.g. reduction in glucose tolerance or aggravation of pre-existing diabetes) as well as an increased risk for cardiovascular diseases may occur. However, prospective data did not confirm the link between treatment with GnRH analogues and an increase in cardiovascular mortality. Patients at high risk for metabolic or cardiovascular diseases should be appropriately monitored.

 
Change to section 4.6 There is an insertion of an additional word, "Fertility": 4.6       Fertility, pregnancy and lactation

Change to section 4.8
insertion of an additional paragraph at the end of section 4.8

 

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 to Pharmacovigilance Section, Irish Medicines Board, Kevin O’Malley House, Earlsfort Centre, Earlsfort Terrace, IRL – Dublin 2. Tel: +353 1 6764971, Fax: +353 1 676 2517, Website: www.imb.ie. e-mail:imbpharmacovigilance@imb.ie. 

Change to section 6.6
insertion of the additional words as highlighted: 6.6       Special precautions for disposal and handling

 

Change to section 10 – date of revision of text is : 26/05/2014

Updated on 7 May 2013 SmPC

Reasons for updating

  • Change to section 6.5 - Nature and contents of container
  • Change to section 6.6 - Special precautions for disposal and other handling

Legal category: Product subject to medical prescription which may be renewed (B)

Free text change information supplied by the pharmaceutical company

Changes to sections 6.5 and 6.6 to reflect the addition of the safety device to the Dual Chamber Syringe for Prostap. The wording now reads as below:

6.5       Nature and contents of container

One dual chamber pre-filled syringe containing 11.25 mg leuprorelin acetate in the front chamber and 1 ml of aqueous sterile solvent in the rear chamber.

 

1 x 23 gauge syringe needle fitted with safety device

1 x syringe plunger

6.6       Special precautions for disposal

Always ensure the safety device to prevent needle-stick injury is deployed after injection.  For single use only. Discard any unused content. Any unused product or waste material should be disposed of in accordance with local requirements.

Updated on 22 February 2013 PIL

Reasons for updating

  • Change of manufacturer
  • Change to warnings or special precautions for use

Updated on 22 June 2012 SmPC

Reasons for updating

  • Change to section 4.4 - Special warnings and precautions for use
  • Change to section 4.8 - Undesirable effects
  • Change to section 10 - Date of revision of the text

Legal category: Product subject to medical prescription which may be renewed (B)

Free text change information supplied by the pharmaceutical company

The IMB has approved new versions of the Prostap DCS SmPCs. The updates are as follows: 

        1.      warning around injection site reactions in section 4.4 (Special warnings and precautions) : “In the rare event of an abscess occurring at the injection site, testosterone level should be monitored as there may be inadequate absorption of leuprorelin from the depot formulation.” 

        2.      Section 4.8- Undesirable effects have been updated to include the following adverse events:
             Uncommon: as with other medicinal products of this class, anaemia has been reported

Rare: reactions at the injection site, e.g., induration, erythema, pain, abscesses, swelling, nodules, ulcers and necrosis have been reported rarely

 

Updated on 19 June 2012 SmPC

Reasons for updating

  • Change to section 4.4 - Special warnings and precautions for use
  • Change to section 4.8 - Undesirable effects
  • Change to section 10 - Date of revision of the text

Legal category: Product subject to medical prescription which may be renewed (B)

Free text change information supplied by the pharmaceutical company

The IMB has approved new versions of the Prostap DCS SmPCs. The updates are as follows:

 

1.      warning around injection site reactions in section 4.4 (Special warnings and precautions) : In the rare event of an abscess occurring at the injection site, testosterone level should be monitored as there may be inadequate absorption of leuprorelin from the depot formulation.”

 

2.      Section 4.8- Undesirable effects have been updated to include the following adverse events:

Uncommon: as with other medicinal products of this class, anaemia has been reported

Rare: reactions at the injection site, e.g., induration, erythema, pain, abscesses, swelling, nodules, ulcers and necrosis have been reported rarely

Updated on 30 August 2011 SmPC

Reasons for updating

  • New SPC for medicines.ie

Legal category: Product subject to medical prescription which may be renewed (B)

Free text change information supplied by the pharmaceutical company

None provided

Updated on 1 April 2010 PIL

Reasons for updating

  • Change to side-effects
  • PIL product / presentation discontinued

Updated on 27 July 2009 PIL

Reasons for updating

  • Change of licence holder
  • Change to date of revision
  • Change to marketing authorisation holder

Updated on 27 April 2009 PIL

Reasons for updating

  • Change to storage instructions
  • Change to side-effects

Updated on 18 June 2008 PIL

Reasons for updating

  • Change to name of manufacturer

Updated on 10 June 2008 PIL

Reasons for updating

  • Change of trade or active ingredient name
  • Change of distributor details
  • Change to date of revision

Updated on 14 January 2005 PIL

Reasons for updating

  • Change of licence holder

Updated on 26 August 2004 PIL

Reasons for updating

  • New PIL for medicines.ie