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XGEVA

*
Pharmacy Only: Prescription

  • Company:

    Amgen Ireland Ltd

  • Status:

    No Recent Update

  • Legal Category:

    Product subject to medical prescription which may not be renewed (A)

  • Active Ingredient(s):

    Denosumab

    *Additional information is available within the SPC or upon request to the company

Updated on 28 July 2022

File name

en_xgeva_approved_pil_v81_IE NI.pdf

Reasons for updating

  • Change to section 2 - excipient warnings

Free text change information supplied by the pharmaceutical company

Section 2 Warnings and Precautions

XGEVA contains sorbitol

This medicine contains 78 mg sorbitol in each vial. If you have been told by your doctor that you have an intolerance to some sugars, contact your doctor before taking this medicine, since it contains sorbitol (E420).


XGEVA contains sodium

This medicine contains less than 1 mmol sodium (23 mg) per 120 mg dose, that is to say essentially ‘sodium‑free’.

 

Date of revision of the text

July 2022

Updated on 26 July 2022

File name

en_xgeva_approved_spc_v81_IE NI .pdf

Reasons for updating

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

Legal category:Product subject to medical prescription which may not be renewed (A)

Free text change information supplied by the pharmaceutical company

Section 4.4 Special Warnings and Precautions

This medicinal product contains sorbitol. The additive effect of concomitantly administered products containing sorbitol (or fructose) and dietary intake of sorbitol (or fructose) should be taken into account. Patients with rare hereditary problems of fructose intolerance should not take this medicinal product.

This medicinal product contains less than 1 mmol sodium (23 mg) per 120 mg dose, that is to say essentially 'sodium-free'.

Section 10 Date of revision of the text

July 2022

Updated on 28 April 2022

File name

en_xgeva_approved_pil_v79.pdf

Reasons for updating

  • Change to section 6 - date of revision
  • Change to MA holder contact details

Updated on 24 July 2020

File name

en_xgeva_approved_spc_v72.pdf

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 not be renewed (A)

Updated on 22 November 2019

File name

en_xgeva_approved_spc_v69.pdf

Reasons for updating

  • Change to section 4.2 - Posology and method of administration
  • 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 not be renewed (A)

Free text change information supplied by the pharmaceutical company

Section 4.2 Posology and method of administration

“Paediatric population

The safety and efficacy of XGEVA have not been established in paediatric patients (age < 18) other than skeletally mature adolescents (aged 12-17 years) with giant cell tumour of bone.

 

XGEVA is not recommended in paediatric patients (age < 18) other than skeletally mature adolescents (aged 12-17 years) with giant cell tumour of bone (see section 4.4).”

 

 

Section 4.8 Undesirable Effects

Per 100 patient-years added to during the first year of treatment

 

“In a long-term phase II open-label clinical trial in patients with giant cell tumour of bone (Study 6, see section 5.1), ONJ was confirmed in 6.8% of patients, including one adolescent (median number of 34 doses; range 4 – 116). At the completion of the trial, median time on trial including safety follow-up phase was 60.9 months (range: 0 – 112.6). The patient-year adjusted incidence of confirmed ONJ was 1.5 per 100 patient-years overall (0.2 per 100 patient-years during the first year of treatment, 1.5 in the second year, 1.8 in the third year, 2.1 in the fourth year, 1.4 in the fifth year, and 2.2 thereafter). The median time to ONJ was 41 months (range: 11 - 96).”

 

Paediatric patients changed from 18 to 28 skeletally mature adolescents enrolled with GCT of bone

Section 5.1 Pharmacodynamic properties

“Immunogenicity

 

In clinical studies, neutralising antibodies have not been observed for denosumab in advanced cancer patients or giant cell tumour of bone patients.”

 

 

“Clinical efficacy and safety in adults and skeletally mature adolescents with giant cell tumour of bone

 

The safety and efficacy of XGEVA was studied in two phase II open‑label, single‑arm trials (studies 5 and 6) that enrolled 529 554 patients with giant cell tumour of bone that was either unresectable or for which surgery would be associated with severe morbidity. Patients received 120 mg XGEVA subcutaneously every 4 weeks with a loading dose of 120 mg on days 8 and 15. Patients who discontinued XGEVA then entered the safety follow-up phase for a minimum of 60 months. Retreatment with XGEVA while in safety follow-up was allowed for subjects who initially demonstrated a response to XGEVA (e.g. in the case of recurrent disease).

 

Study 5 enrolled 37 adult patients with histologically confirmed unresectable or recurrent giant cell tumour of bone. The main outcome measure of the trial was response rate, defined as either at least 90% elimination of giant cells relative to baseline (or complete elimination of giant cells in cases where giant cells represent < 5% of tumour cells), or a lack of progression of the target lesion by radiographic measurements in cases where histopathology was not available. Of the 35 patients included in the efficacy analysis, 85.7% (95% CI: 69.7, 95.2) had a treatment response to XGEVA. All 20 patients (100%) with histology assessments met response criteria. Of the remaining 15 patients, 10 (67%) radiographic measurements showed no progression of the target lesion.

 

Study 6 enrolled 507 535 adult or skeletally mature adolescents with giant cell tumour of bone. Of these patients, 28 were aged 12-17 years. Patients were assigned to one of three cohorts: cohort 1 included patients with surgically unsalvageable disease (e.g. sacral, spinal, or multiple lesions, including pulmonary metastases); cohort 2 included patients with surgically salvageable disease whose planned surgery was associated with severe morbidity (e.g. joint resection, limb amputation, or hemipelvectomy); cohort 3 included patients previously participating in study 5 and rolled over into this study. The primary objective was to evaluate the safety profile of denosumab in subjects with giant cell tumour of bone. The secondary outcome measures of the study included time to disease progression (based on investigator assessment) for cohort 1 and proportion of patients without any surgery at month 6 for cohort 2.

 

 

 

In cohort 1 at the final analysis, 28 of the 260 treated patients (10.8%) had disease progression. In cohort 2, 219 of the 238 (92.0%; 95% CI: 87.8%, 95.1%) evaluable patients treated with XGEVA had not undergone surgery by month 6. Of the 239 subjects in cohort 2 with baseline target lesion location or on-study location not in lungs or soft tissue, a total of 82 subjects (34.3%) were able to avoid on-study surgery.. Overall, efficacy results in skeletally mature adolescents were similar to those observed in adults.”

 

“Paediatric population

 

In study 6, XGEVA has been evaluated in a subset of 18 28 adolescent patients (aged 13‑17 years) with giant cell tumour of bone who had reached skeletal maturity defined by at least 1 mature long bone (e.g. closed epiphyseal growth plate of the humerus) and body weight ≥ 45 kg. One adolescent subject with surgically unsalvageable disease (N=14) had disease recurrence during initial treatment. Thirteen of the 14 subjects with surgically salvageable disease whose planned surgery was associated with severe morbidity had not undergone surgery by month 6.”

 

Section 5.2 Pharmacokinetic properties

“Paediatric population

 

In skeletally-mature adolescents (12-17 years of age) with giant cell tumour of bone who received 120 mg every 4 weeks with a loading dose on days 8 and 15, the pharmacokinetics of denosumab were similar to those observed in adult subjects with GCTB.”

 

Section 10 Date of revision of text

November 2019

EDM Updated on 30 May 2019

File name

XGEVA Patient Reminder Card IE fold out-clean.pdf

Reasons for updating

  • Replace File

Updated on 24 May 2019

File name

en_xgeva_approved_pil_v68.pdf

Reasons for updating

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

Updated on 23 May 2019

File name

en_xgeva_approved_spc_v68.pdf

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 not be renewed (A)

Updated on 16 January 2019

File name

en_xgeva_approved_pil_v65.pdf

Reasons for updating

  • Change to section 4 - possible side effects
  • Change to section 6 - date of revision
  • Removal of Black Inverted Triangle

Updated on 16 January 2019

File name

en_xgeva_approved_SPC.pdf

Reasons for updating

  • Change to section 4.8 - Undesirable effects
  • Change to section 10 - Date of revision of the text
  • Removal of Black Inverted Triangle

Legal category:Product subject to medical prescription which may not be renewed (A)

Free text change information supplied by the pharmaceutical company

change in frequency of AE, Atypical femur fracture

Change in date of revision to November 2018

removal of black triangle

EDM Updated on 19 October 2018

File name

UKIE-NPC-162x-0515-105725 XGEVA IE ONJ card.pdf

Reasons for updating

  • Add New Doc

Free text change information supplied by the pharmaceutical company

This reminder card contains important safety information that patients need to be aware of before and during treatment with denosumab (XGEVA) injections for cancer-related conditions, A side effect called osteonecrosis of the jaw (ONJ, bone damage in the jaw) has been reported commonly (may affect up to 1 in 10 people) in patients receiving XGEVA injections for cancer-related conditions. ONJ can also occur after stopping treatment. It is important to try to prevent ONJ developing as it may be a painful condition that can be difficult to treat. In order to reduce the risk of developing ONJ, there are some precautions patients should take. To request a copy of the patient card, please contact Amgen Medical Information on +44 (0) 1223 436441

File name

en_xgeva_approved_pil-psur11.pdf

Updated on 03 July 2018

File name

en_xgeva_approved_spc_psur11.docx

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 not be renewed (A)

Free text change information supplied by the pharmaceutical company

Table 1. Adverse reactions reported in patients with advanced malignancies involving bone, multiple myeloma, or with giant cell tumour of bone

MedDRA system organ class

Frequency category

Adverse reactions

Neoplasms benign, malignant and unspecified (including cysts and polyps)

Common

New primary malignancy1

 

Description of selected adverse reactions

New primary malignancy

In the primary double blind treatment phases of four phase III active-controlled clinical trials in patients with advanced malignancies involving bone, new primary malignancy was reported in 54/3691 (1.5%) of patients treated with XGEVA (median exposure of 13.8 months; range: 1.0–51.7) and 33/3688 (0.9%) of patients treated with zoledronic acid (median exposure of 12.9 months; range: 1.0-50.8).

 

The cumulative incidence at one year was 1.1 % for denosumab and 0.6 % for zoledronic acid, respectively.

 

No treatment-related pattern in individual cancers or cancer groupings was apparent.

 

Section 10: June 2018 

Updated on 03 July 2018

File name

en_xgeva_approved_pil-psur11.pdf

Reasons for updating

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

Updated on 29 May 2018

File name

en_xgeva_approved_spc_v59.docx

Reasons for updating

  • 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
  • Change to section 10 - Date of revision of the text

Legal category:Product subject to medical prescription which may not be renewed (A)

Updated on 29 May 2018

File name

en_xgeva_approved_pil-v59.pdf

Reasons for updating

  • Change to section 2 - what you need to know - warnings and precautions
  • Change to section 4 - possible side effects
  • Change to section 6 - date of revision

Updated on 06 April 2018

File name

PIL_15079_938.pdf

Reasons for updating

  • New PIL for new product

Updated on 06 April 2018

Reasons for updating

  • New SPC for new product

Legal category:Product subject to medical prescription which may not be renewed (A)

Updated on 06 April 2018

Reasons for updating

  • Change to section 4.1 - Therapeutic indications
  • Change to section 4.2 - Posology and method of administration
  • 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 not be renewed (A)

Free text change information supplied by the pharmaceutical company

Section 4.1 update to indication

Section 4.2 update to reflect change in indication

Section 4.8 updated to reflect new data from Multiple myeloma CTs

Section 5.1 Updated with Multiple myeloma clinical trial data

Section 5.2 Updated with Multiple myeloma clinical trial data

Section 10 Date of revision updated to March 2018

Updated on 06 April 2018

Reasons for updating

  • Change to section 1 - what the product is used for
  • Change to section 4 - possible side effects
  • Change to section 6 - date of revision

Updated on 21 September 2017

Reasons for updating

  • New SPC for new product

Legal category:Product subject to medical prescription which may not be renewed (A)

Updated on 21 September 2017

File name

PIL_15079_472.pdf

Reasons for updating

  • New PIL for new product

Updated on 21 September 2017

Reasons for updating

  • Change to section 4.6 - Pregnancy and lactation
  • Change to section 4.8 - Undesirable effects
  • Change to section 6.1 - List of excipients
  • Change to section 6.6 - Special precautions for disposal and other handling
  • Change to section 10 - Date of revision of the text
  • Correction of spelling/typing errors
  • Improved presentation of SPC

Legal category:Product subject to medical prescription which may not be renewed (A)

Free text change information supplied by the pharmaceutical company

Editorial updates to SPC to align with current EMA template
Additional of polysorbate 20 as an excipient

Updated on 21 September 2017

Reasons for updating

  • Change to section 2 - what you need to know - warnings and precautions
  • Change to section 2 - interactions with other medicines, food or drink
  • Change to section 3 - how to take/use
  • Change to section 6 - what the product contains
  • Change to section 6 - date of revision

Updated on 28 June 2017

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 not be renewed (A)

Free text change information supplied by the pharmaceutical company

Addition of OEAC as a risk to section 4.4 and 4.8
Change of revision date to June 2017

Updated on 23 June 2017

Reasons for updating

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

Updated on 30 March 2017

Reasons for updating

  • Change to section 6 - manufacturer

Updated on 03 January 2017

Reasons for updating

  • Change to section 4.6 - Pregnancy and lactation
  • Change to section 10 - Date of revision of the text

Legal category:Product subject to medical prescription which may not be renewed (A)

Free text change information supplied by the pharmaceutical company

Removal of PSP/LSP
Date of revision

Updated on 03 January 2017

Reasons for updating

  • Change to section 2 - pregnancy, breast feeding and fertility
  • Change to section 6 - date of revision

Updated on 12 April 2016

Reasons for updating

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

Legal category:Product subject to medical prescription which may not be renewed (A)

Free text change information supplied by the pharmaceutical company

Section 4.2 - Reordering of text/addition of subheadings
Section 4.4 - Addition of text to “Warning for excipients”
Section 4.8 - Addition of new paragraph on the overall safety profile

Updated on 12 April 2016

Reasons for updating

  • Change of contraindications
  • Change to date of revision

Updated on 18 December 2015

Reasons for updating

  • Change to section 4.2 - Posology and method of administration
  • Change to section 4.4 - Special warnings and precautions for use
  • Change to section 10 - Date of revision of the text

Legal category:Product subject to medical prescription which may not be renewed (A)

Free text change information supplied by the pharmaceutical company

Section 4.2 - editorial update to section on paediatric population
Section 4.4 - new section on patients with growing sections

Updated on 18 December 2015

Reasons for updating

  • Change to warnings or special precautions for use
  • Change to date of revision

Updated on 29 July 2015

Reasons for updating

  • Change to section 4.2 - Posology and method of administration
  • Change to section 4.8 - Undesirable effects

Legal category:Product subject to medical prescription which may not be renewed (A)

Free text change information supplied by the pharmaceutical company

Section 4.2 - clarification to posology for giant cell tumour of bone (addition of "of the first month of therapy")

Section 4.8 - addition of information on ONJ events over time in patients with non-metastatic prostate cancer

Updated on 20 July 2015

Reasons for updating

  • 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 10 - Date of revision of the text

Legal category:Product subject to medical prescription which may not be renewed (A)

Free text change information supplied by the pharmaceutical company

Section 4.2 - addition of instruction to provide patients with package leaflet and patient card
Section 4.3 - addition of contraindication "unhealed lesions from dental or oral surgery"
Section 4.4 - update to section on ONJ
Section 4.8 - update to section on ONJ

Updated on 20 July 2015

Reasons for updating

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

Updated on 16 September 2014

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 10 September 2014

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 4.6 - 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 10 - Date of revision of the text

Legal category:Product subject to medical prescription which may not be renewed (A)

Free text change information supplied by the pharmaceutical company

Addition of indication for giant cell tumour of bone
Clarification to warnings and precautions for ONJ
Update to pregnancy information

Updated on 26 August 2014

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 not be renewed (A)

Free text change information supplied by the pharmaceutical company

Section 4.4 Special warnings and precautions for use

·         Updated recommendations for monitoring of calcium levels

·         Addition of renal impairment subheading to clarify greater risk of hypocalcaemia and accompanying PTH elevation

·         Strengthened recommendations for precautions for ONJ

 

Section 4.8 Undesirable Effects

·         Addition of musculoskeletal pain as a very common adverse reaction and descriptive text

·         Clarification and addition of descriptive text for symptoms of hypocalcaemia

·         Clarification on exclusion of patients with ONJ risk factors from P3 trials and incidence of ONJ in extension phases

·         Addition of subheading on renal impairment special population

 

Section 10 Date of revision of the text

·         July 2014

Updated on 26 August 2014

Reasons for updating

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

Updated on 03 December 2013

Reasons for updating

  • Addition of black triangle
  • Change to section 4.4 - Special warnings and precautions for use
  • Change to section 4.8 - Undesirable effects
  • Change to Section 4.8 – Undesirable effects - how to report a side effect
  • Change to section 10 - Date of revision of the text

Legal category:Product subject to medical prescription which may not be renewed (A)

Free text change information supplied by the pharmaceutical company

Removal of information on skin infections/cellulitis from section 4.4 and 4.8
Addition of symptoms of hypocalcaemia to section 4.8
Frequency of durg hypersensitivity adverse reaxtion decreased to rare in section 4.8
Update to date of revision
Addition of black triangle and reporting for adverse events

Updated on 03 December 2013

Reasons for updating

  • Change to warnings or special precautions for use
  • Change to side-effects
  • Change to date of revision
  • Addition of information on reporting a side effect.
  • Addition of black triangle

Updated on 06 June 2013

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 not be renewed (A)

Free text change information supplied by the pharmaceutical company

In Section 4.4 (Special warnings and precautions for use) – Addition of text regarding atypical fracture of the femur

In Section 4.8 (Undesirable effects) - Addition of atypical fracture of the femur and anaphylaxis as rare adverse reaction

In Section 10 (Date of revision of the text) -  Updated date of revision of the text

Updated on 06 June 2013

Reasons for updating

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

Updated on 01 March 2013

Reasons for updating

  • 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 10 - Date of revision of the text

Legal category:Product subject to medical prescription which may not be renewed (A)

Free text change information supplied by the pharmaceutical company

Section 4.4 update to ONJ inofrmation to reflect open label extension phase to P3 studies
Section 4.8 update to ONJ inofrmation to reflect open label extension phase to P3 studies
Section 5.1 update to ONJ inofrmation to reflect open label extension phase to P3 studies
Section 10 update to date of revision of text

Updated on 01 March 2013

Reasons for updating

  • Change to date of revision
  • Addition of manufacturer

Updated on 31 August 2012

Reasons for updating

  • 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 not be renewed (A)

Free text change information supplied by the pharmaceutical company

Section 4.2
-Addition of text relating to recommendations for the monitoring of calcium
Section 4.4
-Addition of text for hypocalcaemia manifestation
-Addition of text for severe symptomatic hypocalcaemia reported in the post-marketing setting
Section 4.8
-Addition of text for severe symptomatic hypocalcaemia in the post-marketing setting
Section 10
-Updated date of revision of the text

Updated on 13 July 2012

Reasons for updating

  • Change to section 10 - Date of revision of the text

Legal category:Product subject to medical prescription which may not be renewed (A)

Free text change information supplied by the pharmaceutical company

In section 10 - date of revision of text

Updated on 13 July 2012

Reasons for updating

  • Change to date of revision

Updated on 25 January 2012

Reasons for updating

  • Change to section 6.5 - Nature and contents of container
  • Presentation currently not marketed.

Legal category:Product subject to medical prescription which may not be renewed (A)

Free text change information supplied by the pharmaceutical company

In section 6.5, there was the addition of a 3 pack size.

Updated on 23 January 2012

Reasons for updating

  • Introduction of new pack/pack size
  • Presentation currently not marketed.

Updated on 21 July 2011

Reasons for updating

  • New SPC for new product

Legal category:Product subject to medical prescription which may not be renewed (A)

Free text change information supplied by the pharmaceutical company

None provided

Updated on 21 July 2011

Reasons for updating

  • New PIL for new product