Kyprolis

  • Name:

    Kyprolis

  • Company:
    info
  • Active Ingredients:

    Carfilzomib

  • Legal Category:

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

Patient Information Leaflet Patient Information Leaflet last updated on medicines.ie: 19/11/19

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Summary of Product Characteristics last updated on medicines.ie: 6/5/2020
This medicinal product is subject to additional monitoring. This will allow quick identification of new safety information. Healthcare professionals are asked to report any suspected adverse reactions. See section 4.8 for how to report adverse reactions.

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Amgen Ltd

Amgen Ltd

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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 May 2020 SmPC

Reasons for updating

  • 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

  • In section 4.8 (undesirable effects), cardiomyopathy has been added as an Uncommon AE

Updated on 19 November 2019 PIL

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

Free text change information supplied by the pharmaceutical company

Section 2 Warnings and Precautions

Tell your doctor if you have ever had or might now have a hepatitis B infection. This is because this medicine could cause hepatitis B virus to become active again. Your doctor will check you for signs of this infection before, during and for some time after treatment with this medicine. Tell your doctor right away if you get worsening tiredness, or yellowing of your skin or white part of your eyes.

 

At any time during or after your treatment, tell your doctor or nurse immediately if you: experience blurred, loss of or double vision, difficulty speaking, weakness in an arm or a leg, a change in the way you walk or problems with your balance, persistent numbness, decreased sensation or loss of

sensation, memory loss or confusion. These may all be symptoms of a serious and potentially fatal brain condition known as Progressive Multifocal Leukoencephalopathy (PML). If you had these symptoms prior to treatment with carfilzomib, tell your doctor about any change in these symptoms.

Section 4 Side Effects

  • Fever, chills or shaking, joint pain, muscle pain, facial flushing, or swelling of the face, lips, tongue and/or throat which may cause difficulty breathing or swallowing (angioedema),
  • Yellowing of your skin and eyes (jaundice), abdominal pain or swelling, nausea or vomiting, which could be symptoms of liver problems including liver failure. If you have ever had hepatitis B infection, treatment with this medicine may cause the hepatitis B infection to become active again.

 

Uncommon side effects (may affect up to 1 in 100 people)

  • Hepatitis B infection activated again (viral inflammation of the liver)

Date of revision of the text

November 2019

Updated on 19 November 2019 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 not be renewed (A)

Free text change information supplied by the pharmaceutical company

Section 4.4 Special Warnings and Precautions

Cardiac disorders

New or worsening cardiac failure (e.g. congestive cardiac failure, pulmonary oedema, decreased ejection fraction), myocardial ischaemia and infarction have occurred following administration of Kyprolis. Death due to cardiac arrest has occurred within a day of Kyprolis administration and fatal

outcomes have been reported with cardiac failure and myocardial infarction. For potential dose-related effects, see section 4.8.

 

The risk of cardiac failure is increased in elderly patients (≥ 75 years). The risk of cardiac failure is also increased in Asian patients.

A thorough assessment for cardiovascular risk factors prior to starting treatment is recommended.

 

Patients with signs or symptoms of NYHA Class III or IV cardiac failure, recent history of myocardial infarction (in the last 4 months), and in patients with uncontrolled angina or arrhythmias, should have a comprehensive medical cardiological assessment, prior to starting treatment with Kyprolis.

 

Hypertension

Hypertension, including hypertensive crisis and hypertensive emergency, has been observed with Kyprolis. Some of these events have been fatal. It is recommended to control hypertension prior to starting and during treatment.

 

Venous thrombosisthromboembolic events

Cases of venous thromboembolic events, including deep vein thrombosis and pulmonary embolism with fatal outcomes, have been reported in patients who received Kyprolis.

 

Hepatitis B Virus (HBV) Reactivation

Cases of Hepatitis B Virus (HBV) reactivation have been reported in patients receiving carfilzomib.

 

All patients should be screened for HBV before initiation of treatment with carfilzomib. For patients with positive HBV serology, prophylaxis with antivirals should be considered. They should be monitored for clinical and laboratory signs of HBV reactivation during and after the end of treatment. Experts in the treatment of HBV infection should be consulted, as necessary. The safety of resuming carfilzomib, after HBV reactivation is adequately controlled, is not known. Therefore, resumption of therapy should be discussed with experts in managing HBV.

 

Progressive Multifocal Leukoencephalopathy

Cases of Progressive Multifocal Leukoencephalopathy (PML) have been reported in patients receiving carfilzomib who have had prior or concurrent immunosuppressive therapy.

 

Patients receiving carfilzomib should be monitored for any new or worsening neurologic, cognitive or behavioural signs and symptoms that may be suggestive of PML as part of the differential diagnosis of CNS disorders.

 

If PML is suspected, further administration must be suspended until PML has been excluded by a specialist with appropriate diagnostic testing. If PML is confirmed, carfilzomib must be discontinued.

Section 4.8 Undesirable Effects

Addition of hepatitis B virus reaction as a serious adverse reaction in summary of safety profile paragraph.

 

Addition of Hepatitis B virus reactivation as an Uncommon Adverse Reaction

 

Addition of Angioedema as a Rare Adverse Reaction

Section 10 Date of revision of the text

November 2019

Updated on 16 October 2019 SmPC

Reasons for updating

  • 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 not be renewed (A)

Free text change information supplied by the pharmaceutical company

SPC

 

Section 6.6

General precautions

 

Carfilzomib is a cytotoxic agent. Therefore, caution should be used during handling and preparation of Kyprolis. Use of gloves and other protective equipment is recommended.

 

Section 10 Date of revision of the text

September 2019

 

Updated on 16 October 2019 PIL

Reasons for updating

  • Change to section 6 - date of revision
  • Change to information for healthcare professionals

Free text change information supplied by the pharmaceutical company

PIL

 

HCP Information at the end of PIL

The following information is intended for healthcare professionals only:

Carfilzomib is a cytotoxic agent. Therefore, caution should be used during handling and preparation of Kyprolis. Use of gloves and other protective equipment is recommended.

 

Date of revision of the text

September 2019

Updated on 2 May 2019 PIL

Reasons for updating

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

Updated on 2 May 2019 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 not be renewed (A)

Free text change information supplied by the pharmaceutical company

  • In section 4.8 (undesirable effects) - addition of cytomegalovirus infection (uncommon)
  • In section 10 date of revision of the text - date revised to April 2019

Updated on 24 October 2018

Updated on 23 October 2018 SmPC

Reasons for updating

  • Change to section 4.4 - Special warnings and precautions for use
  • 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

  • In section 4.4 Special Warnings and Precautions - addition of "The risk of cardiac failure is also increased in Asian patients" to the cardiac disorders subheading
  • In section 5.1 Pharmacodynamic properties - removal of "NE = not estimable from table legend for Table 6. Addition of mo = months for figure legends on Figure 1 and Figure 2
  • In section 10 Date of Revision - The date has been amended to September 2018

Updated on 29 May 2018 SmPC

Reasons for updating

  • 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 4.8 Undesirable effects

Clostridium difficile colitis – added as an uncommon adverse reaction

Myocardial infarction – frequency increased to common

 

Changes to frequency of selected adverse reactions:

Cardiac failure, myocardial infarction and myocardial ischaemia

In clinical studies with Kyprolis, cardiac failure was reported in approximately 7% of subjects (< 5% of subjects had grade ≥ 3 events), myocardial infarction was reported in approximately 2% of subjects (< 1.5% of subjects had grade ≥ 3 events) and myocardial ischaemia was reported in approximately 1% of subjects (< 1% of subjects had grade ≥ 3 events). These events typically occurred early in the course of Kyprolis therapy (< 5 cycles). For clinical management of cardiac disorders during Kyprolis treatment, see section 4.4.

 

Hypertension including hypertensive crises

Hypertensive crises (hypertensive urgency or hypertensive emergency) have occurred following administration of Kyprolis. Some of these events have been fatal. In clinical studies, hypertension adverse events occurred in approximately 20% of subjects and approximately 7.5% of subjects had grade ≥ 3 hypertension events, but hypertensive crises occurred in < 0.5% of subjects. The incidence of hypertension adverse events was similar between those with or without a prior medical history of hypertension. For clinical management of hypertension during Kyprolis treatment, see section 4.4.

 

Venous thromboembolic events

Cases of venous thromboembolic events, including deep vein thrombosis and pulmonary embolism with fatal outcomes, have been reported in patients who received Kyprolis (see section 4.4). The overall incidence of venous thromboembolic events was higher in the Kyprolis arms of two phase 3 studies. In study PX-171-009 the incidence of venous thromboembolic events was 15.36% in the KRd arm and 9.0% in the Rd arm. Grade ≥ 3 venous thromboembolic events were reported in 5.6% of patients in the KRd arm and 3.9% of patients in the Rd arm. In study 2011 003 the incidence of venous thromboembolic events was 12.5% in the Kd arm and 3.3% in the bortezomib plus dexamethasone (Vd) arm. Grade ≥ 3 venous thromboembolic events were reported in 3.5% of patients in the Kd arm and 1.8% of patients in the Vd arm.

Section 5.1 Pharmacodynamic Properties

Addition of ASPIRE OS data

Section 10 Date of revision of the text

April 2018

Updated on 29 May 2018 PIL

Reasons for updating

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

Updated on 9 May 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 not be renewed (A)

Free text change information supplied by the pharmaceutical company

Section 4.8 Undesirable effects

Addition of Common adverse reactions:

Herpes zoster * (* Frequency is calculated based on data from clinical trials in which most patients used prophylaxis)

Confusional state 

Section 10 Date of revision of the text

April 2018

Updated on 26 April 2018 PIL

Reasons for updating

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

Updated on 27 February 2018 SmPC

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 5.1 - Pharmacodynamic properties
  • Change to section 6.3 - Shelf life
  • 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 not be renewed (A)

Free text change information supplied by the pharmaceutical company

Section 4.2 Method of administration:

Clarification added: Kyprolis must not be administered as an intravenous push or bolus

 

Section 4.4 Special Warnings and Precautions for Use:

Hypertension

Addition of instruction: It is recommended to control hypertension prior to starting treatment.

​​Acute renal failure

Addition of information: Some of these events have been fatal

 

Section 4.8 Undesirable effects

Summary of safety profile

Rewording of paragraph, additional events included in list of serious adverse reactions, rewording of most common adverse reactions

​​Table 5 Tabulated list of adverse reactions

Update to frequency of some events, addition of new common events influenza like illness, malaise, gastroenteritis

​​Thrombocytopenia/VTA/peripheral neuropathy

Update to frequency of events provided provided in descriptive text

​​

Thrombocytopenia was reported in approximately 4034% of subjects in clinical studies with Kyprolis

and approximately 20% of subjects had grade ≥ 3 events.

​​

In study 2011 003 the incidence of venous thromboembolic events was 10.6 12.5% in the Kd arm and 3.13% in the bortezomib plus dexamethasone (Vd) arm. Grade ≥ 3 venous thromboembolic events were reported in 3.05% of patients in the Kd arm and 1.58% of patients in the Vd arm.

​​

In a randomised, open-label multicentre study in patients receiving Kyprolis 20/56 mg/m2 infused over 30 minutes in combination with dexamethasone (Kd, n = 464) vs bortezomib plus dexamethasone (Vd, n = 465), cases of grade 2 and higher peripheral neuropathy were reported in 67% of patients with relapsed multiple myeloma in the Kd arm, compared with 3235% in the Vd arm at the time of the pre-planned OS analysis

​​

Section 5.1 Pharmacodynamic properties

Addition of Endeavor OS data (table 7) and descriptive text

​​

Section 6.3 Shelf life

Clarification that the powder shelf life refers to unopened vials

​​

Section 6.6 Special precautions for disposal and other handling

7. Kyprolis can be administered directly by intravenous infusion or Ooptionally, Kyprolis can be administered in an intravenous bag. Do not administer as an intravenous push or bolus.

​​

Section 10 Date of revision of the text: January 2018

Updated on 27 February 2018 SmPC

Reasons for updating

  • New SmPC for new product

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

Updated on 27 February 2018 PIL

Reasons for updating

  • New PIL for new product

Updated on 27 February 2018 PIL

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 28 November 2017 PIL

Reasons for updating

  • Change to other sources of information section

Updated on 23 November 2017 PIL

Reasons for updating

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

Updated on 23 November 2017 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 not be renewed (A)

Free text change information supplied by the pharmaceutical company

Addition of tinnitus as a common adverse event

Updated on 31 March 2017 PIL

Reasons for updating

  • Change to section 6 - manufacturer

Updated on 20 December 2016 SmPC

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 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

4.2 - additional information provided for special populations with renal and hepatic impairment
4.4  - clarification "per mL of reconstituted solution" added for sodium content
5.2 - - additional information provided for special populations with renal and hepatic impairment

Updated on 14 November 2016 SmPC

Reasons for updating

  • 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 not be renewed (A)

Free text change information supplied by the pharmaceutical company

Addition of information on needle gauge to use for reconstitution

Updated on 14 November 2016 PIL

Reasons for updating

  • Change to section 6 - date of revision
  • Change to information for healthcare professionals

Updated on 5 September 2016 SmPC

Reasons for updating

  • Change to section 1 - Name of medicinal product
  • Change to section 2 - Qualitative and quantitative composition
  • Change to section 6.5 - Nature and contents of container
  • Change to section 6.6 - Special precautions for disposal and other handling
  • Change to section 8 - MA number
  • 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 two new presentations - 10 mg and 30 mg powder for solution for infusion

1.    Name of the Medicinal Product

Changes include addition of the following information:

Kyprolis 10 mg powder for solution for infusion

Kyprolis 30 mg powder for solution for infusion

2.    Qualitative and Quantitative Composition

Changes include addition of the following information:

Kyprolis 10 mg powder for solution for infusion

Each vial contains 10 mg of carfilzomib.

 

Kyprolis 30 mg powder for solution for infusion

Each vial contains 30 mg of carfilzomib.

 

 

6.5 Nature and contents of container

Changes include addition of the following information:

 

Kyprolis 10 mg powder for solution for infusion

10 mL type I clear glass vial, closed with fluoropolymer laminated elastomeric stopper and aluminium seal with a light blue plastic flip off cap.

 

Kyprolis 30 mg powder for solution for infusion

30 mL type I clear glass vial, closed with fluoropolymer laminated elastomeric stopper and aluminium seal with an orange plastic flip off cap.

 

The following sentence has been updated to include “purple”

50 mL type I clear glass vial, closed with fluoropolymer laminated elastomeric stopper and aluminium seal with a purple plastic flip off cap.

 

6.6 Special precautions for disposal and handling

Step 3 has been updated to state (new text in bold):

Aseptically reconstitute each vial by slowly injecting 5 mL (for 10 mg vial), 15 mL (for 30 mg vial) or 29 mL (for 60 mg vial) sterile water for injections through the stopper and directing the solution onto the INSIDE WALL OF THE VIAL to minimise foaming.

 

8. Marketing Authoirsation Number(s)

Changes include addition of the following information:


EU/1/15/1060/002

EU/1/15/1060/003

10. Date of revision of the text

Date updated to August 2016

Updated on 5 September 2016 PIL

Reasons for updating

  • Change to date of revision
  • Introduction of new pack/pack size

Updated on 7 July 2016 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 4.5 - 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 6.3 - Shelf life
  • 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 not be renewed (A)

Free text change information supplied by the pharmaceutical company

Indication updated to reflect Kyprolis in combination with dexamethasone; posology and other sections updated for these new data
Addition of rhinitis (common) and lung infection (uncommon) to adverse reactions

Updated on 7 July 2016 PIL

Reasons for updating

  • Change to, or new use for medicine
  • Change to side-effects
  • Change to information about pregnancy or lactation
  • Change to date of revision
  • Change to dosage and administration

Updated on 27 May 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 not be renewed (A)

Free text change information supplied by the pharmaceutical company

Section 4.4 addition of information on venous thrombosis and haemorrhage
Section 4.8 addition of intercranial haemorrhage, haemorrhage, pulmonary haemorrhage, gastrointestinal haemorrhage as uncommon adverse reactions

Updated on 27 May 2016 PIL

Reasons for updating

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

Updated on 30 March 2016 SmPC

Reasons for updating

  • Change to section 4.5 - Interaction with other medicinal products and other forms of interaction
  • 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

Update to information on drug drug interactions

Updated on 2 December 2015 PIL

Reasons for updating

  • Improved electronic presentation

Updated on 24 November 2015 SmPC

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 23 November 2015 PIL

Reasons for updating

  • New PIL for new product