Lenvima (lenvatinib)

*
Pharmacy Only: Prescription
  • Company:

    Eisai Ltd
  • Status:

    No Recent Update
  • Legal Category:

    Product subject to medical prescription which may not be renewed (A)
  • Active Ingredient(s):

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

Updated on 14 December 2023

File name

ROI Lenvima PIL Nov 2023.pdf

Reasons for updating

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

Updated on 14 December 2023

File name

ROI Lenvima SmPC Nov 2023.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 24 November 2023

File name

ROI Lenvima PIL Nov 2023.pdf

Reasons for updating

  • Change to section 2 - use in children and adolescents
  • Change to section 6 - date of revision

Updated on 24 November 2023

File name

ROI Lenvima SmPC Nov 2023.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)

Updated on 24 November 2023

File name

ROI Lenvima SmPC Nov 2023.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)

Updated on 07 August 2023

File name

ROI Lenvima PIL July 2023.pdf

Reasons for updating

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

Updated on 07 August 2023

File name

ROI Lenvima SmPC July 2023.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 March 2023

File name

ROI Lenvima SmPC March 2023.pdf

Reasons for updating

  • 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)

Updated on 10 March 2023

File name

ROI Lenvima 4mg & 10mg capsules SmPC Feb 2023.pdf

Reasons for updating

  • Change to section 4.2 - Posology and method of administration
  • 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)

Updated on 10 March 2023

File name

ROI Lenvima 4mg & 10mg capsules PIL Feb 2023.pdf

Reasons for updating

  • Change to section 3 - how to take/use
  • Change to section 6 - date of revision

Updated on 19 January 2023

File name

ROI Lenvima 4mg and 10mg SmPC 07.04.2022.pdf

Reasons for updating

  • Document format updated

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

Updated on 05 May 2022

File name

ROI Lenvima 4mg and 10mg SmPC 07.04.2022.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)

Free text change information supplied by the pharmaceutical company

Documented changes

Sections of the SmPC

Changes/updates

Section 4.8: Undesirable effects

Following a PRAC signal assessment, ‘colitis’ has been added as an adverse event with frequency uncommon for lenvatinib monotherapy and common for combination with pembrolizumab

Section 10: Date of revision of the text

Updated to 04/2022

Updated on 05 May 2022

File name

ROI Lenvima 4mg and 10mg PIL.pdf

Reasons for updating

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

Free text change information supplied by the pharmaceutical company

Documented changes

Sections of the PIL

Changes/updates

Section 4: Possible side effects

Addition of ‘inflammation of the colon (colitis)’ with frequency uncommon under the heading ‘The following side effects may happen with this medicine when given alone’

Section 4: Possible side effects

Addition of ‘inflammation of the colon (colitis)’ with frequency common under the heading ‘The following side effects may happen with this medicine when given in combination with pembrolizumab’

Section 6: Contents of the pack and other information

This leaflet was last revised in April 2022

Updated on 05 May 2022

File name

ROI Lenvima 4mg and 10mg SmPC 07.04.2022.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 03 December 2021

File name

ROI Lenvima SmPC clean - Nov 21.pdf

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 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

Documented changes

Sections of the SmPC

Changes/updates

Section 4.1

Addition of endometrial cancer (EC) indication

Section 4.2

Addition of dosages and dose adjustments for EC

Section 4.4

Addition of liver-related adverse reactions for EC

Section 4.8

Addition of EC undesirable effects.

Section 5.1

Addition of EC pivotal trial data

Section 5.2

Update to age, sex, weight, race within section 5.2

Section 10

The date of revision of text has been changed to 29/11/2021

Updated on 03 December 2021

File name

ROI Lenvima PIl- Nov 21.pdf

Reasons for updating

  • Change to section 1 - what the product is used for
  • Change to section 3 - how to take/use
  • Change to section 4 - possible side effects
  • Change to section 6 - date of revision

Free text change information supplied by the pharmaceutical company

Documented changes

Sections of the PIL

Changes/updates

Section 1

Addition of endometrial cancer (EC) indication

Section 3

Addition of dosages for uterine cancer

Section 4

Addition of EC side effects

Section 6

The date of revision of text has been changed to November 2021

Updated on 25 March 2021

File name

ROI Lenvima SmPC 4mg and 10mg 17 Mar 2021.pdf

Reasons for updating

  • Change to section 5.1 - Pharmacodynamic properties

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

Updated on 25 March 2021

File name

ROI Lenvima SmPC 4mg and 10mg 17 Mar 2021.pdf

Reasons for updating

  • Change to section 4.5 - Interaction with other medicinal products and other forms of interaction
  • Change to section 5.1 - Pharmacodynamic properties

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

Updated on 10 March 2021

File name

ROI Lenvima PIL 4mg and 10mg 04 Mar 2021.pdf

Reasons for updating

  • XPIL Created

Updated on 09 March 2021

File name

ROI Lenvima PIL 4mg and 10mg 04 Mar 2021.pdf

Reasons for updating

  • Change to section 6 - manufacturer

Updated on 18 December 2020

File name

ROI Lenvima SmPC 10 Dec 2020.pdf

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

Documented changes

Sections of the SmPC

Changes/updates

Section 4.8 Undesirable effects

The following information on ethnic groups has been expanded:

 

Ethnic origin

 

DTC

 

Asian patients had a higher (≥ 10% difference) incidence than Caucasian patients of peripheral oedema, hypertension, fatigue, PPE, proteinuria, stomatitis, thrombocytopenia, and myalgia; while Caucasian patients had a higher incidence of diarrhoea, weight decreased, nausea, vomiting, constipation, asthenia, abdominal pain, pain in extremity, and dry mouth. A larger proportion of Asian patients had a lenvatinib dose reduction compared to Caucasian patients. the median time to first dose reduction  and the average daily dose taken were lower in Asian than in Caucasian patients. 

Section 10 Date of Revision of the Text

Date of revision of text has been updated to 12/2020

Updated on 25 November 2020

File name

UK Lenvima PIL 18 Nov 2020.pdf

Reasons for updating

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

Free text change information supplied by the pharmaceutical company

Removal of the black triangle and associated text

Inclusion of osteonecrosis of the jaw

Updated on 25 November 2020

File name

ROI Lenvima PIL 26 May 2020.pdf

Reasons for updating

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

Free text change information supplied by the pharmaceutical company

Removal of the black triangle and associated text

Section 4

Inclusion of Osteonecrosis of the jaw (ONJ)

Updated on 25 November 2020

File name

UK Lenvima SmPC 18 Nov 2020.pdf

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
  • 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

Removal of the black triangle and associated text

Section 4.4:

Osteonecrosis of the jaw (ONJ)

Cases of ONJ have been reported in patients treated with lenvatinib. Some cases were reported in patients who had received prior or concomitant treatment with antiresorptive bone therapy, and/or other angiogenesis inhibitors, e.g. bevacizumab, TKI, mTOR inhibitors. Caution should therefore be exercised when lenvatinib is used either simultaneously or sequentially with antiresorptive therapy and/or other angiogenesis inhibitors.

Invasive dental procedures are an identified risk factor. Prior to treatment with lenvatinib, a dental examination and appropriate preventive dentistry should be considered. In patients who have previously received or are receiving intravenous bisphosphonates, invasive dental procedures should be avoided if possible (see section 4.8).

Section 4.8: Inclusion of osteonecrosis of the jaw as an uncommon adverse effect

Updated on 01 July 2020

File name

ROI Lenvima SmPC 26 May 2020.pdf

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 not be renewed (A)

Free text change information supplied by the pharmaceutical company

This update was to change the MAH and manufacturer to:

Eisai GmbH

Edmund-Rumpler-Straße 3   

60549 Frankfurt am Main

Germany  

The date of revision has been updated in line with EMA guidance to the date of implementation by the MAH, rather than the date of approval

Updated on 01 July 2020

File name

ROI Lenvima PIL 26 May 2020.pdf

Reasons for updating

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

Free text change information supplied by the pharmaceutical company

This update was to change the MAH and manufacturer to:

Eisai GmbH

Edmund-Rumpler-Straße 3   

60549 Frankfurt am Main

Germany  

The date of revision has been updated in line with EMA guidance to the date of implementation by the MAH, rather than the date of approval

Updated on 01 July 2020

File name

UK Lenvima PIL 26 May 2020.pdf

Reasons for updating

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

Free text change information supplied by the pharmaceutical company

This update was to change the MAH and manufacturer to:

Eisai GmbH

Edmund-Rumpler-Straße 3   

60549 Frankfurt am Main

Germany

The date of revision has been updated in line with EMA guidance to the date of implementation by the MAH, rather than the date of approval

Updated on 29 June 2020

File name

ROI Lenvima PIL June 2020.pdf

Reasons for updating

  • Change to section 6 - manufacturer

Free text change information supplied by the pharmaceutical company

Eisai GmbH
Lyoner Straße 36
60528 Frankfurt am Main
Germany

 

Has changed to:

Eisai GmbH
Edmund-Rumpler-Straße 3   
60549 Frankfurt am Main
Germany

Updated on 29 June 2020

File name

ROI Lenvima SmPC Jun 2020.pdf

Reasons for updating

  • Change to section 7 - Marketing authorisation holder

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

Free text change information supplied by the pharmaceutical company

Eisai GmbH

Lyoner Straße 36

60528 Frankfurt am Main

Germany

 

Has changed to:

Eisai GmbH

Edmund-Rumpler-Straße 3   

60549 Frankfurt am Main

Germany

Updated on 29 May 2020

File name

ROI Lenvima PIL May 2020.pdf

Reasons for updating

  • Change to section 4 - possible side effects
  • Change to section 6 - what the product contains

Free text change information supplied by the pharmaceutical company

Hand foot syndrome has been changed to palmar-plantar erythrodysesthesia

Lenvatinib (as mesylate) has been changed to lenvatinib (as mesilate)

Updated on 29 May 2020

File name

ROI Lenvima PIL May 2020.pdf

Reasons for updating

  • Change to section 4 - possible side effects
  • Change to section 6 - what the product contains

Free text change information supplied by the pharmaceutical company

Hand foot syndrome has been changed to palmar-plantar erythrodysesthesia.

Lenvatinib (as mesylate) has been changed to lenvatinib (as mesilate)

 

Updated on 29 May 2020

File name

ROI Lenvima SmPC May 2020.pdf

Reasons for updating

  • Change to section 2 - Qualitative and quantitative composition
  • Change to section 4.2 - Posology and method of administration
  • Change to section 4.4 - Special warnings and precautions for use
  • Change to Section 4.8 – Undesirable effects - how to report a side effect
  • Change to section 5.2 - Pharmacokinetic properties

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

Free text change information supplied by the pharmaceutical company

The update is required for the five year renewal of the marketing authorisation for Lenvima. The sections outlined have been updated with editorial changes to ensure consistency. No additional data have been added to these sections

 

Updated on 17 October 2019

File name

ROI Lenvima PIL October 2019.pdf

Reasons for updating

  • Change to section 6 - what the product contains
  • Change to section 6 - what the product looks like and pack contents
  • Change to section 6 - date of revision

Free text change information supplied by the pharmaceutical company

Documented changes

Sections of the PIL

Changes/updates

Section 6 Contents of the pack and other information

Lenvatinib (as mesilate) has been changed to lenvatinib (as mesylate)

 

The following pack sizes have been added:       

The capsules come in blisters of polyamide/aluminium/PVC with a push through aluminium foil lidding in cartons of 30,60 or 90 hard capsules.

Not all pack sizes may be marketed

 

The date of revision of text has been updated to 10/2019

 

Updated on 17 October 2019

File name

ROI Lenvima SmPC October 2019.pdf

Reasons for updating

  • Change to section 2 - Qualitative and quantitative composition
  • Change to section 6.5 - Nature and contents of container
  • Change to section 8 - Marketing authorisation number(s)
  • 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

Documented changes

Sections of the SmPC

Changes/updates

Section 2 Qualitative and quantitative composition

Mesilate has changed to mesylate

Section 6.5 Nature and contents of container

The wording has changed to include the following:

Polyamide/Aluminium/PVC/Aluminium blisters containing 10 capsules. Each carton contains

30 ,60,or 90 hard  capsules.

 

Not all pack sizes may be marketed.

 

Section 8 Marketing authorisation number(s)

The wording has changed to include the following:

Lenvima 4mg hard capsules

EU/1/15/1002/001

EU/1/15/1002/003

EU/1/15/1002/004

 

Lenvima 10 mg hard capsules

EU/1/15/1002/002

EU/1/15/1002/005

EU/1/15/1002/006

Section 10 Date of Revision of the Text

Date of revision of text has been updated to October 2019

Updated on 29 September 2019

File name

Irish Lenvima PIL Sept 2019.pdf

Reasons for updating

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

Updated on 29 September 2019

File name

Irish Lenvima SmPC September 2019.pdf

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)

Updated on 21 August 2019

File name

Irish Lenvima SmPC June 2019 .pdf

Reasons for updating

  • Change to section 5.2 - Pharmacokinetic properties

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

Free text change information supplied by the pharmaceutical company

Section 5.2 Pharmacokinetic properties

The following text has been added to Special Populations Hepatic Impairment:

It has been determined that plasma protein binding in plasma from hepatically impaired subjects was similar to the respective matched healthy subjects and no concentration dependency was observed. See section 4.2 for dosing recommendation.

The following text has been added to Special Populations Renal Impairment:

It has been determined that plasma protein binding in plasma from renally impaired subjects was similar to the respective matched healthy subjects and no concentration dependency was observed. See section 4.2 for dosing recommendation

Section 10 Date of Revision of the Text

The date of revision of text has been updated to 06/2019

Updated on 20 February 2019

File name

Irish Lenvima PIL February 2019.pdf

Reasons for updating

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

Updated on 20 February 2019

File name

Irish Lenvima SmPC February 2019 .pdf

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 not be renewed (A)

Free text change information supplied by the pharmaceutical company

A new Marketing Authorisation Holder address has been added:

Eisai GmbH

Lyoner Straße 36

60528 Frankfurt am Main

Germany

E-mail: medinfo_de@eisai.net

Updated on 18 December 2018

File name

Irish Lenvima PIL October 2018.pdf

Reasons for updating

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

Updated on 18 December 2018

File name

Irish Lenvima SmPC October 2018 .pdf

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

Updated to amend the existing warnings on proteinuria and non-gastro-intestinal fistula

Section 4.8

Pneumothorax and nephrotic syndrome added as new adverse drug reactions (ADRs) with uncommon frequency

 

Section 10

 

The date of revision of text has been updated to 10/2018

Updated on 20 November 2018

File name

Irish Lenvima PIL September 2018.pdf

Reasons for updating

  • Change to section 4 - possible side effects

Updated on 16 November 2018

File name

Irish Lenvima PIL September 2018.pdf

Reasons for updating

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

Updated on 15 November 2018

File name

Irish Lenvima SmPC September 2018 .pdf

Reasons for updating

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

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

Free text change information supplied by the pharmaceutical company

In section 4.5 (Interactions with other medicinal products and other forms of interaction), the potential for an interaction with CY3A4/Pgp substrates has been removed following a clinical drug-drug interaction (DDI) study in cancer patients which showed that plasma concentrations of midazolam (a sensitive CYP3A and Pgp substrate) were not altered in the presence of lenvatinib. No significant drug-drug interaction is therefore expected between lenvatinib and other CYP3A4/Pgp substrates.

Updated on 28 August 2018

File name

Irish Lenvima PIL August 2018 .pdf

Reasons for updating

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

Updated on 28 August 2018

File name

Irish Lenvima SmPC August 2018 .pdf

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 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)

Updated on 02 August 2018

File name

Irish Lenvima PIL July 2018 .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 02 August 2018

File name

Irish Lenvima SmPC July 2018 .pdf

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)

Updated on 01 August 2018

File name

PIL_16570_77.pdf

Reasons for updating

  • Change to section 2 - what you need to know - warnings and precautions

Updated on 08 June 2017

Reasons for updating

  • New SPC for new product

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

Updated on 08 June 2017

Reasons for updating

  • Change to section 6.3 - Shelf life
  • 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

Documented changes

Sections of the SmPC

Changes/updates

Section 6.3

 Shelf-life has been extended from 3 to 4 years.

Section 10

The Date of revision of text has been updated

Updated on 08 June 2017

Reasons for updating

  • Change to section 6.3 - Shelf life
  • Change to section 10 - Date of revision of the text

Free text change information supplied by the pharmaceutical company

Documented changes

Sections of the SmPC

Changes/updates

Section 6.3

 Shelf-life has been extended from 3 to 4 years.

Section 10

The Date of revision of text has been updated

Updated on 05 May 2017

Reasons for updating

  • Change to section 4.8 - Undesirable effects
  • 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

Documented changes

Sections of the SmPC

Changes/updates

Section 4.8

Updated to add the adverse events “cholecystitis” with a frequency of common, and the adverse events “pancreatitis”, “amylase increased” and “lipase increased” with a frequency of uncommon, common and common respectively.

 

Section 5.2

A correction has been done to ‘Biotransformation’ subsection as below:

 

“The main metabolic pathways in humans were identified as oxidation by aldehyde oxidase, demethylation via CYP3A4, glutathione conjugation with elimination of the O-aryl group (chlorophenyl moiety), and combinations of these pathways followed by further biotransformations (e.g., glucuronidation, hydrolysis of the glutathione moiety, degradation of the cysteine moiety, and intramolecular rearrangement of the cysteinylglycine and cysteine conjugates with subsequent dimerisation).”  

Section 10

The Date of revision of text has been updated

Updated on 05 May 2017

Reasons for updating

  • Change to section 4.8 - Undesirable effects
  • Change to section 5.2 - Pharmacokinetic properties
  • Change to section 10 - Date of revision of the text

Free text change information supplied by the pharmaceutical company

Documented changes

Sections of the SmPC

Changes/updates

Section 4.8

Updated to add the adverse events “cholecystitis” with a frequency of common, and the adverse events “pancreatitis”, “amylase increased” and “lipase increased” with a frequency of uncommon, common and common respectively.

 

Section 5.2

A correction has been done to ‘Biotransformation’ subsection as below:

 

“The main metabolic pathways in humans were identified as oxidation by aldehyde oxidase, demethylation via CYP3A4, glutathione conjugation with elimination of the O-aryl group (chlorophenyl moiety), and combinations of these pathways followed by further biotransformations (e.g., glucuronidation, hydrolysis of the glutathione moiety, degradation of the cysteine moiety, and intramolecular rearrangement of the cysteinylglycine and cysteine conjugates with subsequent dimerisation).”  

Section 10

The Date of revision of text has been updated

Updated on 04 May 2017

File name

PIL_16570_77.pdf

Reasons for updating

  • New PIL for new product

Updated on 26 October 2016

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 5.2 - Pharmacokinetic properties
  • Change to section 9 - Date of first authorisation/renewal of the authorisation
  • Change to section 10 - Date of revision of the text
  • Correction of spelling/typing errors

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

Free text change information supplied by the pharmaceutical company

Documented changes

Sections of the SPC

Changes/updates

Section 4.2

 For lenvatinib related toxicities, “Adverse reactions requiring dose modification of lenvatinib” has been added as Table 1.

Section 4.4

Section 4.4 has been updated to include special warnings/precautions on non-gastrointestinal fistula and diarrhoea.

 

In addition, hypertension, haemorrhage, QT interval prolongation and Impairment of thyroid stimulating hormone suppression/Thyroid dysfunction subheading have been updated with new information.

 

Following wording regarding hypertension has been removed from the SmPC: “For patients with hypertension and proteinuria, treatment with an angiotensin-converting enzyme inhibitor or angiotensin-II receptor antagonist is preferred.”

 

 

 

 

 

 

Section 4.8

 

“Arterial thromboembolism (3.9%)” has been added to the most important serious adverse reactions.

 

New adverse reaction frequency has been added to the SmPC as “Not known (cannot be estimated from available data)”.

 

The table of adverse reactions has been updated to include      “Non-Gastrointestinal fistulak ” as a general disorder and administration site AE under “Not known” frequency.

k:  Non-gastrointestinal fistula includes cases of fistula occurring outside of the stomach and intestines such as tracheal, tracheo-oesophageal, oesophageal, female genital tract fistula, and cutaneous fistula.

New adverse reaction descriptions have been added for:

·        Gastrointestinal perforation and fistula formation

·        Non-Gastrointestinal fistulae

·        QT interval prolongation

·        Diarrhoea

 

 

 

 

 

Description of following adverse reactions have been updated:

·        Renal failure and impairment

·        Cardiac dysfunction

·        Posterior reversible encephalopathy syndrome (PRES) / Reversible posterior leucoencephalopathy syndrome (RPLS)

·        Hepatotoxicity

·        Arterial thromboembolisms

·        Haemorrhage

 

 

 

 

Section 5.2

Change of wording from severe hepatic impairment to severe renal impairment (see below):

 

Lenvatinib exposure, based on AUC0-inf data, was 101%, 90%, and 122% of normal for subjects with mild, moderate, and severe renal impairment, respectively.  It is unknown whether there is a change in the plasma protein binding in renally impaired subjects.  See section 4.2 for dosing recommendation.

 

 

 

 

Section 10

The Date of revision of text has been updated

Updated on 26 October 2016

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 5.2 - Pharmacokinetic properties
  • Change to section 9 - Date of first authorisation/renewal of the authorisation
  • Change to section 10 - Date of revision of the text
  • Correction of spelling/typing errors

Free text change information supplied by the pharmaceutical company

Documented changes

Sections of the SPC

Changes/updates

Section 4.2

 For lenvatinib related toxicities, “Adverse reactions requiring dose modification of lenvatinib” has been added as Table 1.

Section 4.4

Section 4.4 has been updated to include special warnings/precautions on non-gastrointestinal fistula and diarrhoea.

 

In addition, hypertension, haemorrhage, QT interval prolongation and Impairment of thyroid stimulating hormone suppression/Thyroid dysfunction subheading have been updated with new information.

 

Following wording regarding hypertension has been removed from the SmPC: “For patients with hypertension and proteinuria, treatment with an angiotensin-converting enzyme inhibitor or angiotensin-II receptor antagonist is preferred.”

 

 

 

 

 

 

Section 4.8

 

“Arterial thromboembolism (3.9%)” has been added to the most important serious adverse reactions.

 

New adverse reaction frequency has been added to the SmPC as “Not known (cannot be estimated from available data)”.

 

The table of adverse reactions has been updated to include      “Non-Gastrointestinal fistulak ” as a general disorder and administration site AE under “Not known” frequency.

k:  Non-gastrointestinal fistula includes cases of fistula occurring outside of the stomach and intestines such as tracheal, tracheo-oesophageal, oesophageal, female genital tract fistula, and cutaneous fistula.

New adverse reaction descriptions have been added for:

·        Gastrointestinal perforation and fistula formation

·        Non-Gastrointestinal fistulae

·        QT interval prolongation

·        Diarrhoea

 

 

 

 

 

Description of following adverse reactions have been updated:

·        Renal failure and impairment

·        Cardiac dysfunction

·        Posterior reversible encephalopathy syndrome (PRES) / Reversible posterior leucoencephalopathy syndrome (RPLS)

·        Hepatotoxicity

·        Arterial thromboembolisms

·        Haemorrhage

 

 

 

 

Section 5.2

Change of wording from severe hepatic impairment to severe renal impairment (see below):

 

Lenvatinib exposure, based on AUC0-inf data, was 101%, 90%, and 122% of normal for subjects with mild, moderate, and severe renal impairment, respectively.  It is unknown whether there is a change in the plasma protein binding in renally impaired subjects.  See section 4.2 for dosing recommendation.

 

 

 

 

Section 10

The Date of revision of text has been updated

Updated on 31 December 2015

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 31 December 2015

Reasons for updating

  • New SPC for new product

Free text change information supplied by the pharmaceutical company

None provided