TAGRISSO 40 mg and 80mg film-coated tablets

*
Pharmacy Only: Prescription

Updated on 15 February 2024

File name

20240208 Package Leaflet IE MT Tagrisso Tablets 40 mg 80 mg Skin hyperpigmentation ONC 24 0002.pdf

Reasons for updating

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

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4.      Possible side effects

[..]

Uncommon (may affect up to 1 in 100 people)

  • Skin greying or darkening (hyperpigmentation).

[..]

Updated on 15 February 2024

File name

20240208 SPC IE MT Tagrisso Tablets 40 mg 80 mg Skin hyperpigmentation ONC 24 0001.pdf

Reasons for updating

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

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'Skin hyperpigmentation' added to Table 2 in section 4.8.

Updated on 15 February 2024

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20240208 SPC IE MT Tagrisso Tablets 40 mg 80 mg Skin hyperpigmentation ONC 24 0001.pdf

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

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'Skin hyperpigmentation' added to Table 2 in section 4.8.

Updated on 19 October 2023

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20230928 SPC IE MT Tagrisso Tablets 40 mg 80 mg ADAURA OS ONC 23 0037.pdf

Reasons for updating

  • Change to section 5.1 - Pharmacodynamic properties

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Updated on 06 October 2023

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20230928 SPC IE MT Tagrisso Tablets 40 mg 80 mg ADAURA OS ONC 23 0036.pdf

Reasons for updating

  • Change to section 5.1 - Pharmacodynamic properties

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Updated on 28 July 2023

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20230726 SPC IE MT Tagrisso Tabs 40mg80 mg TEN OP Postcode ONC 23 0021.pdf

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

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4.2 Posology and method of administration

[..]

Table 1. Recommended dose modifications for TAGRISSO

[..]

4.4     Special warnings and precautions for use

[..]

Interstitial Lung Disease (ILD)

[..]

ILD or ILD-like adverse reactions were reported in 3.87% of the 1479 patients who received TAGRISSO in the ADAURA, FLAURA and AURA studies. Five fatal cases were reported in the locally advanced or metastatic setting. No fatal cases were reported in the adjuvant setting. The incidence of ILD was 10.9 11.3% in patients of Japanese ethnicity, 1.6% in patients of Asian ethnicity and 2.5% in non-Asian patients (see section 4.8).

[..]

Stevens Johnson syndrome (SJS) Severe Cutaneous Adverse Reactions (SCARs)

Case reports of Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) have been reported with frequency categories of rarely and not known, respectively, in association with TAGRISSO treatment. Before initiating treatment, patients should be advised of signs and symptoms of SJS and TEN. If signs and symptoms suggestive of SJS or TEN appear, TAGRISSO should be interrupted. TAGRISSO should be discontinued immediately if SJS or TEN are diagnosed.

[..]

Table 2. Adverse reactions reported in ADAURA, FLAURA and AURA studiesa

[..]

10.      DATE OF REVISION OF THE TEXT

06 October 2022 26 July 2023


Detailed information on this medicinal product is available on the website of the European Medicines Agency http://www.ema.europa.eu.

 

ONC 22 0023 ONC 23 0021

Updated on 28 July 2023

File name

20230726 Package Leaflet IE MT Tagrisso Tabs 40mg80 mg TEN OP Postcode ONC 23 0022.pdf

Reasons for updating

  • Change to section 4 - possible side effects
  • Change to section 6 - manufacturer

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4. Possible side effects

[..]

Serious side effects

[..]

·              Stevens-Johnson syndrome and toxic epidermal necrolysis, which can appear as reddish target-like macules or circular patches often with central blisters on the trunk, skin peeling, ulcers of mouth, throat, nose, genitals and eyes and be preceded by fever and flu-like symptoms. This side effect Stevens-Johnson syndrome is rare: it may affect up to 1 in 1000 people. The frequency of toxic epidermal necrolysis cannot be determined as cases have only been reported since marketing TAGRISSO.

[..]

Other side effects

[..]

Common

[..]

·              Abnormal blood test results related to Increase of a substance in the blood called creatine phosphokinase (an enzyme released into the blood when muscle is damaged).

[..]

6. Contents of the pack and other information

[..]

Manufacturer

AstraZeneca AB

Gärtunavägen

SE‑151 152 85 57 Södertälje

Sweden


Updated on 17 October 2022

File name

20221006 SPC IE MT Tagrisso Tablets 40 mg 80 mg ODIN ONC 22 0023.pdf

Reasons for updating

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

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Updated on 28 September 2022

File name

20220919 Package Leaflet IE MT Tagrisso Tablets 40 mg 80 mg EU PSUR ONC 22 0021.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 28 September 2022

File name

20220324 Package Leaflet IE MT Tagrisso Tablets 40 mg 80 mg Renewal ONC 22 0008.pdf

Reasons for updating

  • New PIL for new product

Updated on 28 September 2022

File name

20220919 SPC IE MT Tagrisso Tablets 40 mg 80 mg EU PSUR ONC 22 0020.pdf

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)

Updated on 31 March 2022

File name

20220324 SPC IE MT Tagrisso Tablets 40 mg 80 mg Renewal ONC 22 0007.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

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Removal of Black Inverted Triangle

Change to section 4.8 

Change to section 10

Updated on 01 February 2022

File name

20220127 SPC IE MT Tagrisso Tablets 40 mg 80 mg Rat Carcinogenicity ONC 22 0001.pdf

Reasons for updating

  • Change to section 4.8 - Undesirable effects
  • Change to section 5.3 - Preclinical safety data
  • Change to section 10 - Date of revision of the text

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4.8     Undesirable effects

[...]

Table 2. Adverse reactions reported in ADAURA, FLAURA and AURA studiesa

(Findings based on test results presented as CTCAE grade shifts)

Leucocytes decreasedo

Very common (65%)

1.2%

 

 

Lymphocytes decreasedo

Very common (62%)

6.1%

[...]

5.3     Preclinical safety data

The main findings observed in repeat dose toxicity studies in rats and dogs comprised atrophic, inflammatory and/or degenerative changes affecting the epithelia of the cornea (accompanied by corneal translucencies and opacities in dogs at ophthalmology examination), GI tract (including tongue), skin, and male and female reproductive tracts with secondary changes in spleen. These findings occurred at plasma concentrations that were below those seen in patients at the 80 mg therapeutic dose. The findings present following 1 month of dosing were largely reversible within 1 month of cessation of dosing with the exception of partial recovery for some of the corneal changes.

Lens fibre degeneration was found in the 104-week carcinogenicity rat study at exposures 0.2-times the human AUC, at the recommended clinical dose of 80 mg once a day. Lens opacities were first noted from week 52 of this study and showed a gradual increase in incidence and severity with increased duration of dosing. The clinical relevance of this finding cannot be ruled out.

Osimertinib penetrated the intact blood-brain barrier of the cynomolgus monkey (i.v. dosing), rat and mouse (oral administration).

Non-clinical data indicate that osimertinib and its metabolite (AZ5104) inhibit the h-ERG channel, and QTc prolonging effect cannot be excluded.

Osimertinib did not cause genetic damage in in vitro and in vivo assays. Osimertinib showed no carcinogenic potential when administered orally to Tg rasH2 transgenic mice for 26 weeks.  

An increased incidence of proliferative vascular lesions (angiomatous hyperplasia and haemangioma) in the mesenteric lymph node was observed in the rat 104-week carcinogenicity study at exposures 0.2‑times the AUC at the recommended clinical dose of 80 mg once daily, and is unlikely to be relevant for humans.

 

10.     DATE OF REVISION OF THE TEXT

21 May 2021

27th January 2022

Updated on 03 June 2021

File name

20210521 SPC IE MT Tagrisso Tablets 40mg 80mg ADAURA ONC 21 0017.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 5.3 - Preclinical safety data
  • Change to section 10 - Date of revision of the text

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Update to the SmPC following the approval of a variation to extend the indication of Tagrisso to include adjuvant treatment after complete tumour resection in EGFRm NSCLC and consequentially delete the limit for a mutagenic impurity.

Updated on 18 September 2020

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2020903 SPC IE MT Tagrisso Tablets 40mg 80mg Cutaneous Vasculitis ONC 20 0030.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 02 July 2020

File name

20200625 SPC IE MT Tagrisso Tablets 40mg 80 mg AURA3 OS 70percent ONC 20 0017.pdf

Reasons for updating

  • Change to section 5.1 - Pharmacodynamic properties
  • Change to section 10 - Date of revision of the text

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Updated on 30 June 2020

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20200625 SPC IE MT Tagrisso Tablets 40mg 80 mg AURA3 OS 70% ONC 20 0017.pdf

Reasons for updating

  • Change to section 5.1 - Pharmacodynamic properties
  • Change to section 10 - Date of revision of the text

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Updated on 08 April 2020

File name

20200402 SPC IE MT Tagrisso Tablets 40mg 80mg Erythema Multiforme ONC 20 0010.pdf

Reasons for updating

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

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4.8 Undesirable effects

 Erythema multiforme added as an uncommon side effect to Table 2. Adverse reactions reported in FLAURA and AURA studies

Footnote added to Table 2 about incidence of erythema multiforme

10. DATE OF REVISION OF THE TEXT

Updated to 2 April 2020

Updated on 08 April 2020

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20200402 Package Leaflet IE MT Tagrisso Tablets 40mg 80mg Erythema Multiforme ONC 20 0009.pdf

Reasons for updating

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

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(Inserted Text; Deleted Text)

4. Possible side effects

….

Tell your doctor straight away if you notice the following serious side effects:

…..

  • Stevens-Johnson syndrome, which can appear as reddish target-like macules or circular patches often with central blisters on the trunk, skin peeling, ulcers of mouth, throat, nose, genitals and eyes and be preceded by fever and flu-like symptoms. This side effect is rare: it may affect up to 1 in 1000 people. See also Section 2.
  • Target lesions, which are skin reactions that look like rings (suggestive of Erythema multiforme). This side effect is uncommon: it may affect up to 1 in 100 people.

This leaflet was last revised in September 2019 April 2020.

Updated on 18 March 2020

File name

20200312 SPC IE MT Tagrisso Tablets 40mg 80mg FLAURA OS ONC 20 0006.pdf

Reasons for updating

  • Change to section 5.1 - Pharmacodynamic properties
  • Change to section 8 - Marketing authorisation number(s)
  • Change to section 10 - Date of revision of the text

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The following significant changes were made:

Section 5.1 Pharmacodynamic properties

Overall survival (OS) data from interim analysis replaced with final data in text and in Table  3.

% patients alive – 24 and 36 months data added, 18-month % in Tagrisso arm corrected.

Kaplan-Meyer OS curve added as Figure 2.

8. MARKETING AUTHORISATION NUMBER

Description added to authorisation numbers, as per below in green (Section 8), for clarity and to minimise risk of errors.

EU/1/16/1086/001 40 mg 30 film-coated tablets

EU/1/16/1086/002 80 mg 30 film-coated tablets

EU/1/16/1086/003 40 mg 28 film-coated tablets

EU/1/16/1086/004 80 mg 28 film-coated tablets

10 DATE OF REVISION OF THE TEXT

Updated to 12 March 2020.

Updated on 06 November 2019

File name

20191024-spc-im-tagrisso-tablets-40mg 80mg-renal update ONC 19 0013.pdf

Reasons for updating

  • Change to section 4.2 - Posology and method of administration
  • Change to section 5.2 - Pharmacokinetic properties

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Section 4.2 Posology and method of administration: Updated Renal Impairment section with information based on clinical studies and population PK analysis. 

Section 5.2 Pharmacokinetic properties: Addition of data from renal impairment study.

Updated on 25 September 2019

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Package Leaflet-im-tagrisso-tablets-40mg 80mg-Onychalgia update ONC 19 0008.pdf

Reasons for updating

  • Change to section 4 - possible side effects

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Under 'other side effects' the word 'pain' was included for skin and nail problems.

'Skin and nail problems - signs may include pain'

Updated on 25 September 2019

File name

SPC-im-tagrisso-tablets-40mg 80mg-Onychalgia update ONC 19 0007.pdf

Reasons for updating

  • Change to section 4.8 - Undesirable effects

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Section 4.8 Undesirable effects

'Onychalgia' added under Table 2 section h, as a possible skin and subcutanous tissue disorder adverse reaction.

Updated on 30 August 2019

File name

Package Leaflet-im-tagrisso-tablets-40mg 80mg-SJS update ONC 19 0004.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 4 - how to report a side effect
  • Change to section 6 - manufacturer
  • Change to section 6 - date of revision

Updated on 29 August 2019

File name

SPC-im-tagrisso-tablets-40mg 80mg-SJS update ONC 19 0003.pdf

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 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)

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Section 4.2 Posology and method of administration

Change in dose modification after Interstitial Lung Disease (ILD) with cross-reference to Section 4.4:

Table 1 – Permanently dDiscontinue TAGRISSO (see Section 4.4)
 

Section 4.4 Warnings and precautions
ILD

Last paragraph revised to allow possible reintroduction of TAGRISSO after ILD after careful consideration of the individual patient’s benefit-risk (changed from permanent discontinuation)

 Addition of Stevens-Johnson syndrome:

Stevens-Johnson syndrome

Case reports of Stevens-Johnson syndrome (SJS) have been reported rarely in association with TAGRISSO treatment. Before initiating treatment, patients should be advised of signs and symptoms of SJS. If signs and symptoms suggestive of SJS appear, TAGRISSO should be interrupted or discontinued immediately.

 Changes in cardiac contractility:

Deletion of one sentence: Based on the available clinical trial data, it is not possible to determine a causal relationship between effects on changes in cardiac contractility and TAGRISSO.
 

Section 4.8 Undesirable effects

SJS added as a rare event in Table 2

Removal of UK adverse event reporting details and update to HPRA reporting details
 

Section 10 Date of revision of the text

Revision date updated to 26th August 2019

Updated on 10 September 2018

File name

2018-08-31 cSmPC Tagrisso 40mg and 80mg Tablets UIM ONC 18 0023.pdf

Reasons for updating

  • Change to section 4.2 - Posology and method of administration
  • 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 21 June 2018

File name

2018-06-14 cSmPC Tagrisso 40mg and 80mg Tablets UIM ONC 18 0016.docx

Reasons for updating

  • Change to section 4.5 - Interaction with other medicinal products and other forms of interaction
  • 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 19 June 2018

File name

2018-06-07-cSmPCTagrisso40mgand80mgTabletsUIMONC180013.docx

Reasons for updating

  • Change to section 4.5 - Interaction with other medicinal products and other forms of interaction
  • 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 19 June 2018

File name

2018-06-14 cPIL Tagrisso 40mg and 80mg Tablets UIM ONC 18 0017.pdf

Reasons for updating

  • Change to section 2 - interactions with other medicines, food or drink

Updated on 15 June 2018

File name

2018-06-07-cSmPCTagrisso40mgand80mgTabletsUIMONC180013.docx

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 15 June 2018

File name

2018-06-07 cPIL Tagrisso 40mg and 80mg Tablets UIM ONC 18 0014.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 2 - excipient warnings
  • Change to section 4 - possible side effects
  • Change to section 6 - what the product contains
  • Change to section 6 - date of revision

Updated on 15 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 15 September 2017

Reasons for updating

  • Change to Section 4.8 – Undesirable effects - how to report a side effect

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In section 4.8, UK ADR reporting details have been updated.

Updated on 14 September 2017

File name

PIL_17282_649.pdf

Reasons for updating

  • New PIL for new product

Updated on 14 September 2017

Reasons for updating

  • Change to section 4 - how to report a side effect

Updated on 06 September 2017

Reasons for updating

  • New SPC for medicines.ie

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

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None provided

Updated on 06 September 2017

Reasons for updating

  • New PIL for medicines.ie