Imatinib TEVA UK 100 mg and 400 mg film-coated tablets

Public Assessment Report

Decentralised Procedure

IMATINIB TEVA UK 100 MG FILM-COATED TABLETS IMATINIB TEVA UK 400 MG FILM-COATED TABLETS

(imatinib mesilate)

Procedure No: UK/H/2678/001-002/DC

UK Licence No: PL 00289/1516-1517

Teva UK Limited

PAR Imatinib Teva UK 100 mg and 400 mg film-coated tablets UK/H/2678/001-002/DC

2

LAY SUMMARY Imatinib Teva UK 100 mg film-coated tablets Imatinib Teva UK 400 mg film-coated tablets

(imatinib mesilate) This is a summary of the public assessment report (PAR) for Imatinib Teva UK 100 mg film-coated tablets (PL 00289/1516) and Imatinib Teva UK 400 mg film-coated tablets (PL 00289/1517). It explains how Imatinib Teva UK 100 mg and 400 mg film-coated tablets were assessed and their authorisation recommended, as well as their conditions of use. It is not intended to provide practical advice on how to use Imatinib Teva UK 100 mg and 400 mg film-coated tablets. These medicines will be collectively referred to as Imatinib film-coated tablets throughout the remainder of this public assessment report (PAR). For practical information about using Imatinib film-coated tablets, patients should read the package leaflet or contact their doctor or pharmacist. What is Imatinib film-coated tablets and what is it used for? Imatinib film-coated tablets are ‘generic medicines’. This means that Imatinib film-coated tablets are similar to ‘reference medicines’ already authorised in the European Union (EU) called Glivec 100 mg hard capsules and Glivec 400 mg film-coated tablets. Imatinib film-coated tablets is a treatment for adults and children for:

• Chronic myeloid leukaemia (CML). Leukaemia is a cancer of white blood cells. These white cells usually help the body to fight infection. Chronic myeloid leukaemia is a form of leukaemia in which certain abnormal white cells (named myeloid cells) start growing out of control.

• Philadelphia chromosome positive acute lymphoblastic leukaemia (Ph-positive ALL). Leukaemia is a cancer of white blood cells. These white cells usually help the body to fight infection. Acute lymphoblastic leukaemia is a form of leukaemia in which certain abnormal white cells (named lymphoblasts) start growing out of control. Imatinib film-coated tablets inhibits the growth of these cells.

Imatinib film-coated tablets is also a treatment for adults for:

• Myelodysplastic/myeloproliferative diseases (MDS/MPD). These are a group of blood diseases in which some blood cells start growing out of control. Imatinib film-coated tablets inhibits the growth of these cells in a certain subtype of these diseases.

• Hypereosinophilic syndrome (HES) and/or chronic eosinophilic leukaemia (CEL). These are blood diseases in which some blood cells (named eosinophils) start growing out of control. Imatinib film-coated tablets inhibits the growth of these cells in a certain subtype of these diseases.

• Gastrointestinal stromal tumours (GIST). GIST is a cancer of the stomach and bowels. It arises from uncontrolled cell growth of the supporting tissues of these organs.

• Dermatofibrosarcoma protuberans (DFSP). DFSP is a cancer of the tissue beneath the skin in which some cells start growing out of control. Imatinib Teva UK inhibits the growth of these cells.

How is Imatinib film-coated tablets used? Use in adults The patient’s doctor will tell them exactly how many tablets of Imatinib film-coated tablets to take.

• If the patient is being treated for CML: Depending on your condition the usual starting dose is either 400 mg or 600 mg: - 400 mg to be taken once a day,


3

- or 600 mg to be taken once a day.

• If the patient is being treated for GIST: The starting dose is 400 mg, to be taken once a day. For CML and GIST, the patient’s doctor may prescribe a higher or lower dose depending on how the patient responds to the treatment. If the patient’s daily dose is 800 mg, they should take 400 mg in the morning and 400 mg in the evening.

• If the patient is being treated for Ph-positive ALL: The starting dose is 600 mg to be taken once a day.

• If the patient is being treated for MDS/MPD: The starting dose is 400 mg, to be taken once a day.

• If the patient is being treated for HES/CEL: The starting dose is 100 mg, to be taken once a day. The patient’s doctor may decide to increase the dose to 400 mg, to be taken once a day, depending on how the patient responds to treatment.

• If you are being treated for DFSP: The dose is 800 mg per day, to be taken as 400 mg in the morning and 400 mg in the evening.

Use in children and adolescents The doctor will tell the child’s carer how many tablets of Imatinib film-coated tablets to give to their child. The amount of Imatinib film-coated tablets given will depend on the child’s condition, body weight and height. The total daily dose in children must not exceed 800 mg with CML and 600 mg with Ph+ ALL. The treatment can either be given to the child as a once-daily dose or alternatively the daily dose can be split into two administrations (half in the morning and half in the evening). When and how to take Imatinib film-coated tablets

• Take Imatinib film-coated tablets with a meal. This will help protect the patient from stomach problems when taking Imatinib Teva UK.

• Swallow the tablets with a large glass of water. If the patient is unable to swallow the tablets, they can dissolve them in a glass of still water or apple juice:

• Use about 50 ml for each 100 mg tablet or 200 ml for each 400 mg tablet. • Stir with a spoon until the tablets have completely dissolved. • Once the tablet has dissolved, drink everything in the glass straight away. Traces of the dissolved

tablets may be left behind in the glass. The tablet can be divided into equal doses by breaking it through the score line in case the patient’s doctor has prescribed them or their child a dose where half of a tablet is needed. How long to take Imatinib film-coated tablets The patient must keep taking Imatinib film-coated tablets every day for as long as their doctor tells them.

These medicines can only be obtained with a prescription.


4

How do Imatinib film-coated tablets work? Imatinib film-coated tablets contain an active ingredient called imatinib. These medicines work by inhibiting the growth of abnormal cells in chronic myeloid leukaemia (CML). Leukaemia is a cancer of white blood cells. These white cells usually help the body to fight infection. Chronic myeloid leukaemia is a form of leukaemia in which certain abnormal white cells (named myeloid cells) start growing out of control. How has Imatinib film-coated tablets been studied? Because Imatinib film-coated tablets are generic medicines, studies in patients have been limited to tests to determine that they are bioequivalent to the reference medicines, Glivec 100 mg hard capsules and Glivec 400 mg film-coated tablets. Two medicines are bioequivalent when they produce the same levels of the active substance in the body. What are the benefits and risks of Imatinib film-coated tablets? Because Imatinib film-coated tablets are generic medicines that are bioequivalent to the reference medicines, their benefits and risks are taken as being the same as the reference medicines. Why is Imatinib film-coated tablets approved? It was concluded that, in accordance with EU requirements, Imatinib film-coated tablets have been shown to have comparable quality and to be bioequivalent to Glivec 100 mg hard capsules and Glivec 400 mg film-coated tablets. Therefore, the view was that, as for Glivec 100 mg hard capsules and Glivec 400 mg film-coated tablets, the benefit outweighs the identified risk. What measures are being taken to ensure the safe and effective use of Imatinib film-coated tablets? Safety information has been included in the Summary of Product Characteristics and the package leaflet for Imatinib film-coated tablets, including the appropriate precautions to be followed by healthcare professionals and patients. Other information about Imatinib film-coated tablets Austria, Belgium, Bulgaria, Cyprus, the Czech Republic, Germany, Estonia, Greece, Spain, Finland, France, Hungary, Ireland, Iceland, Italy, Lithuania, Luxembourg, Latvia, Malta, the Netherlands, Norway, Poland, Portugal, Romania, Sweden, Slovenia, Slovakia and the UK agreed to grant Marketing Authorisations for Imatinib Teva UK 100 mg and 400 mg film-coated tablets on 13 June 2013. Marketing Authorisations were granted in the UK on 19 December 2013. The full PAR for Imatinib film-coated tablets follows this summary. For more information about treatment with Imatinib film-coated tablets, read the package leaflet or contact your doctor or pharmacist. This summary was last updated in September 2016.


5

TABLE OF CONTENTS

I Introduction Page 6 II Quality aspects Page 8 III Non-clinical aspects Page 10 IV Clinical aspects Page 10 V User consultation Page 12 VI Overall conclusion, benefit/risk assessment and

recommendation Page 12

Table of content of the PAR update for MRP and DCP Page 18 Annex 1 Page 19


6

I INTRODUCTION Based on the review of the data on quality, safety and efficacy, the Member States considered that the applications for Imatinib Teva UK 100 mg and 400 mg film-coated tablets (PL 00289/1516-1517; UK/H/2678/001-002/DC) could be approved. The applications were submitted via the Decentralised Procedure, with the UK as Reference Member State (RMS), and Austria, Belgium, Bulgaria, Cyprus, the Czech Republic, Germany, Estonia, Greece, Spain, Finland, France, Hungary, Ireland, Iceland, Italy, Lithuania, Luxembourg, Latvia, Malta, the Netherlands, Norway, Poland, Portugal, Romania, Sweden, Slovenia and Slovakia as Concerned Member States (CMS). These products can only be obtained with a prescription (legal classification POM). These applications were made under the Decentralised Procedure (DCP), according to Article 10(1) of Directive 2001/83/EC, as amended, claiming to be generic medicinal products of the originator product Glivec 100 mg hard capsules (Novartis Europharm Limited), which was initially granted a Marketing Authorisation in the EU, via the Centralised Procedure, on 07 November 2001. The reference product for the 400 mg strength product is Glivec 400 mg film-coated tablets (Novartis Europharm Limited), which was granted a Marketing Authorisation in the EU, via the Centralised Procedure, on 11 November 2003. The reference product used in the bioequivalence study is Glivec 400 mg film-coated tablets (Novartis Europharm Limited). Imatinib Teva UK is indicated for the treatment of:

• Adult and paediatric patients with newly diagnosed Philadelphia chromosome (bcr-abl) positive (Ph+) chronic myeloid leukaemia (CML) for whom bone marrow transplantation is not considered as the first line of treatment.

• Adult and paediatric patients with Ph+ CML in chronic phase after failure of interferon-alpha therapy or in accelerated phase or blast crisis.

• Adult and paediatric patients with newly diagnosed Philadelphia chromosome positive acute lymphoblastic leukaemia (Ph+ ALL) integrated with chemotherapy.

• Adult patients with relapsed or refractory Ph+ ALL as monotherapy. • Adult patients with myelodysplastic/myeloproliferative diseases (MDS/MPD) associated with

platelet-derived growth factor receptor (PDGFR) gene re-arrangements. • Adult patients with advanced hypereosinophilic syndrome (HES) and/or chronic eosinophilic

leukaemia (CEL) with FIP1L1-PDGFRα rearrangement. The effect of imatinib on the outcome of bone marrow transplantation has not been determined. Imatinib Teva UK is indicated for:

• The treatment of adult patients with Kit (CD 117) positive unresectable and/or metastatic malignant gastrointestinal stromal tumours (GIST).

• The adjuvant treatment of adult patients who are at significant risk of relapse following resection of Kit (CD117)-positive GIST. Patients who have a low or very low risk of recurrence should not receive adjuvant treatment.

• The treatment of adult patients with unresectable dermatofibrosarcoma protuberans (DFSP) and adult patients with recurrent and/or metastatic DFSP who are not eligible for surgery.

In adult and paediatric patients, the effectiveness of imatinib is based on overall haematological and cytogenetic response rates and progression-free survival in CML , on haematological and cytogenetic response rates in Ph+ ALL, MDS/MPD, on haematological response rates in HES/CEL and on objective response rates in adult patients with unresectable and/or metastatic GIST and DFSP and on recurrence-free survival in adjuvant GIST. The experience with Imatinib Teva UK in patients with MDS/MPD associated with PDGFR gene re-arrangements is very limited (see section 5.1 of the SmPC). Except in newly diagnosed chronic phase CML, there are no controlled trials demonstrating a clinical benefit or increased survival for these diseases.


7

These products contain the active substance imatinib. Imatinib is a protein-tyrosine kinase inhibitor which targets the Bcr-Abl tyrosine kinase, resulting in inhibition of proliferation and induction of apoptosis. Imatinib also inhibits the receptor tyrosine kinases for several receptor tyrosine kinases including Kit, the receptor for stem cell factor (SCF), the discoidin domain receptors (DDR1 and DDR2), the colony stimulating factor receptor (CSF-1R) and the platelet-derived growth factor receptors alpha and beta (PDGFR-alpha and PDGFR-beta). Imatinib can also inhibit cellular events mediated by activation of these receptor kinases. No non-clinical studies and, with the exception of the bioequivalence study, no new clinical studies were conducted, which is acceptable given that these applications were based on being generic medicinal products of an originator product that has been licensed for over 10 years. A bioequivalence study was performed, which compared the pharmacokinetics of the test product Imatinib TEVA 400 mg film-coated tablets to those of the reference product Glivec 400 mg film-coated tablets (Novartis Europharm Limited). The bioequivalence study was carried out in accordance with Good Clinical Practice (GCP). The RMS has been assured that acceptable standards of Good Manufacturing Practice are in place for this product type at all sites responsible for the manufacture, assembly and batch release of these products. The RMS and CMS considered that the applications could be approved at the end of procedure on 13 June 2013. After a subsequent national phase, marketing authorisations were granted in the UK on 19 December 2013.


8

II QUALITY ASPECTS II.1 Introduction Each film-coated tablet contains 100mg or 400mg of imatinib (as imatinib mesilate), as the active ingredient. Other ingredients consist of the pharmaceutical excipients, as follows:

Mannitol, crospovidone, sodium starch glycolate (type A), magnesium stearate, colloidal anhydrous silica

Tablet core:

Macrogol poly(vinyl alcohol) grafted copolymer, poly(vinyl alcohol), silica, talc, titanium dioxide (E171), iron oxide yellow (E172), iron oxide red (E172)

Film-coating:

The finished product is presented in the following packaging and pack sizes:

• Polyvinyl chloride/polyethylene/polyvinylidene chloride/aluminium blisters in pack sizes of 60 or 120 film-coated tablets

• Oriented polyamide/polyvinyl chloride/aluminium perforated unit dose blisters in pack sizes of 20 x 1, 60 x 1, 120 x 1 and 180 x1 film-coated tablets

Satisfactory specifications and Certificates of Analysis have been provided for all packaging components. All primary packaging complies with the current European regulations concerning materials in contact with food. II.2 Drug Substance rINN: Imatinib mesilate Chemical name: 4-[(4-Methyl-1-piperazinyl)methyl]-N-[4-methyl-3-[[4-(3-pyridinyl)-2-

pyrimidinyl]aminophenyl]benzamide methanesulfonate salt Structure:

Molecular formula: C29H31N7O_CH4SO3 Molecular weight: 589.7 (mesylate); 493.6 (free base) Appearance: Off-white or slightly yellowish crystalline powder Solubility: Freely soluble in various aqueous buffers, soluble in methanol and slightly soluble

in ethanol


9

An Active Substance Master File (ASMF) has been provided by the active substance manufacturer, covering the manufacture and control of the active substance imatinib mesilate. Synthesis of the drug substance from the designated starting materials has been adequately described and appropriate in-process controls and intermediate specifications are applied. Satisfactory specification tests are in place for all starting materials and reagents and these are supported by relevant certificates of analysis. Appropriate proof-of-structure data have been supplied for the active substance. All potential known impurities have been identified and characterised. An appropriate specification is provided for the active substance. Analytical methods have been appropriately validated and are satisfactory for ensuring compliance with the relevant specifications. Satisfactory Certificates of Analysis have been provided for all working standards. Batch analysis data are provided and comply with the proposed specification. Suitable specifications have been provided for all packaging used. The primary packaging has been shown to comply with current guidelines concerning contact with food. Appropriate stability data have been generated to support a suitable retest period when stored in the proposed packaging. II.3. Medicinal Product Pharmaceutical Development The objective of the development programme was to formulate globally acceptable and stable products that could be considered generic medicinal products of the currently licensed products of Glivec 100 mg hard capsules and Glivec 400 mg film-coated tablets (Novartis Europharm Limited). A satisfactory account of the pharmaceutical development has been provided. With the exception of the Macrogol poly(vinyl alcohol) grafted copolymer and the yellow and red iron oxides, which comply with suitable in-house specifications, all excipients used comply with their respective European Pharmacopoeia monographs. None of the excipients are sourced from animal or human origin. No genetically modified organisms (GMO) have been used in the preparation of this product. Manufacture of the product Satisfactory batch formulae have been provided for the manufacture of the products, along with an appropriate account of the manufacturing process. Suitable in-process controls are in place to ensure the quality of the finished product. Process validation has been carried out on two commercial-scale batches of each strength of finished product. The results are satisfactory. Finished Product Specification The finished product specifications proposed are acceptable. Test methods have been described that have been adequately validated. Batch data have been provided that comply with the release specifications. Certificates of Analysis have been provided for all working standards used. Stability of the product Stability studies were performed, in accordance with current guidelines, on batches of finished product manufactured by the finished product manufacturer and packed in the packaging proposed for


10

marketing. The results from these studies support a shelf-life of 2 years with no special storage conditions. Bioequivalence/bioavailability A bioequivalence study was performed, which compared the pharmacokinetics of the test product Imatinib TEVA UK 400 mg film-coated tablets to those of the reference product Glivec 400 mg film-coated tablets (Novartis Europharm Limited). Summary of Product Characteristics (SmPC), Patient Information Leaflet (PIL) and Labels The SmPCs, PILs and text versions of the labels are acceptable from a pharmaceutical perspective. Marketing Authorisation Application (MAA) form The MAA forms are satisfactory from a pharmaceutical perspective. Quality Overall Summary (Expert report) The pharmaceutical expert report has been written by an appropriately qualified person and is a suitable summary of the pharmaceutical dossier. II.4 Discussion on chemical, pharmaceutical and biological aspects The grant of Marketing Authorisations is recommended. III NON-CLINICAL ASPECTS III.1 Introduction As the pharmacodynamic, pharmacokinetic and toxicological properties of imatinib mesilate are well-known, no further non-clinical studies are required and none have been provided. The applicant’s non-clinical expert report has been written by an appropriately qualified person and is satisfactory, providing an appropriate review of the product’s pharmacology and toxicology. III.2 Pharmacology Not applicable for this product type. Refer to section ‘III.1; Introduction’ detailed above. III.3 Pharmacokinetics Not applicable for this product type. Refer to section ‘III.1; Introduction’ detailed above. III.4 Toxicology Not applicable for this product type. Refer to section ‘III.1; Introduction’ detailed above. III.5 Ecotoxicity/environmental risk assessment (ERA) Suitable justification has been provided for the non-submission of an environmental risk assessment. As this product is intended for generic substitution with products that are currently marketed, no increase in environmental burden is expected. There are no objections to the approval of these products from a non-clinical viewpoint. III.3 CLINICAL ASPECTS IV.1 Introduction The clinical pharmacology of imatinib mesilate is well-known. With the exception of data from the bioequivalence study detailed below, no new pharmacodynamics or pharmacokinetic data are provided or are required for these applications. No new efficacy or safety studies have been performed and none are required for this type of application. A comprehensive review of the published literature has been provided by the applicant,


11

citing the well-established clinical pharmacology, efficacy and safety of imatinib mesilate. IV.2 Pharmacokinetics In support of these applications, the Marketing Authorisation Holder has submitted the following bioequivalence study: A single-dose, randomised, two-period, two-sequence, two-treatment, crossover study to compare the pharmacokinetic profile of Imatinib Teva UK 400 mg film-coated tablets (Test; A) with Glivec 400 mg film-coated tablets (Reference; B) in healthy adult subjects, under fed conditions. Study participants were given each treatment after a high fat, high calorie breakfast and with 240 ml of room temperature water. Blood samples were collected for the measurement of pharmacokinetic parameters pre-dose and up to 48 hours post dose. Each treatment regimen was separated by a 7-day washout period. The main pharmacokinetic results are presented in the table below:

Compared with the reference product, the 90 % confidence intervals for the test product are within 80.00-125.00 % for AUC and Cmax. Imatinib Teva UK 400 mg film-coated tablets can, therefore, be considered to be bioequivalent with Glivec 400 mg film-coated tablets.

As these products meet the bio-waiver criteria specified in the Guideline on the Investigation of Bioequivalence (CPMP/EWP/QWP/1401/98 Rev.1/Corr**), the results and conclusions of the bioequivalence study on the 400 mg strength can be extrapolated to the 100 mg strength film-coated tablets. IV.3 Pharmacodynamics No new pharmacodynamic data were submitted and none were required for applications of this type IV.4 Clinical efficacy No new data on efficacy have been submitted and none are required for this type of application. IV.5 Clinical safety With the exception of the data submitted during the bioequivalence study, no new safety data were submitted and none were required. No new or unexpected safety issues were raised by the bioequivalence data. SmPC, PIL and Labels The SmPCs, PILs and text versions of the labels are acceptable from a clinical perspective.


12

IV.6 Risk Management Plan (RMP) and Pharmacovigilance System The Pharmacovigilance System, as described by the applicant, fulfils the requirements and provides adequate evidence that the applicant has the services of a qualified person responsible for pharmacovigilance, and has the necessary means for the notification of any adverse reaction suspected of occurring either in the Community or in a third country. Suitable justification has been provided for not submitting a risk management plan for this product. Clinical Expert Report The clinical expert report has been written by an appropriately qualified physician and is a suitable summary of the clinical aspects of the dossier. IV.7 Discussion on the clinical aspects The grant of Marketing Authorisations is recommended. V USER CONSULTATION A package leaflet has been evaluated via a user consultation study in accordance with the requirements of Articles 59(3) and 61(1) of Directive 2001/83/EC, as amended. The language used for the purpose of user testing the package information leaflet (PIL) was English. The results show that the package leaflet meets the criteria for readability as set out in the Guideline on the readability of the label and package leaflet of medicinal products for human use. VI OVERALL CONCLUSION AND BENEFIT-RISK ASSESSMENT QUALITY The important quality characteristics of Imatinib Teva UK 100 mg and 400 mg film-coated tablets are well-defined and controlled. The specifications and batch analytical results indicate consistency from batch to batch. There are no outstanding quality issues that would have a negative impact on the benefit-risk balance. NON-CLINICAL No new non-clinical data were submitted and none are required for applications of this type. EFFICACY Bioequivalence has been demonstrated between the applicant’s products and the reference products. SAFETY No new or unexpected safety concerns arose from these applications. PRODUCT LITERATURE The SmPCs, PILs and text versions of labelling are satisfactory and consistent with those for the reference products. BENEFIT-RISK ASSESSMENT The quality of the products is acceptable, and no new non-clinical or clinical safety concerns have been identified. Extensive clinical experience with imatinib mesilate is considered to have demonstrated the therapeutic value of the compound. The benefit-risk assessment is, therefore, considered to be positive.


13

Summary of Product Characteristics (SmPC), Patient Information Leaflet (PIL) and Labels In accordance with Directive 2010/84/EU the Summaries of Product Characteristics (SmPC) and Patient Information Leaflets (PIL) for products granted Marketing Authorisations at a national level are available on the MHRA website. The following text is the approved label text for Imatinib Teva UK 100 mg film-coated tablets (PL 00289/1516). No label mock-ups have been provided for this product. In accordance with medicines legislation, the product shall not be marketed in the UK until approval of the label mock-ups has been obtained.


14


15


16

The following text is the approved label text for Imatinib Teva UK 400 mg film-coated tablets (PL 00289/1517). No label mock-ups have been provided for this product. In accordance with medicines legislation, the product shall not be marketed in the UK until approval of the label mock-ups has been obtained.


17


18


19

Table of content of the PAR update for MRP and DCP

Steps taken after the initial procedure with an influence on the Public Assessment Report

Scope Procedure

number Product information affected

Date of start of the procedure

Date of end of procedure

Approval/ non approval

Assessment report attached Y/N (version)

To update sections 4.1, 4.2, 4.4, 4.5, 4.6 & 5.1 of the SmPC to bring it in line with the reference product Glivec and QRD template. The following indications are introduced: “adult patients with newly diagnosed Philadelphia chromosome (bcr-abl) positive (Ph+) chronic leukemia (CML) for whom bone marrow transplantation is not considered first line treatment” And “adult patients with Ph+ CML in chronic phase after failure of interferon-alpha therapy, or in accelerated phase or blast crisis”.

UK/H/2678/001-002/IB/0015

Leaflet and SmPC.

28/07/2016 24/08/2016 Approved Yes-see annex 1


20

ANNEX 1 Our Reference: PL 00289/1516-0017 PL 00289/1517-0019 Product: Imatinib Teva UK 100 mg film-coated tablets

Imatinib Teva UK 400 mg film-coated tablets Marketing Authorisation Holder: Teva UK Limited Active Ingredient(s): Imatinib mesilate Type of Procedure: Mutual Recogniton Submission Type: Variation Submission Category: Type IB Submission Complexity: Standard EU Procedure Number (if applicable): UK/H/2678/001-002/IB/0015 Reason: To update sections 4.1, 4.2, 4.4, 4.5, 4.6 & 5.1 of the SmPC to bring it in line with the reference product Glivec and QRD template. The following indications are introduced: “adult patients with newly diagnosed Philadelphia chromosome (bcr-abl) positive (Ph+) chronic leukemia (CML) for whom bone marrow transplantation is not considered first line treatment” And “adult patients with Ph+ CML in chronic phase after failure of interferon-alpha therapy, or in accelerated phase or blast crisis”. Supporting Evidence Revised SmPC fragments and patient information leaflets (PILs). Evaluation The proposed changes to the SmPC and PILs are acceptable. The updated SmPC fragments and PILs have been incorporated into the Marketing Authorisations. Conclusion Approved on 24 August 2016.

Imatinib TEVA UK 100 mg and 400 mg film-coated tablets

Documents

Transcript of Imatinib TEVA UK 100 mg and 400 mg film-coated tablets