Pradaxa 110 mg hard capsules
*Company:
Boehringer Ingelheim LimitedStatus:
No Recent UpdateLegal Category:
Product subject to medical prescription which may be renewed (B)Active Ingredient(s):
*Additional information is available within the SPC or upon request to the company
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NP-IE-100713 Cardiovascular PRADAXA Pradaxa Pediatrics RMM - Prescriber Guide - IE.pdf
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NP-IE-100713 Cardiovascular PRADAXA Pradaxa Pediatrics RMM - Prescriber Guide - IE.pdf
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NP-IE-100713 Cardiovascular PRADAXA Pradaxa Pediatrics RMM - Prescriber Guide - IE.pdf
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PAC text -pradaxa-capsules-II-147-G.pdf
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Updated on 02 January 2024
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IE-MT-NI - PIL text 110 mg capsules – Var-II-147-G.pdf
Reasons for updating
- Change to section 3 - how to take/use
- Change to section 4 - possible side effects
- Change to section 4 - how to report a side effect
- Change to section 6 - date of revision
Updated on 02 January 2024
File name
P1;110 mg-EU-SPC-48.pdf
Reasons for updating
- Change to section 2 - Qualitative and quantitative composition
- Change to section 3 - Pharmaceutical form
- Change to section 4.1 - Therapeutic indications
- Change to section 4.2 - Posology and method of administration
- Change to section 4.3 - Contraindications
- Change to section 4.4 - Special warnings and precautions for use
- Change to section 4.5 - 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 4.8 – Undesirable effects - how to report a side effect
- Change to section 4.9 - Overdose
- Change to section 5.1 - Pharmacodynamic properties
- Change to section 5.2 - Pharmacokinetic properties
- Change to section 6.5 - Nature and contents of container
- Change to section 9 - Date of first authorisation/renewal of the authorisation
- Change to section 10 - Date of revision of the text
Legal category:Product subject to medical prescription which may be renewed (B)
Free text change information supplied by the pharmaceutical company
- Section 4.1: Update to the indication for paediatric patients as follows:
‘Treatment of venous thromboembolic events (VTE) and prevention of recurrent VTE in paediatric patients from birth the time the child is able to swallow soft food to less than 18 years of age.’
- Section 4.2: Deletion of the statement ‘
Pradaxa powder and solvent for oral solution should only be used in children aged less than 1 year.’ - Section 5.2: Update to the renal insufficiency/CrCL information in the ‘Special populations’ section
- Sections 2, 3, 4.1, 4.2, 4.3, 4.4, 4.5, 4.6, 4.8, 4.9, 5.1, 5.2, 6.5, 9: Editorial/format updates
- Section 10: The date of revision has been updated to 11 December 2023
- Editorial/format updates in line with the QRD template have also been made throughout the SmPCs.
Updated on 02 March 2023
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P1;110 mg-EU-SPC-47.pdf
Reasons for updating
- Document format updated
Legal category:Product subject to medical prescription which may be renewed (B)
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NP-IE-100605 Cardiovascular PRADAXA Paediatric Prescriber Guide - IE.pdf
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Updated on 22 February 2022
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IE-MT-NI – PIL text 110mg capsules – Var 128.pdf
Reasons for updating
- Change to section 3 - how to take/use
- Change to section 6 - date of revision
Updated on 22 February 2022
File name
P1;110 mg-EU-SPC-47.pdf
Reasons for updating
- Change to section 4.2 - Posology and method of administration
- Change to section 10 - Date of revision of the text
Legal category:Product subject to medical prescription which may be renewed (B)
Free text change information supplied by the pharmaceutical company
The SmPCs have been updated in the following sections
- Section 4.2: Update to the dosing table scheme (no change to the dose) for the treatment of VTE and prevention of recurrent VTE in paediatric patients, including other minor clarification updates
- Section 10: The date of revision has been updated
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NP-IE-100491 Cardiovascular PRADAXA - Paediatric Prescriber Guide IE Version V2 .pdf
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- Add New Doc
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PAC - 316506-02 - 15.02.2021 - PCP046209-002 - AMT 103919 - CROPPED.pdf
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Updated on 11 January 2022
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IE-MT-NI – PIL text 110mg – paed.+IA-125g+Brexit+UK(NI).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 - use in children and adolescents
- Change to section 2 - interactions with other medicines, food or drink
- Change to section 2 - pregnancy, breast feeding and fertility
- Change to section 3 - use in children/adolescents
- Change to section 3 - how to take/use
- Change to section 3 - overdose, missed or forgotten doses
- Change to section 4 - possible side effects
- Change to section 4 - how to report a side effect
- Change to section 6 - what the product looks like and pack contents
- Change to section 6 - marketing authorisation holder
- Change to section 6 - manufacturer
- Change to section 6 - date of revision
- Change to other sources of information section
Updated on 11 January 2022
File name
P1;110 mg-EU-SPC-46.pdf
Reasons for updating
- Change to section 3 - Pharmaceutical form
- Change to section 4.1 - Therapeutic indications
- Change to section 4.2 - Posology and method of administration
- Change to section 4.3 - Contraindications
- Change to section 4.4 - Special warnings and precautions for use
- Change to section 4.5 - Interaction with other medicinal products and other forms of interaction
- Change to section 4.7 - Effects on ability to drive and use machines
- Change to section 4.8 - Undesirable effects
- Change to section 4.9 - Overdose
- 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 6.1 - List of excipients
- Change to section 6.5 - Nature and contents of container
- 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 be renewed (B)
Free text change information supplied by the pharmaceutical company
- Section 4.1: Addition of the paediatric indication: ‘Treatment of VTE and prevention of recurrent VTE in paediatric patients from birth to less than 18 years of age’
- Sections 4.2, 4.3, 4.4, 4.5, 4.8, 4.9, 5.1, 5.2: Consequential paediatric indication related updates are made in these sections
- Sections 3, 4.2, 4.3, 4.4, 4.5, 4.7 4.8, 4.9, 5.1, 5.2, 6.1, 6.5, 7: Minor editorial/clarification updates are made in these sections
- Sections 4.8, 5.1: Updates with regards to clinical trials/studies related information are made in these sections
- Section 5.3: Addition of information regarding juvenile toxicity study
- Section 4.8: Addition of information in the ‘Bleeding reactions’ section regarding anticoagulant-related nephropathy in patients with predisposing risk factors
- Section 10: The date of revision has been updated to align with the Commission Decision (CD) date of 09 December 2021.
- Apart from the above updates, the heading of the SmPCs now indicates United Kingdom (Northern Ireland), Republic of Ireland and Malta and section 4.8 of the SmPCs now indicates United Kingdom (Northern Ireland) in AE reporting section.
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IRE - NP-IE-100234 Cardiovascular Pradaxa RMM - SPAF & DVT PE.pdf
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IRE - NP-IE-100235 Cardiovascular Pradaxa RMM - pVTE.pdf
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Updated on 01 July 2020
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Var II-123 - 110 mg PIL annex text - UK & IE.pdf
Reasons for updating
- Change to section 4 - possible side effects
- Change to section 6 - date of revision
- Change to other sources of information section
Updated on 30 June 2020
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P1;110 mg-All-SPC-45 - Approved.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 be renewed (B)
Free text change information supplied by the pharmaceutical company
- Section 4.8: Updated to add ‘Neutropenia’ and ‘Agranulocytosis’ as Adverse reactions (Frequency: Not known) for all strengths, including addition of information regarding reporting of Neutropenia and Agranulocytosis under the section ‘Description of selected adverse reactions’.
- Section 10: Date of revision has been updated
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IE-SPAF+DVT-PE - NP-IE-100234 - Feb 2020.pdf
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IE-PG-pVTEp - NP-IE-100235 - Feb 2020.pdf
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Updated on 09 January 2020
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Var II-118g - 110 mg PIL annex text - UK & IE.pdf
Reasons for updating
- Change to section 2 - what you need to know - contraindications
- Change to section 2 - interactions with other medicines, food or drink
- Change to section 4 - possible side effects
- Change to section 4 - how to report a side effect
- Change to section 6 - date of revision
Updated on 09 January 2020
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P1;110 mg-All-SPC-44-Approved.pdf
Reasons for updating
- Change to section 4.3 - Contraindications
- Change to section 4.5 - Interaction with other medicinal products and other forms of interaction
- 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 be renewed (B)
Free text change information supplied by the pharmaceutical company
· Section 4.3: Updated to add concomitant treatment of fixed-dose combination of glecaprevir/pibrentasvir (P-gp inhibitor) as a contraindication.
· Section 4.5: Updated to add information regarding interaction of dabigatran etexilate and fixed-dose combination of glecaprevir/pibrentasvir (P-gp inhibitor).
· Section 4.8: Updated to add ‘alopecia’ as an Adverse reaction (Frequency: Not known) + minor editorial update regarding description wording of Table 10. The Irish AE reporting details have also been updated.
· Section 10: Date of revision has been updated to 16 December 2019
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NP-IE-100027 Prescriber Guide - SPAF & DVT PE - Jun 2019.pdf
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NP-IE-100028 Prescriber Guide - pVTE - Jun 2019.pdf
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Updated on 20 May 2019
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Type IAin PRAC - 110 mg PIL annex text - UK & IE.pdf
Reasons for updating
- Change to section 2 - what you need to know - warnings and precautions
- Change to section 6 - date of revision
Updated on 20 May 2019
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P1;110 mg-All-SPC-43.pdf
Reasons for updating
- Change to section 4.4 - Special warnings and precautions for use
- Change to section 10 - Date of revision of the text
Legal category:Product subject to medical prescription which may be renewed (B)
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Section 4.4: To include warning regarding thromboembolic risk in patients with antiphospholipid syndrome.
Section 10: Date of revision has been updated to May 2019
Updated on 07 May 2019
File name
Var 114 110 mg.pdf
Reasons for updating
- Change to section 2 - what you need to know - contraindications
- Change to section 3 - how to take/use
- Change to section 4 - possible side effects
- Change to section 6 - date of revision
- Change to other sources of information section
Updated on 03 May 2019
File name
P1;110 mg-All-SPC-42 Approved.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 4.9 - Overdose
- 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 be renewed (B)
Free text change information supplied by the pharmaceutical company
- Sections 4.4, 4.8, 4.9, 5.1 & 5.2: Editorial updates.
- Section 5.1: To include wording regarding Medicare study (Graham et al)
- Section 10 updated
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cropped PAC 306013-05 06-02-18.pdf
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13496 SPAF_DVTE-PE Prescriber guide_210mmSQ Ireland AW2.pdf
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pVTE Prescriber guide IREDBG-161046(3)v2.1.pdf
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Updated on 04 July 2018
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P1;110 mg-All-SPC-41 med-ie.docx
Reasons for updating
- Change to section 5.1 - Pharmacodynamic properties
Legal category:Product subject to medical prescription which may be renewed (B)
Updated on 03 July 2018
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V0108 110 mg.pdf
Reasons for updating
- Change to section 6 - what the product contains
- Change to section 6 - date of revision
- Change to MA holder contact details
Updated on 26 June 2018
File name
P1;110 mg-All-SPC-40 med-ie.docx
Reasons for updating
- Change to section 4.2 - Posology and method of administration
- Change to section 4.3 - Contraindications
- Change to section 4.4 - Special warnings and precautions for use
- Change to section 4.5 - Interaction with other medicinal products and other forms of interaction
- Change to section 4.8 - Undesirable effects
- Change to section 5.1 - Pharmacodynamic properties
- 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
Legal category:Product subject to medical prescription which may be renewed (B)
File name
pVTE Prescriber guide IREDBG-161046[2].pdf
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- Add New Doc
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Pradaxa (dabigatran etexilate) Prescriber Guide for primary prevention of venous thromboembolic events (VTE) following elective total hip or knee replacement surgery
Updated on 14 February 2018
File name
PIL_13865_108.pdf
Reasons for updating
- New PIL for new product
Updated on 14 February 2018
Reasons for updating
- Correction of spelling/typing errors
- Improved presentation of PIL
Updated on 05 February 2018
Reasons for updating
- Change to Section 1 - what the product is
- Change to section 1 - what the product is used for
- Change to section 2 - what you need to know - contraindications
- Change to section 2 - what you need to know - warnings and precautions
- Change to section 2 - use in children and adolescents
- Change to section 2 - interactions with other medicines, food or drink
- Change to section 3 - how to take/use
- Change to section 3 - overdose, missed or forgotten doses
- Change to section 4 - possible side effects
- Change to section 5 - how to store or dispose
- 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
- Change to other sources of information section
Updated on 01 February 2018
Reasons for updating
- New SPC for new product
Legal category:Product subject to medical prescription which may be renewed (B)
Updated on 01 February 2018
Reasons for updating
- Change to section 3 - Pharmaceutical form
- Change to section 4.1 - Therapeutic indications
- Change to section 4.2 - Posology and method of administration
- Change to section 4.3 - Contraindications
- Change to section 4.4 - Special warnings and precautions for use
- Change to section 4.5 - 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 4.9 - Overdose
- 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 6.1 - List of excipients
- Change to section 6.3 - Shelf life
- 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 10 - Date of revision of the text
Legal category:Product subject to medical prescription which may be renewed (B)
Free text change information supplied by the pharmaceutical company
Renewal: EMEA/H/C/000829/R/105. Sections 3, 4.1, 4.6, 4.9, 5.1, 5.2, 5.3, 6.1, 6.3, 6.5, 6.6, – minor rewording/editorial changes
Main changes:
4.2 - dose recommendation and duration of treatment information now tabulated (subsequent table numbers updated). Duplicated statements/information removed. New section ‘Discontinuation of Pradaxa’. Other editorial changes.;
4.3- inclusion of the wording ‘with the following strong P-gp inhibitors’ in the contraindications ‘Concomitant treatment with the following strong P-gp inhibitors: systemic ketoconazole, cyclosporine, itraconazole and dronedarone (see section 4.5)’;
4.4 - mainly editorial changes. P-gp information in the table expanded;
4.5 - information tabulated. Some changes to figures e.g. percentages replaced by ‘x- fold’ or percentages deleted/other text changes;
4.8 - patient numbers per study/indication now included in a table; new text re: bleeding reactions; major bleeding definitions removed;
10 – Date of revision updated
Updated on 06 November 2017
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 - 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 be renewed (B)
Free text change information supplied by the pharmaceutical company
Sections 4.2 (Posology and method of administration) and 4.4 (Special warnings and precautions for use) have been updated to include information regarding Catheter ablation for atrial fibrillation.
Section 4.8 (Undesirable effects) has been updated to include revised details for AE reporting in the UK and Section 10 (Date of revision of the text) includes the date of approval - 19 October 2017.Updated on 05 June 2017
Reasons for updating
- Change to section 2 - excipient warnings
- 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
Updated on 01 June 2017
Reasons for updating
- Change to section 2 - Qualitative and quantitative composition
- Change to section 3 - Pharmaceutical form
- Change to section 4.4 - Special warnings and precautions for use
- Change to section 6.1 - List of excipients
- Change to section 10 - Date of revision of the text
Legal category:Product subject to medical prescription which may be renewed (B)
Free text change information supplied by the pharmaceutical company
Change of capsule colour including removal of sunset yellow - Sections 2 - Qualitative and Quantitative Composition, 3 – Pharmaceutical Form, 4.4 – Special warnings and precautions and 6.1 – List of excipients have been updated
Updated on 04 April 2017
Reasons for updating
- 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 be renewed (B)
Free text change information supplied by the pharmaceutical company
The date of revision of the text in the SPCs has been updated to 02 February 2017 (date of positive opinion).
Updated on 11 March 2016
Reasons for updating
- Change to improve clarity and readability
Updated on 08 March 2016
Reasons for updating
- Change to section 6.6 - Special precautions for disposal and other handling
Legal category:Product subject to medical prescription which may be renewed (B)
Free text change information supplied by the pharmaceutical company
Deletion of the statement ‘Any unused product or waste material should be disposed of in accordance with local requirements.’ from Section 6.6 Special precautions for disposal and other handling. The internal reference number of the SPCs has been updated but the date of the SPC is unchanged.
Updated on 02 March 2016
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 4.9 - Overdose
- 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 be renewed (B)
Free text change information supplied by the pharmaceutical company
SPC Sections 4.4 (special warnings and precautions for use) and 4.9 (Overdose) have been updated to include information relating to the reversal agent Praxbind and to provide more information on surgery and interventions (section 4.4.).
Please also note that some editorial changes have been made to sections 2, 4.2 and 5.1.
Section 10 has been updated to 28 January 2016
Updated on 09 February 2016
Reasons for updating
- Change to date of revision
- Change to improve clarity and readability
Updated on 20 January 2016
Reasons for updating
- 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 10 - Date of revision of the text
Legal category:Product subject to medical prescription which may be renewed (B)
Free text change information supplied by the pharmaceutical company
Section 10 has been updated to 17 December 2015
Updated on 27 October 2015
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 be renewed (B)
Free text change information supplied by the pharmaceutical company
SPC Section 5.1 Pharmacodynamic Properties; pharmacodynamics effects section has been updated.
Section 10 has been updated to 20 October 2015
Updated on 02 September 2015
Reasons for updating
- 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 be renewed (B)
Free text change information supplied by the pharmaceutical company
SPC Section 5.2 Pharmacokinetic Properties, last paragraph of the ‘Absorption’ subsection. Details of this change are given below with the change highlighted in red.
‘The oral bioavailability may be increased by 75 % after a single dose and 37 % at steady state compared to the reference capsule formulation when the pellets are taken without the Hydroxypropylmethylcellulose (HPMC) capsule shell. Hence, the integrity of the HPMC capsules should always be preserved in clinical use to avoid unintentionally increased bioavailability of dabigatran etexilate. Therefore, patients should be advised not to open the capsules and taking the pellets alone (e.g. sprinkled over food or into beverages) (see section 4.2).’
Section 10 has been updated to 07/2015
Updated on 13 February 2015
Reasons for updating
- Change of inactive ingredient
- Change to side-effects
- Change to date of revision
- Correction of spelling/typing errors
Updated on 30 January 2015
Reasons for updating
- 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 5.1 - Pharmacodynamic properties
- Change to section 6.1 - List of excipients
- Change to section 10 - Date of revision of the text
Legal category:Product subject to medical prescription which may be renewed (B)
Free text change information supplied by the pharmaceutical company
Sections 4.8 and 5.1: updates to efficacy and safety data
Headings were added to all tables (sections 4.4 and 4.8).
Section 4.8 has been updated to include the new contact details for AE reporting for Malta and in section 6.1 to revise the information on the printing ink used
Section 10 has been updated to 12/2014
Updated on 05 November 2014
Reasons for updating
- Change to section 4.2 - Posology and method of administration
- Change to Section 4.8 – Undesirable effects - how to report a side effect
- 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 be renewed (B)
Free text change information supplied by the pharmaceutical company
Minor changes to section 4.2 for the orthopaedic VTE indication with regards to the initial dose for patients who should receive a lower dose.
Section 4.8 has also been updated to include the new details for the Irish Health authority (HPRA formerly IMB). Other minor editorial/formatting changes have also been made.
Section 5.1 correction of typographical error thrombine to thrombin; to include safety information from the RELY-ABLE study
Section 10 has been updated to 09/2014
Updated on 17 July 2014
Reasons for updating
- Change to, or new use for medicine
- Change to side-effects
- Change to drug interactions
- Change to date of revision
- Change to dosage and administration
Updated on 15 July 2014
Reasons for updating
- Change to section 4.1 - Therapeutic indications
- Change to section 4.2 - Posology and method of administration
- Change to section 4.4 - Special warnings and precautions for use
- Change to section 4.5 - Interaction with other medicinal products and other forms of interaction
- 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
Legal category:Product subject to medical prescription which may be renewed (B)
Free text change information supplied by the pharmaceutical company
4.1 Therapeutic indications
Treatment of deep vein thrombosis (DVT) and pulmonary embolism (PE), and prevention of recurrent
DVT and PE in adults
4.2 Posology and method of administration
Extensive changes throughout section 4.2
4.4 Special warnings and precautions for use
Extensive changes throughout section 4.4
4.5 Interaction with other medicinal products and other forms of interaction
For patients with NVAF treated for prevention of stroke and SEE and for DVT/PE patients,
concomitantly receiving dabigatran etexilate and verapamil, the dose of Pradaxa should be reduced to
220 mg taken as one 110 mg capsule twice daily (see section 4.2).
Close clinical surveillance is recommended when dabigatran etexilate is combined with verapamil and
particularly in the occurrence of bleeding, notably in patients having a mild to moderate renal
impairment.
4.8 Undesirable effects
Extensive changes throughout section 4.8
5.1 Pharmacodynamic properties
Extensive changes throughout section 5.1
5.2 Pharmacokinetic properties
The median CrCL in the RE-COVER study was 100.4 mL/min. 21.7 % of patients had mild renal
impairment (CrCL > 50 - < 80 mL/min) and 4.5% of patients had a moderate renal impairment (CrCL
between 30 and 50 mL/min). Patients with mild and moderate renal impairment had at steady state an
average 1.8-fold and 3.6-fold higher pre-dose dabigatran plasma concentrations compared with
patients with CrCL > 80 mL/min, respectively. Similar values for CrCL were found in RE-COVER II.
The median CrCL in the RE-MEDY and RE-SONATE studies were 99.0 mL/min and 99.7 mL/min,
respectively. 22.9 % and 22.5 % of the patients had a CrCL > 50-< 80 mL/min, and 4.1 % and 4.8 %
had a CrCL between 30 and 50 mL/min in in the RE-MEDY and RE-SONATE studies.
5.3 Preclinical safety data
Dabigatran, the active moiety of dabigatran etexilate mesilate, is persistent in the environment.
10. DATE OF REVISION OF THE TEXT
Updated to June 2014
Updated on 12 June 2014
Reasons for updating
- Change to section 4.2 - Posology and method of administration
- Change to section 4.3 - Contraindications
- 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 be renewed (B)
Free text change information supplied by the pharmaceutical company
- Section 4.2
The paragraph under Switching (prevention of VTE) Parenteral anticoagulants to Pradaxa has been updated:
Discontinue the parenteral anticoagulant and start dDabigatran etexilate should be given 0‑2 hours prior to the time that the next dose of the alternate therapy would be due, or at the time of discontinuation in case of continuous treatment (e.g. intravenous Unfractionated Heparin (UFH)) (see section 4.5).
The paragraph under Switching (SPAF) Parenteral anticoagulants to Pradaxa has been updated:
Discontinue the parenteral anticoagulant and start dDabigatran etexilate should be given 0‑2 hours prior to the time that the next dose of the alternate therapy would be due, or at the time of discontinuation in case of continuous treatment (e.g. intravenous Unfractionated Heparin (UFH)) (see section 4.5).
- Section 4.3
Concomitant treatment with any other anticoagulants e.g. unfractionated heparin (UFH), low molecular weight heparins (enoxaparin, dalteparin etc), heparin derivatives (fondaparinux etc), oral anticoagulants (warfarin, rivaroxaban, apixaban etc) except under specific the circumstances of switching anticoagulant therapy to or from Pradaxa (see section 4.2) or when UFH is given at doses necessary to maintain an open central venous or arterial catheter (see section 4.5)
- Section 4.5
Addition of the following paragraph:
Concomitant administration of a loading dose of 180 mg ticagrelor and 110 mg dabigatran etexilate (in steady state) increased the dabigatran AUCτ,ss and Cmax,ss by 1.49-fold and 1.65-fold (+49% and
65%), respectively, compared with dabigatran etexilate given alone. When a loading dose of 180 mg
ticagrelor was given 2 hours after 110 mg dabigatran etexilate (in steady state), the increase of
dabigatran AUCτ,ss and Cmax,ss was reduced to 1.27-fold and 1.23-fold (+27% and 23%),
respectively, compared with dabigatran etexilate given alone. This staggered intake is the
recommended administration for start of ticagrelor with a loading dose.
Concomitant administration of 90 mg ticagrelor BID (maintenance dose) with 110 mg dabigatran
etexilate increased the adjusted dabigatran AUCτ,ss and Cmax,ss 1.26-fold and 1.29-fold,
respectively, compared with dabigatran etexilate given alone.
- Section 10 Date of revision of the text has also been updated to 05/2014
Updated on 29 January 2014
Reasons for updating
- Change of contraindications
- Change to drug interactions
- Change to date of revision
Updated on 28 January 2014
Reasons for updating
- Change to section 4.1 - Therapeutic indications
- Change to section 4.2 - Posology and method of administration
- Change to section 4.3 - Contraindications
- 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 4.8 - 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 be renewed (B)
Free text change information supplied by the pharmaceutical company
Numerous changes to this section.
Section 4.2 – Posology and method of administration
The words “nonvalvular atrial fibrillation” have been removed and replaced with NVAF.
Section 4.3 – Contraindications
Tacrolimus has been removed from the 2nd last bullet point
Section 4.4 Special warnings and precautions
The words “nonvalvular atrial fibrillation” have been removed and replaced with NVAF.
Section 4.5 – Interactions
The following statement has been added under Transporter interactions; P-gp inhibitors:
“Concomitant treatment with tacrolimus is not recommended”
“posaconazole” has been added into the sentence:
“Caution should be exercised with mild to moderate P gp inhibitors (e.g. amiodarone, posaconazole, quinidine, verapamil and ticagrelor) (see sections 4.2 and 4.4).”
Tacrolimus has been removed from the “Ticagrelor” section:
“The following potent P gp inhibitors have not been clinically studied but from in vitro results a similar effect as with ketoconazole may be expected:
Itraconazole and cyclosporine, which are contra indicated (see section 4.3).”
The words “nonvalvular atrial fibrillation” have been removed and replaced with NVAF.
The following paragraphs have been added into the “Ticagrelor” section:
“Tacrolimus has been found in vitro to have a similar level of inhibitory effect on P-gp as that seen with itraconazole and cyclosporine. Dabigatran etexilate has not been clinically studied together with tacrolimus. However, limited clinical data with another P-gp substrate (everolimus) suggest that the inhibition of P-gp with tacrolimus is weaker than that observed with strong P-gp inhibitors. Based on these data concomitant treatment with tacrolimus is not recommended.
Posaconazole also inhibits P-gp to some extent but has not been clinically studied. Caution should be exercised when Pradaxa is co-administered with posaconazole.”
The following statement has been deleted from the “Ticagrelor” section:
“Neither clinical nor in vitro test results are available for posaconazole which is not recommended for concomitant treatment with Pradaxa.”
Section 4.8 – Undesirable effects
The words “nonvalvular atrial fibrillation” have been removed and replaced with NVAF.
Section 5.1 Pharmacodynamic properties
The words “nonvalvular atrial fibrillation” have been removed and replaced with NVAF.
Section 10 – date of revision
Updated to 12/2013
Updated on 22 October 2013
Reasons for updating
- Change to section 4.2 - Posology and method of administration
- 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 be renewed (B)
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Section 4.8 inclusion of a reference to oesophageal ulcer plus inclusion of information relating to reporting of suspected adverse reactions.
Section 10 Date of revision has been revised to 09/2013.
Updated on 16 October 2013
Reasons for updating
- Change to side-effects
- Change to further information section
- Change to date of revision
- Change to dosage and administration
- Addition of information on reporting a side effect.
Updated on 04 September 2013
Reasons for updating
- Change to section 4.4 - Special warnings and precautions for use
- Change to section 10 - Date of revision of the text
Legal category:Product subject to medical prescription which may be renewed (B)
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The header has changed to “Postoperative phase”
Addition of sentence:
“Dabigatran etexilate should be restarted after the invasive procedure or surgical intervention as soon as possible provided the clinical situation allows and adequate haemostasis has been established.”
Removal of sentence:
“Resume treatment after complete haemostasis is achieved.”
10. Date of revision
Updated to 08/2013
Updated on 05 August 2013
Reasons for updating
- Change to section 4.3 - Contraindications
- Change to section 10 - Date of revision of the text
Legal category:Product subject to medical prescription which may be renewed (B)
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Revision of the contraindication section
10. Date of revision
has also been updated
Updated on 24 June 2013
Reasons for updating
- Change to side-effects
- Change to date of revision
Updated on 11 June 2013
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 4.5 - Interaction with other medicinal products and other forms of interaction
- 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 be renewed (B)
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Revision of the calculation method of the approved side effects frequencies. In addition, the term ‘genitourological haemorrhage’ has been changed to ‘genitourological haemorrhage, including haematuria’.
section 4.4 (special warnings and precautions for use)
Addition of a warning regarding the increase of dabigatran exposure with concomitant intake of ticagrelor
section 4.5 (interaction with other medicinal products and other forms of interaction)
Inclusion of the data for ticagrelor
section 4.2 (posology and method of administration), 4.4, 4.5 and 5.2 (pharmacokinetic properties)
Updates regarding P-gp related wording.
section 10 (date of revision of the text)
Updated to 04/2013
Updated on 01 March 2013
Reasons for updating
- Change of contraindications
- Change to instructions about overdose
- Change to storage instructions
- Change to side-effects
- Change to drug interactions
- Change to information about pregnancy or lactation
- Change to information about driving or using machinery
- Change to how the medicine works
- Change to further information section
- Change to date of revision
- Change to dosage and administration
- Change to warnings or special precautions for use
Updated on 14 February 2013
Reasons for updating
- Change to section 2 - Qualitative and quantitative composition
- Change to section 3 - Pharmaceutical form
- Change to section 4.2 - Posology and method of administration
- Change to section 4.3 - Contraindications
- Change to section 4.4 - Special warnings and precautions for use
- Change to section 4.5 - Interaction with other medicinal products and other forms of interaction
- Change to section 4.6 - Pregnancy and lactation
- Change to section 4.7 - Effects on ability to drive and use machines
- Change to section 4.8 - Undesirable effects
- Change to section 4.9 - Overdose
- Change to section 5.1 - Pharmacodynamic properties
- Change to section 5.2 - Pharmacokinetic properties
- Change to section 6.1 - List of excipients
- Change to section 6.5 - Nature and contents of container
- Change to section 9 - Date of renewal of authorisation
- Change to section 10 - Date of revision of the text
Legal category:Product subject to medical prescription which may be renewed (B)
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Update to section 4.3 – addition of prosthetic heart valves contraindication with cross-reference to section 5.1; plus editorial changes
Update to section 4.4 – deletion of sub-section relating to prosthetic heart valves; plus editorial changes
Update to section 5.1 – addition of a new sub-section ‘Clinical trials for the prevention of thromboembolism in patients with prosthetic heart valves’; plus editorial changes
Minor updates to sections 2, 3, 4.2, 4.5, 4.6, 4.7, 4.9, 5.2, 6.1, 6.5, 9 and 10. These section updates also include some format changes e.g. in vitro now in italics.
Updated on 21 September 2012
Reasons for updating
- Change to section 4.3 - Contraindications
- 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 6.5 - Nature and contents of container
- 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 be renewed (B)
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An additional new pack (white blister) (section 6.5) and the relevant new marketing authorisation number (section 8) has also been added.
Section 10 has also been updated.
Updated on 20 September 2012
Reasons for updating
- Change to MA holder contact details
- Introduction of new pack/pack size
- Change of contraindications
- Change to drug interactions
- Change to date of revision
Updated on 22 August 2012
Reasons for updating
- Change to section 4.2 - Posology and method of administration
- Change to section 4.4 - Special warnings and precautions for use
- Change to section 4.5 - Interaction with other medicinal products and other forms of interaction
- Change to section 4.9 - Overdose
- Change to section 5.1 - Pharmacodynamic properties
- Change to section 6.5 - Nature and contents of container
- 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 be renewed (B)
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Minor editorial changes, removal of underlining.
Section 4.4
The following statement was added:
‘Patients with prosthetic heart valves
The safety and efficacy of Pradaxa has not been studied in patients with prosthetic heart valves. Therefore, use of Pradaxa is not recommended in these patients.’
Section 4.5
Minor editorial change - font.
Section 4.9
Correction of a minor spelling mistake.
Section 5.1
Minor editorial change - Line spacing.
Section 6.5
Addition of '...and a multipack containing 2 packs of 50 x 1 hard capsules (100 hard capsules) ...'
Section 8
Addition of MA number for new pack size EU/1/08/442/015.
Section 10
Date of revision of text amended to 07/2012 from 06/2012.
Updated on 02 August 2012
Reasons for updating
- Change to warnings or special precautions for use
- Change of contraindications
- Change to date of revision
Updated on 23 July 2012
Reasons for updating
- Change to section 4.3 - Contraindications
- 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 4.9 - Overdose
- Change to section 5.1 - Pharmacodynamic properties
- Change to section 5.2 - Pharmacokinetic properties
- Change to section 10 - Date of revision of the text
- Change to section 4.2 - Posology and method of administration
Legal category:Product subject to medical prescription which may be renewed (B)
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4.3 (contraindications) has been updated
4.4 (special warnings and precautions), further information has been included regarding factors which may increase the haemorrhagic risk
4.5 (interactions) - has been updated.
4.9 (overdose) - additional paragraph has been added to this section.
5.1 (pharmacodynamic properties – Addition of information regarding concomitant use of ASA or clopidogrel in the RELY study.
5.2 (pharmacokinetic properties - minor editorial update only) have been revised.
10 (date of revision of the text) has also been updated
Updated on 19 June 2012
Reasons for updating
- Change to section 4.2 - Posology and method of administration
- Change to section 4.4 - Special warnings and precautions for use
- Change to section 4.8 - Undesirable effects
- Change to section 4.9 - Overdose
- 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 be renewed (B)
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4.2 Posology and method of administration
4.4 Special warnings and precautions for use
4.8 Undesirable effects
5.1 Pharmacodynamic properties
5.2 Pharmacokinetic properties
The addition of wording regarding haemodialysis have been made to sections
4.9 Overdose
5.2 Pharmacokinetic properties
Section 10 Date of revision of the text has also been updated
Updated on 01 May 2012
Reasons for updating
- 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 7 - Marketing authorisation holder
- Change to section 10 - Date of revision of the text
Legal category:Product subject to medical prescription which may be renewed (B)
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Addition of wording related to concomitant treatments and bleeding risk along with editorial changes.
Section 7
Addition of Binger Str. 173
Section 10
Date revised to 04/2012
Updated on 30 April 2012
Reasons for updating
- Change to drug interactions
- Change to date of revision
- Change to MA holder contact details
Updated on 12 March 2012
Reasons for updating
- Change to warnings or special precautions for use
- Change of contraindications
- Change to storage instructions
- Change to side-effects
- Change to drug interactions
- Change to further information section
- Change to date of revision
- Change to dosage and administration
Updated on 02 March 2012
Reasons for updating
- Change to section 4.3 - Contraindications
- Change to section 4.8 - Undesirable effects
- Change to section 9 - Date of renewal of authorisation
- Change to section 10 - Date of revision of the text
- Change to section 5.1 - Pharmacodynamic properties
- Change to section 6.3 - Shelf life
Legal category:Product subject to medical prescription which may be renewed (B)
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Minor amendment has been made to this section.
4.8 Undesirable effects
Additional side effect - Haemoptysis has been added with”Uncommon” frequencies for Primary VTE prevention after hip or knee replacement surgery.
Hepatic function abnormal/Liver function Test abnormal - frequencies have changed from “Uncommon” to “Common”.
Bloody discharge – frequencies have changed from “Uncommon” to “Rare” for Primary VTE prevention after hip or knee replacement surgery
Incision site haemorrhage – frequencies have changed from “Rare” to “Uncommon”
Wound drainage – frequencies have changed from “Uncommon” to “Rare” for Primary VTE prevention after hip or knee replacement surgery
5.1 Pharmacodynamic properties
Addition of “see section 4.2 for information on paediatric use” added to last paragraph under Paediatric population.
6.3 Shelf life
The shelf life has been changed from 2 years to 3 years.
The use by date once bottle is opened has been changed from within 30 days to 4 months.
9 Date of first authorisation/renewal of the authorisation
Minor update of the section
10 Date of revision
Date updated to 02/2012
Updated on 20 December 2011
Reasons for updating
- Change to section 4.2 - Posology and method of administration
- Change to section 4.3 - Contraindications
- Change to section 4.4 - Special warnings and precautions for use
- Change to section 10 - Date of revision of the text
Legal category:Product subject to medical prescription which may be renewed (B)
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To include recommendations to assess renal function in patients being considered for or already being treated with Pradaxa.
Section 4.3
Added a cross reference to section 4.2 for the contra-indication “patients with severe renal impairment (CrCL <30 ml/min)”
Section 4.4
Minor changes to 3rd paragraph under “haemorrhagic risk”.
Section 10
Date updated to 11/2011
Updated on 26 August 2011
Reasons for updating
- Change to section 4.3 - Contraindications
- 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 4.9 - Overdose
- 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 6.3 - Shelf life
- Change to section 6.5 - Nature and contents of container
- Change to section 8 - MA number
- Change to section 10 - Date of revision of the text
- Change to section 4.1 - Therapeutic indications
- Change to section 4.2 - Posology and method of administration
Legal category:Product subject to medical prescription which may be renewed (B)
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Section 4.1
Inclusion of new Indication 'Prevention of stroke and systemic embolism in adult patients with nonvalvular atrial fibrillation'.
Section 4.2
Major update, following inclusion of new indication.
Section 4.3
Concomitant treatment with cyclosporine, itraconazole and tacrolimus added.
Section 4.4
Major update, following inclusion of new indication.
Section 4.5
Major update, following inclusion of new indication and re-wording of several paragraphs and Anticoagulants and antiplatelet aggregation agents paragraph amended. Paragraphs added on Clopidogrel, ASA, NSAIDs, and LMWH.
Paragraph on P-gp inhibitors updated. Cyclosporine, itraconazole and tacrolimus added to contraindicated, paragraph on P-gp inducers updated.
Section 4.6
Lactation amended to Breast-feeding, paragraph added to fertility.
Section 4.8
Major update, following inclusion of new indication.
Section 4.9
Information on overdose re-written.
Section 5.1
Major update, following inclusion of new indication.
'More that 99% of efficacy and safety data were generated in Caucasians' deleted and replaced wtih 'No clinically relevant ethnic differences among Caucasians, African American, Hispanic, Japanese or Chinese patients were observed.'
Minor changes to paragraph on 'Clinical trials in Venous Thromboembolism (VTE) prophylaxis following major joint replacement surgery'.
Section 5.2
Editorial changes, inclusion of Table 8 'Half life of total dabigatran in healthy subjects and subjects with impaired renal function', amendment of paragraphs on Elderly patients, Body weight, Gender, and Ethinic origin.
Section 5.3
' Carcinogenicity studies have not yet been completed with dabigatran' deleted and 'In lifetime toxicology studies in rats and mice, there was no evidence for a tumorigenic potential of dabigatran up to maximum doses of 200 mg/kg.' added.
Section 6.3
Shelf life amended from 3 years to 2 years.
Section 6.5
'and a multipack containing 3 packs of 60 x 1 hard capsules (180 hard capsules)' added.
Section 8
'EU/1/08/442/014' added.
Section 10
Date of revision amended.
Updated on 26 August 2011
Reasons for updating
- Addition of separate PILs covering individual presentations
Updated on 23 February 2011
Reasons for updating
- Change to dosage and administration
- Change to side-effects
- Change to date of revision
Updated on 15 February 2011
Reasons for updating
- Change to section 4.2 - Posology and method of administration
- Change to section 4.5 - Interaction with other medicinal products and other forms of interaction
- 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 be renewed (B)
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Sections 4.2, 4.5, 4.8 and 5.2 have been updated to make other editorial changes
Section 10 Date of revision of the text has also been updated.
Updated on 14 February 2011
Reasons for updating
- Correction of spelling/typing errors
Updated on 31 January 2011
Reasons for updating
- Change of contraindications
- Change to drug interactions
- Change to date of revision
- Change to MA holder contact details
Updated on 26 January 2011
Reasons for updating
- Change to section 4.2 - Posology and method of administration
- Change to section 4.3 - Contraindications
- Change to section 4.4 - Special warnings and precautions for use
- Change to section 4.5 - 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 be renewed (B)
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As part of this update section 4.3 has been revised to add concomitant treatment with systemic ketoconazole as a contraindication and to remove concomitant treatment with quinidine as a contraindication. Information regarding quinidine is now included in other sections of the SPC.
Section 10:
Date of revision of the text has also been updated.
Updated on 26 November 2010
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 be renewed (B)
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Section 4.8 (Undesirable effects)
Frequencies of undesirable effects have been updated.
Section 10 (Date of revision of the text)
Updated to 25th Oct 2010.
Updated on 26 November 2010
Reasons for updating
- Change to side-effects
- Change to date of revision
Updated on 20 September 2010
Reasons for updating
- Change to section 4.4 - Special warnings and precautions for use
- Change to section 10 - Date of revision of the text
Legal category:Product subject to medical prescription which may be renewed (B)
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Details of Changes
Section 4.4
The following information has been added in the subsection 'Haemorrhagic risk':
The activated partial thromboplastin time (aPTT) test is widely available and provides an approximate indication of the anticoagulation intensity achieved with dabigatran. In patients who are bleeding or at risk of bleeding, the aPTT test may be useful to assist in determining an excess of anticoagulant activity. However, the aPTT test has limited sensitivity and is not suitable for precise quantification of anticoagulant effect, especially at high plasma concentrations of dabigatran. High aPTT values should be interpreted with caution. If required, more sensitive quantitative tests such as calibrated diluted Thrombin Time should be performed.
Section 10
Updated to 26 August 2010.
Updated on 02 August 2010
Reasons for updating
- Change to warnings or special precautions for use
- Change to dosage and administration
Updated on 20 July 2010
Reasons for updating
- Change to section 4.2 - Posology and method of administration
- 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 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 be renewed (B)
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Changed Sections
4.2, 4.5, 4.6, 5.1, 5.2, 8, 10.
Main Changes
4.2
The following statement has been added:
Patients should be instructed not to open the capsule as this may increase the risk of bleeding (see section 5.2.)
The following statement has been added regarding the paediatric population:
Paediatric population
There is no relevant use of Pradaxa in the paediatric population in the indication: primary prevention of venous thromboembolic events in patients who have undergone elective total hip replacement surgery or total knee replacement surgery.
5.1
The following statement has been added regarding the paediatric population:
Paediatric population:
The European Medicines Agency has waived the obligation to submit the results of studies with Pradaxa in all subsets of the paediatric population in prevention of thromboembolic events in the granted indication.
5.2
The following statement has been added:
The oral bioavailability may be increased by 75 % compared to the reference capsule formulation when the pellets are taken without the HPMC capsule shell. Hence, the integrity of the HPMC capsules should always be preserved in clinical use to avoid unintentionally increased bioavailability of dabigatran etexilate. Therefore, patients should be advised not to open the capsules and taking the pellets alone (e.g. sprinkled over food or into beverages) (see section 4.2).
10
Date of revision of the text: 01 July 2010
Updated on 22 December 2009
Reasons for updating
- Change to drug interactions
- Change to dosage and administration
Updated on 26 November 2009
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 4.5 - 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 be renewed (B)
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Reason for update: Changes to sections 4.2 (Posology and method of administration), 4.4 (Special warnings and precautions for use) and 4.5 (Interaction with other medicinal products and other forms of interaction).
Main changes
The most significant change is the update to information regarding a potential interaction with verapamil, indicating that a reduced dose of 150 mg is recommended when Pradaxa and verapamil are given concomitantly. The following is an extract from section 4.2, Posology and method of administration:
“Dosing should be reduced to 150 mg Pradaxa daily in patients who received concomitantly dabigatran etexilate and amiodarone or verapamil (see sections 4.4 and 4.5).
In patient with moderate renal impairment and concomitantly treated with dabigatran etexilate and verapamil, a dose reduction of Pradaxa to 75 mg daily should be considered (see sections 4.4 and 4.5).”
In addition, the following warning has been added to section 4.4, Special warnings and precautions for use:
“Plasma concentrations of dabigatran might be elevated when co-administered with strong P-gp inhibitors (e.g. verapamil, amiodarone). This may increase the risk of bleeding and these patients should be closely clinically monitored (looking for signs of bleeding and anaemia) (see sections 4.2 and 4.5).”
Full details on the verapamil/ dabigatran interaction are included in section 4.5, Interaction with other medicinal products and other forms of interaction:
“Transporter interactions:
Amiodarone, verapamil and clarithromycin are inhibitors of the efflux transporter P-glycoprotein and dabigatran etexilate a substrate of this transporter.
Verapamil: When dabigatran etexilate (150 mg) was coadministered with oral verapamil, the Cmax and AUC of dabigatran were increased but magnitude of this change differs depending on timing of administration and formulation of verapamil.
The greatest elevation of dabigatran exposure was observed with the first dose of an immediate release formulation of verapamil administered one hour prior to dabigatran etexilate intake (increase of Cmax by about 180 % and AUC by about 150 %). The effect was progressively decreased with administration of an extended release formulation (increased of Cmax by about 90 % and AUC by about 70 %) or administration of multiple doses of verapamil (increased of Cmax by about 60 % and AUC by about 50 %).
Therefore, close clinical surveillance (looking for signs of bleeding or anemia) is required when dabigatran is co-administrered with verapamil. In patient with normal renal function after the surgery, receiving dabigatran etexilate and verapamil concomitantly, the dose of Pradaxa should be reduced to 150 mg daily. In patient with moderate renal impairment and concomitantly treated with dabigatran etexilate and verapamil, a dose reduction of Pradaxa to 75 mg daily should be considered (see sections 4.2 and 4.4).
There was no meaningful interaction observed when verapamil was given 2 hours after dabigatran etexilate (increased of Cmax by about 10 % and AUC by about 20 %). This is explained by completed dabigatran absorption after 2 hours (see section 4.4)”
The following information on clarithromycin has also been added to Section 4.5:
“Clarithromycin: When clarithromycin (500 mg bid) was administered together with dabigatran etexilate in healthy volunteers, increase of AUC by about 19 % and Cmax by about 15 % was observed without any clinical safety concern. However, in patients receiving dabigatran, a clinically relevant interaction cannot be excluded when combined with clarithromycin. Therefore, a close monitoring should be exercised when dabigatran etexilate is combined with clarithromycine and particularly in the occurrence of bleeding, notably in patient having a mild to moderate renal function.”
Updated on 08 June 2009
Reasons for updating
- Change to side-effects
Updated on 15 May 2009
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 be renewed (B)
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"Although rare in frequency in clinical trials, major or severe bleeding may occur and, regardless of location, may lead to disabling, life-threatening or even fatal outcomes
Updated on 01 April 2009
Reasons for updating
- Change to section 5.1 - Pharmacodynamic properties
- Change to section 6.5 - Nature and contents of container
- Change to section 10 - Date of revision of the text
Legal category:Product subject to medical prescription which may be renewed (B)
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Updated on 30 October 2008
Reasons for updating
- Change to section 6.3 - Shelf life
- Change to section 6.5 - Nature and contents of container
- Change to section 10 - Date of revision of the text
Legal category:Product subject to medical prescription which may be renewed (B)
Free text change information supplied by the pharmaceutical company
The shelf life of the product has been extended from two years to three years.
Updated on 29 October 2008
Reasons for updating
- New PIL for new product
Updated on 01 October 2008
Reasons for updating
- New SPC for new product
Legal category:Product subject to medical prescription which may be renewed (B)