EU RISK MANAGEMENT PLAN FOR HYOSCINE BUTYLBROMIDE PRELIMINARY SECTION Active substance(s) (INN or common name) Hyoscine butylbromide Belladonna alkaloids, semisynthetic, quarternary Pharmaco-therapeutic group (ATC Code) ammonium compounds (ATC code A03BB01) Name of Marketing Authorization Holder or Applicant Boehringer Ingelheim Limited Medicinal product(s) to which this RMP refers Hyoscine butylbromide (BUSCOPAN) (tablet and ampoule) Product(s) concerned (brand name(s)) BUSCOPAN ® (tablet and ampoule) Data lock point (DLP) for current Risk Management Plan 01-JUN-2016 (RMP) Version number of the current RMP Version 2.1_CA Date of final sign-off Property of the Sanofi group - strictly confidential Page 1 QSD-010763 Version 4.0 RISK MANAGEMENT PLAN - Preliminary Section FINAL DLP:01-JUN-2016 Product Code - Hyoscine butylbromide Version 2.1_CA Table 1 - RMP version to be assessed as part of this application RMP Version number Version 2.1_CA Data lock point for this RMP 01-JUN-2016 Date of final sign off Rationale for submitting an updated RMP Not applicable Summary of significant changes in this RMP Safety concerns: The important identified risk “Tachycardia in patients with cardiac risk factors (parenteral formulation)” was added. RMP: Risk Management Plan. Table 2 - Other RMP versions under evaluation RMP Version number Submitted on Submitted within Not applicable - - RMP: Risk Management Plan. Table 3 - Details of the currently approved RMP Version number 2.0 Approved with procedure - Date of approval (opinion date) - RMP: Risk Management Plan. Table 4 - QPPV name and signature QPPV name Dr. Sabine Jeck-Thole QPPV signature Electronic signature on file QPPV: Qualified Person for Pharmacovigilance. Property of the Sanofi group - strictly confidential Page 2 QSD-010763 Version 4.0 RISK MANAGEMENT PLAN - Preliminary Section FINAL DLP:01-JUN-2016 Product Code - Hyoscine butylbromide Version 2.1_CA TABLE OF CONTENT Property of the Sanofi group - strictly confidential Page 3 QSD-010763 Version 4.0 RISK MANAGEMENT PLAN - Preliminary Section FINAL DLP:01-JUN-2016 Product Code - Hyoscine butylbromide Version 2.1_CA LIST OF TABLES Table 1 - RMP version to be assessed as part of this application .................................................................. 2 Table 2 - Other RMP versions under evaluation ............................................................................................. 2 Table 3 - Details of the currently approved RMP ............................................................................................ 2 Table 4 - QPPV name and signature .............................................................................................................. 2 Table 5 - Overview of the RMP Parts and Modules in the current RMP ......................................................... 6 Property of the Sanofi group - strictly confidential Page 4 QSD-010763 Version 4.0 RISK MANAGEMENT PLAN - Preliminary Section FINAL DLP:01-JUN-2016 Product Code - Hyoscine butylbromide Version 2.1_CA ABBREVIATIONS ATC: Anatomical Therapeutic Chemical DLP: Data Lock Point INN: International Nonproprietary Name QPPV: Qualified Person for Pharmacovigilance RMP: Risk Management Plan Property of the Sanofi group - strictly confidential Page 5 QSD-010763 Version 4.0 RISK MANAGEMENT PLAN - Preliminary Section FINAL DLP:01-JUN-2016 Product Code - Hyoscine butylbromide Version 2.1_CA Table 5 - Overview of the RMP Parts and Modules in the current RMP Date of Rationale for update Module version PART MODULE or ANNEX approval number (opinion date) In the context of GVP V Part I – Product(s) revision 2, use of the 2.1_CA Not applicable overview corresponding EU-RMP template. In the context of GVP V revision 2, use of the Part II - Safety SI - Epidemiology of the 2.1_CA Not applicable specification indication(s) and target population(s) corresponding EU-RMP template. In the context of GVP V revision 2, use of the SII - Non-clinical part of the safety 2.1_CA Not applicable specification corresponding EU-RMP template. In the context of GVP V revision 2, use of the SIII - Clinical trial exposure 2.1_CA Not applicable corresponding EU-RMP template. In the context of GVP V revision 2, use of the SIV - Populations not studied in 2.1_CA Not applicable clinical trials corresponding EU-RMP template. In the context of GVP V revision 2, use of the SV - Post-authorization experience 2.1_CA Not applicable corresponding EU-RMP template. In the context of GVP V revision 2, use of the SVI - Additional EU requirements 2.1_CA Not applicable for the safety specification corresponding EU-RMP template. In the context of GVP V revision 2, use of the SVII - Identified and potential risks 2.1_CA Not applicable corresponding EU-RMP template. In the context of GVP V revision 2, use of the SVIII - Summary of the safety 2.1_CA Not applicable concerns corresponding EU-RMP template. Property of the Sanofi group - strictly confidential Page 6 QSD-010763 Version 4.0 RISK MANAGEMENT PLAN - Preliminary Section FINAL DLP:01-JUN-2016 Product Code - Hyoscine butylbromide Version 2.1_CA Part III - In the context of GVP V Pharmacovigilance plan revision 2, use of the (including post- 2.1_CA Not applicable corresponding EU-RMP authorization safety studies) template. Part IV - Plans for post- In the context of GVP V authorization efficacy revision 2, use of the 2.1_CA Not applicable studies corresponding EU-RMP template. Part V - Risk In the context of GVP V minimization measures revision 2, use of the (including evaluation of 2.1_CA Not applicable corresponding EU-RMP effectiveness of risk minimization activities) template. Part VI - Summary of In the context of GVP V the risk management plan revision 2, use of the 2.1_CA Not applicable corresponding EU-RMP template. Part VII - Annexes Annex 1 – Eudravigilance Not applicable Not applicable Not applicable Interface Annex 2 – Tabulated summary of In the context of GVP V revision 2, use of the planned, on-going and completed 2.1_CA Not applicable studies in the pharmacovigilance corresponding EU-RMP plan template. Annex 3 – Protocols for proposed, on-going, and completed Not applicable Not applicable Not applicable studies in the pharmacovigilance plan Annex 4 – Specific adverse event Not applicable Not applicable Not applicable follow-up forms Annex 5 – Protocols for proposed Not applicable Not applicable Not applicable and on-going studies in Part IV Annex 6 – Details of proposed Not applicable Not applicable Not applicable additional risk minimization activities In the context of GVP V revision 2, use of the Annex 7 – Other supporting data 2.1_CA Not applicable (including referenced material) corresponding EU-RMP template. In the context of GVP V Annex 8 - Summary of changes revision 2, use of the to the risk management plan over 2.1_CA Not applicable time corresponding EU-RMP template. Property of the Sanofi group - strictly confidential Page 7 QSD-010763 Version 4.0 RISK MANAGEMENT PLAN - PART I PRODUCT(S) OVERVIEW Active substance(s) (INN or common name) Hyoscine butylbromide Product(s) concerned (brand name(s)) BUSCOPAN ® tablet and ampoule) Name of Marketing Authorization Holder or Applicant Boehringer Ingelheim Limited Data lock point (DLP) for this module 01-JUN-2016 Version number of Risk Management Plan (RMP) when this Version 2.1_CA module was last updated Property of the Sanofi group - strictly confidential Page 1 QSD-010763 Version 4.0 RISK MANAGEMENT PLAN - PART I FINAL DLP:01-JUN-2016 Product Code - Hyoscine butylbromide Version 2.1_CA TABLE OF CONTENTS PRODUCT(S) OVERVIEW.............................................................................................................................. 1 TABLE OF CONTENTS .................................................................................................................................. 2 LIST OF TABLES ........................................................................................................................................... 3 ABBREVIATIONS ........................................................................................................................................... 4 REFERENCES ................................................................................................................................................ 9 Property of the Sanofi group - strictly confidential Page 2 QSD-010763 Version 4.0 RISK MANAGEMENT PLAN - PART I FINAL DLP:01-JUN-2016 Product Code - Hyoscine butylbromide Version 2.1_CA LIST OF TABLES Table 1 - Product Overview ............................................................................................................................. 5 Property of the Sanofi group - strictly confidential Page 3 QSD-010763 Version 4.0 RISK MANAGEMENT PLAN - PART I FINAL DLP:01-JUN-2016 Product Code - Hyoscine butylbromide Version 2.1_CA ABBREVIATIONS ATC: Anatomical Therapeutic Chemical DLP: Data Lock Point e-CTD: Electronic Common Technical Document EEA: European Economic Area EU: European Union INN: International Nonproprietary Name RMP: Risk Management Plan Property of the Sanofi group - strictly confidential Page 4 QSD-010763 Version 4.0 RISK MANAGEMENT PLAN - PART I FINAL DLP:01-JUN-2016 Product Code - Hyoscine butylbromide Version 2.1_CA Table 1 - Product Overview Active substance(s) Hyoscine butylbromide (INN or common name) Pharmacotherapeutic group(s) Belladonna alkaloids, semisynthetic, quarternary ammonium compounds (ATC Code) (ATC code A03BB01) Marketing Authorization Holder Boehringer Ingelheim