Drug safety of oral iron chelator deferiprone in children: = Arzneimittelsicherheit des oralen Eisenchelators Deferipron bei Kindern
Gespeichert in:
1. Verfasser: | |
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Format: | Abschlussarbeit Buch |
Sprache: | English |
Veröffentlicht: |
Erlangen ; Nürnberg
[2017]
|
Schlagworte: | |
Online-Zugang: | Inhaltsverzeichnis |
Beschreibung: | xi, 193 Seiten Illustrationen, Diagramme 30 cm |
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245 | 1 | 0 | |a Drug safety of oral iron chelator deferiprone in children |b = Arzneimittelsicherheit des oralen Eisenchelators Deferipron bei Kindern |c vorgelegt von Sebastian Botzenhardt |
246 | 1 | 3 | |a Arzneimittelsicherheit des oralen Eisenchelators Deferipron bei Kindern |
246 | 1 | 1 | |a Arzneimittelsicherheit des oralen Eisenchelators Deferipron bei Kindern |
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502 | |b Dissertation |c Friedrich-Alexander-Universität Erlangen-Nürnberg |d 2017 | ||
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Datensatz im Suchindex
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adam_text | CONTENTS
DISCLOSURE.......................................................................................................................
V
ABSTRACT...................................................................................................................................................VI
ZUSAMMENFASSUNG..............................................................................................................................
IX
1 GENERAL
INTRODUCTION.............................................................................................................1
1.1 BACKGROUND AND
RATIONALE...........................................................................................................
2
1.2 DRUG USE IN
PAEDIATRICS.................................................................................................................5
1.2.1 CLINICAL
PHARMACOLOGY...............................................................................................................
5
1.2.2 OFF-LABEL
USE.................................................................................................................................7
1.2.3 EU REGULATORY
INITIATIVES............................................................................................................
8
1.2.4 ADVERSE DRUG
REACTIONS...............................................................................................................
9
1.2.5 PHARMACOVIGILANCE AND PHARMACOEPIDEMIOLOGY
....................................................................
11
1.3 HEREDITARY HAEMOGLOBINOPATHIES
.............................................................................................
13
1.3.1
CLASSIFICATION............................................................................................................................
13
1.3.2 SICKLE CELL
DISEASE.......................................................................................................................14
1.3.3
THALASSAEMIA............................................................................................................................
15
1.4
SS-THALASSAEMIA............................................................................................................................
16
1.4.1
PATHOPHYSIOLOGY........................................................................................................................16
1.4.2
EPIDEMIOLOGY............................................................................................................................
17
1.4.3 CLINICAL MANIFESTATIONS AND MANAGEMENT
.............................................................................
19
1.5 TRANSFUSIONAL IRON
OVERLOAD......................................................................................................22
1.5.1 IRON
METABOLISM......................................................................................................................
22
1.5.2
PATHOPHYSIOLOGY.......................................................................................................................
23
1.5.3
MONITORING...............................................................................................................................
23
1.5.4
COMPLICATIONS..........................................................................................................................23
1.5.5 T
REATMENT................................................................................................................................
24
1.6
DEFERIPRONE................................................................................................................................
26
1.6.1 PHARMACEUTICAL
CHEMISTRY.......................................................................................................
26
1.6.2
PHARMACODYNAMICS.................................................................................................................
27
1.6.3
PHARMACOKINETICS.....................................................................................................................28
1.6.4
PHARMACOGENETICS....................................................................................................................29
1.6.5 DRUG
FORMULATIONS..................................................................................................................
29
1.6.6 CLINICAL
EFFICACY........................................................................................................................
30
1.6.7 CLINICAL
SAFETY...........................................................................................................................
31
1.6.8 COMPLIANCE AND QUALITY OF
LIFE.........................................................................................
35
1.6.9 MARKETING AND
PHARMACOECONOMICS......................................................................................
35
2 PART I: SAFETY OF IRON CHELATORS IN YOUNG PATIENTS WITH
HAEMOGLOBINOPATHIES...........................................................................................................
37
2.1
INTRODUCTION................................................................................................................................
38
2.2
METHODS........................................................................................................................................39
2.2.1 DATA SOURCES AND SEARCH
STRATEGY............................................................................................
39
2.2.2 STUDY
SELECTION..........................................................................................................................39
2.2.3 DATA
COLLECTION..........................................................................................................................40
2.2.4 QUALITY
ASSESSMENT...................................................................................................................
40
2.2.5 DATA
SYNTHESIS...........................................................................................................................40
2.3
RESULTS...........................................................................................................................................41
2.3.1 LITERATURE SEARCH
RESULTS..........................................................................................................
41
2.3.2 META-ANALYSIS OF REPORTED AE INCIDENCES
..............................................................................
47
2.3.3 QUALITY ASSESSMENT
RESULTS................................................ 47
2.3.4 DEFEROXAMINE (DFO)
MONOTHERAPY.......................................................................................
50
2.3.5 DEFERIPRONE (DFP)
MONOTHERAPY...........................................................................................
50
2.3.6 DEFERASIROX (DFX)
MONOTHERAPY............................................................................................
51
2.3.7 SEQUENTIAL DEFERIPRONE AND DEFEROXAMINE COMBINATION (SEQ DFP+DFO)
........................
52
2.3.8 SEQUENTIAL DEFERASIROX AND DEFEROXAMINE COMBINATION (SEQ
DFX+DFO).........................52
2.3.9 SIMULTANEOUS DEFERIPRONE AND DEFEROXAMINE COMBINATION (SIM
DFP+DFO)
....................
52
2.3.10 SIMULTANEOUS DEFERIPRONE AND DEFERASIROX COMBINATION (SIM
DFP+DFX)
........................
53
2.3.11 DISCONTINUATION RATE DUE TO ADVERSE
EVENTS............................................................................53
2.4
DISCUSSION....................................................................................................................................
54
2.4.1 STRENGTHS AND
LIMITATIONS.........................................................................................................
54
2.4.2 ADVERSE EFFECTS REPORTING
QUALITY............................................................................................54
2.4.3 GENERAL
CONSIDERATIONS............................................................................................................
55
2.4.4 SAFETY PROFILE OF DEFEROXAMINE
(DFO)....................................................................................
55
2.4.5 SAFETY PROFILE OF DEFERIPRONE
(DFP)........................................................................................56
2.4.6 SAFETY PROFILE OF DEFERASIROX
(DFX).........................................................................................
57
2.4.7 SAFETY PROFILE OF COMBINED IRON CHELATION REGIMENS
.............................................................
58
3 PART II: SAFETY OF DEFERIPRONE THERAPY IN CHINESE CHILDREN WITH
THALASSAEMIA...............................................................................................................................
59
3.1
INTRODUCTION................................................................................................................................60
3.2
METHODS.......................................................................................................................................
61
3.2.1 STUDY
DESIGN.............................................................................................................................
61
3.2.2 DATA
SOURCE...............................................................................................................................
61
3.2.3 DATA
COLLECTION.........................................................................................................................
61
3.2.4 STUDY POPULATION AND OBSERVATION PERIOD
.............................................................................
62
3.2.5 ADVERSE DRUG REACTION
IDENTIFICATION......................................................................................
62
3.2.6 STATISTICAL
ANALYSIS.....................................................................................................................63
3.3
RESULTS..........................................................................................................................................
64
3.3.1 PATIENT
CHARACTERISTICS..............................................................................................................
64
3.3.2 IDENTIFIED ADVERSE DRUG
REACTIONS............................................................................................65
3.3.3 NEUTROPENIA AND
AGRANULOCYTOSIS...........................................................................................66
3.3.4 OTHER IDENTIFIED
ADRS.............................................................................................................
67
3.3.5 TREATMENT
DISCONTINUATIONS....................................................................................................69
3.4
DISCUSSION....................................................................................................................................70
3.4.1 STRENGTHS AND
LIMITATIONS........................................................................................................70
3.4.2 NEUTROPENIA AND
AGRANULOCYTOSIS...........................................................................................70
3.4.3 OTHER ADVERSE DRUG
REACTIONS...................................................................................................71
3.4.4 TREATMENT
DURATION..................................................................................................................72
4 PART ILLS LONG-TERM SAFETY OF DEFERIPRONE IN PAEDIATRIC PATIENTS WITH
SS-THALASSAEMIA
MAJOR............................................................................................................
73
4.1
INTRODUCTION................................................................................................................................74
4.2
METHODS.......................................................................................................................................75
4.2.1 STUDY DESIGN AND PATIENT RECRUITMENT
..........................................
75
4.2.2 DATA
COLLECTION.........................................................................................................................
76
4.2.3
DEFINITIONS................................................................................................................................77
4.2.4 ADVERSE DRUG REACTION IDENTIFICATION
PROCESS.........................................................................79
4.2.5 SAMPLE
SIZE...............................................................................................................................80
4.2.6 STATISTICAL METHODS AND DATA MANAGEMENT
............................................................................
80
4.3
RESULTS..........................................................................................................................................82
4.3.1 STUDY
POPULATION.....................................................................................................................82
4.3.2 CHELATION
CHARACTERISTICS.........................................................................................................84
4.3.3 LABORATORY
PARAMETERS............................................................................................................86
4.3.4 IDENTIFIED ADVERSE DRUG REACTIONS TO
DEFERIPRONE...................................................................88
4.3.5 END OF FOLLOW-UP AND PERMANENT DFP
WITHDRAWAL...............................................................95
4.3.6 POTENTIAL RISK FACTORS FOR ADR OCCURRENCE AND DFP DISCONTINUATION
.................................
98
4.4
DISCUSSION...................................................................................................................................
99
4.4.1 STRENGTHS AND
LIMITATIONS.......................................................................................................
99
4.4.2 OBSTACLES DURING STUDY
IMPLEMENTATION..............................................................................
100
4.4.3 LABORATORY PARAMETERS AND CLINICAL
EFFECTIVENESS................................................................101
4.4.4 NEUTROPENIA AND
AGRANULOCYTOSIS.........................................................................................101
4.4.5
ARTHROPATHY...........................................................................................................................102
4.4.6 INCREASED
TRANSAMINASES........................................................................................................103
4.4.7 GASTROINTESTINAL
DISORDERS......................................................................................................103
4.4.8 ADR-RELATED DRUG
WITHDRAWALS.............................................................................................
103
5 GENERAL
CONCLUSION..............................................................................................................
105
5.1 RESULTS OF THIS WORK IN THE CONTEXT OF EXISTING
DATA.............................................................106
5.1.1 OVERALL
FINDINGS......................................................................................................................
106
5.1.2 PERMANENT THERAPY
DISCONTINUATIONS....................................................................................107
5.1.3
AGRANULOCYTOSIS......................................................................................................................
107
5.1.4 N
EUTROPENIA............................................................................................................................
108
5.1.5
ARTHROPATHY...........................................................................................................................
109
5.1.6 INCREASED
TRANSAMINASES.........................................................................................................109
5.1.7 GASTROINTESTINAL
DISORDERS......................................................................................................109
5.1.8
THROMBOCYTOPENIA................................................................................................................
109
5.1.9 OTHER ADVERSE DRUG
REACTIONS.................................................................................................
110
5.2 RECOMMENDATIONS ON DFP SAFETY IN CHILDREN AND ADOLESCENTS
........................................
I L L
5.3
PERSPECTIVE.................................................................................................................................
113
ACKNOWLEDGEMENTS..............................................................................................................
114
REFERENCES............................................................................................................................................
116
ABBREVIATIONS.....................................................................................................................................132
LIST OF
FIGURES.....................................................................................................................................134
LIST OF
TABLES.......................................................................................................................................135
CURRICULUM VITAE
.........................
136
LIST OF PUBLICATIONS AND
PRESENTATIONS...........................................................................138
APPENDIX.................................................................................................................................................
140
APPENDIX 1: SYSTEMATIC LITERATURE SEARCH
STRATEGIES..........................................................................141
APPENDIX 2: FOREST PLOTS OF POOLED ADVERSE EVENT INCIDENCES FROM
PUBLISHED LITERATURE
..........
146
APPENDIX 3: IDENTIFIED CASES OF SERIOUS ADRS TO DEFERIPRONE IN CHINESE
CHILDREN
.....................
159
APPENDIX 4: USED CAUSALITY AND SEVERITY ASSESSMENT ALGORITHMS
....................................................
162
APPENDIX 5: DEEP-3 CASE REPORT FORM
(CRF)...................................................................................
164
APPENDIX 6: DEEP-3 ELECTRONIC CASE REPORT FORM (ECRF)
EXCERPT.................................................. 192
|
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author | Botzenhardt, Sebastian 1985- |
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ctrlnum | (OCoLC)1017028615 (DE-599)DNB1141938766 |
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language | English |
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spelling | Botzenhardt, Sebastian 1985- Verfasser (DE-588)1141938375 aut Drug safety of oral iron chelator deferiprone in children = Arzneimittelsicherheit des oralen Eisenchelators Deferipron bei Kindern vorgelegt von Sebastian Botzenhardt Arzneimittelsicherheit des oralen Eisenchelators Deferipron bei Kindern Erlangen ; Nürnberg [2017] xi, 193 Seiten Illustrationen, Diagramme 30 cm txt rdacontent n rdamedia nc rdacarrier Dissertation Friedrich-Alexander-Universität Erlangen-Nürnberg 2017 Eisenkomplexe (DE-588)4222910-8 gnd rswk-swf Kind (DE-588)4030550-8 gnd rswk-swf Komplexbildner (DE-588)4164886-9 gnd rswk-swf Thalassämie (DE-588)4184972-3 gnd rswk-swf Metallchelate (DE-588)4169575-6 gnd rswk-swf Arzneimittelsicherheit (DE-588)4143182-0 gnd rswk-swf (DE-588)4113937-9 Hochschulschrift gnd-content Kind (DE-588)4030550-8 s Thalassämie (DE-588)4184972-3 s Arzneimittelsicherheit (DE-588)4143182-0 s Komplexbildner (DE-588)4164886-9 s Eisenkomplexe (DE-588)4222910-8 s Metallchelate (DE-588)4169575-6 s DE-604 DNB Datenaustausch application/pdf http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=029948267&sequence=000001&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA Inhaltsverzeichnis |
spellingShingle | Botzenhardt, Sebastian 1985- Drug safety of oral iron chelator deferiprone in children = Arzneimittelsicherheit des oralen Eisenchelators Deferipron bei Kindern Eisenkomplexe (DE-588)4222910-8 gnd Kind (DE-588)4030550-8 gnd Komplexbildner (DE-588)4164886-9 gnd Thalassämie (DE-588)4184972-3 gnd Metallchelate (DE-588)4169575-6 gnd Arzneimittelsicherheit (DE-588)4143182-0 gnd |
subject_GND | (DE-588)4222910-8 (DE-588)4030550-8 (DE-588)4164886-9 (DE-588)4184972-3 (DE-588)4169575-6 (DE-588)4143182-0 (DE-588)4113937-9 |
title | Drug safety of oral iron chelator deferiprone in children = Arzneimittelsicherheit des oralen Eisenchelators Deferipron bei Kindern |
title_alt | Arzneimittelsicherheit des oralen Eisenchelators Deferipron bei Kindern |
title_auth | Drug safety of oral iron chelator deferiprone in children = Arzneimittelsicherheit des oralen Eisenchelators Deferipron bei Kindern |
title_exact_search | Drug safety of oral iron chelator deferiprone in children = Arzneimittelsicherheit des oralen Eisenchelators Deferipron bei Kindern |
title_full | Drug safety of oral iron chelator deferiprone in children = Arzneimittelsicherheit des oralen Eisenchelators Deferipron bei Kindern vorgelegt von Sebastian Botzenhardt |
title_fullStr | Drug safety of oral iron chelator deferiprone in children = Arzneimittelsicherheit des oralen Eisenchelators Deferipron bei Kindern vorgelegt von Sebastian Botzenhardt |
title_full_unstemmed | Drug safety of oral iron chelator deferiprone in children = Arzneimittelsicherheit des oralen Eisenchelators Deferipron bei Kindern vorgelegt von Sebastian Botzenhardt |
title_short | Drug safety of oral iron chelator deferiprone in children |
title_sort | drug safety of oral iron chelator deferiprone in children arzneimittelsicherheit des oralen eisenchelators deferipron bei kindern |
title_sub | = Arzneimittelsicherheit des oralen Eisenchelators Deferipron bei Kindern |
topic | Eisenkomplexe (DE-588)4222910-8 gnd Kind (DE-588)4030550-8 gnd Komplexbildner (DE-588)4164886-9 gnd Thalassämie (DE-588)4184972-3 gnd Metallchelate (DE-588)4169575-6 gnd Arzneimittelsicherheit (DE-588)4143182-0 gnd |
topic_facet | Eisenkomplexe Kind Komplexbildner Thalassämie Metallchelate Arzneimittelsicherheit Hochschulschrift |
url | http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=029948267&sequence=000001&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA |
work_keys_str_mv | AT botzenhardtsebastian drugsafetyoforalironchelatordeferiproneinchildrenarzneimittelsicherheitdesoraleneisenchelatorsdeferipronbeikindern AT botzenhardtsebastian arzneimittelsicherheitdesoraleneisenchelatorsdeferipronbeikindern |