title: Safety analysis of 10 clinical trials and for 13 years after first approval of ioflupane 123I injection (DaTscan).
abstract: Ioflupane is an analog of cocaine that binds reversibly with high affinity to the dopamine transporter (DaT) protein, a marker for presynaptic terminals in dopaminergic nigrostriatal neurons. Ioflupane (123)I Injection is also known as DaTscan or DaTSCAN ((123)I-ioflupane is also called (123)I-2-β-carbomethoxy-3β-(4-iodophenyl)-N-(3-fluoropropyl)nortropane or (123)I-FP-CIT). The diagnostic efficacy of DaTscan has been described elsewhere. Here, we present a comprehensive analysis of the safety of DaTscan starting from initiation of clinical development through 13 y after the date of first market approval. Safety data in the sponsor's clinical development safety database from 10 completed DaTscan clinical trials were pooled, and postapproval experience was summarized from standardized aggregate safety reports submitted to regulatory agencies. A total of 1,180 clinical trial subjects (92% of 1,284 subjects planned to receive DaTscan in the clinical trials) received DaTscan. Percentages of subjects with adverse events by category were as follows: all (22%), considered at least possibly related to DaTscan by the investigator (4%), any severe (3%), headache (4%), nausea (2%), dizziness (2%), nasopharyngitis (1%), and injection site hematoma (1%). Four percent of subjects had at least 1 serious adverse event; 5 subjects (<1%) had serious adverse events that led to death. All serious adverse events, including those that led to death, were deemed by an expert clinician to be unrelated to DaTscan. An estimated half a million market doses of DaTscan (for single use) were administered from July 2000 through the July 2013 reporting period. In postapproval safety assessment, 1 death was reported 20 d after (and unrelated to) DaTscan administration. Two spontaneously reported serious adverse drug reactions (ADRs) and 32 spontaneously reported nonserious ADRs were submitted, approximately half of which are identified in labeling. Headache (in clinical trials) and injection site pain (postapproval) were the most commonly reported events or reactions. Although adverse events were reported for 1 in 5 clinical trial subjects, most were mild and considered unrelated to DaTscan administration. Severe events were uncommon, and no serious adverse event occurring in more than 1 subject was deemed related to DaTscan administration. In postapproval experience, the frequency of ADRs spontaneously reported was less than 1 per 10,000 doses administered. Comprehensive safety data show that DaTscan was well tolerated.
authors.affiliation: Institute of Neurological Sciences, Department of Neurology, Southern General Hospital, University of Glasgow, Glasgow, Scotland, United Kingdom.
authors.forename: Donald G
authors.initials: DG
authors.lastname: Grosset
authors.affiliation: Department of Nuclear Medicine, Municipal Hospital Karlsruhe, Inc., Karlsruhe, Germany.
authors.forename: Klaus
authors.initials: K
authors.lastname: Tatsch
authors.affiliation: Department of Neurology, Philipps-University of Marburg, Marburg, Germany.
authors.forename: Wolfgang H
authors.initials: WH
authors.lastname: Oertel
authors.affiliation: Neurology Service, Hospital Clínic de Barcelona, Universitat de Barcelona, IDIBAPS, Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Barcelona, Catalonia, Spain.
authors.forename: Eduardo
authors.initials: E
authors.lastname: Tolosa
authors.affiliation: Department of Clinical Neurology, Nottingham University Hospitals NHS Trust, Nottingham, United Kingdom.
authors.forename: Nin
authors.initials: N
authors.lastname: Bajaj
authors.affiliation: Department of Neurology and Stereotactic Neurosurgery, Otto-von-Guericke-University, Magdeburg, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Kupsch
authors.affiliation: Department of Psychiatry, University of Cambridge, and Cambridgeshire and Peterborough Foundation NHS Foundation Trust, Cambridge, United Kingdom.
authors.forename: John T
authors.initials: JT
authors.lastname: O'Brien
authors.affiliation: The Institute for Neurodegenerative Disorders, New Haven, Connecticut.
authors.forename: John
authors.initials: J
authors.lastname: Seibyl
authors.affiliation: Mental Health Sciences Unit, University College London, Bloomsbury Campus, London, United Kingdom North Essex Partnership NHS Foundation Trust, Essex, United Kingdom.
authors.forename: Zuzana
authors.initials: Z
authors.lastname: Walker
authors.affiliation: Life Sciences, GE Healthcare, Princeton, New Jersey; and.
authors.forename: Paul
authors.initials: P
authors.lastname: Sherwin
authors.affiliation: H2O Clinical, LLC, Hunt Valley, Maryland.
authors.forename: Chris
authors.initials: C
authors.lastname: Chen
authors.affiliation: Life Sciences, GE Healthcare, Princeton, New Jersey; and grachevi@hotmail.com.
authors.forename: Igor D
authors.initials: ID
authors.lastname: Grachev
mesh_terms: D000368:Aged; D002986:Clinical Trials as Topic; D017277:Drug Approval; D005260:Female; D033161:Government Regulation; D006801:Humans; D007267:Injections; D008297:Male; D008875:Middle Aged; D009662:Nortropanes / Q000008:administration & dosage / Q000009:adverse effects*; D012449:Safety
chemical_list: D009662:Nortropanes; C519528:ioflupane
keywords: Parkinson disease/parkinsonism; SPECT; clinical trials systematic review/meta-analysis; dementia with Lewy bodies; patient safety