title: Pharmacovigilance and reporting oversight in US FDA fast-track process: bisphosphonates and osteonecrosis of the jaw.
abstract: More than half of all serious adverse reactions are identified 7 or more years after a drug receives approval from the US Food and Drug Administration (FDA). In 2002, 9 months after the intravenous bisphosphonate zoledronic acid received regulatory approval for marketing, the FDA received reports of nine patients with cancer, who were treated with zoledronic acid, who unexpectedly developed osteonecrosis of the jaw. During the next 2 years, three oral surgeons described 104 patients with cancer with osteonecrosis of the jaw in the medical literature and identified intravenous bisphosphonate therapy as being common to the care of these patients. In subspecialty medical, radiology, and dental journals, case reports and case series described clinical features of osteonecrosis of the jaw in patients with cancer who were treated with bisphosphonates. Manufacturer-sponsored epidemiological studies reported the first estimates of the incidence of this toxic effect, ranging from 0.1% to 1.8%. By contrast, independent epidemiological efforts from clinicians and the International Myeloma Foundation reported incidence estimates between 5% and 10%. Between 2003 and 2005, warnings about the risks of bisphosphonate-associated osteonecrosis were disseminated by national regulatory agencies, the manufacturers of bisphosphonates, and the International Myeloma Foundation. From 2006, independent clinical recommendations for diagnosis, prevention, and treatment of this toxic effect have been disseminated by manufacturers, national regulatory authorities, the International Myeloma Foundation, and medical specialty organisations. Furthermore, independent efforts by pharmaceutical manufacturers, dental and medical professionals, a non-profit organisation (the International Myeloma Foundation), patients, and regulatory authorities has led to the rapid identification and dissemination of safety information for this serious adverse reaction. Better coordination of safety-related pharmacovigilance initiatives is now needed.
authors.affiliation: Divisions of Hematology/Oncology and Geriatric Medicine, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL USA.
authors.forename: Beatrice J
authors.initials: BJ
authors.lastname: Edwards
authors.forename: Mrinal
authors.initials: M
authors.lastname: Gounder
authors.forename: June M
authors.initials: JM
authors.lastname: McKoy
authors.forename: Ian
authors.initials: I
authors.lastname: Boyd
authors.forename: Mathew
authors.initials: M
authors.lastname: Farrugia
authors.forename: Cesar
authors.initials: C
authors.lastname: Migliorati
authors.forename: Robert
authors.initials: R
authors.lastname: Marx
authors.forename: Salvatore
authors.initials: S
authors.lastname: Ruggiero
authors.forename: Meletios
authors.initials: M
authors.lastname: Dimopoulos
authors.forename: Dennis W
authors.initials: DW
authors.lastname: Raisch
authors.forename: Seema
authors.initials: S
authors.lastname: Singhal
authors.forename: Ken
authors.initials: K
authors.lastname: Carson
authors.forename: Eniola
authors.initials: E
authors.lastname: Obadina
authors.forename: Steve
authors.initials: S
authors.lastname: Trifilio
authors.forename: Dennis
authors.initials: D
authors.lastname: West
authors.forename: Jayesh
authors.initials: J
authors.lastname: Mehta
authors.forename: Charles L
authors.initials: CL
authors.lastname: Bennett
mesh_terms: D000284:Administration, Oral; D016907:Adverse Drug Reaction Reporting Systems; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects*; D050071:Bone Density Conservation Agents / Q000009:adverse effects; D004164:Diphosphonates / Q000008:administration & dosage / Q000009:adverse effects*; D017277:Drug Approval; D005260:Female; D006801:Humans; D007093:Imidazoles / Q000009:adverse effects; D015994:Incidence; D007262:Infusions, Intravenous; D007568:Jaw / Q000187:drug effects* / Q000473:pathology; D008297:Male; D010020:Osteonecrosis / Q000139:chemically induced* / Q000453:epidemiology / Q000601:surgery; D000077268:Pamidronate; D015985:Precipitating Factors; D014081:Tooth Extraction; D014481:United States / Q000453:epidemiology; D014486:United States Food and Drug Administration; D000077211:Zoledronic Acid
chemical_list: D000970:Antineoplastic Agents; D050071:Bone Density Conservation Agents; D004164:Diphosphonates; D007093:Imidazoles; D000077211:Zoledronic Acid; D000077268:Pamidronate