| アブストラクト | BACKGROUND: The 3 fluoroquinolone (FQ) antibiotics - ciprofoxacin, levofoxacin, and moxifoxacin - are commonly administered to oncology patients. Although these oral antibiotics are approved by the US Food and Drug Administration (FDA) for treatment of urinary tract infections, acute bacterial sinusitis, or bacterial infection in patients with chronic obstructive pulmonary disease, they are commonly prescribed off-label to neutropenic cancer patients for the prevention and treatment of infections associated with febrile neutropenia. New serious FQ-associated safety concerns have been identified through novel collaborations between FQ-treated persons who have developed long-term neuropsychiatric (NP) toxicity, pharmacovigilance experts, and basic scientists. OBJECTIVE: To conduct basic science and clinical investigations of a newly identified adverse drug reaction, termed FQ-associated disability. METHODS: 5 groups of C57BL/6 mice receiving the antibiotic ciprofoxacin in 10-mg increments (10 mg/kg-50 mg/kg) and 1 group of control mice were evaluated. The Southern Network on Adverse Reactions (SONAR) and a social network of FQ-treated persons with long-term NP toxicity (the Floxed Network) conducted a web-based survey. The clinical toxicity manifestations reported by 94 respondents to the web-based survey of persons who had received 1 or more doses of an FQ prescribed for any indication (generally at FDA-approved dosages) and who subsequently experienced possible adverse drug reactions were compared with adverse event information included on the product label for levofoxacin and with FQ-associated adverse events reported to the FDA's MedWatch program. RESULTS: Mice treated with ciprofoxacin had lower grip strengths, reduced balance, and depressive behavior compared with the controls. For the survey, 93 of 94 respondents reported FQ-associated events including anxiety, depression, insomnia, panic attacks, clouded thinking, depersonalization, suicidal thoughts, psychosis, nightmares, and impaired memory beginning within days of FQ initiation or days to months of FQ discontinuation. The FDA Adverse Event Reporting System (FAERS) included 210,705 adverse events and 2,991 fatalities for FQs. Levofoxacin and ciprofoxacin toxicities were neurologic (30% and 26%, respectively), tendon damage (8% and 6%), and psychiatric (10% and 2%). In 2013, an FDA safety review reported that FQs affect mammalian topoisomerase II, especially in mitochondria. In 2013 and 2014, SONAR fled citizen petitions requesting black box revisions identifying neuropsychiatric toxicities and mitochrondrial toxicity as serious levofoxacin-associated adverse drug reactions. In 2015, FDA advisors recommended that FQ product labels be revised to include information about this newly identified disability syndrome termed "FQ-associated disability" (FQAD). LIMITATIONS: Basic science studies evaluated NP toxicity for only 1 FQ, ciprofoxacin. CONCLUSION: Pharmacovigilance investigators, a social network, and basic scientists can collaborate on pharmacovigilance investigations. Revised product labels describing a new serious adverse drug reaction, levofoxacin-associated long-term disability, as recommended by an FDA advisory committee, are advised. |
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| ジャーナル名 | The Journal of community and supportive oncology |
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| 投稿日 | 2016/3/10 |
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| 投稿者 | Kaur, Kamaljeet; Fayad, Raja; Saxena, Arpit; Frizzell, Norma; Chanda, Anindya; Das, Suvarthi; Chatterjee, Saurabh; Hegde, Shweta; Baliga, Manjeshwar Shrinath; Ponemone, Venkatesh; Rorro, Matthew; Greene, Jennifer; Elraheb, Yasmine; Redd, Alan J; Bian, John; Restaino, John; Norris, LeAnn B; Qureshi, Zaina P; Love, Bryan L; Brookstaver, Brandon; Georgantopoulos, Peter; Sartor, Oliver; Raisch, Dennis W; Rao, Gowtham; Lu, Kevin; Ray, Paul; Hrusheshky, William; Schulz, Richard; Ablin, Richard; Noxon, Virginia; Bennett, Charles L |
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| 組織名 | Applied Physiology Division, Department of Exercise Science, University of South;Carolina, Columbia, South Carolina, USA.;Center for Colon Cancer Research, University of South Carolina, Columbia, South;Carolina, USA.;Department of Pharmacology, Physiology and Neuroscience, USC Shoool of Medicine,;University of South Carolina, Columbia, South Carolina, USA.;Department of Environment Health Sciences, University of South Carolina,;Columbia, South Carolina, USA.;Department of Research, Father Muller Medical College, Mangalore, Karnataka,;India.;Fortis-Totipotent RX Centre for Cellular Medicine, Delhi, India.;Department of Anthropology, University of Kansas, Lawrence, Kansas, USA.;Southern Network on Adverse Reactions (SONAR), South Carolina Center of Economic;Excellence for Medication Safety, College of Pharmacy, University of South;Dorn Research Institute, Columbia, South Carolina, USA.;Arnold School of Public Health, University of South Carolina, Columbia, South;Tulane University School of Medicine, New Orleans, Louisiana, USA.;College of Pharmacy, University of New Mexico, Albuquerque, New Mexico, USA.;Oncology Analytics Inc, Plantation, Florida, USA.;Department of Pathology, University of Arizona College of Medicine, The Arizona;Cancer Institute and BIO5 Institute, Tucson, Arizona, USA.;Carolina, Columbia, South Carolina, USA. bennettc@sccp.sc.edu. |
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| Pubmed リンク | https://www.ncbi.nlm.nih.gov/pubmed/26955658/ |
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