Editorial Note: Twenty-five years ago, Diane Fried took Floxin, a fluorquinolone antibiotic and a predecessor of Levaquin and Cipro, and was severely damaged as a consequence, leading her husband to write Bitter Pills. Three years ago we featured two posts on fluoroquinolone antibiotic problems under the heading of Flox-Tox. We have also featured posts on the closely related Lariam – mefloquine – and its toxicities.
This is a group of drugs that pretty often produce quite terrible problems. To my amazement doctors in hospital settings prescribe them as though there is little difference between them and other antibiotics. For those of you frightened by what you read below and on other RxISK posts – there is a simple strategy that seems to work. When you go into hospital or to a doctor and they ask if you have any allergies – Say yes – fluoroquinolones like Levaquin and Cipro.
An article has just been published by SONAR, from Charlie Bennett and colleagues on the problems linked to these drugs. The press release is reproduced below and the article is Here.
FQAD
Flouroquinolone-associated disability is a life-threatening toxicity, recognized by a Food and Drug Administration safety reviewer and an FDA Advisory Committee and now described in the medical literature.
A research project funded by the National Cancer Institute and a large grant from the State of South Carolina and led by Charles L Bennett MD PhD MPP, the SmartState Chair and Director of the Southern Network on Adverse Reactions (SONAR) has reported on a serious toxicity caused by fluoroquinolone (FQ) antibiotics. This toxicity, while serious and life-threatening, has been unrecognized for over two decades. FQs have been amongst the most commonly administered drugs for years. A serious newly termed toxicity, FQ-associated disability (FQAD), has been identified amongst several hundred previously healthy individuals who have been unable to work or perform activities of daily living after as few as one or two doses of a FQ.
This toxicity was investigated by novel collaborations of stakeholders, pharmacovigilance experts, and basic scientists. (SONAR), a pharmaceutical watchdog organization based at the University of South Carolina, filed a Citizen Petition with the FDA about this toxicity in August 2014 requesting a Black Box warning on the product label- a response from the FDA is pending, although on November 5, 2015, an FDA advisory committee voted overwhelmingly that such a change is needed.
In the SONAR basic science study, groups of mice receiving 10 milligram ciprofloxacin increments (10 to 50 mg/kg) and control mice were evaluated. SONAR and a social network of FQ-treated persons with NP dysfunction (the “Floxed Network”) also conducted a web-based survey. Finally, SONAR and the Floxed Network compared survey, product labels, and FDA‘s Adverse Event Reporting System (FAERS) reports. The mice study showed that ciprofloxacin administration led to lower grip strengths, reduced balance, and depressive behavior in treated versus control mice.
Clinically, 93 of 94 survey 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. FDA databases include 210,705 adverse events and 2,991 fatalities for FQs. Levofloxacin and ciprofloxacin toxicities were neurologic (30% and 26%, respectively), tendon damage (8% and 6%, respectively) and psychiatric (10% and 2%, respectively). In 2013, an FDA safety review reported that FQs affect mammalian topoisomerase II, especially in mitochondria.
Fifty television stations reported on the Petitions and on the 2013 FDA Safety Review and interviewed persons with FQ-associated toxicity over the past year. This study, published on February 1, 2016 in the Journal of Community and Supportive Oncology highlights the importance of collaborations among pharmacovigilance investigators, a social network, and basic scientists in evaluating FQAD. At the FDA November 5, 2015 advisory meeting, a FDA safety reviewer independently reported on 178 FQAD events included in FDA databases. The patients had a median age of 46 years, 85% were female, >95% had received two days or less of a FQ, and the affected individuals were disabled for at least one month. Also, 22 persons personally presented their individual case histories at the FDA Advisory Committee meeting. Of these individuals, 85% were female, their median age was 44 years, 95% had received two doses or less of a FQAD although some individuals had delayed onset of FQAD, and disability persisted for > 1 year in all but one individual. Revised product labels describing FQAD, as overwhelmingly recommended by the FDA Advisory Committee in November, are advised.
Coda: One of the people most closely linked with spreading word about FluoroQuinolone Toxicity was Jay S Cohen, who died last December just as this book came out.
Chapter One and Chapter Two of Jay’s book are here.