Various Qoutes from Dr. Peter Ball and Glenn Tillotson

Comparative tolerability of the newer fluoroquinolone antibacterials
Ball P, Mandell L, Niki Y, Tillotson G
Drug Saf 1999 Nov;21(5):407-21

“…However, postmarketing surveillance has revealed significant hepatotoxicity with trovafloxacin…. In perspective, rare but serious hepatotoxicity has been reported with other fluoroquinolones and the overall incidence of trovafloxacin hepatotoxicity is not dissimilar to that reported with flucloxacillin and amoxicillin-clavulanic acid… rare but serious hepatotoxicity has been reported with other fluoroquinolones…. Prolongation of the QTc interval is also a class effect,… Tendinitis and rupture, usually of the Achilles tendon, are rare, class-effects of fluoroquinolones,…

Semin Respir Infect 2001 Sep;16(3):215-24
Future of the quinolones.
Ball P.
School of Biomedical Sciences, University of St. Andrews, St. Andrews, Fife, Scotland.

” New fluoroquinolones and fluoronaphthyridones continue to provide the mainstay of antibiotic development, despite recent events associated with unexpected or uncharacteristically severe adverse drug reactions. These have included hepatotoxicity caused by trovafloxacin (suspended), cardiotoxicity associated with grepafloxacin, and phototoxicity caused by clinafloxacin (both withdrawn). Prolongation of the QT interval appears to be an emergent class effect, the implications of which are not yet fully understood. However, the second-generation agents ciprofloxacin and, latterly, levofloxacin have excellent safety profiles… and to be remarkably free of clinically significant adverse effects.


9th European Congress of Clinical Microbiology and Infectious Diseases
Berlin, Germany / March 21-24, 1999

"Ten years ago I would have been howled down for including fluoroquinolones in a list of agents for the management of community-acquired pneumonia," remarked Dr. Peter Ball, Senior Lecturer at the Department of Bio-Medical Sciences, University of St. Andrews, St. Andrews, Scotland. "Nowadays," he said, "the IDSA guidelines have endorsed their use in almost every classification (P. Ball)

"Why should we use these new fluoroquinolones?" Dr. Ball asked. The advantages, he answered, include excellent activity against both typical and atypical respiratory pathogens, very high penetration into tissues and fluids where the infections are centered, activity with once-daily intravenous or oral administration and excellent tolerability”

“Dr. Ball believes, too, that the incidence of dizziness and lightheadedness sometimes attributed to trovafloxacin is not entirely justified”

“"The more than 400,000 patients from post- marketing surveillance studies I have reviewed reveal this to be a very, very small problem," he said. On the other hand, Dr. Ball noted that 97% of patients taking grepafloxacin think that the drug affected their sense of taste and many of them have refused to continue taking the compound for that reason”


Trovafloxacin (Trovan) withdrawn due to severe liver damage
Dr. Ball “excellent tolerability”

Grepafloxacin Voluntarily withdrawn because of the possibility of torsades de pointes occurring with its use.

Safety of the Fluoroquinolone Antibiotics: Focus on Molecular Structure CME
Stacy J. Childs, MD, University of Colorado Health Sciences Center, Denver
[Infect Urol 13(1):3-10, 2000. © 2000 Cliggott Publishing Co., Division of SCP/Cliggott Communications, Inc.]
“…] The pathophysiology of adverse hepatic events (trovafloxacin) and hypoglycemia (trovafloxacin and temafloxacin) remains unknown. It has been suggested that the addition of 2,4-difluorophenyl moieties at C1 may be the culprit for the toxic effects associated with both these agents, although there is no definitive evidence. A proposed mechanism is that this component may be metabolically cleaved off and act as a hapten, triggering an array of unusual immunologic sequelae, including hepatic eosinophilia (Peter Ball, MD, University of St Andrews, Scotland, personal communication, 1999). “

Safety Profile of Moxifloxacin
Professor Lionel Mandell (Departments of Medicine and Infectious Diseases, McMaster University, Canada) reviewed safety issues with the fluoroquinolones as a class.

Dr Peter Ball (Department of Medical Science, University of St Andrews, Scotland) provided an update on the safety of moxifloxacin.

“Although their use in hundreds of millions of patients worldwide has demonstrated that the fluoroquinolones are generally well tolerated,”

“Most adverse effects with the fluoroquinolones are mild, transient and rarely result in discontinuation of therapy.”

“. The overall incidence of quinolone-related adverse events is similar for moxifloxacin and comparator drugs, discontinuation rates are also similar and serious adverse events are extremely rare”

Other quotes of interest from various articles:

“. A small number of patients receiving fluoroquinolones developed visual disturbances including color distortion and diplopia (Ball, 1989).”

“…the development of severe neuropsychiatric problems including hallucinations and psychosis were reported. The reactions occurred predominantly in the elderly and may have involved predisposing factors (Ball, 1989; Jungst & Mohr, 1988). “

“. Abdominal pain, dyspepsia, anorexia, vomiting, and nausea have been reported with therapeutic use of these agents (Boerema et al, 1985; Holmes et al, 1985; Ball, 1989; Rahm & Schacht, 1989; Prod Info Trovan(R), 1997; Prod Info Raxar(R), 1997). “

“PSEUDOMEMBRANOUS COLITIS has been reported on rare occasions with both OFLOXACIN and CIPROFLOXACIN (Ball, 1989; Rahm & Schacht, 1989; Jungst & Mohr, 1988).”

“- At therapeutic doses hematuria, crystalluria, and interstitial nephritis have been associated with CIPROFLOXACIN therapy in humans. No permanent renal impairment has resulted from ciprofloxacin therapy (Ball, 1989; Hootkins et al, 1989; Garlando et al, 1985). “

“A small number of patients receiving fluoroquinolones developed visual disturbances including color distortion and diplopia (Ball, 1989).”

“Headache, nervousness, anxiety, lightheadedness, and dizziness have been observed during therapeutic use of these agents (Boerema et al, 1985; Holmes et al, 1985; Ball, 1989; Rahm & Schacht, 1989; Prod Info Raxar(R), 1997; Prod Info Trovan(R), 1997; Gajjar et al, 2000)”

“PSEUDOMEMBRANOUS COLITIS has been reported on rare occasions with both OFLOXACIN and CIPROFLOXACIN (Ball, 1989; Rahm & Schacht, 1989; Jungst & Mohr, 1988). “

“At therapeutic doses hematuria, crystalluria, and interstitial nephritis have been associated with CIPROFLOXACIN therapy in humans. No permanent renal impairment has resulted from ciprofloxacin therapy (Ball, 1989; Hootkins et al, 1989; Garlando et al, 1985). “


Safety of the new fluoroquinolones compared with ciprofloxacin.
Ball P.
“Ciprofloxacin is well tolerated; the incidence of adverse events is low and serious adverse events are rare.”

Tolerability of fluoroquinolone antibiotics. Past, present and future.
Ball P, Tillotson G.
Infectious Diseases Unit, Victoria Hospital, Kirkcaldy, Fife, Scotland.
.
“The new fluoroquinolones are essentially a well tolerated group of antibacterials”

 

Editorial Comment by the Foundaton:

The following have been removed from clinical practice, approval denied or their use severely restricted by the FDA.


Trovafloxacin (Trovan) withdrawn due to severe liver damage

Grepafloxacin Voluntarily withdrawn because of the possibility of torsades de pointes occurring with its use.

Clinafloxacin Removed from clinical use due to severe toxicity (i.e.: severe
phototoxicity and hypoglycemia)

Enoxacin (Penetrex) Removed from clinical use by the manufacturer due to
severe toxicity concerns

Gemifloxacin (Factive) Glaxo SmithKline received a non-approval letter from the FDA for the treatment of respiratory tract infections.

Sparfloxacin ( Zagam) Removed from clinical use due to severe toxicity (i.e.: qt time)

Temafloxacin (Omniflox) Removed from clinical use due to severe toxicity (i.e.: haemolytic hepatic reactions)


Almost fifty percent of the fluoroquinolones introduced since 1973 have been sidelined due to severe toxicity issues.

In light of this one has to have serious concerns regarding Dr. Ball’s continuing insistence that these drugs are safe and such reports do not alter their safety profiles. On one hand he is quoted as stating how serious the adverse events are and on the other (especially concerning CIPRO) he states how wonderful and free of adverse events they are. Speaking from both sides of his mouth.

Moderator