Professor Claude Carbon

20 June, 2018

Professor Carbon confirmed gastrointestinal problems account for the largestpercentage of adverse drug reactions with fluoroquinolones.however,those of most clinical concern involve the central nervous and cardiovascular systems,hepatatotoxicity and phototoxicity.

European data from 5,388 patients treated with levofloxacin showed that 12% had an adverse event possibly related to the drug, but only 1% were classified as serious.In the comparator arm, 41% had an adverse event, with 13% likely to be related tothe antibiotic.

Factors influencing adverse drug reactions associated with levofloxacin have been investigated. Results from a double-blind trial confirm that there is no significant impact of dose, or patient age on the rate of adverse events. In addition, there were no significant drug-interactions noted, although absorption is impaired when administered concomitantly with antacids or iron compounds.

A pharmacovigilance study with more than 130 million registered prescriptions for levofloxacin demonstrated that the probability for any serious adverse events are minimal. Tendinitis occurred in 1 case per 500,000 prescriptions, hepatic abnormalities in 1 per 650,000, anaphylactic reactions or convulsions in 1 per one million, psychosis in 1 per 6 million, phototoxicity in 1 per 12 million and torsade de pointes in 1 case per 15 million prescriptions. In comparison, major ADRs have been noted for other fluoroquinolones within a very short time frame, following far fewer prescriptions.

Results from animal and clinical studies confirm levofloxacin is not associated with significant hepatotoxicity, with less than 1% of patients developing an abnormality in one of their liver function tests. In contrast, trovafloxacin is recognised as causing hepatic problems, with 9% of patients developing a large increase in transaminase levels. Fourteen cases of severe liver injury have been associated with trovafloxacin, leading to its withdrawal from the market in Europe.

Cardiovascular abnormalities have been reported with some fluoroquinolones. However, levofloxacin appears very safe, unlike sparfloxacin which causes 1.2 to 3% of patients to develop QT prolongation. This has been reported in only 1 case per 15 million prescriptions for levofloxacin.Moxifloxacin is also associated with a significant QT prolongation of 6 milliseconds compared to only 1 millisecond for non-fluoroquinolone agents.

Phototoxicity is more common to 8-halogenated fluoroquinolones. Using very well validated models, ofloxacin and levofloxacin have shown a very low phototoxic potential.There is then a rapid four-fold increase in risk for lomefloxacin, and an even higher risk for sparfloxacin, enoxacin and pefloxacin.

CNS adverse events associated with fluoroquinolones include insomnia, dizziness, and convulsions, the incidence of the latter increasing when co-administered with non-steroidal anti-inflammatory drugs. The incidence of CNS events for individual fluoroquinolones relates to the potential for GABA binding. Studies using rat hippocampal slices show that levofloxacin, ofloxacin and moxifloxacin have the lowest potential to induce CNS adverse events.These results help confirm that levofloxacin is an extremely safe agent in comparison to other fluoroquinolones.