Source: Pancreas  |  Posted 6 years ago

By Ed Susman

WASHINGTON, DC -- December 19, 2005 -- Although case reports of interactions between the oxazolidinone anti-infective linezolid and selective serotonin reuptake inhibitors (SSRIs), doctors were unable to find that effect in phase 3 and 4 trials.

"A review of adverse events from 15 phase 3 and 4 clinical trials showed no evidence of an increased incidence of signs and symptoms of serotonin syndrome in patients treated concomitantly with linezolid and a selective serotonin reuptake inhibitor or cyclic and other antidepressants," said Meryl Mendelson, MD, medical director, Pfizer Global Pharmaceuticals, New York, New York.

However, Dr. Mendelson noted that because linezolid is a weak monoamine oxidase inhibitor the potential exists for some interaction and doctors should remain vigilant for signs of serotonin syndrome and withdraw use of 1 of the drugs if such a reaction occurs.

Serotonin syndrome includes symptoms such as mental status changes, behavioral changes, hyperthermia, and altered neuromuscular activity, Dr. Mendelson explained in her late-breaker poster presentation here on December 18[^]th[] at the 45[^]th[] Annual Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC).

When she scrutinized adverse effects between linezolid and comparator antibiotics among patients on antidepressants there were no appreciable differences in events between the groups as a whole or when compared by groups of adverse effects.

Group 1 adverse events were hyperthermia, diaphoresis, or flushing. Group 2 events were confusion, sedation, delirium, or central nervous system depression. Group 3 events were restlessness, tremor, or myoclonus.

Dr. Mendelson said that when linezolid and SSRIs were combined there were 3 group 1 events reported in the 117 subjects, for a rate of 2.6%. When the comparator antibiotic was taken along with the SSRI there were 8 adverse events in the 127 patients (6.3%).

There were 2 group 2 adverse events reported among the 117 subjects when linezolid and SSRIs were combined, for a 1.7% rate. When the comparator antibiotic was taken along with the SSRIs, there were 3 adverse events in the 127 patients (2.4%).

When linezolid and SSRIs were combined there was 1 group 3 adverse events (0.9%), and when the comparator antibiotic was taken there were no adverse events.

When a similar comparison was made between the antibiotics and cyclic antidepressants, there were no appreciable differences in outcomes when linezolid was matched against its comparator agent, Dr. Mendelson said. In this grouping 112 patients were on linezolid and 115 took the comparator drug along with the cyclic antidepressant.

[Presentation title: Evaluation of Potential Drug Interactions of Linezolid With Selective Serotonin Reuptake Inhibitors and Other Antidepressants: Analysis of Phase 3 and 4 Clinical Trials. Abstract LB2-1]