Linezolid Injection and Fluoxetine: Interaction Details

a) In a retrospective cohort study in older adults who were prescribed oral linezolid 600 mg twice daily (N=1134), serotonin syndrome occurred in fewer than 6 patients (less than 0.5%) who were taking a concomitant antidepressant (n=215). In the propensity score-matched cohort (n=332), there was no difference in the risk of clinically significant serotonin syndrome in patients taking concomitant antidepressants and linezolid compared with patients taking linezolid without antidepressants (adjusted risk difference, -1.2%; 95% CI, -2.9% to 0.5%). There was also no difference in the rate of altered mental status or confusion, hospitalization, or death from any cause between groups. Patients were aged 66 years or older, and of those taking an antidepressant, 47.9% were taking an SSRI, 16.7% were taking an SNRI, 7% were taking a tricyclic antidepressant, 3.3% were taking a norepinephrine and dopamine reuptake inhibitor, and none were taking an MAOI ¹.

b) A 4-year-old girl, weighing 12.8 kg, experienced serotonin syndrome-like symptoms following concomitant use of linezolid and FLUoxetine. Eleven days after receiving FLUoxetine 5 mg daily for acute stress disorder in response to a burn injury, the patient received oral linezolid 140 mg every 12 hours. Two days later, she was premedicated with oral fentanyl 200 mcg prior to a wound debridement procedure. Shortly afterwards, she became agitated and had myoclonus in her arms and legs. She also had mydriasis, was unable to visually track across midline, and her gaze deviated to the lower left quadrant. Discontinuation of FLUoxetine and initiation of oral diphenhydramine 25 mg led to partial improvement in symptoms. Subsequently, linezolid was discontinued and replaced with an alternate antibiotic. Symptoms of agitation, myoclonic movements, and nystagmus resolved over the next 2 days ⁴.

c) The concomitant administration of FLUoxetine and linezolid was associated with mild symptoms of serotonin syndrome in a 23-year-old man as described in a case report. The patient, who had recently achieved complete remission of acute myelogenous leukemia and was admitted for maintenance chemotherapy, routinely received treatment with oral FLUoxetine 60 mg once daily, oral methadone 75 mg once daily, oral voriconazole 300 mg twice daily, transdermal nicotine patch 21 mg (changed daily), oral LORazepam 2 mg twice daily (with 1 mg doses as needed every 4 hours), and oral QUEtiapine 200 mg every evening. On day 9 of admission, the FLUoxetine dose was increased to 80 mg daily for mood instability, and linezolid 600 mg every 12 hours was initiated on day 43. Within 12 hours of initiating linezolid, the patient experienced physical discomfort and severe abdominal pain (described as feeling like a "runner's cramp" and making it "difficult to breathe"). The discomfort continued following another 4 doses of linezolid over the next day. On day 47, linezolid was discontinued, after a total of 6 linezolid doses, and the pain and other symptoms resolved within 48 hours. During linezolid therapy, vital signs and laboratory results were unremarkable, except for chemotherapy-induced neutropenia, thrombocytopenia, and anemia ⁵.

d) A retrospective chart review identified one highly probable case of serotonin syndrome in a patient who received concomitant therapy with linezolid and venlafaxine, followed by citalopram. Charts of 72 inpatients who received linezolid and an SSRI or venlafaxine within 14 days of each other were reviewed for a diagnosis of serotonin syndrome (SS) using the Sternbach and the Hunter serotonin toxicity criteria. Of these patients, 52 (72%) were treated concomitantly with linezolid and an SSRI or venlafaxine. Four patients met the criteria for having either high or low probability of SS. Of these, one case involved an 81-year-old woman who was determined to have a high probability of SS after receiving concomitant linezolid and venlafaxine followed by citalopram. Linezolid was given for a vancomycin-resistant Enterococcus UTI. When the patient presented, she refused to eat, was confused as to time and place, and began shouting. Although she appeared to have met 6 of the Sternbach criteria and 4 of the Hunter criteria for SS, a diagnosis of SS was not documented in her chart. Her blood pressure was 180 mmHg with a heart rate of 120 beats/min and a respiratory rate of 50 breaths/min. The following day, she barely spoke and could not be aroused; additional symptoms included lethargy, extremity twitching and jerking, eyes rolled back in her head, and labored breathing. Linezolid was discontinued, and she was sedated and intubated. Five days following onset of symptoms and 2 days after linezolid was stopped, she was extubated and had returned to baseline mental status with the ability to communicate ².

e) In one case report, a 39-year-old woman experienced symptoms of serotonin syndrome after concomitant treatment with FLUoxetine and linezolid. She was admitted to the emergency room after being found unresponsive at home. This patient had a history of depression, suicide attempts and alcohol dependency. Before admission, her medications consisted of disulfiram, FLUoxetine, busPIRone, cyclobenzaprine, and folate. All medications were discontinued upon admission. The patient was given 2 doses of physostigmine for anticholinergic symptoms believed to be caused by a cyclobenzaprine overdose. Two days after admission, the patient became sedated, developed tachycardia, and had sporadic agitation presumably due to alcohol withdrawal. She was given LORazepam and haloperidol for the alcohol withdrawal and agitation. On day 5, she was intubated for respiratory depression thought to be from either pneumonia or respiratory suppression from LORazepam. The patient received vancomycin for MRSA (sputum) and on day 13, was extubated and her mental status improved. On day 18, vancomycin was changed to linezolid. Immediate changes in her mental status were apparent. She experienced convulsions, tremors, weakness, and perspiration. After 2 doses of linezolid, the patient had a temperature of 98 degrees, blood pressure of 140/90 mmHg, a heart rate of 170, and respirations of 18. Linezolid was discontinued and the vancomycin regimen restarted. The patient was diagnosed with benzodiazepine withdrawal, neuroleptic syndrome, sepsis, meningitis, and serotonin syndrome. Serotonin syndrome was diagnosed as a likely drug interaction between linezolid and FLUoxetine ⁶.