Fluoxetine with Linezolid Interaction Details

Brand Names Associated with Fluoxetine

Brand Names Associated with Linezolid

Medical Content Editor Dr. Brian Staiger, PharmD
Last updated Nov 13, 2023

Interaction Effect

An increased risk of serotonin syndrome (hypertension, tachycardia, hyperthermia, myoclonus, mental status changes)

Interaction Summary

Concurrent use of FLUoxetine and an MAOI, such as linezolid, is contraindicated. If urgent treatment with linezolid is necessary in a patient receiving FLUoxetine, alternatives are not available, and risk/benefit has been evaluated, promptly discontinue FLUoxetine and then linezolid may be administered. Monitor for serotonin syndrome for 5 weeks or until 24 hours after the last dose of linezolid, whichever comes first. Treatment with FLUoxetine can be resumed 24 hours after the last dose of linezolid. In a retrospective cohort study in older adults, serotonin syndrome occurred in less than 0.5% of patients who were taking a concurrent antidepressant and linezolid. In the propensity score-matched cohort, there was no difference in the risk of serotonin syndrome in patients taking concomitant antidepressants and linezolid compared with patients not taking antidepressants. There was also no difference in the rate of altered mental status or confusion, hospitalization, or death from any cause between groups .

Severity

Contraindicated

Onset

Unspecified

Evidence

Probable

How To Manage Interaction

Concurrent use of FLUoxetine and an MAOI, such as linezolid, is contraindicated. If urgent treatment with linezolid is necessary in a patient receiving FLUoxetine, alternatives are not available, and risk/benefit has been evaluated, promptly discontinue FLUoxetine and then linezolid may be administered. Monitor for serotonin syndrome for 5 weeks or until 24 hours after the last linezolid dose, whichever comes first. FLUoxetine can be resumed 24 hours after the last linezolid dose.

Mechanism Of Interaction

Additive serotonergic effects

Literature Reports

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 .

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 .

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 .

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 .

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 .

Fluoxetine Overview

• Fluoxetine is used to treat depression, obsessive-compulsive disorder (bothersome thoughts that won't go away and the need to perform certain actions over and over), some eating disorders, and panic attacks (sudden, unexpected attacks of extreme fear and worry about these attacks). Fluoxetine is also used to relieve the symptoms of premenstrual dysphoric disorder, including mood swings, irritability, bloating, and breast tenderness. It is also used along with olanzapine (Zyprexa) to treat depression that did not respond to other medications and episodes of depression in people with bipolar I disorder (manic-depressive disorder; a disease that causes episodes of depression, episodes of mania, and other abnormal moods). Fluoxetine is in a class of medications called selective serotonin reuptake inhibitors (SSRIs). It works by increasing the amount of serotonin, a natural substance in the brain that helps maintain mental balance.

Linezolid Overview

• Linezolid is used to treat infections, including pneumonia, and infections of the skin . Linezolid is in a class of antibacterials called oxazolidinones. It works by stopping the growth of bacteria.

• Antibiotics such as linezolid will not work for colds, flu, and other viral infections. Using antibiotics when they are not needed increases your risk of getting an infection later that resists antibiotic treatment.

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Definitions

Severity Categories

Contraindicated

These drugs, generally, should not be used together simultaneously due to the high risk of severe adverse effects. Combining these medications can lead to dangerous health outcomes and should be strictly avoided unless otherwise instructed by your provider.

Major

This interaction could result in very serious and potentially life-threatening consequences. If you are taking this drug combination, it is very important to be under close medical supervision to minimize severe side effects and ensure your safety. It may be necessary to change a medication or dosage to prevent harm.

Moderate

This interaction has the potential to worsen your medical condition or alter the effectiveness of your treatment. It's important that you are monitored closely and you potentially may need to make adjustments in your treatment plan or drug dosage to maintain optimal health.

Minor

While this interaction is unlikely to cause significant problems, it could intensify side effects or reduce the effectiveness of one or both medications. Monitoring for changes in symptoms and your condition is recommended, and adjustments may be made if needed to manage any increased or more pronounced side effects.

Onset

Rapid: Onset of drug interaction typically occurs within 24 hours of co-administration.

Delayed: Onset of drug interaction typically occurs more than 24 hours after co-administration.

Evidence

Level of documentation of the interaction.

Established: The interaction is documented and substantiated in peer-reviewed medical literature.

Theoretical: This interaction is not fully supported by current medical evidence or well-documented sources, but it is based on known drug mechanisms, drug effects, and other relevant information.

How To Manage The Interaction

Provides a detailed discussion on how patients and clinicians can approach the identified drug interaction as well as offers guidance on what to expect and strategies to potentially mitigate the effects of the interaction. This may include recommendations on adjusting medication dosages, altering the timing of drug administration, or closely monitoring for specific symptoms.

It's important to note that all medical situations are unique, and management approaches should be tailored to individual circumstances. Patients should always consult their healthcare provider for personalized advice and guidance on managing drug interactions effectively.

Mechanism Of Interaction

The theorized or clinically determined reason (i.e., mechanism) why the drug-drug interaction occurs.

Disclaimer: The information provided on this page is for informational purposes only and should not be considered medical advice. Always consult with a qualified healthcare professional regarding your specific circumstances and medical conditions.

Where Does Our Information Come From?

Information for our drug interactions is compiled from several drug compendia, including:

• Gold Standard Drug Database
• Micromedex
• Lexicomp
• DrugBank

The prescribing information for each drug, as published on DailyMED, is also used. 

Individual drug-drug interaction detail pages contain references specific to that interaction. You can click on the reference number within brackets '[]' to see what reference was utilized.

The information posted is fact-checked by HelloPharmacist clinicians and reviewed quarterly.