Linezolid with Paroxetine Interaction Details

Brand Names Associated with Linezolid

Brand Names Associated with Paroxetine

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 linezolid, an MAOI, and PARoxetine is contraindicated. Wait at least 14 days after discontinuing an MAOI intended to treat psychiatric disorders before initiating PARoxetine. Wait at least 14 days after discontinuing PARoxetine before initiating therapy with an MAOI intended to treat psychiatric disorders. Do not initiate PARoxetine in a patient being treated with linezolid. If it is necessary to initiate treatment with an MAOI such as linezolid in a patient taking PARoxetine, discontinue PARoxetine before initiating treatment with 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 linezolid, an MAOI, and PARoxetine is contraindicated. Wait at least 14 days after discontinuing an MAOI intended to treat psychiatric disorders before initiating PARoxetine. Wait at least 14 days after discontinuing PARoxetine before initiating therapy with an MAOI intended to treat psychiatric disorders. Do not initiate PARoxetine in a patient being treated with linezolid. If it is necessary to initiate treatment with an MAOI such as linezolid in a patient taking PARoxetine, discontinue PARoxetine before initiating treatment with linezolid.

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) Linezolid may cause serotonin syndrome in patients receiving SSRIs. A 56-year-old woman with a history of depression, chronic hepatitis C infection, hypertension, diabetes, and cervical stenosis was admitted for elective laminectomy. There was evidence of hepatic cirrhosis with an abdominal CT scan. Her medications preoperatively included PARoxetine, interferon-alpha, felodipine, terazosin, lisinopril, insulin, methocarbamol, morphine sulfate, and ibuprofen. The last dose of PARoxetine was administered on postoperative day 14. At that point it was discovered that the patient had an infected surgical site and empiric therapy with vancomycin was initiated. The patient remained febrile, however, and linezolid was substituted for vancomycin. Within 24 hours, the patient developed delirium, hypertension, hostility, anger, and tremors. Serotonin syndrome was diagnosed and linezolid therapy was discontinued. Vancomycin was reinstated and within 48 hours the patient returned to her baseline mental status. The serum half-life of PARoxetine is 21 hours. It is likely that the inhibitory effect of linezolid combined with residual PARoxetine activity produced serotonin syndrome in this patient. This particular patient may have been at increased risk for this syndrome because of her other medications as well as a decreased hepatic clearance. The author suggests that in high-risk patients, a 2-week washout period is advised between the discontinuation of SSRIs and initiation of linezolid .

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.

Paroxetine Overview

• Paroxetine tablets, suspension (liquid), and extended-release (long-acting) tablets are used to treat depression, panic disorder (sudden, unexpected attacks of extreme fear and worry about these attacks), and social anxiety disorder (extreme fear of interacting with others or performing in front of others that interferes with normal life). Paroxetine tablets and suspension are also used to treat obsessive-compulsive disorder (bothersome thoughts that won't go away and the need to perform certain actions over and over), generalized anxiety disorder (GAD; excessive worrying that is difficult to control), and posttraumatic stress disorder (disturbing psychological symptoms that develop after a frightening experience). Paroxetine extended-release tablets are also used to treat premenstrual dysphoric disorder (PMDD, physical and psychological symptoms that occur before the onset of the menstrual period each month). Paroxetine capsules (Brisdelle) are used to treat hot flashes (sudden feelings of warmth, especially in the face, neck, and chest) in women who are experiencing menopause (stage of life when menstrual periods become less frequent and stop and women may experience other symptoms and body changes). Paroxetine is in a class of medications called selective serotonin-reuptake inhibitors (SSRIs). It treats depression and other mental illnesses by increasing the amount of serotonin, a natural substance in the brain that helps maintain mental balance. There is not enough information available at this time to know how paroxetine works to treat hot flashes.

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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.