Linezolid with Lithium Interaction Details
Brand Names Associated with Linezolid
- Linezolid
- Zyvox®
Brand Names Associated with Lithium
- Eskalith®
- Eskalith® CR
- Lithium
- Lithobid®
Medical Content Editor Dr. Brian Staiger, PharmD
Last updated
Nov 21, 2023
Interaction Effect
An increased risk of serotonin syndrome
Interaction Summary
Lithium has been involved in drug interactions associated with the development of serotonin syndrome. Linezolid is a reversible, nonselective inhibitor of monoamine oxidase. Although coadministration of linezolid and serotonergic agents did not result in serotonin syndrome in phase 1, 2, or 3 clinical trials, there have been spontaneous reports of serotonin syndrome associated with concomitant use of linezolid and lithium, coadministered with other serotonergic agents . If concurrent use of linezolid and a serotonergic agent is clinically warranted, monitor patients closely for signs and symptoms of serotonin syndrome. Serotonin syndrome can be life-threatening. If serotonin syndrome develops, discontinue the offending agents and provide supportive care and other therapy as necessary .
Severity
Major
Onset
Unspecified
Evidence
Probable
How To Manage Interaction
Serotonin toxicity has been reported in 2 individuals with the concurrent use of linezolid and lithium, coadministered with other serotonergic agents. If concurrent use of linezolid and lithium, particularly with additional serotonergic agents, is clinically necessary, monitor patients closely for signs and symptoms of serotonin syndrome, such as neuromuscular abnormalities (including hyperreflexia, tremor, muscle rigidity, clonus, peripheral hypertonicity, and shivering), autonomic hyperactivity (including tachycardia, mydriasis, diaphoresis, and diarrhea), and mental status changes (including agitation and delirium). Serotonin syndrome can be life-threatening. If serotonin syndrome develops, discontinue the offending agents and provide supportive care and other therapy as necessary .
Mechanism Of Interaction
Additive serotonergic effects
Literature Reports
A) In a review of post-marketing data, 1 case of serotonin toxicity was reported during concurrent use of linezolid and lithium, which was coadministered with other serotonergic agents. A review was conducted of post-marketing adverse events reported to the US Food and Drug Administration's Adverse Event Reporting System (AERS) database between November 1997 and September 2003 regarding serotonin toxicity with linezolid use. A serotonin toxicity case was defined as having: (a) linezolid as the primary suspect drug, (b) concomitant administration of 1 or more secondary suspect drug with CNS serotonergic activity, and (c) serotonin toxicity, as defined by the modified Hunter Serotonin Toxicity Criteria or by the reporter of the adverse event. A total of 29 cases were identified (age range 17 to 83 years), where linezolid was used concomitantly with 1 drug (n=20), with 2 drugs (n=6), and with 3 or more drugs (n=3). While SSRIs were the most common class of drugs received concomitantly with linezolid (n=26), other drug classes included tricyclic antidepressants (n=6), and atypical antidepressants (n=4). Additionally, drugs used concurrently included carbidopa-levodopa (n=2), dextromethorphan (n=1), lithium (n=1), metoclopramide (n=1), risperiDONE (n=1), and traMADol (n=1). Symptoms of serotonin toxicity included tremor, fever, seizure, clonus, sweating, agitation, akathisia, rigors, twitching, and muscle rigidity. Intervention including hospitalization was required in 13 patients, and 3 deaths were reported with concurrent SSRI use. For the 1 case identified with the concurrent use of linezolid and lithium, additional serotonergic drugs included bupropion, sertraline, and traZODone .
B) A case report described serotonin syndrome in a 36-year-old woman following the concomitant use of linezolid and lithium. The patient, who had no history of seizures and whose regimen included lithium, venlafaxine, and imipramine for bipolar disorder, depression, and headaches, respectively, presented to the emergency room (ER) with seizures. Ten days prior to presenting to the ER, the patient received vancomycin for treatment of MRSA empyema. However, therapy was switched to linezolid approximately 36 hours before her ER visit. At presentation, she had a blood pressure (BP) of 234/196 mmHg, a heart rate of 160 beats/min, respiratory rate of 24 breaths/min, and diaphoresis. Her pupils were dilatated with slow reaction to light and she was unresponsive to verbal instructions. The patient was intubated and administered multiple doses of lorazepam, which lessened her tremors and decreased BP to 150/85 mmHg. Her serum lithium level was 1.2 mEq/L and there were no electrolyte abnormalities. Within 3 hours of intubation, mental status and breathing pattern normalized and the patient was extubated. While both imipramine and venlafaxine were withheld, lithium was continued and linezolid was replaced with trimethoprim and sulfamethoxazole. The patient remained alert and oriented over the following days and had reduced anxiety. Three weeks following discharge, the patient reported tremors and anxiety after reinstituting venlafaxine and imipramine. It was postulated that her 3 chronic serotonergic medications led to a baseline hyperserotonergic state, which was acutely aggravated by the addition of linezolid .
Linezolid Overview
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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.
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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.
Lithium Overview
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Lithium is used to treat and prevent episodes of mania (frenzied, abnormally excited mood) in people with bipolar disorder (manic-depressive disorder; a disease that causes episodes of depression, episodes of mania, and other abnormal moods). Lithium is in a class of medications called antimanic agents. It works by decreasing abnormal activity in the brain.
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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:
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.