Linezolid with Venlafaxine Interaction Details

Brand Names Associated with Linezolid

Brand Names Associated with Venlafaxine

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

Interaction Effect

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

Interaction Summary

Concurrent use of linezolid and venlafaxine is contraindicated. If urgent treatment with linezolid is necessary and alternatives are not available, promptly discontinue venlafaxine and then linezolid may be administered after the risk/benefit has been evaluated. Monitor for serotonin syndrome for 7 days or until 24 hours after the last dose of linezolid, whichever comes first. Venlafaxine can be resumed 24 hours after the last dose of linezolid. Several case reports in patients who received concomitant linezolid and venlafaxine therapy have illustrated a delayed onset (greater than 24 hours) of clinical findings consistent with serotonin syndrome, all of which resolved with dose reduction or drug withdrawal . 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 .

Severity

Contraindicated

Onset

Unspecified

Evidence

Probable

How To Manage Interaction

Concurrent use of venlafaxine and linezolid (an MAOI) is contraindicated. If urgent treatment with linezolid is necessary and alternatives are not available, promptly discontinue venlafaxine and then linezolid may be administered after the risk/benefit has been evaluated. Monitor for serotonin syndrome for 7 days or until 24 hours after the last dose of linezolid, whichever comes first. Venlafaxine can be resumed 24 hours after the last dose of linezolid.

Mechanism Of Interaction

Additive serotonergic effects

Literature Reports

A) In a retrospective cohort study (N=1134), serotonin syndrome occurred in fewer than 6 patients (less than 0.5%) who were taking a concurrent antidepressant and linezolid (n=215). In a propensity score-matched cohort (n=332), there was no significant difference in the risk of serotonin syndrome in patients taking concomitant antidepressants and linezolid compared with patients not taking antidepressants (adjusted risk difference, -1.2%; 95% CI, -2.9% to 0.5%). There was also no significant difference in the rate of altered mental status or confusion, hospitalization, or death from any cause between groups. Clinically significant serotonin syndrome was defined as requiring an ambulatory care visit, emergency department visit, or hospitalization. Patients were 66 years of age or older, all were taking linezolid 600 mg orally twice daily, and of those taking antidepressants, 103 (47.9%) were taking an SSRI, 36 (16.7%) were taking an SNRI, 15 (7%) were taking a tricyclic antidepressant, 7 (3.3%) were taking a norepinephrine and dopamine reuptake inhibitor .

B) A case report described serotonin toxicity in a 58-year-old woman following concomitant use of linezolid and venlafaxine. The patient, who had a history of urological problems after bladder resection for transitional cell carcinoma 18 years earlier and had undergone a bilateral total hip arthroplasty (THA), was being treated with venlafaxine 75 mg for severe depression and prior episodes of self-harm. She presented with symptoms of systemic infection. Increased activity at the site of the bilateral THA was revealed and a diagnosis of MRSA infection was made. Subsequently, the patient was initiated on vancomycin and rifampicin intravenously. A 2-stage revision THA was performed due to the MRSA infection. Because of problems with intravenous antibiotic administration, her regimen was changed to oral linezolid and oral rifampicin 2 weeks postoperatively. On day 4 following linezolid initiation, acute disorientation was observed. Physical examination and CT scan of the head did not reveal any abnormal findings or autonomic dysfunction. Over the next 24 hours, however, her condition deteriorated. Subsequently, linezolid and venlafaxine were stopped due to possible serotonin toxicity. The patient's condition normalized 48 hours after linezolid and venlafaxine were discontinued .

C) A case report described serotonin syndrome in a 36-year-old woman following the concomitant use of linezolid and venlafaxine. 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 .

D) In one case report, a 30-year-old woman experienced symptoms of serotonin syndrome after concomitant treatment with linezolid and venlafaxine. After having received treatment since the age of 15 years for depression, social anxiety, bulimia, and alcohol/benzodiazepine abuse, she had become drug- and alcohol-free and was receiving extended-release venlafaxine 225 mg daily. After two weeks of treatment with linezolid, the patient complained of dizziness, syncope, and ataxia. At presentation, the patient appeared confused and disheveled. Venlafaxine was discontinued and intensive therapy was instituted. Although her neurological symptoms dissipated, she continued to experience rapid mood shifts, irritability, impulsivity, and insomnia for which quetiapine 25 mg 3 times daily was prescribed. Two weeks later, venlafaxine was gradually reinitiated .

E) 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 diagnosed with a high probability of having SS after receiving concomitant linezolid and venlafaxine followed by citalopram. Linezolid was given for a vancomycin-resistant Enterococcus urinary tract infection. 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 mm Hg 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 .

F) A case report described serotonin toxicity in a 38-year-old woman following the concomitant administration of linezolid and venlafaxine. The patient, who had cystic fibrosis, fibromyalgia, and a recent rib fracture was admitted after 3 weeks of coughing, progressive dyspnea, and green-colored sputum. She had been receiving extended-release venlafaxine 300 mg once daily and gabapentin 100 mg 3 times daily for one year, and hydromorphone 1 mg every 4 hours as needed for the preceding 3 weeks. Due to a history of vancomycin intolerance, she was prescribed linezolid 600 mg IV every 12 hours for confirmed methicillin-resistant Staphylococcus aureus infection. Four days later, the patient had a blood pressure (BP) of 150/90 mmHg and experienced hot flashes, dyspnea, and tiredness. Eight days following linezolid initiation, the venlafaxine dose was reduced to 150 mg daily. The patient's hot flashes and headache persisted; additionally, she reported nervousness, muscle rigidity of the mouth, fine tremors (fingers), and involuntary arm, trunk, and leg movements. However, approximately 2 days after the venlafaxine dose reduction, her BP normalized to 142/84 mmHg; other symptoms dissipated the next day. Upon discharge on day 10, the patient was prescribed oral linezolid 600 mg twice daily for 4 days and venlafaxine 150 mg once daily. In the subsequent 2-year period, the patient received two 10-day courses of linezolid while receiving concomitant venlafaxine 187.5 mg and 225 mg daily with no symptoms of serotonin toxicity .

G) Serotonin syndrome was reported in the case of an 85-year-old man who was receiving venlafaxine 150 mg daily for depression and oral linezolid 600 mg twice daily with ciprofloxacin and rifampicin for a closed wound due to the removal of a chronically infected hip prothesis. His medical history included Parkinson's disease, ischemic heart disease, atrial fibrillation, diabetes, and a permanent pacemaker. After 20 days of receiving oral antibiotic therapy, the patient was reportedly confused and disoriented with intermittent aggression and abnormal sleep patterns. A brain CT scan and serum chemistries were all normal with no evidence of sepsis; vital signs were also within normal limits. Four days later, the patient was transferred to an acute care rehabilitation hospital due to drowsiness. He had a fever of 37.6 degrees Celsius and a decreased level of consciousness, along with generalized myoclonic jerks and decreasing plantar reflexes. Linezolid and venlafaxine were discontinued due to a suspected drug interaction. Within 2 days, the patient's mental status had returned to normal .

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.

Venlafaxine Overview

• Venlafaxine is used to treat depression. Venlafaxine extended-release (long-acting) capsules are also used to treat generalized anxiety disorder (GAD; excessive worrying that is difficult to control), social anxiety disorder (extreme fear of interacting with others or performing in front of others that interferes with normal life), and panic disorder (sudden, unexpected attacks of extreme fear and worry about these attacks). Venlafaxine is in a class of medications called selective serotonin and norepinephrine reuptake inhibitors (SNRIs). It works by increasing the amounts of serotonin and norepinephrine, natural substances in the brain that help maintain mental balance.

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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.