Summary

Linezolid and sertraline have a significant drug interaction that can lead to serotonin syndrome, a potentially life-threatening condition. This interaction occurs because linezolid has weak monoamine oxidase inhibitor (MAOI) properties that can enhance serotonin levels when combined with the SSRI sertraline.

Introduction

Linezolid is an oxazolidinone antibiotic used to treat serious gram-positive bacterial infections, including methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci (VRE). Sertraline is a selective serotonin reuptake inhibitor (SSRI) antidepressant commonly prescribed for depression, anxiety disorders, and other psychiatric conditions. Both medications are frequently used in clinical practice, making awareness of their interaction crucial for healthcare providers.

Mechanism of Interaction

The interaction between linezolid and sertraline occurs through linezolid's weak but clinically significant monoamine oxidase (MAO) inhibitory activity. Linezolid reversibly inhibits MAO-A and MAO-B enzymes, which are responsible for breaking down serotonin, norepinephrine, and dopamine. When combined with sertraline, which blocks serotonin reuptake, this dual mechanism can lead to excessive accumulation of serotonin in synaptic clefts, potentially triggering serotonin syndrome.

Risks and Symptoms

The primary risk of combining linezolid and sertraline is serotonin syndrome, which can range from mild to life-threatening. Symptoms may include altered mental status, autonomic instability (hyperthermia, tachycardia, blood pressure changes), and neuromuscular abnormalities (tremor, rigidity, hyperreflexia, clonus). Severe cases can progress to hyperthermia, rhabdomyolysis, seizures, and death. The risk is considered moderate to high, and cases have been reported in the literature with this specific combination.

Management and Precautions

When possible, avoid concurrent use of linezolid and sertraline. If co-administration is necessary, consider discontinuing sertraline at least 1-2 weeks before starting linezolid (allowing for sertraline's elimination half-life). Monitor patients closely for signs and symptoms of serotonin syndrome, including mental status changes, hyperthermia, muscle rigidity, and autonomic instability. Alternative antibiotics without MAO inhibitory properties should be considered when clinically appropriate. If serotonin syndrome develops, discontinue both medications immediately and provide supportive care.

Linezolid interactions with food and lifestyle

Linezolid has significant interactions with tyramine-rich foods that require careful dietary restrictions. Patients taking linezolid should avoid or limit foods high in tyramine including aged cheeses, cured meats, fermented foods, red wine, beer, and certain vegetables like sauerkraut. Consuming large amounts of tyramine while on linezolid can lead to dangerous increases in blood pressure (hypertensive crisis). Additionally, linezolid can interact with foods and beverages containing high amounts of caffeine, potentially causing increased blood pressure and heart rate. Patients should limit caffeine intake from coffee, tea, energy drinks, and chocolate while taking this medication. Alcohol should be avoided or used with extreme caution as it may increase the risk of side effects and can interact with linezolid's mechanism of action.

Sertraline interactions with food and lifestyle

Alcohol: Sertraline may increase the effects of alcohol and impair mental and motor skills. Patients should avoid or limit alcohol consumption while taking sertraline as recommended by major clinical guidelines and drug databases. The combination can increase sedation, dizziness, and impair cognitive function.