Summary

Fluoxetine and linezolid 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) activity, which can dangerously increase serotonin levels when combined with the SSRI fluoxetine.

Introduction

Fluoxetine (brand name Prozac) is a selective serotonin reuptake inhibitor (SSRI) antidepressant commonly prescribed for depression, anxiety disorders, and obsessive-compulsive disorder. It works by increasing serotonin levels in the brain. Linezolid (brand name Zyvox) is an oxazolidinone antibiotic used to treat serious gram-positive bacterial infections, including methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci (VRE). While primarily an antibiotic, linezolid also possesses weak but clinically significant monoamine oxidase inhibitor properties.

Mechanism of Interaction

The interaction between fluoxetine and linezolid occurs through complementary mechanisms that both increase serotonin availability. Fluoxetine blocks the serotonin transporter, preventing the reuptake of serotonin from synapses and increasing extracellular serotonin concentrations. Linezolid, while primarily an antibiotic, reversibly inhibits monoamine oxidase A and B enzymes, which are responsible for breaking down serotonin, norepinephrine, and dopamine. When used together, fluoxetine increases serotonin release while linezolid decreases serotonin metabolism, creating a synergistic effect that can lead to excessive serotonin accumulation and potentially trigger serotonin syndrome.

Risks and Symptoms

The primary risk of combining fluoxetine and linezolid is serotonin syndrome, a potentially fatal condition characterized by altered mental status, autonomic instability, and neuromuscular abnormalities. Symptoms may include confusion, agitation, hyperthermia, diaphoresis, tremor, muscle rigidity, hyperreflexia, and in severe cases, seizures, coma, and cardiovascular collapse. The risk is particularly elevated in patients taking higher doses of fluoxetine, those with impaired drug metabolism, or when linezolid is used for extended periods. Additional risks include hypertensive crisis due to linezolid's MAOI activity and potential for drug accumulation in patients with renal or hepatic impairment.

Management and Precautions

Fluoxetine interactions with food and lifestyle

Alcohol: Fluoxetine may increase the sedative effects of alcohol and impair cognitive and motor performance. Patients should avoid or limit alcohol consumption while taking fluoxetine. Grapefruit juice: May increase fluoxetine blood levels, though this interaction is generally considered minor. St. John's Wort: Should be avoided as it may increase the risk of serotonin syndrome when combined with fluoxetine.

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.