Summary

The combination of bupropion and linezolid poses a significant risk for serotonin syndrome due to linezolid's monoamine oxidase inhibitory properties. This interaction is considered clinically significant and requires careful monitoring or alternative therapy consideration.

Introduction

Bupropion is an atypical antidepressant and smoking cessation aid that works primarily as a norepinephrine-dopamine reuptake inhibitor (NDRI). It is commonly prescribed for major depressive disorder, seasonal affective disorder, and as an aid for smoking cessation under the brand names Wellbutrin, Zyban, and others. Linezolid 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 monoamine oxidase (MAO) inhibitory properties, which can lead to significant drug interactions with certain psychiatric medications.

Mechanism of Interaction

The interaction between bupropion and linezolid occurs through linezolid's weak but clinically relevant monoamine oxidase inhibitory activity. Linezolid reversibly inhibits both MAO-A and MAO-B enzymes, which are responsible for metabolizing neurotransmitters including serotonin, norepinephrine, and dopamine. When combined with bupropion, which increases norepinephrine and dopamine levels by blocking their reuptake, this can lead to excessive accumulation of these neurotransmitters. Although bupropion has minimal direct serotonergic activity, the combination can still contribute to serotonin syndrome, particularly when other serotonergic mechanisms are involved or in susceptible patients.

Risks and Symptoms

The primary risk of combining bupropion and linezolid is the development of serotonin syndrome, a potentially life-threatening condition characterized by altered mental status, autonomic instability, and neuromuscular abnormalities. Symptoms may include confusion, agitation, hyperthermia, diaphoresis, tremor, muscle rigidity, and in severe cases, seizures and cardiovascular collapse. Additional risks include hypertensive crisis due to excessive norepinephrine levels, increased seizure risk (particularly concerning given bupropion's seizure-lowering threshold), and potential cardiovascular complications. The interaction is considered moderate to major in clinical significance, with case reports documenting serious adverse events when these medications are used concurrently.

Management and Precautions

Bupropion interactions with food and lifestyle

Alcohol: Bupropion may lower the seizure threshold, and concurrent alcohol use can further increase seizure risk. Patients should avoid or limit alcohol consumption while taking bupropion. Sudden discontinuation of alcohol in patients with alcohol dependence may also increase seizure risk. Smoking cessation: While bupropion is used for smoking cessation, patients should be aware that nicotine withdrawal itself can affect seizure threshold. Close monitoring is recommended during the quit process. High-fat meals: Taking bupropion with high-fat meals may increase drug absorption and potentially increase side effects. Consider taking with light meals or on an empty stomach as tolerated.

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.