Summary

Linezolid and bupropion have a significant drug interaction due to linezolid's monoamine oxidase inhibitor (MAOI) properties and bupropion's effects on neurotransmitter reuptake. This combination can increase the risk of serotonin syndrome and other serious adverse effects.

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). It possesses weak, reversible monoamine oxidase inhibitor (MAOI) activity. Bupropion is an atypical antidepressant and smoking cessation aid that works as a norepinephrine-dopamine reuptake inhibitor (NDRI). It is also used for seasonal affective disorder and as an adjunct for weight management.

Mechanism of Interaction

The interaction between linezolid and bupropion occurs through linezolid's weak but clinically significant MAOI activity. Linezolid inhibits both MAO-A and MAO-B enzymes, which are responsible for metabolizing neurotransmitters including serotonin, norepinephrine, and dopamine. When combined with bupropion, which blocks the reuptake of norepinephrine and dopamine, there is an increased risk of excessive accumulation of these neurotransmitters. This can lead to serotonin syndrome, hypertensive crisis, and other serious neurological and cardiovascular complications.

Risks and Symptoms

The primary risks of combining linezolid and bupropion include serotonin syndrome, characterized by altered mental status, autonomic instability, and neuromuscular abnormalities. Patients may experience hyperthermia, hypertension, tachycardia, confusion, agitation, tremor, and muscle rigidity. Hypertensive crisis is another serious concern, potentially leading to stroke or cardiac events. The interaction is considered clinically significant and can be life-threatening, particularly in patients with underlying cardiovascular conditions or those taking additional serotonergic medications.

Management and Precautions

Concurrent use of linezolid and bupropion should generally be avoided. If linezolid treatment is essential, bupropion should be discontinued at least 2 weeks before starting linezolid therapy, allowing adequate washout time. If both medications are absolutely necessary, close monitoring in a hospital setting is required, with frequent assessment of vital signs, mental status, and neurological symptoms. Alternative antibiotics without MAOI activity should be considered when possible. Patients should be educated about signs and symptoms of serotonin syndrome and advised to seek immediate medical attention if symptoms develop.

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.

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.