Summary

Linezolid and meperidine have a significant drug interaction that can lead to serotonin syndrome, a potentially life-threatening condition. This interaction occurs because linezolid has monoamine oxidase inhibitor (MAOI) properties that can dangerously interact with meperidine's serotonergic 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). Meperidine (pethidine) is an opioid analgesic used for moderate to severe pain management. Both medications have unique pharmacological properties that create a clinically significant interaction when used together.

Mechanism of Interaction

The interaction between linezolid and meperidine occurs through linezolid's weak but clinically relevant monoamine oxidase inhibitor (MAOI) activity. Linezolid inhibits both MAO-A and MAO-B enzymes, which are responsible for metabolizing serotonin, norepinephrine, and dopamine. Meperidine blocks serotonin reuptake and releases stored serotonin, leading to increased serotonergic activity. When combined, this dual mechanism can result in excessive serotonin accumulation, potentially triggering serotonin syndrome.

Risks and Symptoms

The primary risk of combining linezolid and meperidine is serotonin syndrome, which can manifest as altered mental status, autonomic instability (hyperthermia, tachycardia, hypertension), and neuromuscular abnormalities (tremor, rigidity, hyperreflexia). Severe cases can progress to hyperthermia, seizures, coma, and death. Additional risks include enhanced CNS depression, respiratory depression, and cardiovascular complications. The interaction is considered contraindicated due to the severity of potential outcomes.

Management and Precautions

Concurrent use of linezolid and meperidine should be avoided whenever possible. If pain management is needed in patients receiving linezolid, alternative opioids such as morphine, fentanyl, or oxycodone are preferred options. If the combination cannot be avoided, patients require intensive monitoring for signs of serotonin syndrome, including frequent vital signs, neurological assessments, and continuous cardiac monitoring. Healthcare providers should educate patients about early warning signs and ensure immediate medical attention if symptoms develop. Consider discontinuing one or both medications if serotonin syndrome is suspected.

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.

Meperidine interactions with food and lifestyle

Alcohol: Concurrent use of meperidine with alcohol can cause dangerous central nervous system depression, leading to severe sedation, respiratory depression, and potentially life-threatening complications. Patients should avoid alcohol consumption while taking meperidine. MAO inhibitors: Meperidine should not be used within 14 days of taking monoamine oxidase inhibitors (MAOIs) due to risk of serotonin syndrome, which can be fatal. This includes certain foods high in tyramine when combined with MAOIs, though the primary concern is the drug-drug interaction rather than food alone.