Linezolid is used to treat a vancomycin-resistant Enterococcus (VRE) infection. A patient on linezolid also takes sertraline for depression. Which adverse interaction is most concerning?
- A QTc prolongation due to dual serotonergic and sodium channel blockade
- B Bone marrow suppression due to synergistic inhibition of mitochondrial protein synthesis
- C Serotonin syndrome due to linezolid's weak MAO inhibitory activity combined with sertraline's serotonin reuptake inhibition ✓
- D Peripheral neuropathy from combined vitamin B6 antagonism
Correct answer: C. Serotonin syndrome due to linezolid's weak MAO inhibitory activity combined with sertraline's serotonin reuptake inhibition
Explanation
Linezolid is a weak, non-selective monoamine oxidase inhibitor (MAOI) in addition to being a protein synthesis inhibitor. When combined with serotonergic drugs such as SSRIs (sertraline), it can precipitate serotonin syndrome characterised by hyperthermia, agitation, myoclonus, hyperreflexia and autonomic instability. This interaction is a black-box warning. Myelosuppression (thrombocytopaenia) is a dose-related toxicity of linezolid but not synergistically worsened by sertraline; QTc prolongation is not a primary concern.
Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.
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