Drug interactions between Adapin and Zyvox

doxepin ↔ linezolid

Applies to:Adapin (doxepin) and Zyvox (linezolid)

CONTRAINDICATED: Concomitant use of linezolid and serotonergic agents may potentiate the risk of serotonin syndrome, which is a rare but serious and potentially fatal condition thought to result from hyperstimulation of brainstem 5-HT1A and 2A receptors. Linezolid is a reversible, nonselective monoamine oxidase inhibitor (MAOI) and can enhance serotonergic effects by inhibiting serotonin metabolism. Rare cases of serotonin syndrome have been reported in association with linezolid, most often in combination with serotonin reuptake inhibitors. Symptoms of the serotonin syndrome may include mental status changes such as irritability, altered consciousness, confusion, hallucination, and coma; autonomic dysfunction such as tachycardia, hyperthermia, diaphoresis, shivering, blood pressure lability, and mydriasis; neuromuscular abnormalities such as hyperreflexia, myoclonus, tremor, rigidity, and ataxia; and gastrointestinal symptoms such as abdominal cramping, nausea, vomiting, and diarrhea.

MANAGEMENT: Linezolid should not be administered to patients receiving serotonergic agents, and vice versa, unless close monitoring for the development of serotonin syndrome can be provided. In nonemergency situations when treatment with linezolid is contemplated and planned, patients receiving serotonergic agents should discontinue these medications for at least 4 to 5 half-lives if possible. Most serotonergic psychiatric drugs should be stopped at least 2 weeks in advance of linezolid treatment, while fluoxetine should be stopped at least 5 weeks in advance due to its prolonged half-life. Treatment with serotonergic medications may be resumed 24 hours after the last dose of linezolid. In emergency situations requiring urgent treatment with linezolid (e.g., vancomycin-resistant Enterococcus faecium (VRE) infections; nosocomial pneumonia and complicated skin and skin structure infections, including cases caused by methicillin-resistant Staphylococcus aureus), the availability of alternative interventions should be considered and the benefit of linezolid treatment should be weighed against the risk of serotonin toxicity. If linezolid is required in a patient receiving a serotonergic drug, the serotonergic drug must be immediately stopped, and the patient closely monitored for emergent symptoms of CNS toxicity for two weeks (five weeks if fluoxetine was taken) or until 24 hours after the last dose of linezolid, whichever comes first. Patients and/or their caregivers should be advised to seek medical attention if potential symptoms of serotonin syndrome develop.