Drug Interactions between dextromethorphan / triprolidine and tedizolid

MONITOR: Central nervous system- and/or respiratory-depressant effects may be additively or synergistically increased in patients taking multiple drugs that cause these effects, especially in elderly or debilitated patients. Sedation and impairment of attention, judgment, thinking, and psychomotor skills may increase.

MANAGEMENT: During concomitant use of these drugs, patients should be monitored for potentially excessive or prolonged CNS and respiratory depression. Cautious dosage titration may be required, particularly at treatment initiation. Ambulatory patients should be counseled to avoid hazardous activities requiring mental alertness and motor coordination until they know how these agents affect them, and to notify their physician if they experience excessive or prolonged CNS effects that interfere with their normal activities.

MONITOR: The concurrent use of tedizolid with agents that have serotonergic activity including serotonin reuptake inhibitors, monoamine oxidase inhibitors (MAOIs), tricyclic antidepressants, 5-HT1 receptor agonists, ergot alkaloids, cyclobenzaprine, lithium, St. John's wort, phenylpiperidine opioids, dextromethorphan, and tryptophan may elevate the risk of developing serotonin syndrome. The proposed mechanism is tedizolid-mediated non-selective and reversible inhibition of monoamine oxidase (MAO), with more potent inhibition of MAO-A than linezolid in vitro. In a retrospective cohort study from January 2015 to July 2023 of 479 adult patients receiving tedizolid, 62% (297/479) received concomitant serotonergic agents, but suspected serotonin syndrome requiring tedizolid discontinuation was found to be rare, occurring in only 0.4% (2/479) of cases. Symptoms of serotonin syndrome may include mental status changes such as irritability, altered consciousness, confusion, hallucination, and coma; autonomic dysfunction such as tachycardia, hyperthermia, diaphoresis, shivering, unstable blood pressure, and mydriasis; neuromuscular abnormalities such as hyperreflexia, myoclonus, tremor, rigidity, and ataxia; and gastrointestinal symptoms such as abdominal cramping, nausea, vomiting, and diarrhea.

MANAGEMENT: Caution and closer monitoring for serotonin syndrome are recommended during concomitant treatment with tedizolid and serotonergic agents, especially during dose escalations, and patients should be instructed to notify their healthcare provider if they experience symptoms of serotonin syndrome. Due to variability and occasionally prolonged half-lives of these coadministered agents, consulting individual product labeling for specific guidance is advised. If serotonin syndrome is suspected, discontinuation of therapy or dose reductions should be considered depending on the severity of the symptoms, and supportive care should be provided. Moderately ill patients may benefit from serotonin antagonists like cyproheptadine or chlorpromazine. Severe cases require consultation with a toxicologist and may need sedation, neuromuscular paralysis, intubation, and mechanical ventilation.