Drug Interactions between Meprozine and tedizolid

ADJUST DOSE: The central nervous system and respiratory depressant effects of meperidine may be potentiated by concomitant use of other agents with CNS depressant effects. An increased risk of serious adverse reactions such as respiratory depression, hypotension, profound sedation, syncope, coma, and even death should be considered, particularly in elderly or debilitated patients.

MANAGEMENT: Caution and dosage adjustments are advisable when meperidine is used in combination with other narcotic analgesics, general anesthetics, phenothiazines, sedative-hypnotics, tranquilizers, tricyclic antidepressants, or other CNS depressants such as alcohol. A lower dosage of meperidine should be considered initially, then titrated carefully according to pain level and clinical response. Meperidine dosage reductions of 25% to 50% have been recommended for patients receiving phenothiazines and other tranquilizers. Patients should be advised to avoid rising abruptly from a sitting or recumbent position, and to notify their physician if they experience dizziness, lightheadedness, orthostasis, syncope, tachycardia, or excessive CNS effects that interfere with their normal activities. Patients should also avoid driving or operating hazardous machinery until they know how these medications affect them.

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.