Drug Interactions between homatropine / hydrocodone and tedizolid

MONITOR: Coadministration of opioids with anticholinergic agents may result in additive central nervous system (CNS), gastrointestinal, and genitourinary effects. The risk and/or severity of adverse effects such as sedation, dizziness, confusion, cognitive and psychomotor impairment, dry mouth, constipation, and urinary retention may increase. Severe constipation may lead to paralytic ileus in some cases.

MANAGEMENT: Caution and close monitoring of central nervous system, gastrointestinal, and genitourinary adverse effects are recommended when opioids are used with anticholinergic agents. 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.