Drug Interaction Report

MONITOR: This warning does not apply to the naloxone component in non-injectable formulations of naloxone-containing combination medicines. Naloxone injection is an antagonist that will reverse the actions of opiates. This reversal can occur when the opiate drug is being used clinically and when it is being abused. Physically dependent patients may experience withdrawal symptoms. Abrupt postoperative opioid reversal has resulted in hypotension, ventricular tachycardia and fibrillation, pulmonary edema, cardiac arrest, encephalopathy, and death.

MANAGEMENT: Patients receiving naloxone injection should be monitored for changes in vital signs, nausea, vomiting, diarrhea, aches, fever, runny nose, sneezing, nervousness, irritability, shivering, abdominal cramps.

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.

GENERALLY AVOID: Alcohol may potentiate the central nervous system (CNS) depressant effects of opioid analgesics including oxycodone. Concomitant use may result in additive CNS depression and impairment of judgment, thinking, and psychomotor skills. In more severe cases, hypotension, respiratory depression, profound sedation, coma, or even death may occur.

GENERALLY AVOID: Grapefruit juice may increase the plasma concentrations of oxycodone. The proposed mechanism is inhibition of CYP450 3A4-mediated metabolism of oxycodone by certain compounds present in grapefruit, resulting in decreased formation of metabolites noroxycodone and noroxymorphone and increased formation of oxymorphone due to a presumed shifting of oxycodone metabolism towards the CYP450 2D6-mediated route. In 12 healthy, nonsmoking volunteers, administration of a single 10 mg oral dose of oxycodone hydrochloride on day 4 of a grapefruit juice treatment phase (200 mL three times a day for 5 days) increased mean oxycodone peak plasma concentration (Cmax), systemic exposure (AUC) and half-life by 48%, 67% and 17% (from 3.5 to 4.1 hours), respectively, compared to administration during an equivalent water treatment phase. Grapefruit juice also decreased the metabolite-to-parent AUC ratio of noroxycodone by 44% and that of noroxymorphone by 45%. In addition, oxymorphone Cmax and AUC increased by 32% and 56%, but the metabolite-to-parent AUC ratio remained unchanged. Pharmacodynamic changes were modest and only self-reported performance was significantly impaired after grapefruit juice. Analgesic effects were not affected.

MANAGEMENT: Patients should not consume alcoholic beverages or use drug products that contain alcohol during treatment with oxycodone. Any history of alcohol or illicit drug use should be considered when prescribing oxycodone, and therapy initiated at a lower dosage if necessary. Patients should be closely monitored for signs and symptoms of sedation, respiratory depression, and hypotension. Due to a high degree of interpatient variability with respect to grapefruit juice interactions, patients treated with oxycodone may also want to avoid or limit the consumption of grapefruit and grapefruit juice.