Drug Interaction Report

MONITOR CLOSELY: Coadministration with enzyme-inducing anticonvulsants may decrease the plasma concentrations of opioids that are primarily metabolized by CYP450 3A4 such as butorphanol, fentanyl, hydrocodone, and oxycodone. Reduced efficacy or withdrawal symptoms may occur in patients maintained on their narcotic pain regimen following the addition of an enzyme-inducing anticonvulsant. Conversely, discontinuation of the anticonvulsant may increase opioid plasma concentrations and potentiate the risk of overdose and fatal respiratory depression.

MANAGEMENT: Pharmacologic response to the opioid should be monitored more closely whenever an enzyme-inducing anticonvulsant is added to or withdrawn from therapy, and the opioid dosage adjusted as necessary. Due to the potential for additive central nervous system depressant effects, ambulatory patients should be counseled to avoid hazardous activities requiring mental alertness and motor coordination until they know how these agents affect them.

GENERALLY AVOID: Alcohol may potentiate the central nervous system (CNS) depressant effects of opioid analgesics including oliceridine. 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 or grapefruit juice may increase the plasma concentrations of oliceridine by inhibiting the CYP450 3A4-mediated metabolism of oliceridine, although the interaction has not been studied. In general, the effect of grapefruit juice is concentration-, dose- and preparation-dependent, and can vary widely among brands. Certain preparations of grapefruit juice (e.g., high dose, double strength) have sometimes demonstrated potent inhibition of CYP450 3A4, while other preparations (e.g., low dose, single strength) have typically demonstrated moderate inhibition. Pharmacokinetic interactions involving grapefruit juice are also subject to a high degree of interpatient variability, thus the extent to which a given patient may be affected is difficult to predict.

MANAGEMENT: Patients should not consume alcoholic beverages or use drug products that contain alcohol during treatment with oliceridine. Any history of alcohol or illicit drug use should be considered when prescribing oliceridine, 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 oliceridine should preferably avoid the consumption of grapefruit and grapefruit juice.