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Drug Interactions between cinacalcet and Olinvyk

This report displays the potential drug interactions for the following 2 drugs:

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Interactions between your drugs

Major

cinacalcet oliceridine

Applies to: cinacalcet and Olinvyk (oliceridine)

MONITOR CLOSELY: Coadministration with moderate or potent inhibitors of CYP450 2D6 and/or 3A4 may increase the plasma concentrations and adverse opioid effects of oliceridine, which is primarily metabolized by both isoenzymes in vitro. In addition, oliceridine concentrations may decrease following discontinuation of a concomitant moderate or potent CYP450 2D6 or 3A4 inhibitor, possibly resulting in decreased opioid efficacy or withdrawal syndrome. The effect of a CYP450 2D6 inhibitor on the pharmacokinetics of oliceridine has not been studied. However, it may be similar to that reported in CYP450 2D6 poor metabolizers, whose plasma clearance of oliceridine is reduced by approximately 50% compared to those who are nonpoor CYP450 2D6 metabolizers. The clearance may be further reduced with the addition of a CYP450 3A4 inhibitor. When a single 0.25 mg dose of oliceridine was given to poor metabolizers of CYP450 2D6 following pretreatment with the potent CYP450 3A4 inhibitor itraconazole (200 mg once daily for 5 days), oliceridine systemic exposure (AUC) increased by approximately 80% while peak plasma concentration (Cmax) was not significantly affected. Furthermore, mean oliceridine clearance decreased to approximately 30% of that observed in nonpoor metabolizers of CYP450 2D6. The interaction has not been studied with other, less potent CYP450 3A4 inhibitors.

MANAGEMENT: Caution is recommended if oliceridine is used in combination with moderate or potent inhibitors of CYP450 2D6 or 3A4. If concomitant use is considered necessary, patients may require less frequent dosing of oliceridine and should be closely monitored for respiratory depression, sedation, and QT prolongation. If a moderate or potent CYP450 2D6 or 3A4 inhibitor is discontinued, an increase of the oliceridine dosage may be considered while monitoring for signs of opioid withdrawal until stable drug effects are achieved. Due to the prolonged duration of CYP450 2D6 inhibition by the moderate CYP450 2D6 inhibitor rolapitant, prolonged monitoring for adverse effects of oliceridine for at least 28 days after administration of rolapitant may be required.

References

  1. "Product Information. Varubi (rolapitant)." Tesaro Inc. (2015):
  2. "Product Information. Olinvyk (oliceridine)." Trevena Inc (2020):

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Drug and food interactions

Major

oliceridine food

Applies to: Olinvyk (oliceridine)

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.

References

  1. "Product Information. Olinvyk (oliceridine)." Trevena Inc (2020):

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Moderate

cinacalcet food

Applies to: cinacalcet

ADJUST DOSING INTERVAL: Food enhances the oral absorption and bioavailability of cinacalcet. According to the product labeling for cinacalcet, administration with a high-fat meal increased the peak plasma concentration (Cmax) and area under the concentration-time curve (AUC) of cinacalcet by 82% and 68%, respectively, compared to administration in the fasting state. The Cmax and AUC were increased 65% and 50%, respectively, when cinacalcet was administered with a low-fat meal compared to fasting.

MANAGEMENT: To ensure maximal oral absorption, cinacalcet should be administered with or immediately after a meal. The tablets should be taken whole and not divided or crushed.

References

  1. "Product Information. Sensipar (cinacalcet)." Amgen USA (2004):

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Therapeutic duplication warnings

No warnings were found for your selected drugs.

Therapeutic duplication warnings are only returned when drugs within the same group exceed the recommended therapeutic duplication maximum.

See also

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Drug Interaction Classification

These classifications are only a guideline. The relevance of a particular drug interaction to a specific individual is difficult to determine. Always consult your healthcare provider before starting or stopping any medication.
Major Highly clinically significant. Avoid combinations; the risk of the interaction outweighs the benefit.
Moderate Moderately clinically significant. Usually avoid combinations; use it only under special circumstances.
Minor Minimally clinically significant. Minimize risk; assess risk and consider an alternative drug, take steps to circumvent the interaction risk and/or institute a monitoring plan.
Unknown No interaction information available.

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.

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