Oxycodone with Netupitant Interaction Details

Brand Names Associated with Oxycodone

Medical Content Editor Dr. Brian Staiger, PharmD
Last updated Nov 13, 2023

Interaction Effect

Increased oxycodone exposure

Interaction Summary

Avoid concomitant use of oxycodone (a CYP3A4 substrate) with netupitant (a moderate inhibitor of CYP3A4) for 1 week. If oxycodone must be administered within 1 week of netupitant, consider reducing the dose of oxycodone. Use caution when initiating or discontinuing concurrent treatment with oxycodone and CYP3A4 inhibitors (netupitant and fosnetupitant). Concomitant use with a CYP3A4 inhibitor may increase and prolong oxycodone plasma concentrations and lead to life-threatening or fatal respiratory depression. These effects may be more pronounced when an inhibitor is added after a stable dose of oxycodone is achieved. If concomitant use with a CYP3A4 inhibitor is clinically required, monitor patients frequently for signs of sedation or respiratory depression. Consider dosage reduction of oxycodone until stable plasma concentrations are achieved. If the inhibitor is discontinued, monitor for signs of opioid withdrawal and consider increasing the oxycodone dosage until stable drug effects are achieved. Strongly consider prescribing naloxone for the emergency treatment of opioid overdose. A published study showed that the coadministration of the antifungal drug voriconazole( a CYP3A4 inhibitor), increased oxycodone AUC and Cmax by 3.6 and 1.7 fold respectively . The mean AUC and Cmax of the CYP3A4 substrate erythromycin was increased following the coadministration of netupitant in a pharmacokinetic study. Increases in the AUC of dexamethasone, a CYP3A4 probe substrate, remained for up to 8 days following a single dose of netupitant .

Severity

Major

Onset

Unspecified

Evidence

Theoretical

How To Manage Interaction

Avoid concomitant use of oxycodone (a CYP3A4 substrate) with netupitant (a moderate inhibitor of CYP3A4) for 1 week. If oxycodone must be administered within 1 week of netupitant, consider reducing the dose of oxycodone. Use caution when initiating or discontinuing concurrent treatment with oxycodone and CYP3A4 inhibitors (netupitant and fosnetupitant). Concomitant use with a CYP3A4 inhibitor may increase and prolong oxycodone plasma concentrations and lead to life-threatening or fatal respiratory depression. These effects may be more pronounced when an inhibitor is added after a stable dose of oxycodone is achieved. If concomitant use with a CYP3A4 inhibitor is clinically required, monitor patients frequently for signs of sedation or respiratory depression. Consider dosage reduction of oxycodone until stable plasma concentrations are achieved. If the inhibitor is discontinued, monitor for signs of opioid withdrawal and consider increasing the oxycodone dosage until stable drug effects are achieved. Strongly consider prescribing naloxone for the emergency treatment of opioid overdose .

Mechanism Of Interaction

Inhibition of CYP3A4-mediated oxycodone metabolism

Literature Reports

A) In one study where the duration of CYP3A4 inhibition was assessed using dexamethasone as a CYP3A4 probe substrate, the mean AUC of dexamethasone increased by 1.6-fold on day 1, 2.4-fold on day 4, 1.5-fold on day 6, and 1.2-fold on day 8 after a single dose of the combination netupitant 300 mg/palonosetron 0.5 mg was coadministered to participants on day 1. The participants had been treated with a dexamethasone regimen of 12 mg on day 1 followed by 8 mg on days 2, 3, 4, 6, 8, and 10 .

B) A pharmacokinetic study demonstrated that when erythromycin 500 mg was coadministered with netupitant 300 mg, the mean AUC of erythromycin increased by 56% and the Cmax increased by 92% .

C) A published study showed that the coadministration of the antifungal drug voriconazole( a CYP3A4 inhibitor), increased oxycodone AUC and Cmax by 3.6 and 1.7 fold respectively .

Oxycodone Overview

• Oxycodone is used to relieve moderate to severe pain. Oxycodone extended-release tablets and extended-release capsules are used to relieve severe pain in people who are expected to need pain medication around the clock for a long time and who cannot be treated with other medications. Oxycodone extended-release tablets and extended-release capsules should not be used to treat pain that can be controlled by medication that is taken as needed. Oxycodone extended-release tablets, extended-release capsules, and concentrated solution should only be used to treat people who are tolerant (used to the effects of the medication) to opioid medications because they have taken this type of medication for at least one week. Oxycodone is in a class of medications called opiate (narcotic) analgesics. It works by changing the way the brain and nervous system respond to pain.

• Oxycodone is also available in combination with acetaminophen (Oxycet, Percocet, Roxicet, Xartemis XR, others); aspirin (Percodan); and ibuprofen. This monograph only includes information about the use of oxycodone alone. If you are taking an oxycodone combination product, be sure to read information about all the ingredients in the product you are taking and ask your doctor or pharmacist for more information.

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Definitions

Severity Categories

Contraindicated

These drugs, generally, should not be used together simultaneously due to the high risk of severe adverse effects. Combining these medications can lead to dangerous health outcomes and should be strictly avoided unless otherwise instructed by your provider.

Major

This interaction could result in very serious and potentially life-threatening consequences. If you are taking this drug combination, it is very important to be under close medical supervision to minimize severe side effects and ensure your safety. It may be necessary to change a medication or dosage to prevent harm.

Moderate

This interaction has the potential to worsen your medical condition or alter the effectiveness of your treatment. It's important that you are monitored closely and you potentially may need to make adjustments in your treatment plan or drug dosage to maintain optimal health.

Minor

While this interaction is unlikely to cause significant problems, it could intensify side effects or reduce the effectiveness of one or both medications. Monitoring for changes in symptoms and your condition is recommended, and adjustments may be made if needed to manage any increased or more pronounced side effects.

Onset

Rapid: Onset of drug interaction typically occurs within 24 hours of co-administration.

Delayed: Onset of drug interaction typically occurs more than 24 hours after co-administration.

Evidence

Level of documentation of the interaction.

Established: The interaction is documented and substantiated in peer-reviewed medical literature.

Theoretical: This interaction is not fully supported by current medical evidence or well-documented sources, but it is based on known drug mechanisms, drug effects, and other relevant information.

How To Manage The Interaction

Provides a detailed discussion on how patients and clinicians can approach the identified drug interaction as well as offers guidance on what to expect and strategies to potentially mitigate the effects of the interaction. This may include recommendations on adjusting medication dosages, altering the timing of drug administration, or closely monitoring for specific symptoms.

It's important to note that all medical situations are unique, and management approaches should be tailored to individual circumstances. Patients should always consult their healthcare provider for personalized advice and guidance on managing drug interactions effectively.

Mechanism Of Interaction

The theorized or clinically determined reason (i.e., mechanism) why the drug-drug interaction occurs.

Disclaimer: The information provided on this page is for informational purposes only and should not be considered medical advice. Always consult with a qualified healthcare professional regarding your specific circumstances and medical conditions.

Where Does Our Information Come From?

Information for our drug interactions is compiled from several drug compendia, including:

• Gold Standard Drug Database
• Micromedex
• Lexicomp
• DrugBank

The prescribing information for each drug, as published on DailyMED, is also used. 

Individual drug-drug interaction detail pages contain references specific to that interaction. You can click on the reference number within brackets '[]' to see what reference was utilized.

The information posted is fact-checked by HelloPharmacist clinicians and reviewed quarterly.