Oxycodone with Posaconazole Interaction Details

Brand Names Associated with Oxycodone

Brand Names Associated with Posaconazole

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

Interaction Effect

Increased oxycodone exposure

Interaction Summary

Use caution when initiating or discontinuing concurrent treatment with oxycodone and CYP3A4 inhibitors. 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 voriconazole, increased oxycodone AUC and Cmax by 3.6 and 1.7 fold respectively . Oxycodone AUC and Cmax values increased by 170% and 100%, respectively, when added to the CYP3A4 inhibitor, ketoconazole at 400 mg/day .

Severity

Major

Onset

Unspecified

Evidence

Theoretical

How To Manage Interaction

Use caution when initiating or discontinuing concurrent treatment with oxycodone and CYP3A4 inhibitors. 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) Voriconazole significantly increased oxycodone plasma concentrations and decreased clearance according to a randomized, placebo-controlled, crossover study in 12 healthy volunteers. Adults (age range, 19 to 25 years) were randomized to either placebo (control phase) or to voriconazole (400 mg orally twice daily on day 1, followed by 200 mg orally every 12 hours for 5 more doses). On day 3, all subjects received a single oral dose of oxycodone 10 mg. The washout interval between the phases was 4 weeks. During the voriconazole phase, compared to placebo, there was a mean 3.6-fold (range 2.7- to 5.6-fold, p less than 0.001) increase in oxycodone AUC, a mean 1.7-fold (range 1.4- to 2.2-fold, p less than 0.001) increase in oxycodone Cmax, and a mean 2-fold (range 1.4- to 2.5-fold, p less than 0.001) increase in oxycodone half-life. Compared with placebo, concomitant administration of voriconazole decreased the clearance/bioavailability ratio of oxycodone by 71% (p less than 0.001). The oxycodone metabolite-to-parent drug AUC ratio was increased by 88% for oxymorphone (p less than 0.01) and decreased by 92% for noroxycodone (p less than 0.001). Compared to placebo, voriconazole increased oxycodone-induced miosis (p less than 0.001); however, analgesic effects were not altered .

B) Oxycodone AUC and Cmax values increased by 170% and 100%, respectively, when added to the CYP3A4 inhibitor, ketoconazole at 400 mg/day .

C) A published study showed that the coadministration of 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.

Posaconazole Overview

• Posaconazole is used to prevent serious fungal infections that can spread throughout the body in adults and children 2 years of age and older with a weakened ability to fight infection. Posaconazole delayed-release tablets are used to treat invasive aspergillosis (a serious fungal infection that begins in the lungs and spreads through the bloodstream to other organs) in adults and teenagers 13 years of age and older. Posaconazole oral suspension is also used to treat yeast infections of the mouth and throat including yeast infections in adults and teenagers 13 years of age and older that could not be treated successfully with other medications. Posaconazole is in a class of medications called azole antifungals. It works by slowing the growth of fungi that cause infection.

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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.