Oxycodone with St John's Wort Interaction Details

Brand Names Associated with Oxycodone

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

Interaction Effect

Decreased plasma levels and efficacy of oxycodone and increased risk of serotonin syndrome

Interaction Summary

Use caution if St. John's Wort, a CYP3A4 inducer, is taken with oxycodone. Concomitant use with a CYP3A4 inducer may reduce oxycodone efficacy or cause abstinence syndrome in physically dependent patients. In a randomized trial in 12 healthy volunteers, the combination of St John's Wort and oxycodone resulted in lower plasma levels and more rapid clearance of oxycodone compared with placebo and oxycodone. Self-reported levels of analgesia were lower during the phase when St John's Wort was administered, although measurement of response to cold stimuli was not significantly altered . Discontinuation of St. John's wort may decrease oxycodone clearance and increase drug levels, which can manifest as life-threatening or fatal respiratory depression. Because both oxycodone and St. John's wort both affect the serotonergic neurotransmitter system, coadministration may also result in serotonin syndrome. Monitor the patient for signs of withdrawal, or that oxycodone is not controlling pain and for serotonin syndrome during concomitant use, especially during treatment initiation and dosage adjustment. Consider dosage adjustments until stable plasma concentrations are achieved. Monitor for signs of respiratory depression during discontinuation of St. John's wort .

Severity

Moderate

Onset

Unspecified

Evidence

Established

How To Manage Interaction

Use caution if St. John's Wort, a CYP3A4 inducer, is taken with oxycodone. Concomitant use with a CYP3A4 inducer may reduce oxycodone efficacy or cause abstinence syndrome in physically dependent patients. Conversely, discontinuation of St. John's wort may decrease oxycodone clearance and increase drug levels, which can manifest as life-threatening or fatal respiratory depression. Because both oxycodone and St. John's wort both affect the serotonergic neurotransmitter system, coadministration may also result in serotonin syndrome. Monitor the patient for signs of withdrawal, or that oxycodone is not controlling pain and for serotonin syndrome during concomitant use, especially during treatment initiation and dosage adjustment. Consider dosage adjustments until stable plasma concentrations are achieved. Monitor for signs of respiratory depression during discontinuation of St. John's wort.

Mechanism Of Interaction

Increased CYP3A metabolism of oxycodone; additive serotonergic effect

Literature Reports

A) In a randomized trial of 12 healthy volunteers, the combination of St John's Wort and oxycodone resulted in lower plasma levels and more rapid clearance of oxycodone. Following a washout period for all other medications and supplements, participants were randomized to St John's Wort 300 mg three times daily for 15 days, or placebo. On the 14th day, participants entered a medical facility and were given a single oral dose of oxycodone 15 mg. During regular intervals within the first 12 hours after oxycodone administration, each patient's response to cold stimulus was measured by plunging their left hand into ice-water, measuring the time when pain was initially noted, and recording the intensity of pain at 60 seconds. Two weeks later, all participants repeated the same process with the opposite treatment regimen. A lower maximal oxycodone plasma concentration (Cmax) was observed during the St John's wort phase, compared with the placebo phase (24 ng/mL [76 nanomol/L] vs 33.6 ng/mL [106.5 nanomol/L] respectively). Similarly, a shorter oxycodone elimination half-life was observed during St John's wort administration, compared with placebo (3 hours vs 3.8 hours, respectively). St. John's wort also reduced AUC of oral oxycodone by 50% (range, 37% to 57%). Self-reported levels of analgesia were lower during the St John's wort phase, although responses to cold stimuli were not significantly altered .

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.

Return To Our Drug Interaction Homepage

Feedback, Question Or Comment About This Information?

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.