Oxycodone with Clorazepate Interaction Details

Brand Names Associated with Oxycodone

Brand Names Associated with Clorazepate

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

Interaction Effect

Increased risk of respiratory and CNS depression

Interaction Summary

Concomitant use of oxycodone and CNS depressants may increase the risk of respiratory and CNS depression. Between 2004 and 2011, the number of drug-related overdose deaths, the number of nonmedical use-related emergency department visits involving opioids and benzodiazepines, and the number of opioid overdose deaths in which benzodiazepines played a role increased. Two studies have shown that when opioids and benzodiazepines are co-prescribed, the risk of overdose death increases. Coadministration of oxycodone and a CNS depressant may result in additive CNS depression and an increased risk of respiratory depression, profound sedation, coma, and death. Reserve concomitant prescribing for use in patients for whom alternative treatment options are inadequate. If concomitant use is necessary, use the lowest effective dosage and minimum duration of use. Monitor for sedation and respiratory depression and strongly consider prescribing naloxone for the emergency treatment of opioid overdose  Initiate oxycodone extended-release (ER) tablets and oxycodone/naloxone combination at one-third to one-half of the usual dose  and oxycodone/acetaminophen ER tablets at a reduced dose of 1 tablet every 12 hours .

Severity

Major

Onset

Unspecified

Evidence

Theoretical

How To Manage Interaction

Coadministration of oxycodone and a CNS depressant may result in additive CNS depression and an increased risk of respiratory depression, profound sedation, coma, and death. Reserve concomitant prescribing for use in patients for whom alternative treatment options are inadequate. If concomitant use is necessary, use the lowest effective dosage and minimum duration of use. Monitor for sedation and respiratory depression and strongly consider prescribing naloxone for the emergency treatment of opioid overdose. Initiate oxycodone extended-release tablets and oxycodone/naloxone combination at one-third to one-half of the usual initial dosage  and initiate oxycodone/acetaminophen extended-release tablets at a reduced dose of 1 tablet every 12 hours .

Mechanism Of Interaction

Additive CNS depression

Literature Reports

A) From 2004 to 2011, drug-related overdose deaths, either from taking prescribed or greater than prescribed doses, and involving both opioids and benzodiazepines, significantly increased from 0.6 to 1.7 per 100,000 population. During this same time, the number of nonmedical use-related emergency department visits where both opioid analgesics and benzodiazepines were involved significantly increased from 11 to 34.2 per 100,000. Additionally, opioid overdose deaths in which benzodiazepines also played a factor significantly rose from 18% to 31% .

B) One study, conducted in North Carolina, found overdose death rates were 10 times higher among patients who were co-prescribed opioids and benzodiazepines than among patients who were prescribed opioids alone (7 vs 0.7 per 10,000 person-years). Another study examined data from the Veterans Health Administration and compared risk of fatal overdose in patients taking opioids with no history of a benzodiazepine prescription, patients taking opioids with a history of benzodiazepine prescription, and patients taking opioids with a current benzodiazepine prescription. The conclusion was patients who had a history of a benzodiazepine prescription and patients with a current benzodiazepine prescription had a significantly increased risk of fatal overdose, 2.33 times and 3.86 times, respectively, versus patients taking opioids with no history of a benzodiazepine prescription. The risk continued to increase as the daily benzodiazepine dose increased .

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.

Clorazepate Overview

• Clorazepate is used to relieve anxiety. Clorazepate is also used along with other medications to treat certain types of seizures. It is also used to relieve unpleasant symptoms that may be experienced by people who have stopped drinking alcohol after drinking large amounts for a long time. Clorazepate is in a class of medications called benzodiazepines. It works by decreasing abnormal electrical activity in the brain.

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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.