Codeine with Clorazepate Interaction Details

Brand Names Associated with Codeine

Brand Names Associated with Clorazepate

Medical Content Editor Dr. Brian Staiger, PharmD
Last updated Dec 31, 2023

Interaction Effect

An increased risk of respiratory and CNS depression

Interaction Summary

Avoid concomitant use of opioid cough medication formulations and CNS depressants. Concomitant use of opioid analgesics with benzodiazepines has been associated with increased rates of emergency department visits and fatal overdose. Concomitant use of codeine with CNS depressants can increase the risk of hypotension, respiratory depression, profound sedation, coma and death. Reserve concomitant prescribing of these drugs for use in patients for whom alternative treatment options are inadequate. Limit dosages and durations to the minimum required. Follow patients closely for signs of respiratory depression and sedation. If concomitant use is warranted, consider prescribing naloxone for the emergency treatment of opioid overdose .

Severity

Major

Onset

Unspecified

Evidence

Theoretical

How To Manage Interaction

Avoid concomitant use of opioid cough medication formulations and CNS depressants. Concomitant use of codeine with CNS depressants can increase the risk of hypotension, respiratory depression, profound sedation, coma and death . Reserve the concomitant use of non-cough codeine products and CNS depressants to patients for whom alternatives are inadequate. If concomitant use is necessary, use the lowest dose and shortest duration necessary to achieve treatment goals. Consider using a lower dose of codeine or the CNS depressant and closely monitor for sedation and respiratory depression . If concomitant use is warranted, consider prescribing naloxone for the emergency treatment of opioid overdose .

Mechanism Of Interaction

Additive CNS depression

Literature Reports

A) In a study, the rate of nonmedical use-related emergency department visits occurring between 2004 and 2011 and involving opioid analgesics and benzodiazepines significantly increased from 11 to 34.2 per 100,000. Drug overdose deaths due to prescribed and greater than prescribed doses of both drug classes also significantly increased from 0.6 to 1.7 per 100,000, and overdoses deaths due to benzodiazepines significantly increased from 18% to 31% .

B) In a prospective cohort study, the rate of overdose deaths involving the dispensing of both opioid analgesics and benzodiazepines was 10 times higher compared with dispensing of opioid analgesics alone (7 vs 0.7 per 10,000 person years) .

C) In a cohort study of data from 2004 to 2009, the risk of fatal overdose significantly increased by 2.33 fold in patients taking opioid analgesics with a history of a benzodiazepine prescription and increased by 3.86 fold in those with a current benzodiazepine prescription compared with those taking opioid analgesics without a history of a benzodiazepine prescription. The risk of drug overdose deaths increased with increasing daily doses of benzodiazepines .

Codeine Overview

• Codeine is used to relieve mild to moderate pain. It is also used, usually in combination with other medications, to reduce coughing. Codeine will help relieve symptoms but will not treat the cause of symptoms or speed recovery. Codeine belongs to a class of medications called opiate (narcotic) analgesics and to a class of medications called antitussives. When codeine is used to treat pain, it works by changing the way the brain and nervous system respond to pain. When codeine is used to reduce coughing, it works by decreasing the activity in the part of the brain that causes coughing.

• Codeine is also available in combination with acetaminophen (Capital and Codeine, Tylenol with Codeine), aspirin, carisoprodol, and promethazine and as an ingredient in many cough and cold medications. This monograph only includes information about the use of codeine. If you are taking a codeine 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.