Codeine with Naltrexone Interaction Details

Brand Names Associated with Codeine

Brand Names Associated with Naltrexone

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

Interaction Effect

Precipitation of opioid withdrawal symptoms; decreased opioid effectiveness

Interaction Summary

The concurrent administration of naltrexone and opioids is contraindicated. Naltrexone will reverse the effects of narcotic analgesics in dependent persons, resulting in withdrawal symptoms within 5 minutes of ingestion . Patients should be opioid-free (including traMADol) for a minimum of 7 to 10 days before initiating treatment with naltrexone or naltrexone-containing products such as bupropion/naltrexone; up to 2 weeks may be required for patients previously taking methadone or buprenorphine . Even when naltrexone therapy is initiated properly, the blockade can be overcome with very high dosages of opiates, posing the risk of fatal overdose in patients attempting to surmount the blockade on their own . The combination substance morphine sulfate/naltrexone hydrochloride is indicated to treat moderate to severe pain as directed .

Severity

Contraindicated

Onset

Rapid

Evidence

Probable

How To Manage Interaction

The concurrent administration of naltrexone and opioid analgesics is contraindicated. However, the oral combination of morphine sulfate/naltrexone hydrochloride capsule, which contains pellets of an extended-release oral morphine sulfate surrounding an inner core of naltrexone hydrochloride, is indicated to treat moderate to severe pain . In general, to avoid triggering an acute abstinence syndrome, patients must be opioid-free (including traMADol) for a minimum of 7 to 10 days before initiating treatment with naltrexone or naltrexone containing products such as bupropion/naltrexone; up to 2 weeks may be required for patients previously taking methadone or buprenorphine . A Narcan(R) (naloxone) challenge test can be utilized before treatment with naltrexone to rule out concurrent use of opioids. Naltrexone may diminish the effectiveness of antidiarrheal or antitussive treatments containing opioids .

Mechanism Of Interaction

Competitive binding at opioid receptors

Literature Reports

A) Significant improvement after the additions of oral naltrexone occurred in a patient with painful peripheral neuropathy. A 61-year-old male patient with diabetes complained of pain and paresthesias in the feet, distal legs, and fingers. His finger stick glucose measurements were in the 250 range. He was taking methadone 80 mg/day and oxycodone 5 mg 4 times daily for breakthrough pain. Both medications were reduced by 50% a week before presentation due to concerns about medication-seeking behavior. Over the next several months he underwent numerous dose adjustments but the pain would return. He also complained of nausea. Eight months after presentation, the patient was taking methadone 60 mg 4 times daily and methylphenidate 30 mg twice daily for opioid-induced sedation. "Ultra-low" dose naltrexone was initiated at 1 mcg twice daily. The patient reported improvement within 1 day. His pain decreased significantly and the chronic nausea resolved. The methadone dose was decreased to 50 mg four times daily and methylphenidate dose remained unchanged. The patient remained with the same degree of pain relief 1 month later. The same dose of methadone and 50% of the short-acting opioid were used .

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.

Naltrexone Overview

• Naltrexone is used along with counseling and social support to help people who have stopped drinking alcohol and using street drugs continue to avoid drinking or using drugs. Naltrexone should not be used to treat people who are still using street drugs or drinking large amounts of alcohol. Naltrexone is in a class of medications called opiate antagonists. It works by decreasing the craving for alcohol and blocking the effects of opiate medications and opioid street drugs.

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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.