Desvenlafaxine with Codeine Interaction Details

Brand Names Associated with Desvenlafaxine

Brand Names Associated with Codeine

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

Interaction Effect

Increased CYP2D6 substrate exposure and an increased risk of serotonin syndrome (hypertension, tachycardia, hyperthermia, myoclonus, mental status changes)

Interaction Summary

Coadministration of desvenlafaxine, a weak CYP2D6 inhibitor and serotonergic drug, with another serotonergic agent that is also a CYP2D6 substrate may result in increased drug exposure and increased risk of serotonin syndrome. Serotonin syndrome may be life-threatening. Symptoms may include mental status changes (eg, agitation, hallucinations, coma), autonomic instability (eg, tachycardia, labile blood pressure, hyperthermia), neuromuscular aberrations (eg, hyperreflexia, incoordination), and gastrointestinal symptoms (eg, nausea, vomiting, diarrhea). If serotonin syndrome develops, discontinue both agents and initiate supportive symptomatic therapy. If concomitant use is required, no dose adjustment of the CYP2D6 substrate is needed with concurrent desvenlafaxine 100 mg/day or less. Reduce the CYP2D6 substrate dose by 50% if using concurrently with desvenlafaxine 400 mg/day (unapproved dosing) and increase the CYP2D6 substrate to the original dose if concurrent desvenlafaxine 400 mg/day is discontinued. Monitor all patients closely for signs and symptoms of serotonin syndrome, especially during treatment initiation and dose increases of either drug.

Severity

Major

Onset

Unspecified

Evidence

Probable

How To Manage Interaction

Use extreme caution with coadministration of desvenlafaxine (a weak CYP2D6 inhibitor and serotonergic agent) with serotonergic drugs that are also CYP2D6 substrates. Coadministration may result in additive serotonergic effects and may increase CYP2D6 substrate exposure. If concurrent use is required, CYP2D6 substrates may be given at the recommended dose when coadministered with desvenlafaxine 100 mg/day or less. Reduce the CYP2D6 substrate dose by 50% if using concurrently with desvenlafaxine 400 mg/day (unapproved dosing); increase the CYP2D6 substrate to the original dose if concurrent desvenlafaxine 400 mg/day is discontinued. Careful monitoring for signs and symptoms of serotonin syndrome is recommended, especially during treatment initiation and dose increases. Drug discontinuation and supportive symptomatic treatment is recommended if serotonin syndrome develops.

Mechanism Of Interaction

Inhibition of CYP2D6-mediated metabolism by desvenlafaxine; additive serotonergic effects

Literature Reports

A) Coadministration of desipramine (a CYP2D6 substrate) 50 mg with desvenlafaxine 400 mg/day (unapproved dosing) in a clinical study resulted in an increase of approximately 50% for the Cmax and 90% for the AUC of desipramine. The differences in desipramine metabolism were not considered clinically relevant when the dose of desvenlafaxine was 100 mg/day (25% increase in Cmax and 17% in AUC) .

Desvenlafaxine Overview

• Desvenlafaxine is used to treat depression. Desvenlafaxine is in a class of medications called selective serotonin and norepinephrine reuptake inhibitors (SNRIs). It works by increasing the amounts of serotonin and norepinephrine, natural substances in the brain that help maintain mental balance.

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.

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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.