Venlafaxine with Dextromethorphan Interaction Details

Brand Names Associated with Venlafaxine

Brand Names Associated with Dextromethorphan

Medical Content Editor Dr. Brian Staiger, PharmD
Last updated Nov 12, 2023

Interaction Effect

Increased dextromethorphan plasma concentrations and increased risk of serotonin syndrome

Interaction Summary

Venlafaxine is a relatively weak CYP2D6 inhibitor and dextromethorphan is a CYP2D6 substrate. While not specifically studied with venlafaxine, the concomitant use of paroxetine (another SSRI) with the combination of dextromethorphan/quinidine in one study resulted in increased AUC and Cmax of paroxetine, dextromethorphan, and quinidine. As the concomitant use of dextromethorphan with venlafaxine may increase the risk of serotonin syndrome, initial dose reductions of dextromethorphan may be warranted  along with monitoring for signs/symptoms of serotonin syndrome (eg, altered mental status, hypertension, restlessness, myoclonus, hyperthermia, hyperreflexia, diaphoresis, shivering, and tremor).

Severity

Major

Onset

Delayed

Evidence

Theoretical

How To Manage Interaction

Use caution when prescribing dextromethorphan to patients who are taking an SSRI (such as venlafaxine), as concomitant use may result in an increased risk of serotonin syndrome. Initial dose reductions of dextromethorphan may be warranted when administered with CYP2D6 inhibitors, such as venlafaxine.

Mechanism Of Interaction

Inhibition of CYP2D6-mediated dextromethorphan metabolism by venlafaxine

Literature Reports

A) In a group of 14 healthy subjects, the administration of paroxetine (20 mg once daily for 12 days) followed by a combination of dextromethorphan 30 mg/quinidine 30 mg (twice daily for 8 days) resulted in an increase in paroxetine AUC and Cmax (1.7- and 1.5-fold, respectively) and a decrease in dextrorphan AUC and Cmax (34% and 33%, respectively). The dextromethorphan/quinidine exposure did not change significantly. In a second group of 13 healthy subjects, the administration of dextromethorphan 30 mg/quinidine 30 mg (twice daily for 8 days) followed by paroxetine (20 mg once daily for 12 days) resulted in an increase in dextromethorphan AUC and Cmax (1.5- and 1.4-fold, respectively), a decrease in dextrorphan AUC and Cmax (14% and 18%, respectively), an increase in quinidine AUC and Cmax (1.4- and 1.3-fold, respectively), and an increase in paroxetine AUC and Cmax (2.3- and 2-fold, respectively) .

Venlafaxine Overview

• Venlafaxine is used to treat depression. Venlafaxine extended-release (long-acting) capsules are also used to treat generalized anxiety disorder (GAD; excessive worrying that is difficult to control), social anxiety disorder (extreme fear of interacting with others or performing in front of others that interferes with normal life), and panic disorder (sudden, unexpected attacks of extreme fear and worry about these attacks). Venlafaxine 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.

Dextromethorphan Overview

• Dextromethorphan is used to temporarily relieve cough caused by the common cold, the flu, or other conditions. Dextromethorphan will relieve a cough but will not treat the cause of the cough or speed recovery. Dextromethorphan is in a class of medications called antitussives. It works by decreasing activity in the part of the brain that causes coughing.

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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.