Venlafaxine with Entacapone Interaction Details
Brand Names Associated with Venlafaxine
- Effexor®
- Effexor® XR
- Venlafaxine
Brand Names Associated with Entacapone
- Comtan®
- Entacapone
- Stalevo® (as a combination product containing Carbidopa, Entacapone, Levodopa)

Medical Content Editor Dr. Brian Staiger, PharmD
Last updated
Nov 12, 2023
Interaction Effect
An increased risk of tachycardia, hypertension, and arrhythmias
Interaction Summary
Entacapone is an inhibitor of catechol-o-methyltransferase (COMT), and inhibits the metabolism of norepinephrine and related catecholamines. Venlafaxine is a norepinephrine reuptake inhibitor; the concurrent administration of entacapone and venlafaxine may theoretically provoke a supratherapeutic increase in norepinephrine serum concentrations, increasing the risk of cardiovascular adverse events.
Severity
Major
Onset
Rapid
Evidence
Theoretical
How To Manage Interaction
Coadministration of entacapone with venlafaxine is not recommended. Caution should be exercised if coadministration of these two drugs are unavoidable. Patients should be monitored for excessively increased heart rate, increased blood pressure, and cardiac arrhythmias.
Mechanism Of Interaction
Augmented inhibition of norepinephrine metabolism and clearance
Venlafaxine Overview
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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.
Entacapone Overview
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Entacapone is an inhibitor of catechol-O-methyltransferase (COMT). It is used in combination with levodopa and carbidopa (Sinemet) to treat the end-of-dose 'wearing-off' symptoms of Parkinson's disease. Entacapone helps the levodopa and carbidopa work better by allowing more of it to reach the brain, where it has its effects.
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This medication is sometimes prescribed for other uses; 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:
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.