Venlafaxine with Moclobemide Interaction Details
Brand Names Associated with Venlafaxine
- Effexor®
- Effexor® XR
- Venlafaxine
Medical Content Editor Dr. Brian Staiger, PharmD
Last updated
Nov 12, 2023
Interaction Effect
CNS toxicity or serotonin syndrome (hypertension, hyperthermia, myoclonus, mental status changes)
Interaction Summary
Concurrent administration or overlapping therapy with venlafaxine and a monoamine oxidase (MAO) inhibitor may result in CNS toxicity or serotonin syndrome, a hyperserotonergic state characterized by symptoms such as restlessness, myoclonus, changes in mental status, hyperreflexia, diaphoresis, shivering, and tremor. Serious, even fatal, reactions have been reported with concomitant use of serotonin specific reuptake inhibitors and MAO inhibitors. Concomitant use is contraindicated.
Severity
Contraindicated
Onset
Rapid
Evidence
Probable
How To Manage Interaction
Concurrent use of venlafaxine and a MAO inhibitor is contraindicated. Wait at least 14 days after discontinuing a MAO inhibitor before initiating therapy with venlafaxine. Wait at least seven days after discontinuing venlafaxine before initiating therapy with a MAO inhibitor.
Mechanism Of Interaction
Inhibition of serotonin metabolism by monoamine oxidase
Literature Reports
A) Concomitant use of selective serotonin reuptake inhibitors and monoamine oxidase inhibitors can produce a toxic reaction known as serotonin syndrome . Serotonin syndrome is a condition of serotonergic hyperstimulation and manifests as restlessness, myoclonus, changes in mental status, hyperreflexia, diaphoresis, shivering, and tremor. If the syndrome is not recognized and correctly treated, death can result.
B) Two cases suggestive of an interaction between fluoxetine and selegiline, a selective monoamine oxidase B inhibitor, have been reported . One case involved a first episode of mania being observed approximately one month after adding selegiline to fluoxetine therapy. The patient improved two months after both drugs were discontinued, and no further details were provided. The second case involved diaphoresis, vasoconstriction, and cyanosis of the hands which occurred in close temporal relationship to adding fluoxetine and selegiline. Both drugs were discontinued, with relatively quick resolution of symptoms. Rechallenge with fluoxetine alone occurred without incident.
C) Five fatal overdose cases due to serotonin syndrome have been reported . In three of the five cases, the drug combination that induced the fatal syndrome was moclobemide, a selective monoamine oxidase inhibitor, and citalopram. Of the three patients, blood concentrations of moclobemide ranged from five times the therapeutic level to 50 times the therapeutic level, and citalopram concentrations ranged from normal therapeutic levels to five times the therapeutic level.
D) A 34-year-old man experienced serotonin syndrome after ingesting venlafaxine 2.625 g and moclobemide 3 g with an unknown amount of alcohol. The patient displayed tachycardia (126 beats/min), tachypnea (26 breaths/min), altered mental status, hypertonia, and had a creatine phosphokinase (CPK) of 1006 U/L. Moclobemide, which is a reversible MAOI in therapeutic doses, may act like an irreversible MAOI with large doses, increasing the level of serotonin in the synaptic cleft .
E) A 32-year-old man taking moclobemide 20 mg twice daily and diazepam 15 mg daily was given venlafaxine 150 mg by a friend. Approximately 40 minutes afterward, he developed dizziness, vomiting, diaphoresis, hallucination and agitation. He also demonstrated muscle rigidity and ocular oscillation. Blood pressure was noted to be 162/107 mm Hg. He was treated with diazepam 10 mg and chlorpromazine 12.5 mg and his condition improved significantly .
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.
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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.