Fluoxetine with Toloxatone Interaction Details
Brand Names Associated with Fluoxetine
- Fluoxetine
- Prozac®
- Prozac® Weekly
- Rapiflux®
- Sarafem®
- Selfemra®
- Symbyax® (as a combination product containing Fluoxetine, Olanzapine)
Medical Content Editor Dr. Brian Staiger, PharmD
Last updated
Nov 11, 2023
Interaction Effect
CNS toxicity or serotonin syndrome (hypertension, hyperthermia, myoclonus, mental status changes)
Interaction Summary
Concurrent administration or overlapping therapy with fluoxetine 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. As a reversible and selective monoamine oxidase inhibitor, toloxatone may not potentiate the effects of selective serotonin reuptake inhibitors to the same frequency, extent, and duration observed with other MAOIs. However, until further studies confirm the safety and efficacy of this combined therapy, concomitant use is contraindicated.
Severity
Contraindicated
Onset
Rapid
Evidence
Probable
How To Manage Interaction
Concurrent use of fluoxetine and toloxatone is contraindicated. Wait at least two weeks after discontinuing a MAO inhibitor before initiating fluoxetine therapy. In addition, wait at least five weeks after discontinuing fluoxetine before initiating therapy with a MAO inhibitor.
Mechanism Of Interaction
Inhibition of serotonin metabolism by monoamine oxidase
Literature Reports
A) Concomitant use of serotonin specific 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) It has been suggested that fluoxetine therapy be discontinued for at least five weeks before beginning therapy with a monoamine oxidase inhibitor. A 28-year old woman discontinued fluoxetine for six weeks before starting therapy with tranylcypromine. Over the next few days the patient developed fever, paresthesias, confusion, abdominal cramping, and various other CNS symptoms. Upon discontinuation of tranylcypromine, the patient's symptoms began to resolve. Blood samples taken three days after discontinuation of tranylcypromine revealed no presence of fluoxetine; however, the norfluoxetine level was 84 ng/mL (284 nanomol/L) .
C) Adverse reactions reported when fluoxetine was given concomitantly with phenelzine (n=9) or tranylcypromine (n=4) include tremor (50%), agitation or restlessness (42%), mental status changes (42%), myoclonus (33%), diarrhea (33%), and blood pressure changes (25%) . All but one of the patients were taking other medications (ie, benzodiazepines, neuroleptics, anticonvulsants, antidepressants) that may have contributed to the adverse reactions.
D) Ten hours after her last dose of fluoxetine, a 45-year-old woman began tranylcypromine therapy . Headache, muscle contractions, insomnia, and unsteady gait were reported on the second day. Thioridazine and tryptophan were added to her therapy. The patient experienced fever, rigidity of the arms and legs, and hyperreflexia. She died in the intensive care unit of a hospital 44 hours later.
E) Two cases reports suggested a possible interaction between fluoxetine and selegiline . 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.
Fluoxetine Overview
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Fluoxetine is used to treat depression, obsessive-compulsive disorder (bothersome thoughts that won't go away and the need to perform certain actions over and over), some eating disorders, and panic attacks (sudden, unexpected attacks of extreme fear and worry about these attacks). Fluoxetine is also used to relieve the symptoms of premenstrual dysphoric disorder, including mood swings, irritability, bloating, and breast tenderness. It is also used along with olanzapine (Zyprexa) to treat depression that did not respond to other medications and episodes of depression in people with bipolar I disorder (manic-depressive disorder; a disease that causes episodes of depression, episodes of mania, and other abnormal moods). Fluoxetine is in a class of medications called selective serotonin reuptake inhibitors (SSRIs). It works by increasing the amount of serotonin, a natural substance in the brain that helps 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.