Trazodone with Ginkgo Interaction Details
Brand Names Associated with Trazodone
- Desyrel®
- Oleptro®
- Trazodone
- Trialodine®
Medical Content Editor Dr. Brian Staiger, PharmD
Last updated
Nov 11, 2023
Interaction Effect
Excessive sedation and potential coma
Interaction Summary
A single case report has described a semicomatose state following use of gingko with traZODone. Since no rechallenge of either agent alone or together was performed, it is inconclusive if the reaction was due to the combination or an unusual reaction to either agent alone. Ginkgo may have partial agonist activity at GABA receptors, as well as the ability to induce cytochrome P450 3A4 (CYP3A4) activity, producing more of the active metabolite of traZODone, mCPP, which further enhances the release of GABA . In contrast, ginkgo inhibited CYP3A4 in vitro . However, in vitro findings may not translate into the same in vivo findings, therefore the clinical significance of this in vitro finding is unknown.
Severity
Major
Onset
Rapid
Evidence
Probable
How To Manage Interaction
A single case report has described a semicomatose state following use of gingko with traZODone. Since no rechallenge of either agent alone or together was performed, it is inconclusive if the reaction was due to the combination or an unusual adverse reaction to either agent alone. Until more is known about this potential interaction, avoid concomitant use of ginkgo and traZODone. If the use of both cannot be avoided, use a low dose of traZODone and monitor the patient carefully for signs of excessive sedation.
Mechanism Of Interaction
Induction of cytochrome P450 3A4 by ginkgo to produce more of the active metabolite mCPP of traZODone
Literature Reports
A) An 80-year-old female diagnosed with probable Alzheimer's disease was prescribed ginkgo biloba 80 mg twice daily and traZODone 20 mg twice daily following treatment failure after 3 months with bromazepam 3.5 mg daily, donepezil 5 mg at bedtime, and vitamin E 600 mg twice daily. Bromazepam, donepezil, and vitamin E were discontinued. On the third day of treatment with gingko and traZODone, the patient developed gait instability and drowsiness, fell asleep one hour later, and was unable to be awakened. Blood pressure was 120/55, Glasgow coma scale was 6/15. Flumazenil 1 mg was given and the patient woke immediately. traZODone and ginkgo were discontinued, replaced by bromazepam. At evaluation 2 months later, cognitive function and behavior were unchanged. The mechanism of the interaction between gingko and traZODone was hypothesized to be due to a combination of weak GABA agonist activity of ginkgo, and induction of CYP 3A4 by ginkgo, leading to increased production of the active metabolite of traZODone, mCPP which further increased GABA release .
B) Ginkgo biloba inhibited CYP3A4 in vitro with an IC50 of 4.75 mmol. Ketoconazole, a known CYP3A4 inhibitor, was compared with ginkgo and other phytochemicals, had an IC50 of 7.18 x 10-4 mmol, making it 23.3 times more inhibitory than the most inhibitory plant phytochemical (goldenseal) with an IC50 of 0.03 mmol. Ginkgo was a much weaker inhibitor of CYP3A4; however, clinically significant drug interactions may occur with the inhibitory phytochemicals tested and drugs metabolized by CYP3A4 .
Trazodone Overview
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Trazodone is used to treat depression. Trazodone is in a class of medications called serotonin modulators. 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.