Diazepam with Ginkgo Interaction Details
Brand Names Associated with Diazepam
- Diazepam
- Diazepam Intensol®
- Valium®
- Valrelease®
Medical Content Editor Dr. Brian Staiger, PharmD
Last updated
Nov 19, 2023
Interaction Effect
Decreased anticonvulsant effectiveness
Interaction Summary
In a case report, 2 patients with epilepsy previously well controlled by valproate sodium developed a recurrence of seizures after ingesting ginkgo extract. Seizure control was regained after ginkgo was withdrawn. An infant developed seizures after exposure to 4'-O-methylpyridoxine arising from ingestion of ginkgo seeds . The compound 4'-O-methylpyridoxine, a neurotoxin, is found in ginkgo seeds (used as food in Japan) as well as in leaves, the ginkgo component from which commercially available extracts are derived . The majority of ginkgo leaf products should not contain sufficient amounts of 4'-O-methylpyridoxine to cause seizures. However, ginkgo products are not commonly assayed to assure that 4'-O-methylpyridixone is not contained in the commercial product. Of concern are those instances where, depending on the harvest season and the potential introduction of contamination, 4'-O-methylpyridoxine may be present in sufficient amounts to be problematic in vulnerable populations (eg, infants or those with known seizure disorders).
Severity
Moderate
Onset
Delayed
Evidence
Probable
How To Manage Interaction
Avoid concomitant use of ginkgo and anticonvulsants in patients with epilepsy. If seizures occur for the first time or recur in patients previously controlled by anticonvulsant medication, inquire about the use of ginkgo seed or leaf extract. If possible, an assay should be conducted on the specific product to ascertain if 4'-O-methylpyridoxine is present.
Mechanism Of Interaction
Neurotoxin 4'-O-methylpyridoxine (found in leaves and seeds of ginkgo biloba) may cause seizures
Literature Reports
A) The serum of a 21-month-old patient with gin-nan food poisoning was assayed for 4'-O-methylpyridoxine levels. The serum concentration was 0.9 micrograms/milliliter (mcg/mL) at 8.5 hours after ingesting ginkgo seeds, decreasing to 0.05 mcg/mL at 15.5 hours. The authors concluded that the 4'-O-methylpyridoxine content was responsible for the tonic/clonic convulsions and loss of consciousness observed. They further observed that infants are particularly vulnerable .
B) Four to six milligrams of the neurotoxin 4'-O-methylpyridoxine have been isolated from 2 kilograms of Ginkgo biloba leaves which is the source of commercially-available products. Highest amounts were found in seeds (85 micrograms (mcg)/seed) and leaves (5 mcg/leaf) derived from the tree at the end of July and beginning of August. The albumen of the seed can contain 105.15 mcg/gram dry weight, but this is reduced to 0.75-1.32 mcg/gram dry weight when boiled. The unprocessed seed coats contain from 5.44-7.15 mcg/gram dry weight. The neurotoxin in ginkgo leaf was detected in medications and it was even detectable in homeopathic preparations. Specifically, 8.13 mcg/mL of 4'-O-methylpyridoxine was found in Tebonin Forte(R), 9.77 mcg/mL in Rokan(R), 3.80 mcg/mL in Kaveri Forte(R), and 7.18 mcg/mL in Gingium(R). Based on recommended daily intake, this translates into a maximum daily intake of 4'-O-methylpyridoxine of 48.78 mcg, 58.62 mcg, 11.40 mcg, and 43.08 mcg for Tebonin Forte(R), Rokan(R), Kaveri Forte(R), and Gingium(R), respectively. Among the homeopathic products, Ginkgo biloba Urtinktur Hanosan(R) and Ginkgo biloba Urtinktur DHU(R) contained 0.301 mcg/mL and 0.589 mcg/mL of 4'-O-methylpyridoxine, respectively. However, the authors note that the amount contained in medicinal extracts of ginkgo leaves may be too low to be of clinical significance. Concern remains with the variance in 4'-O-methylpyridoxine content depending on the season during which the ginkgo was harvested .
C) Seizures recurred in 2 patients, both with epilepsy that was well controlled prior to ingesting ginkgo biloba (Gb). The patients (an 84-year-old woman and a 78-year-old man) had been free of seizures for at least 18 months prior to beginning therapy with Gb 120 milligrams daily to treat cognitive decline. Both patients developed seizures within 2 weeks of beginning Gb therapy, and both remained seizure-free (without changing anticonvulsant therapy) after discontinuing Gb .
Diazepam Overview
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Diazepam is used to relieve anxiety and to control agitation caused by alcohol withdrawal. It is also used along with other medications to control muscle spasms and spasticity caused by certain neurological disorders such as cerebral palsy (condition that causes difficulty with movement and balance), paraplegia (inability to move parts of the body), athetosis (abnormal muscle contractions), and stiff-man syndrome (a rare disorder with muscle rigidity and stiffness). Diazepam is also used along with other medications to control seizures. Diazepam is in a class of medications called benzodiazepines. It works by calming abnormal overactivity in the brain.
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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.