Drug Interaction Report
2 potential interactions and/or warnings found for the following 2 drugs:
- Depakote ER (divalproex sodium)
- ginkgo
Interactions between your drugs
divalproex sodium ginkgo
Applies to: Depakote ER (divalproex sodium), ginkgo
GENERALLY AVOID: Certain preparations of ginkgo biloba have been reported to induce seizures and may antagonize the effects of anticonvulsants. Ginkgo products may contain varying amounts of 4'-O-methylpyridoxine (ginkgotoxin), a known neurotoxin found primarily in ginkgo biloba seeds but also detected in lesser amounts in the leaves. In vivo, 4'-O-methylpyridoxine competes with vitamin B6, which causes an indirect inhibition of glutamate decarboxylase and subsequent decrease in the formation of gamma-aminobutyric acid (GABA) in the brain. There have been published case reports of generalized convulsions and vomiting within several hours after ingestion of large amounts of ginkgo nuts/seeds, including in young children and healthy individuals with no known personal or family history of epilepsy. Many more cases, including fatalities, occurred in Japan in the 1930s to the 1960s during a food shortage when ginkgo nuts served as an important source of food. Some investigators have suggested that the amounts of ginkgotoxin in commercial extracts are too low to exert a detrimental effect. Nevertheless, a case report describes two elderly, previously well-controlled epileptic patients who presented with recurrent seizures within two weeks of initiating treatment with a ginkgo extract. Both patients remained seizure-free several months after discontinuing the extract, with no alteration to their anticonvulsant medications.
MANAGEMENT: Patients should consult a healthcare provider before taking any herbal or alternative medicine. Because of inconsistencies in formulation and potency of commercial herbal preparations, there is no way to verify without laboratory testing if and in what quantity 4'-O-methylpyridoxine may be present in a given ginkgo preparation. Patients treated with anticonvulsants should preferably avoid the use of products containing ginkgo biloba.
References (8)
- Miller LG (1998) "Herbal medicinals: selected clinical considerations focusing on known or potential drug-herb interactions." Arch Intern Med, 158, p. 2200-11
- Gregory PJ (2001) "Seizure associated with Ginkgo biloba?." Ann Intern Med, 134, p. 344
- Miwa H, Iijima M, Tanaka S, Mizuno Y (2001) "Generalized convulsions after consuming a large amount of Gingko nuts." Epilepsia, 42, p. 280-1
- Kajiyama Y, Fujii K, Takeuchi H, Manabe Y (2002) "Ginkgo seed poisoning." Pediatrics, 109, p. 325-7
- Kupiec T, Raj V (2005) "Fatal seizures due to potential herb-drug interactions with Ginkgo biloba." J Anal Toxicol, 29, p. 755-8
- Harms SL, Garrard J, Schwinghammer P, Eberly LE, Chang Y, Leppik IE (2006) "Ginkgo biloba use in nursing home elderly with epilepsy or seizure disorder." Epilepsia, 47, p. 323-9
- Granger AS (2001) "Ginkgo biloba precipitating epileptic seizures." Age Ageing, 30, p. 523-5
- Spinella M (2001) "Herbal medicines and epilepsy: the potential for benefit and adverse effects." Epilepsy Behav, 2, p. 524-32
Drug and food interactions
divalproex sodium food
Applies to: Depakote ER (divalproex sodium)
GENERALLY AVOID: Alcohol may potentiate some of the pharmacologic effects of CNS-active agents. Use in combination may result in additive central nervous system depression and/or impairment of judgment, thinking, and psychomotor skills.
MANAGEMENT: Patients receiving CNS-active agents should be warned of this interaction and advised to avoid or limit consumption of alcohol. Ambulatory patients should be counseled to avoid hazardous activities requiring complete mental alertness and motor coordination until they know how these agents affect them, and to notify their physician if they experience excessive or prolonged CNS effects that interfere with their normal activities.
References (4)
- Warrington SJ, Ankier SI, Turner P (1986) "Evaluation of possible interactions between ethanol and trazodone or amitriptyline." Neuropsychobiology, 15, p. 31-7
- Gilman AG, eds., Nies AS, Rall TW, Taylor P (1990) "Goodman and Gilman's the Pharmacological Basis of Therapeutics." New York, NY: Pergamon Press Inc.
- (2012) "Product Information. Fycompa (perampanel)." Eisai Inc
- (2015) "Product Information. Rexulti (brexpiprazole)." Otsuka American Pharmaceuticals Inc
Therapeutic duplication warnings
No duplication warnings were found for your selected drugs.
Therapeutic duplication warnings are only returned when drugs within the same group exceed the recommended therapeutic duplication maximum.
Drug Interaction Classification
Highly clinically significant. Avoid combinations; the risk of the interaction outweighs the benefit. | |
Moderately clinically significant. Usually avoid combinations; use it only under special circumstances. | |
Minimally clinically significant. Minimize risk; assess risk and consider an alternative drug, take steps to circumvent the interaction risk and/or institute a monitoring plan. | |
No interaction information available. |
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