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Drug Interactions between Ginkgo Biloba and guaifenesin / theophylline

This report displays the potential drug interactions for the following 2 drugs:

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Interactions between your drugs

Moderate

theophylline ginkgo

Applies to: guaifenesin / theophylline and Ginkgo Biloba (ginkgo)

GENERALLY AVOID: Certain preparations of ginkgo biloba have been reported to induce seizures. There may be a theoretical risk of increased seizure potential when used with other agents that can lower the seizure threshold such as selective serotonin reuptake inhibitors (SSRI antidepressants or anorectics), monoamine oxidase inhibitors, neuroleptic agents, central nervous system stimulants, opioids, tricyclic antidepressants, other tricyclic compounds (e.g., cyclobenzaprine, phenothiazines), carbapenems, cholinergic agents, fluoroquinolones, interferons, chloroquine, mefloquine, lindane, and theophylline. 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 agents that can lower the seizure threshold should preferably avoid the use of products containing ginkgo biloba.

References

  1. Miller LG "Herbal medicinals: selected clinical considerations focusing on known or potential drug-herb interactions." Arch Intern Med 158 (1998): 2200-11
  2. Gregory PJ "Seizure associated with Ginkgo biloba?." Ann Intern Med 134 (2001): 344
  3. Miwa H, Iijima M, Tanaka S, Mizuno Y "Generalized convulsions after consuming a large amount of Gingko nuts." Epilepsia 42 (2001): 280-1
  4. Kajiyama Y, Fujii K, Takeuchi H, Manabe Y "Ginkgo seed poisoning." Pediatrics 109 (2002): 325-7
  5. Kupiec T, Raj V "Fatal seizures due to potential herb-drug interactions with Ginkgo biloba." J Anal Toxicol 29 (2005): 755-8
  6. Harms SL, Garrard J, Schwinghammer P, Eberly LE, Chang Y, Leppik IE "Ginkgo biloba use in nursing home elderly with epilepsy or seizure disorder." Epilepsia 47 (2006): 323-9
  7. Granger AS "Ginkgo biloba precipitating epileptic seizures." Age Ageing 30 (2001): 523-5
  8. Spinella M "Herbal medicines and epilepsy: the potential for benefit and adverse effects." Epilepsy Behav 2 (2001): 524-32
View all 8 references

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Drug and food interactions

Moderate

theophylline food

Applies to: guaifenesin / theophylline

GENERALLY AVOID: Coadministration with caffeine may increase the serum concentrations of theophylline. The proposed mechanism involves competitive inhibition of theophylline metabolism via CYP450 1A2, as well as metabolic conversion of caffeine to theophylline in vivo and saturation of theophylline metabolism at higher serum concentrations. In six healthy male volunteers (all smokers), serum concentrations of theophylline (administered as aminophylline 400 mg single oral dose) were significantly higher following consumption of caffeine (2 to 7 cups of instant coffee over 24 hours, equivalent to approximately 120 to 630 mg of caffeine) than after caffeine deprivation for 48 hours. Caffeine consumption also increased the apparent elimination half-life of theophylline by an average of 32% and reduced its total body clearance by 23%. In another study, steady-state concentration and area under the concentration-time curve of theophylline (1200 mg intravenously over 24 hours) increased by 23% and 40%, respectively, in eight healthy volunteers following administration of caffeine (300 mg orally three times a day).

MANAGEMENT: Given the narrow therapeutic index of theophylline, patients should limit or avoid significant fluctuations in their intake of pharmacologic as well as dietary caffeine.

ADJUST DOSING INTERVAL: Administration of theophylline with continuous enteral nutrition may reduce the serum levels or the rate of absorption of theophylline. The mechanism has not been reported. In one case, theophylline levels decreased by 53% in a patient receiving continuous nasogastric tube feedings and occurred with both theophylline tablet and liquid formulations, but not with intravenous aminophylline.

MANAGEMENT: When administered to patients receiving continuous enteral nutrition , some experts recommend that the tube feeding should be interrupted for at least 1 hour before and 1 hour after the dose of theophylline is given; rapid-release formulations are preferable, and theophylline levels should be monitored.

References

  1. Jonkman JH, Sollie FA, Sauter R, Steinijans VW "The influence of caffeine on the steady-state pharmacokinetics of theophylline." Clin Pharmacol Ther 49 (1991): 248-55
  2. Sato J, Nakata H, Owada E, Kikuta T, Umetsu M, Ito K "Influence of usual intake of dietary caffeine on single-dose kinetics of theophylline in healthy human subjects." Eur J Clin Pharmacol 44 (1993): 295-8
  3. Wohlt PD, Zheng L, Gunderson S, Balzar SA, Johnson BD, Fish JT "Recommendations for the use of medications with continuous enteral nutrition." Am J Health Syst Pharm 66 (2009): 1438-67

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Moderate

theophylline food

Applies to: guaifenesin / theophylline

GENERALLY AVOID: Coadministration with caffeine may increase the serum concentrations of theophylline. The proposed mechanism involves competitive inhibition of theophylline metabolism via CYP450 1A2, as well as metabolic conversion of caffeine to theophylline in vivo and saturation of theophylline metabolism at higher serum concentrations. In six healthy male volunteers (all smokers), serum concentrations of theophylline (administered as aminophylline 400 mg single oral dose) were significantly higher following consumption of caffeine (2 to 7 cups of instant coffee over 24 hours, equivalent to approximately 120 to 630 mg of caffeine) than after caffeine deprivation for 48 hours. Caffeine consumption also increased the apparent elimination half-life of theophylline by an average of 32% and reduced its total body clearance by 23%. In another study, steady-state concentration and area under the concentration-time curve of theophylline (1200 mg intravenously over 24 hours) increased by 23% and 40%, respectively, in eight healthy volunteers following administration of caffeine (300 mg orally three times a day).

MANAGEMENT: Given the narrow therapeutic index of theophylline, patients should limit or avoid significant fluctuations in their intake of pharmacologic as well as dietary caffeine.

References

  1. Jonkman JH, Sollie FA, Sauter R, Steinijans VW "The influence of caffeine on the steady-state pharmacokinetics of theophylline." Clin Pharmacol Ther 49 (1991): 248-55
  2. Sato J, Nakata H, Owada E, Kikuta T, Umetsu M, Ito K "Influence of usual intake of dietary caffeine on single-dose kinetics of theophylline in healthy human subjects." Eur J Clin Pharmacol 44 (1993): 295-8

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Therapeutic duplication warnings

No 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.

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Drug Interaction Classification

These classifications are only a guideline. The relevance of a particular drug interaction to a specific individual is difficult to determine. Always consult your healthcare provider before starting or stopping any medication.
Major Highly clinically significant. Avoid combinations; the risk of the interaction outweighs the benefit.
Moderate Moderately clinically significant. Usually avoid combinations; use it only under special circumstances.
Minor 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.
Unknown No interaction information available.

Further information

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