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Drug Interactions between ginkgo and Percodan

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

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Interactions between your drugs

Moderate

aspirin ginkgo

Applies to: Percodan (aspirin / oxycodone) and ginkgo

GENERALLY AVOID: Ginkgo may potentiate the risk of bleeding associated with anticoagulants, platelet inhibitors, nonsteroidal anti-inflammatory drugs (NSAIDs), and thrombolytic agents. Ginkgolide B, a component of ginkgo, inhibits platelet-activating factor by displacing it from its receptor-binding site, resulting in reduced platelet aggregation. There have been isolated reports of bleeding complications (e.g., spontaneous intracranial bleeding; spontaneous hyphema; peri- and postoperative bleeding) and prolonged bleeding times associated with the ingestion of ginkgo, some of which resolved following discontinuation of ginkgo use. Possible interactions with warfarin and aspirin have also been described in the medical literature. A patient stabilized on warfarin for five years developed intracerebral hemorrhage two months after starting ginkgo, and another who had been taking aspirin 325 mg/day for three years developed spontaneous bleeding of the iris into the anterior chamber of the eye one week after he began using ginkgo. In contrast, an investigative study found no significant effect of ginkgo pretreatment for 7 days on clotting status or the pharmacokinetics or pharmacodynamics of a single 25 mg dose of warfarin in 12 healthy volunteers. Another study consisting of 24 patients stabilized on warfarin for at least several months also found no significant effect of ginkgo on INR or warfarin dosage compared to placebo, and no major bleedings were observed in the study. However, it is important to recognize that pharmacologic effects of herbal products may be highly variable due to inconsistencies in formulation and potency of commercial preparations.

MANAGEMENT: Patients should consult a healthcare provider before taking any herbal or alternative medicine. In general, consumption of ginkgo should be avoided during use of coagulation-modifying agents and at least two weeks prior to surgery. In patients who have used this herb extensively prior to receiving anticoagulation, antiplatelet, NSAID or thrombolytic therapy, the potential for an interaction should be considered. Close clinical and laboratory observation for hematologic complications is recommended. Patients should be advised to promptly report any signs of bleeding to their physician, including pain, swelling, headache, dizziness, weakness, prolonged bleeding from cuts, increased menstrual flow, vaginal bleeding, nosebleeds, bleeding of gums from brushing, unusual bleeding or bruising, red or brown urine, or red or black stools.

References

  1. Miller LG (1998) "Herbal medicinals: selected clinical considerations focusing on known or potential drug-herb interactions." Arch Intern Med, 158, p. 2200-11
  2. Rosenblatt M, Mindel J (1997) "Spontaneous hyphema associated with ingestion of Ginkgo biloba extract." N Engl J Med, 336, p. 1108
  3. Rowin J, Lewis SL (1996) "Spontaneous bilateral subdural hematomas associated with chronic Gingko biloba ingestion." Neurology, 46, p. 1775-6
  4. Chung KF, McCusker M, Page CP, Dent G, Guinot P, Barnes PJ (1987) "Effect of ginkgolide mixture (BN 52063) in antagonising skin and platelet responses to platelet acitivating factor in man." Lancet, 1, p. 248-51
  5. Fugh-Berman A (2000) "Herb-drug interactions." Lancet, 355, p. 134-8
  6. Heck AM, DeWitt BA, Lukes AL (2000) "Potential interactions between alternative therapies and warfarin." Am J Health Syst Pharm, 57, 1221-7; quiz 1228-30
  7. Vaes LP, Chyka PA (2000) "Interactions of warfarin with garlic, ginger, or ginseng: nature of evidence." Ann Pharmacother, 34, p. 1478-82
  8. Fessenden JM, Wittenborn W, Clarke L (2001) "Gingko biloba: A case report of herbal medicine and bleeding postoperatively from a laparoscopic cholecystectomy." Am Surg, 67, p. 33-5
  9. Benjamin J, Muir T, Briggs K, Pentland B (2001) "A case of cerebral haemorrhage - can Ginkgo biloba be implicated?." Postgrad Med J, 77, p. 112-3
  10. Izzo AA, Ernst E (2001) "Interactions between herbal medicines and prescribed drugs: a systematic review." Drugs, 61, p. 2163-75
  11. Evans V (2000) "Herbs and the brain: friend or foe? The effects of ginkgo and garlic on warfarin use." J Neurosci Nurs, 32, p. 229-32
  12. Cupp MJ (1999) "Herbal remedies: adverse effects and drug interactions." Am Fam Physician, 59, p. 1239-45
  13. Matthews MK Jr (1998) "Association of Ginko biloba with intracerebral hemorrhage." Neurology, 50, p. 1933-4
  14. Engelsen J, Nielsen JD, Winther K (2002) "Effect of coenzyme Q10 and Ginkgo biloba on warfarin dosage in stable, long-term warfarin treated outpatients. A randomised, double blind, placebo-crossover trial." Thromb Haemost, 87, p. 1075-6
  15. Fong KC, Kinnear PE (2003) "Retrobulbar haemorrhage associated with chronic Gingko biloba ingestion." Postgrad Med J, 79, p. 531-2
  16. Sierpina VS, Wollschlaeger B, Blumenthal M (2003) "Ginkgo biloba." Am Fam Physician, 68, p. 923-6
  17. Jiang X, Williams KM, Liauw WS, et al. (2005) "Effect of ginkgo and ginger on the pharmacokinetics and pharmacodynamics of warfarin in healthy subjects." Br J Clin Pharmacol, 59, p. 425-32
  18. Jayasekera N, Moghal A, Kashif F, Karalliedde L (2005) "Herbal medicines and postoperative haemorrhage." Anaesthesia, 60, p. 725-6
  19. Wolf HR (2006) "Does Ginkgo biloba special extract EGb 761 provide additional effects on coagulation and bleeding when added to acetylsalicylic acid 500 mg daily?" Drugs R D, 7, p. 163-72
View all 19 references

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Moderate

oxyCODONE ginkgo

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

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Drug and food interactions

Major

oxyCODONE food

Applies to: Percodan (aspirin / oxycodone)

GENERALLY AVOID: Alcohol may potentiate the central nervous system (CNS) depressant effects of opioid analgesics including oxycodone. Concomitant use may result in additive CNS depression and impairment of judgment, thinking, and psychomotor skills. In more severe cases, hypotension, respiratory depression, profound sedation, coma, or even death may occur.

GENERALLY AVOID: Grapefruit juice may increase the plasma concentrations of oxycodone. The proposed mechanism is inhibition of CYP450 3A4-mediated metabolism of oxycodone by certain compounds present in grapefruit, resulting in decreased formation of metabolites noroxycodone and noroxymorphone and increased formation of oxymorphone due to a presumed shifting of oxycodone metabolism towards the CYP450 2D6-mediated route. In 12 healthy, nonsmoking volunteers, administration of a single 10 mg oral dose of oxycodone hydrochloride on day 4 of a grapefruit juice treatment phase (200 mL three times a day for 5 days) increased mean oxycodone peak plasma concentration (Cmax), systemic exposure (AUC) and half-life by 48%, 67% and 17% (from 3.5 to 4.1 hours), respectively, compared to administration during an equivalent water treatment phase. Grapefruit juice also decreased the metabolite-to-parent AUC ratio of noroxycodone by 44% and that of noroxymorphone by 45%. In addition, oxymorphone Cmax and AUC increased by 32% and 56%, but the metabolite-to-parent AUC ratio remained unchanged. Pharmacodynamic changes were modest and only self-reported performance was significantly impaired after grapefruit juice. Analgesic effects were not affected.

MANAGEMENT: Patients should not consume alcoholic beverages or use drug products that contain alcohol during treatment with oxycodone. Any history of alcohol or illicit drug use should be considered when prescribing oxycodone, and therapy initiated at a lower dosage if necessary. Patients should be closely monitored for signs and symptoms of sedation, respiratory depression, and hypotension. Due to a high degree of interpatient variability with respect to grapefruit juice interactions, patients treated with oxycodone may also want to avoid or limit the consumption of grapefruit and grapefruit juice.

References

  1. Nieminen TH, Hagelberg NM, Saari TI, et al. (2010) "Grapefruit juice enhances the exposure to oral oxycodone." Basic Clin Pharmacol Toxicol, 107, p. 782-8

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Moderate

aspirin food

Applies to: Percodan (aspirin / oxycodone)

GENERALLY AVOID: The concurrent use of aspirin or nonsteroidal anti-inflammatory drugs (NSAIDs) and ethanol may lead to gastrointestinal (GI) blood loss. The mechanism may be due to a combined local effect as well as inhibition of prostaglandins leading to decreased integrity of the GI lining.

MANAGEMENT: Patients should be counseled on this potential interaction and advised to refrain from alcohol consumption while taking aspirin or NSAIDs.

References

  1. (2002) "Product Information. Motrin (ibuprofen)." Pharmacia and Upjohn

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Minor

aspirin food

Applies to: Percodan (aspirin / oxycodone)

One study has reported that coadministration of caffeine and aspirin lead to a 25% increase in the rate of appearance and 17% increase in maximum concentration of salicylate in the plasma. A significantly higher area under the plasma concentration time curve of salicylate was also reported when both drugs were administered together. The exact mechanism of this interaction has not been specified. Physicians and patients should be aware that coadministration of aspirin and caffeine may lead to higher salicylate levels faster.

References

  1. Yoovathaworn KC, Sriwatanakul K, Thithapandha A (1986) "Influence of caffeine on aspirin pharmacokinetics." Eur J Drug Metab Pharmacokinet, 11, p. 71-6

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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

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.