Drug Interactions between aspirin / carisoprodol / codeine and ginkgo

GENERALLY AVOID: Concomitant use of opioids with benzodiazepines or other central nervous system (CNS) depressants (e.g., nonbenzodiazepine sedatives/hypnotics, anxiolytics, muscle relaxants, general anesthetics, antipsychotics, other opioids, alcohol) may result in profound sedation, respiratory depression, coma, and death. The risk of hypotension may also be increased with some CNS depressants (e.g., alcohol, benzodiazepines, phenothiazines).

MANAGEMENT: The use of opioids in conjunction with benzodiazepines or other CNS depressants should generally be avoided unless alternative treatment options are inadequate. If coadministration is necessary, the dosage and duration of each drug should be limited to the minimum required to achieve desired clinical effect, with cautious titration and dosage adjustments when needed. Patients should be monitored closely for signs and symptoms of respiratory depression and sedation, and advised to avoid driving or operating hazardous machinery until they know how these medications affect them. Cough medications containing opioids (e.g., codeine, hydrocodone) should not be prescribed to patients using benzodiazepines or other CNS depressants including alcohol. For patients who have been receiving extended therapy with both an opioid and a benzodiazepine and require discontinuation of either medication, a gradual tapering of dose is advised, since abrupt withdrawal may lead to withdrawal symptoms. Severe cases of benzodiazepine withdrawal, primarily in patients who have received excessive doses over a prolonged period, may result in numbness and tingling of extremities, hypersensitivity to light and noise, hallucinations, and epileptic seizures.

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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.

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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.

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