A good deal of the evidence on herb-to-drug interactions discussed in this article is based on case reports, which are sometimes incomplete. Hence, the likelihood of herb-drug interactions is theoretically higher than are two popular herbal products marketed to treat liver disorders and depression. For health care providers: a summary of key research results about herb-drug interactions and safety information.
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John's wort extract exhibited significant receptor affinity for MAO, but the investigators stated that concentrations of the crude extract required for this activity are unlikely to be achieved after oral administration. No instances of an interaction between tyramine-containing foods and St. John's wort have been reported, but drug interactions may be of concern. One report 12 described a year-old woman who had taken St. John's wort powder, in a dosage of mg per day for 10 days, and then took one mg dose of paroxetine Paxil.
She became incoherent and lethargic and also complained of nausea, weakness and fatigue. Interestingly, the woman had been taking paroxetine, in a dosage of 40 mg per day, for eight months; she discontinued the paroxetine when she started taking St. Studies have shown that St. John's wort extract inhibits serotonin, 13 dopamine and norepinephrine reuptake in vitro. John's wort and antidepressants until further information is available.
Given that the half-life of hypericin is 24 to 48 hours, 15 a conservative recommendation would be to wait until two weeks after a patient has stopped taking St. John's wort and then prescribe an antidepressant. Despite the paucity of evidence for food and drug interactions with St. John's wort, patients who use this herb and then begin taking antidepressants or other serotonergic drugs should be observed carefully for adverse effects. Side effects of St. John's wort include dry mouth, dizziness and confusion.
Phototoxicity manifested as elevated, itching, erythematous lesions has also been reported in association with the use of St. In one case report, 18 a year-old woman developed stinging pain on sun-exposed areas after four weeks of self-treatment with ground St.
Her pain was worsened by cold, minimal mechanical stimuli and sun exposure. After she stopped taking St. John's wort, her symptoms resolved gradually over two months. The patient's symptoms were attributed to demyelination of cutaneous axons caused by photoactivated hypericins. Ephedrine and related alkaloids are the pharmacologically active moieties of the extract of Ephedra a genus of shrubs.
The extract of some species also contains pseudoephedrine. Ephedrine-containing products are also marketed as decongestants, bronchodilators and stimulants. In the past few years, the FDA has investigated more than reports of adverse reactions associated with more than different products that contained or were thought to contain Ephedra alkaloids.
Approximately 56 percent of the reported adverse effects occurred in persons younger than 40 years old; about another 25 percent occurred in persons 40 to 49 years of age. The relatively young age group in which serious cardiovascular events have occurred is of concern. In response to the reports of cardiovascular effects, the FDA has proposed a dosage limit of 8 mg every six hours 24 mg per day for ephedra alkaloids. The proposed rule also calls for a label advising consumers not to use an ephedrine-containing product for more than seven days and warning that exceeding the recommended dosage may result in heart attack, stroke, seizure or death.
The Association of Food and Drug Officials AFDO , which represents state food and health department officials, believes that serious adverse effects to ephedrine-containing products may occur even at a dosage of 24 mg per day. Ephedra-containing products have also been associated with the development of kidney stones. Ephedrine, pseudoephedrine and metabolites comprised almost percent of a radiolucent stone removed from a year-old male body builder who took up to 12 Pro-Lift tablets daily.
Each tablet was found to contain approximately 10 mg of ephedrine. Information from a large kidney stone database shows that this is not an isolated incident; over ephedrine-containing kidney stones were identified from January to June It is not known how many of these stones were associated with the use of herbal ephedrine-containing products.
The risks of using ephedrine-containing supplements appear to outweigh the benefits. Consequently, patients should be advised not to use these products if they are sensitive to the effects of sympathomimetic agents. Concomitant use of ephedrine-containing products and caffeine or other stimulants should also be discouraged. Little scientific evidence shows that ginseng is effective for any purpose. Nonetheless, this herb has been purported to strengthen normal body functions, increase resistance to stress and improve sexual function.
A year-old man with a mechanical heart valve who was taking warfarin to prevent thromboembolic events experienced a decline in International Normalized Ratio INR from 3. His other medications included diltiazem Cardizem , nitroglycerin and salsalate Disalcid ; he had been taking all three drugs for at least three years. The patient denied changes in drug therapy or diet, and he stated that he was not taking dietary supplements other than the ginseng product.
Two weeks after he discontinued use of the ginseng product, his INR was 3. Because of the risks associated with a decreased INR, the patient was not rechallenged with ginseng. Until studies or additional case reports can verify the interaction between ginseng and warfarin, it would be prudent to closely monitor patients on warfarin who begin taking dietary supplements that contain this herb.
A possible mechanism for this interaction is not yet known. Kava is an herbal sedative with purported antianxiety or calming effects. In one case series involving four patients, 29 kava was associated with extrapyramidal effects at dosages of to mg per day. Symptoms occurred 90 minutes after one patient took a single mg dose, four hours after one patient took a single mg dose, four days after one patient began taking mg three times daily, and 10 days after one patient began taking mg twice daily.
The extrapyramidal side effects included oral and lingual dyskinesia, torticollis, painful twisting movements of the trunk, oculogyric crisis and exacerbation of Parkinson's disease. Kava has also been shown to have additive effects with central nervous system depressants. A patient who was taking alprazolam Xanax , cimetidine Tagamet and terazosin Hytrin became lethargic and disoriented after ingesting kava.
Kava should not be used with benzodiazepines, barbiturates, antipsychotics and alcohol. In addition, patients with Parkinson's disease should be discouraged from using kava products.
Kava dermopathy has been reported with the use of kava as a traditional South Pacific beverage. Recently, two cases associated with use of commercially available kava preparations were reported.
Erythematous, infiltrated plaques then developed on his face, chest and back. A similar case involved a year-old woman who presented with papules and plaques on her face, arms, back and chest after taking a kava extract for three weeks.
In both cases, biopsy revealed lymphocytic infiltration of the dermis with destruction of the sebaceous glands. Because kava is lipophilic, it was hypothesized that kava can concentrate in sebaceous oils and trigger an immune response, resulting in a drug reaction. Because dietary supplements are becoming increasingly popular, physicians need to ask questions about the use of herbal products as part of the medication history Table 3. Interactions between food and drugs may inadvertently reduce or increase the drug effect.
The majority of clinically relevant food-drug interactions are caused by food induced changes in the bioavailability of the drug [ 15 ]. There are three types of accepted drug-food interactions based on their nature and mechanisms. They cause either an increase or decrease in the oral bioavailability of a drug. The precipitant agent may modify the function of enzymes or transport mechanisms that are responsible for biotransformation. Changes in the cellular or tissue distribution, systemic transport, or penetration to specific organs or tissues can occur.
In the last two decades there has been a considerable increase in the herbal remedy market. Interactions between herbal remedies and drugs have been put on the agenda and received increased attention [ 17 ].
Both serious and less serious adverse interactions have been reported e. The typical herb user was female, aged 30 to 69 years, with higher education or hospitalized in the last year. Forty-one per cent of USA adults reported the use of herbal remedies to self-treat before seeking medical care from a physician [ 20 ]. Drug-herb interactions are based on the same pharmacokinetic and pharmacodynamic principles as drug-drug interactions.
Ginkgo biloba and Warfarin: Ginkgo biloba may also interact with warfarin Coumadin. A year-old woman who had been taking warfarin for five years after coronary bypass surgery suffered a left parietal hemorrhage after using a ginkgo product for two months.
No change was noted in her prothrombin time. The intracerebral bleeding was attributed to the antiplatelet effects of ginkgo [ 21 ]. Ginseng and anti-clotting agents: Ginseng may cause decreased effectiveness of certain anti-clotting medications.
Persons using ginseng see increased heart rate or high blood pressure. It may cause bleeding in women after menopause [ 22 ]. The current available evidence suggests that all herbal medicines should be discontinued two weeks prior to surgery to avoid any complications [ 23 ].
Garlic with antiplatelet agents: Garlic is very commonly used for carminative and thermogenic properties. Interaction between garlic and antiplatelet is a moderate type of herbal - drug interaction.
When garlic is taken with antiplatelet agents increases the risk of bleeding and may be fatal to the patient [ 24 ]. Ginger is primarily used to treat nausea, but it is also used as an anti-inflammatory, a pain remedy, a warming remedy and a cholesterol-lowering herb. Although severe interaction of ginger with any drug has not been reported but some herbalists recommend avoiding use by patients taking anticoagulant medications; no adverse interactions have been reported [ 25 ].
Immunostimulant effect of licorice herb may offset immunosuppressant effects of drug taken with it and may reduce immunosuppressant levels [ 26 ]. Grapefruit juice — Drug interactions: Foods are intended to be safe for human consumption but there are few foods which show interactions with the dugs when taken along with them.
Grapefruit juice show interaction with around 20 drugs by increasing their oral bioavailability. A placebo-controlled, double-blind, randomized trial of an extract of Ginkgo biloba for dementia. No alteration in platelet function or coagulation induced by EGb in a controlled study. The effect of herbal medicines on platelet function: Effect of Ginkgo biloba EGb and aspirin on platelet aggregation and platelet function analysis among older adults at risk of cardiovascular disease: Inhibition of platelet activating factor PAF -induced aggregation of human thrombocytes by ginkgolides: Antiplatelet and anticoagulant effects of Panax notoginseng: Ginsenosides from American ginseng: Antiplatelet components in Panax ginseng.
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Influence of traditional Chinese anti-inflammatory medicinal plants on leukocyte and platelet functions. Phenolic compounds with radical scavenging and cyclooxygenase-2 COX-2 inhibitory activities from Dioscorea opposita. Platelet anti-aggregating activities of bupleurumin from the aerial parts of Bupleurum falcatum.
Inhibition of platelet activation and endothelial cell injury by flavanol and saikosaponin compounds. Platelet anti-aggregatory and blood anti-coagulant effects of compounds isolated from Paeonia lactiflora and Paeonia suffruticosa.
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Traditional Chinese medicine: herb-drug interactions with aspirin
Keywords: herb–drug interactions, risk management .. in current Dutch recommendations on how to deal with herb–drug interactions [43, 44]. For this reason, the adverse effects and drug interactions associated with herbal remedies are largely unknown. Ginkgo biloba extract. Herb-drug interactions are drug interactions that occur between herbal medicines and conventional drugs. These types of interactions may be more common.