Herb-Drug Interactions:An Evidence-Based Table

By Mary L. Hardy, MD

As patients’ use of herbal products increases, so do physicians’ concerns regarding the possibility of herb-drug interactions. Uncertainty in this area is rife (e.g., active constituents, mechanisms of action, consistency of products) and complicates the assessment of available data. Current literature consists mainly of case reports that often are not adequately investigated. There are few clinical trials and the pharmacologic data available have not been assessed for clinical relevance.

Further, patients have been reluctant to fully disclose their use of natural products to their physicians, so interactions generally only come to light when a serious problem occurs. Most doctors, without adequate training in this area, feel uncomfortable commenting on or even reporting cases that involve the use of herbal medications. Too much of our experience is theoretical or anecdotal.

For commonly used herbs and commonly prescribed drugs, I have assembled a detailed compendium of herb-drug interactions. This table is designed to provide clinicians with guidance in assessing the potential for interaction. It cites a mechanism for interaction where one is known or postulated. It reports the level of evidence for that interaction. It also offers a clinically useful scale for the evidence, outlined in Table 1.

The drug-herb interaction table is not exhaustive and should be considered a work in progress. New data will become available, and as we learn more about which herbs interact with which drugs, we will report significant findings in future newsletters. A limited bibliography is available on request. (Dr. Hardy is Medical Director at Cedars-Sinai Integrative Medicine Medical Group in Los Angeles.)

Table 1-Level of Evidence to Support Use
CT = Controlled trial CS = Case series
CR = Case report AS = Animal study
TU = Traditional use P = Pharmacology
TH = Theoretical

Herb-Drug Interactions
Drug Category Herbs Herb Effect Mechanism (Evidence Type)
Alkaloids High tannin-containing (e.g., caffeine-containing herbs, cat's claw, tea, uva ursi) Decreased plasma levels Precipitation of alkaloids by tannins (TU)
Anesthetics Kava, valerian Prolongation of sedation time Additive effect (CR)
Antihypertensives a. Licorice Decreased therapeutic effect a. Increased salt and water retention (CR)
b. Sympathomimetic herbs (e.g., ephedra) b. Opposition of therapeutic action (P)
Antiarrhythmics Cathartic laxatives (e.g., aloe, cascara, senna, yellow dock), diuretics (e.g., celery seed, corn silk, horsetail, juniper), licorice Increased side effects (arrhythmia) Increased potassium loss (P)
Antiarrhythmics Anticholinergic herbs (not generally used clinically, e.g., belladonna) Decreased therapeutic effect Decreased absorption (P, TH)
Anticoagulants Antiplatelet-aggregating (e.g., Panax ginseng, feverfew, garlic, ginkgo) Increased side effect (bleeding) Inhibition of platelet aggregation through inhibition of thromboxane synthetase (ginger) (P); arachadonic acid production (feverfew) (P); inhibition of epinephrine induced in vitro (garlic) (P); platelet thromboxane synthetase aggregation (garlic) (P, CR); inhibition of platelet activating factor (ginkgo) (CR)
Anticoagulants: Warfarin Panax ginseng, St. John's wort Opposition of therapeutic effect; decreased enzyme bioavailability Unknown (CR); hepatic induction (CS)
Anticoagulants: Warfarin Coumarin-rich herbs,(e.g., sweet clover, danshen), white clover Increased therapeutic effect Only danshen has been observed to do this clinically. Increased maximum concentration and decreased volume of distribution (CR, P)
Anticoagulants: Warfarin Vitamin K-rich herbs (e.g., collard, kale, spinach) Decreased therapeutic effect Opposes activity (CR, P)
Anticonvulsants a. GLA-rich herbs b. Thujone-containing herbs (e.g., cedar, tansy, sage) Decreased therapeutic effect GLA (CR) and thujone may decrease seizure threshold; mechanism unknown
Anticonvulsants Salicylate-rich herbs (e.g., cramp bark, willow, wintergreen) Increased therapeutic effect Transient; unknown mechanism (CR)
Drug Category Herbs Herb Effect Mechanism (Evidence Type)
Anticonvulsants: Phenytoin Shankapulshpi (Ayurvedic preparation with multiple herbs) Opposition of therapeutic action Decreased effectiveness of drug; decreased drug levels (CR)
Antiplatelet-aggregating Antiplatelet-aggregating (e.g., Panax ginseng, feverfew, garlic, ginkgo) Increased side effect (bleeding) Similar therapeutic action (P, CR)
Barbiturates Valerian Increased therapeutic effect;increased side effects Shown to prolong barbiturate-induced sleep (AS)
Benzodiazepines St. John's wort, kava Decreased therapeutic efficacy; may increase side effects; increased sedation Herb binds to GABA receptor site (AS, P)
Cardiac glycosides Cardiac glycoside-containing herbs (e.g., foxglove, lily of the valley) a. Enhanced therapeutic effect
b. Increased side effects (arrhythmia)
Same active constituents (TH)
Cardiac glycosides Cathartic laxative herbs (e.g., aloe, cascara, senna, yellow dock), licorice, diuretic herbs (e.g., celery seed, corn silk, horsetail, juniper) Increased side effects (arrhythmia) Increased potassium loss (TH)
Cardiac glycosides Quinine-containing herb (e.g., cinchona bark) Increased plasma levels (TH)
Cholesterol-lowering drugs Garlic, artichoke, ginger, fenugreek Increased therapeutic effect Similar clinical effect via different mechanism (TH)
Corticosteroids Cathartic laxative herbs (e.g., aloe, cascara, senna, yellow dock), diuretic herbs (e.g., celery seed, corn silk, horsetail, juniper) Increased side effects Both cause increased potassium loss (TH)
Corticosteroids Licorice Increased plasma levels Increased half-life (increased bioavailability) (CR); inhibition of ll-ß-dehydrogenase (P)
Corticosteroids Panax ginseng Increased side effects Similar side effects of CNS stimulation and insomnia (CR)
Digoxin Siberian ginseng Increased plasma level Mechanism unknown; validated by rechallenge (CR)
Digoxin a. Kyushin (Chinese remedy containing the venom of the Chinese toad)
b. Panax ginseng
Increased serum levels Interferes with assay (P, CR) without toxic effects
Diuretic: Lasix Panax ginseng Decreased therapeutic effect Diuretic resistance with ginseng; unknown mechanism (CR)
Diuretic: Potassium sparing Licorice Decreased therapeutic effect Interferes with potassium-sparing effects by wasting K+
Estrogen replacement therapy a. Herbs high in phytoestrogens (e.g., soy, fenugreek, licorice, black cohosh) a. Increased therapeutic a. Never reported (TH)effect to excess
b. Panax ginseng b. Increased side effect (estrogen excess) b. Reported in few cases to produce postmenopausal bleeding or mastalgia (CR)
General medication High-fiber herbs (e.g., flax, psyllium, acacia, slippery elm, marshmallow) Decreased absorption (P)
Drug Category Herbs Herb Effect Mechanism (Evidence Type)
General medication "Hot" remedies (e.g., ginger, garlic, black pepper, red pepper) Increased absorption Taken internally, "hot" remedies lead to vasodilatation of gut wall and increased absorption (TU)
GI motility drugs Anticholinergic herbs (not generally used clinically, e.g., belladonna) Decreased activity Opposition of therapeutic activity
Hepatotoxic drugs Hepatotoxic herbs (e.g., borage, coltsfoot, comfrey, rue, tansy) Increased side effect (hepatotoxicity) Additive toxicity from similar side effects (CR)
Hypoglycemic agents: Oral and insulin Hypoglycemic (e.g., Panax ginseng, garlic, fenugreek, bitter melon, aloe, gymnema) Enhanced therapeutic effect a. Direct hypoglycemic activity (CR, AS, P) b. Decreased glucose absorption
Hypoglycemic agents: Oral and insulin Hyperglycemic (e.g., cocoa, rosemary, stinging nettle) Decreased therapeutic effect Direct opposition of therapeutic action (CS)
Immune suppressants Echinacea, astragalus Opposition of therapeutic action General immune stimulation by these herbs may interfere with ability of immunosuppressive drugs to prevent tissue rejection; never reported (TH)
Iron Tannin-rich herbs (e.g., caffeine-containing herbs, cat's claw, tea, uva ursi) Decreased therapeutic Tannin binds with iron, effect decreasing absorption (TH, P)
Lithium Diuretic herbs (e.g., celery seed, corn silk, horsetail, juniper) Increased side effects Decreased sodium leads to increased lithium toxicity
Lower seizure threshold (drugs that) GLA-rich herbs (e.g., evening primrose, borage, black currant) Increased side effect to additive side effect Decreased seizure threshold (CR)
Methotrexate and similar cytotoxic drugs Salicylate herbs (e.g., cramp bark, willow, wintergreen) Increased plasma levels (toxicity) Decreased excretion (TH)
Minerals Fiber-containing herbs (e.g., flax, psyllium, acacia, slippery elm, marshmallow) Decreased bioavailability Psyllium has been reported to decrease the absorption of Ca, Mg, Cu, Zn (CR)
Monoamine oxidase inhibitors (MAOIs) Panax ginseng, bioactive amines, licorice Increased side effects Additive side effects may lead to toxicity; glycyrrhizin is reported to be a very potent MAOI (TH, CR)
Monoamine oxidase inhibitors (MAOIs) Ginkgo Increased therapeutic effect; Inhibition of monoamine increased side effects oxidase (P)
Nonsteroidal anti-inflammatory drugs (NSAIDs) Gastric irritant herbs (e.g., caffeine, rue, uva ursi) Increased side effects Similar side effects may increase risk of gastric erosion and bleeding (TH)
Nonsteroidal anti-inflammatory drugs (NSAIDs) Nettles Increased therapeutic effect Potentiation of the anti-inflammatory activity of NSAIDs (CT)
Opioids Panax ginseng Decreased therapeutic effects Animal model demonstrated the blunting of the analgesic effects of morphine via a non-opioid receptor-mediated mechanism (AS)
Photosensitizing drugs Photosensitizing herbs (e.g., St. John's wort, angelica, rue, fennel) Increased side effects Furanocoumarins found often in umbelliferae resemble pso-ralens (P, AS, CR)
Salicylates Herbs that alkalinize urine (e.g., uva ursi) Decreased plasma levels Increased urinary excretion (P)
Sedative hypnotics Opioid herbs (e.g., opium poppy, California poppy) Increased side effects (CNS depression) Additive side effects
Sedative hypnotics including alcohol Sedative herbs (e.g., hops, kava, valerian) Increased therapeutic action; increased side effects (CNS depression) Additive effects lead to CNS depression except valerian does not potentiate the effects of alcohol (AS, P)
SSRIs St. John's wort Increased therapeutic activity; increased side effects May contribute to serotonin syndrome—similar action (TH)
Statin drugs Red yeast (Cholestin®) Increased therapeutic effect Similar active compounds; not known if taking both products simultaneously increases side effects of statin drugs (TH)
Thyroid hormone a. Horseradish a. Decreased therapeutic effect a. Depressed thyroid function
b. Kelp b. Increased therapeutic effect b. Iodine in kelp may result in hyperthyroidism (TH)