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Interactions Between Herbs and
Cardiac Medications

Volume IV, Number 2 | March/April 2001
Mandy C. Leonard, Pharm.D., BCPS

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Introduction

The true prevalence of drug-drug interactions is unknown. One study of 1000 elderly patients admitted to a hospital from the Emergency Department discovered that 538 patients were exposed to 1087 drug-drug interactions; 30 patients experienced adverse effects as a consequence of these interactions. There is also a scarcity of adverse reaction and interaction reports for herbs. This probably reflects a combination of under reporting and the benign nature of most herbs used.

Drug-Herb Interactions

In order to make decisions regarding drug interactions with natural medicines, one needs accurate and complete information. Because the "contents" of natural medicines are not standardized (e.g., purity, potency, batch-to-batch variability), the information needed to determine the occurrence of a drug-herb interaction is NOT frequently available or is difficult to evaluate. Other factors that complicate the assessment of drug interactions with natural products are: 1) failure to inform physician, nurse, or pharmacist of concomitant use of natural products, 2) incomplete or inaccurate product information, 3) multiple ingredients, 4) product adulteration, and 5) product misidentification. Additionally, there is a lack of clinical data in the medical and scientific literature documenting and describing the occurrence of drug-herb interactions. The majority of reported drug-herb interactions are ANECDOTAL (single reports). These reports frequently lack relevant information to determine a causal relationship.

As with drug-drug interactions, drugs and herbs may interact by pharmacokinetic and pharmacodynamic mechanisms. Pharmacokinetic interactions are those in which drug absorption, distribution, metabolism, or excretion are altered (e.g., many times plasma drug concentrations are altered). An example of a pharmacokinetic interaction is grapefruit juice interacting with cyclosporine. A component of grapefruit juice is suspected to inhibit the gut wall enzyme, specifically the cytochrome P450 3A4 isoenzyme responsible for the metabolism of cyclosporine (i.e., increased cyclosporine levels). With pharmacodynamic interactions, the pharmacologic activity of the drug is altered (e.g., synergism or antagonism). An example of a pharmacodynamic interaction is St. John's Wort and paroxetine. Patients may experience enhanced CNS effects (i.e., increased serotonin levels) with concurrent use of St. John's Wort and paroxetine

Documented Warfarin-Herb Interactions

Coenzyme Q (ubiquinone or ubidecarenone)

Coenzyme Q has been used in the management of mitochondrial disease, heart failure, hypertension, angina, and arrhythmias. It is thought to work by being a free-radical scavenger, antioxidant, and membrane stabilizer. Coenzyme Q is structurally related to Vitamin K (menaquinone); therefore, it possesses procoagulant properties. There are two case reports of Coenzyme Q interacting with warfarin.

Case #1: A 72 year-old female experienced a decreased response to warfarin while taking Coenzyme Q. A therapeutic INR was achieved after discontinuing Coenzyme Q. (Abstract from Ugeskr Laeger 1998;160:3226-7)

Case #2: A 68 year-old male was stabilized on warfarin (INR 2 to 3) for 6 years. He had a history of pulmonary and cerebrovascular emboli. The patient's INR decreased to 1.31 after taking 30 mg/day of Coenzyme Q for 2 weeks. A therapeutic INR was achieved after discontinuing Coenzyme Q. (Lancet 1994;344:1372-3)

Recommendation: It is recommended to avoid Coenzyme Q in warfarin-treated patients due to the risk of thrombotic complications. However, if the patient insists, monitor the INR within the first 2 weeks and then as needed.

Danshen (Salvia miltiorrhiza-root)

Danshen has been used in the management of cardiovascular diseases. It has been associated with decreasing blood pressure, inhibiting platelet aggregation, and coronary artery vasodilation. Animal data (in rats) demonstrated a decrease in the elimination half-life of warfarin. There are three case reports of danshen interacting with warfarin.

Case #1: A 62 year-old male taking warfarin (5 mg/day) for a mitral valve replacement (MVR) with stable INR for several weeks was admitted to a hospital with pleural and pericardial effusion. The INR was >8.4 and Hg was 7.6 mg/mL. He was taking danshen extract for 2 weeks. (Ann Thor Surg 1998;66:941-2)

Case #2: A 48 year-old female was taking warfarin 4 mg/day. After taking danshen every other day for 4 weeks, her INR increased to 5.6. A therapeutic INR was achieved after discontinuing danshen. (J Intern Med 1997;241:337-9)

Case #3: A 66 year-old male stabilized on warfarin 2.5 mg/day for 1 year (INR 2.0) was admitted to the hospital for a bleeding gastric carcinoma. His INR upon admission was 5.5. The patient reported taking danshen 3 to 5 days before admission. A therapeutic INR was achieved after discontinuing danshen. (Aust N Z J Med 1995;25:258)

Recommendation: It is contraindicated to use warfarin and danshen concurrently.

Dong quai (Angelica sinensis)

Dong quai has been used in the management of menopausal symptoms and menstrual disorders. It is thought to possess antiinflammatory, antispasmodic, and estrogenic properties. Additionally, dong quai contains at least six coumarin derivatives (i.e., potential to inhibit platelet activation and aggregation). Animal data suggest increased prothrombin times when dong quai is administered concomitantly with warfarin. There is one case report of dong quai interacting with warfarin.

Case #1: A 46 year-old female was stabilized on warfarin (5 mg/day) for 2 years (INR 2 to 3). After taking dong quai 565 mg QD or BID for 4 weeks (for management of menopausal symptoms), her INR increased to 4.9. The patient denied any alterations in medications, diet, alcohol, or other lifestyle factors. A therapeutic INR was achieved after discontinuing dong quai. (Pharmacother 1999;19:870-6)

Recommendation: It is recommended to avoid dong quai in warfarin-treated patients due to lack of data.

Ginkgo (Ginkgo biloba)

Ginkgo is used mainly to enhance memory. It is thought to improve blood flow to both the heart and brain. It also has been documented to inhibit platelet activating factor. There is one case report of gingko interacting with warfarin.

Case #1: A 78 year-old female was maintained on warfarin (no dose stated) for atrial fibrillation. The patient experienced a 2 day history of inability to feed self, apraxia, and change in cognitive function. A CT scan revealed a left parietal hemorrhage. Her prothrombin time was 16.9. The patient was taking gingko biloba (no dose stated) for two months before onset of hemorrhage.

Recommendation: It is recommended to avoid gingko in warfarin-treated patients due to the lack of data. However, if the patient insists, monitor the INR as well as educate the patient on the signs and symptoms of bleeding.

Ginseng (Panax species)

Ginseng has been used to treat fatigue as well as an adaptogenic. It is thought to increase adrenal hormone synthesis, decrease blood glucose concentrations, and promote immunomodulation. The active constituents in ginseng are the ginsenosides. There is one case report of ginseng interacting with warfarin.

Case #1: A 47 year-old male was stabilized on warfarin (7.5 mg every Tuesday and 5 mg on all other days) for nine months (INR 3 to 4). His other medications were diltiazem, nitroglycerin, and salsalate. After taking Oriental ginseng TID for two weeks, his INR decreased to 1.5. The patient experienced no thrombotic episode. A therapeutic INR was achieved after discontinuing the ginseng. (Am J Health Syst Pharm 1997;54:692-3)

Recommendation: It is recommended to avoid ginseng in warfarin-treated patients because of the risk of thrombotic complications.

Green tea (Camellia sinensis)

Green tea is used in the treatment of gastrointestinal disorders and to prevent cancer. Dried green tea leaves contain a substantial amount of Vitamin K. Green tea is not considered a significant source of Vitamin K; however, consuming large amounts may antagonize the effects of warfarin. There is one case report of green tea interacting with warfarin.

Case #1: A 44 year-old patient was on warfarin for a mechanical heart valve (INR 3.79). The patient experienced a decreased response to warfarin (INR 1.37) after consuming a large amount of green tea (1 gallon/day for 1 week.) (Ann Pharmacother 1999; 33:426-8)

Recommendation: It is recommended that warfarin-treated patients only consume moderate amounts of green tea.

Consult Table 1 for documented and potential interactions between herbs and blood modifiers. Additionally, consult Table 2 for documented and potential interactions between herbs and cardiovascular medications.

Table 1:  Interactions between Herbs and Blood Modifiers
Medication Natural Medicine
Anticoagulants/ Antiplatelets Acerola, Agrimony (Vitamin K costituents), American Ginseng, Arnica (coumarin constituents), Bilberry (antiaggregation effect on platelets), Bogbean (hemolytic activity), Boldo (coumarin constituents), Bromelain, Capsicum (increase fibrinolytic activity), Cayenne (reduce platelet aggregation and increase fibrinolytic activity), Celery (coumarin constituent), Chlorella, Danshen, Dong Quai (coumarin constituents), English Chamomile (coumarin constituents), European Mistletoe (agglutinating activity); Fenugreek (coumarin constituents), Feverfew (reduce platelet aggregation and increase fibrinolytic activity), Fish Oils (decrease platelet adhesiveness), Gamma Linolenic Acid (contained in borage seed oil), Garlic (inhibit platelet aggregation and increase fibrinolytic properties), Ginger (inhibit platelet aggregation), Ginko leaf extract (inhibit platelet activating factor), Goldenseal, Guar Gum, Horse Chestnut Seed (coumarin constituents), Panax Ginseng, Papain, Passionflower (coumarin constituents), Plantain (Vitamin K constituents), Red Clover (coumarin constituents), Siberian Ginseng, Stinging Nettle (Vitamin K constituents), Sweet Clover (contains dicoumarol), Vitamins C, E (inhibits platelet aggregation and adhesiveness), and K, Willow Bark (salicylate constituent)
Heparin Goldenseal (possess coagulant activity)
Warfarin
(Coumadin ®)
Acerola, Angelica (inhibit platelet aggregation), Anise (coumarin constituents), Chlorella, Coenzyme Q, Devil's Claw, Dong Quai (contains coumarin derivatives), Fenugreek, Feverfew (reduce platelet aggregation and increase fibrinolytc activity), Garlic (inhibit platelet aggregation and increase fibrinolytic properties), Ginger (inhibit platelet aggregation), Ginko leaf extract (inhibit platelet activating factor), Panax Ginseng (diminished platelet adhesiveness), Papain, St. John's Wort, Vitamins C, E, and K
 
Table 2:  Interactions between Herbs and Cardiovascular Agents
Medication Natural Medicine
Antiarrhymthic
Aloe Latex (possible loss of intestinal potassium leading to a decrease in serum potassium)
Antihypertensives Devil's Claw, European Mistletoe, Fish Oils, Ginger, Goldenseal, Hawthorne, Licorice, Stinging Nettle, Yohimbe
Calcium Channel Blockers Dong Quai (synergistic effects), Ginger (increase calcium uptake by heart muscle), Grapefruit juice, St. John's Wort
Carvedilol (Coreg &reg) Grapefruit juice
Cardiac Glycosides Alder Buckthorn (loss of serum potassium), Aloe Latex (possible loss of intestinal potassium leading to a decrease in serum potassium), Cascara (loss of serum potassium), Ephedra (dysrhythmias), European Buckthorn (loss of serum potassium), Licorice (potentiate actions)
Coronary Vasodilators Hawthorn (additive effects)
Digoxin (Lanoxin &reg) Aloe (possible loss of intestinal potassium leading to a decrease in serum potassium), Digitalis, Ephedra, Guar Gum, Hawthorn (increased cardiac toxicity, Licorice (loss of serum potassium), Pectin, Psyllium (decreased absorption), Siberian Ginseng (increased digoxin levels), St. John's Wort
HGM-CoA Reductase Inhibitors Grapefruit juice
Potassium-depleting Diuretics Licorice (additive effects)
Thiazide Diuretics Ginko leaf extract


Summary

Based on currently available information, there are insufficient data to determine the CLINICAL importance of most drug-herb interactions. Controlled clinical studies are needed. Additionally, questions regarding the use of natural medicines should be a part of the patient history. Until the standardization of herbal products occurs, it is unlikely that drug-herb interaction information will be available except as ANECDOTAL reports. Therefore, closely monitor patients receiving narrow therapeutic index medications.

References Available Upon Request

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Copyright © 2000-2017 The Cleveland Clinic Foundation. All Rights Reserved.
Center for Continuing Education | 1950 Richmond Road, TR204, Lyndhurst, OH 44124