|
Interactions Between Herbs
and Cardiac Medications
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.
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
|
