Herbal interactions with warfarin

Herbal Interactions with Warfarin
Mario de Lemos, Pharm. D. student, Rubina Sunderji, Pharm.D.

May 1999 Drug & Therapeutics Newsletter
(C) 1999, CSU-Pharmaceutical Sciences
Vancouver Hospital & Health Sciences Centre

Several case reports of interactions between various herbal products and warfarin have been reported recently.^1-12As warfarin has a narrow therapeutic window, it is important to be aware of these potential interactions to prevent anticoagulant under- or overdosage. Table 3 summarizes interactions between commonly used herbal products and warfarin.^1-17

Case reports

Heavy use of garlic (Allium sativum) supplement was associated with one case of spontaneous spinal epidural hematoma¹and two cases of prolonged clotting time with increased post-operative bleeding.^2,3The authors suggest that garlic supplements should be stopped for at least 10-14 days prior to surgery.^2,3Although none of these patients were receiving concurrent warfarin, it is prudent to avoid garlic supplements in patients taking warfarin. Ginkgo (Ginkgo biloba) at a daily dose of 80-160 mg was associated with 5 cases of hemorrhage: subdural hematoma (2)^4,5, hyphema (1)⁶, intracerebral hemorrhage (1)⁷ and subarachnoid hemorrhage (1)⁸. In three of these cases, the time to onset of the adverse effect was relatively short from the time of starting Ginkgo, from 1 week⁵to less than 2 months^6,7. Although only one case involved concurrent warfarin⁷ and another involved aspirin⁶, patients taking warfarin should avoid Ginkgo due to the possible increased risk of hemorrhage. Danshen (Salvia miltiorrhiza) was found to potentiate anticoagulation in three patients stabilized on warfarin.^9-11 The INR was increased from around 2.0-3.0 to over 5.5 after taking danshen for 2-4 weeks. Ginseng was reported to reduce INR from 3.0-4.0 to 1.5 in a patient stabilized on warfarin after taking ginseng capsules for 2 weeks.¹²

Other commonly used herbal products which have NOT been reported to interfere with warfarin include alfalfa, bee pollen, betel nut, blue-green algae, chamomile tea, devil’s claw, dong quai, evening primrose oil, kelp, milk thisle, royal jelly, saw palmetto, St. John’s wort, and valerian.^13-16 A lack of reported cases however does not imply the safety of these products when administered with concurrent warfarin, as few of these combinations have been studied specifically to determine the impact of herbal medications on anticoagulation. For example, some herbs (e.g. chamomile¹⁴) contain coumarins although their effects on the anticoagulant system is unknown.¹⁷

Table 3. Drug Interactions between Warfarin and Herbal Products

Herb	Common Usage	Interaction	Evidence of Interaction
Danshen^9-11,18	Coronary heart disease, supplement post surgery	8 INR by 9 warfarin elimination; also 9 platelet aggregation	case reports (see text)
Echinacea purpurea¹⁹	Stimulates immune response to infections	8 INR by 9 warfarin metabolism by 9 CYP3A4 liver enzyme	potential†
Feverfew	Migraine, rheumatoid arthritis	8 risk of bleed by 9 platelet aggregation	potential†
Garlic^1-3	Atherosclerosis, hypertension	8 risk of bleed by 9 platelet aggregation	case reports (see text)
Ginger	Nausea	8 risk of bleed by 9 platelet aggregation	potential†
Gingko biloba^4-8	Dementia	8 risk of bleed by 9 platelet aggregation	case reports (see text)
Ginseng¹²	Stress, physical endurance	9 INR, unknown mechanism	case reports (see text)
Green tea & herbal teas made with tonka beans, melilot or woodruff²⁰	Beverage	9 INR due to high vitamin K content	potential†

† Interaction based on in vitro studies with herb

Conclusion

Due to the limited data available, patients should be advised about the potential interaction of herbal products with warfarin.

References

Rose KD et al. Spontaneous spinal epidural hematoma with associated platelet dysfunction from excessive garlic ingestion: a case report. Neurosurgery 1990;26:880-2.
Burnham BE. Garlic as a possible risk for postoperative bleeding. Plast Reconstr Surg 1995;95:211.
German K et al. Garlic and the risk of TURP bleeding. Br J Urol 1995;76:518.
Rowin J et al. Spontaneous bilateral subdural hematomas associated with chronic Ginkgo biloba ingestion. Neurology 1996;46:1775-6.
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Rosenblatt M, Mindel J. Spontaneous hyphema associated with ingestion of Ginkgo biloba extract. N Engl J Med 1997;336:1108.
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Tam LS et al. Warfarin interactions with Chinese traditional medicines: danshen and methyl salicylate medicated oil. Aust NZ J Med 1995;25:258.
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Hoult JRS et al. Pharmacological and biochemical actions of simple coumarins: natural products with therapeutic potential. Gen Pharmacol 1996;27:713-22.

Chan K et al. The effects of Danshen (Salvia miltiorrhiza) on warfarin pharmacodynamics and pharmacokinetic of warfarin enantiomers in rats. J Pharm Pharmacol 1995;47:402-6.

Winslow LC et al. Herbs as medicines. Arch Intern Med 1998;158:2192-9.

Verduyn I. Diet guidelines while taking Coumadin or warfarin. Vancouver (BC): Dept. of Food & Nutrition Services, Vancouver General Hospital; May 1997. Patient Information Pamphlet #PE-5600.

Further references available on request.