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The phenomenal growth in the use of herbal remedies is creating an urgent need for health care practitioners across the country to be able to provide information and recommendations to their patients about the potential benefits and risks of these products.
Within their daily practices, consultant pharmacists can identify patients who are taking these supplements under physicians’ orders. Most of us suspect, however, that many more patients, supplied by well-meaning family members, are probably taking these supplements unbeknownst to health care providers.
The age-specific physiologic changes inherent in the elderly population, in addition to their often complex medical regimens, comorbidities, and frequent use of drugs with a “narrow therapeutic index” (NTI), require careful evaluation when adding any new treatment, particularly those with relatively unknown toxicity and interaction profiles. In particular, knowledge of the potential drug interactions associated with herbal supplements is of primary importance to the consultant pharmacist, who may be called upon to advise on the prevention of these potential interactions or to help identify them if they occur.
For example, certain herbal remedies have been shown to affect bleeding times. Ginkgo biloba, ginseng, and garlic (sometimes called “the three Gs”), as well as the popular herbal feverfew, have all been found to have antiplatelet activity, posing a potential threat to patients receiving anticoagulant therapy.
Some of the active ingredients of ginkgo have been shown to antagonize the effect of platelet-activating factor. There have been at least four reported cases of patients experiencing episodes of spontaneous bleeding while taking ginkgo. A recent case report in the New England Journal of Medicine describes a case of a 70-year-old man with spontaneous bleeding from the iris into the anterior chamber of the eye within a week of beginning daily ginkgo supplementation in addition to his normal regimen of 325 mg of aspirin daily.1 Other case reports suggest that spontaneous bleeding may occur even in the absence of anticoagulant medication.2,3
At least 28 active constituents of ginseng (known as “ginsenosides”) have been isolated, each with unique pharmacologic effects.4 Ginsenoside Rg2 inhibits platelet aggregation, and ginsenoside Ro is proposed to inhibit the conversion of fibrinogen to fibrin. However, it also appears that ginseng may interact with warfarin to cause a decrease in the international normalized ratio (INR). A 47-year-old man whose INR on warfarin had previously ranged from 3 to 4 was noted to have a drop in INR to 1.5 two weeks after taking GinsanaTM, a popular brand of ginseng. The patient denied any other changes in diet or medication, and his INR rose to 3.3 two weeks after discontinuing the ginseng.5
By inhibiting platelets via interfering with thromboxane synthesis, large doses of garlic may also decrease clotting time.6
Feverfew, touted for its proposed benefits in the treatment of migraines, has been shown to inhibit cyclo-oxygenase and phospholipase A2, thereby potentiating the antiplatelet effects of aspirin and interacting with other anticoagulants.6
Because of the current uncertainties regarding the precise mechanism of action of these herbal products, it is generally advised that the use of these supplements be avoided in patients receiving aspirin or warfarin.
Similar problems may arise among patients taking the popular herbal St. John’s wort. Studies have shown that St. John’s wort inhibits serotonin,8 dopamine, and norepinephrine release in vitro.9 Considering the 24- to 48-hour half-life of St. John’s wort, it may be prudent to recommend that patients wait one to two weeks after discontinuing St. John’s wort before starting on a conventional antidepressant.
Because herbal remedies are obtained from various plants, the potential for allergic reactions may be significant, especially in those individuals who suffer from allergies to ragweed and other seasonal plants and weeds.
Natural products may interact with selected NTI drugs and other agents commonly prescribed in the elderly, resulting in adverse events. Table 1 summarizes selected interactions of potential concern for the elderly.
TABLE 1. Potential Interactions Between Natural Products and Drugs Commonly Prescribed in the Elderly10,11 | |||
| Drug | Natural Product | Potential Interaction | |
| Digoxin | Aloe | Internal use may cause hypokalemia | |
| Hawthorn | Increased cardiac toxicity | ||
| Licorice | Diuretic effect may cause hypokalemia | ||
| Psyllium | Decreased digoxin absorption | ||
| Siberian ginseng | Increased digoxin levels | ||
| Hypoglycemic agents | Herbs with diuretic principles (e.g., broom, buchu, dandelion, juniper) | May antagonize hypoglycemic effect | |
| Herbs containing hypo- or hyperglycemic principles (e.g., chromium, fenugreek, ginseng) | May antagonize or potentiate hypoglycemic effect | ||
| Lithium | Herbs containing diuretic principles (e.g., broom, buchu, dandelion, juniper) | May increase effects of lithium; possible toxicity | |
| Theophylline | Ma huang | Theophylline toxicity | |
| Warfarin | Cayenne, feverfew, garlic, ginkgo biloba | Decreased platelet aggregation | |
| Ginger | Prolonged bleeding time resulting from inhibition of thromboxane synthetase | ||
| Ginseng | Decreased anticoagulant activity or decreased INR | ||
| Quinine | Increased anticoagulant activity | ||
| Ticlodipine, clopidogrel, and dipyridamole | Ginkgo biloba | Increased anticoagulant activity | |
| Benzodiazepines | Kava | Additive CNS effects | |
| Antidepressants | St. John’s wort | Increased inhibition of serotonin, dopamine, and norepinephrine reuptake | |
Caren McHenry Martin, PharmD
Neil Medical Group
Greensboro, North Carolina
References:
1. Rosenblatt M, Mindel J. Spontaneous hyphema associated with ingestion of Ginkgo biloba extract. N Engl J Med. 1997;336:1108. Letter.
2. Rowin J, Lewis SL. Spontaneous bilateral subdural hematomas associated with chronic Ginkgo biloba ingestion. Neurology. 1996; 46:1775-6.
3. Gilbert GJ. Ginkgo biloba. Neurology 1997; 48:1137. Letter.
4. Chong SKF, Oberholzer VG. Ginseng: is there a use in clinical medicine? Postgrad Med J 1988; 64:841-6.
5. Janetzky K, Morreale AP. Probable interaction between warfarin and ginseng. Am J Health Syst Pharm 1997; 54: 692-3.
6. Klepser TB, Klepser, ME. Unsafe and potentially safe herbal remedies. Am J Health Syst Pharm 1999;56: 125-36.
7. Schelosky L, Raffauf C, Jendroska K et al. Kava and dopamine antagonism (letter). J Neurol Neurosurg Psychiatry 1995;58:639-40.
8. Muller WE, Rolli M, Schafer C et al. Effects of Hypericum extract (LI 160) in biochemical models of antidepressant activity. Pharmacopsychiatry 1997;30 (suppl 2):102-7.
9. Perovic S, Muller WE. Pharmacological profile of Hypericum extract. Effect on serotonin uptake by postsynaptic receptors. Arzneimittelforschung 1995;45: 1145-8.
10. Cupp MJ. Herbal Remidies: adverse effects and drug interactions. Am Fam Physician 1999; 59:1239-44
11. Drug Facts and Comparisons News, May 1999.