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Herb-Drug Interaction: The Top Ten List

Herb-Drug Interaction: The Top Ten List. George T. Grossberg, M.D. Department of Neurology & Psychiatry Saint Louis, University School of Medicine St. Louis, Missouri. Presentation Architecture. Prevalence of Herb Use & Regulatory Issues Illustrative Case Study

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Herb-Drug Interaction: The Top Ten List

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  1. Herb-Drug Interaction: The Top Ten List George T. Grossberg, M.D. Department of Neurology & Psychiatry Saint Louis, University School of Medicine St. Louis, Missouri

  2. Presentation Architecture • Prevalence of Herb Use & Regulatory Issues • Illustrative Case Study • Top Ten Most Commonly Purchased herbs • German Commission E • Conclusions

  3. Issues Relative to Herb Use in the U.S. • Prevalence = > than 60 million patients(1) • Federal Dietary Supplements Health Education Act (DSHEA) - Sale of dietary supplements allowed without need to prove safety or efficacy if – - “this product is not intended to diagnose, treat, cure, or prevent any disease”… is on product(2,3) (1)Grossberg GT, Fox B. The Essential Herb-Drug-Vitamin Interaction Guide, New York: Broadway Books, 2007. (2)Cohen MH. Complementary and integrative medical therapies, the FDA, and the NIH: definitions and regulation. Dermatol Ther. 203; 16(2):77-84. (3)Rousseaux CG, Schachter H. Regulatory Issues concerning the safety, efficacy and quality of herbal remedies. Birth Defects Res B Dev Reprod Toxicol. 203;(68(6):505-510.

  4. Herb-Drug Interactions – A Silent Problem • Patients Do not report herb use to physicians - Don’t consider herbs to be medications - Believe herbs must be safe – are “natural” and do not require a prescription • Physicians don’t specifically inquire about herb use

  5. Physicians need to be aware of all herbs, vitamins, supplements, and OTC remedies their patients are taking

  6. Case Study • 76 y/o man is extensively worked up for recent onset microscopic hematuria • Physician unaware that patient recently began taking “Memory Formula”, which is a gingko containing supplement.

  7. Top Ten List Garlic • German Commission E: “May be useful for hypertension, elevated cholesterol & atherosclerosis”(6) • Alteration of platelet function - ↑ bleeds • May ↓ BP; esp. with antihypertensives • May ↓ efficacy of retroviral agents(1,9) Allium sativum (1)Grossbeerg GT, Fox B. The Essential Herb-Drug-Vitamin Interaction Guide. New York: Broadway Books, 2007. (6)Klein S, editor, Rister R, author, Riggins C, editor. The Complete German Commission E Monographs: Therapeutic Guide to Herbal Medicine. New York: American Botanical Council, 1998. (9)Borrelli F, Capasso R, Izzo AA. Garlic: adverse effects and drug interactions in humans. Mol Nutr Food Res. 2007;51(1):1386-97.

  8. Echinacea • German Commission E: “May help the common cold & increase immunity”(6) • Relatively safe(10) • In high doses (>3000 mg) may ↑ risk of hepato-toxicity if combined with acetaminophen or atorvastatin(1) E. pallida;E. purpurea; E. augustifolia (1)Grossberg GT, Fox B. The Essential Herb-Drug-Vitamin Interaction Guide. New York: Broadway Books, 2007. (6)Klein S, editor, Rister R, author, Riggins C, editor. The Complete German Commission E Monographs: Therapeutic Guide to Herbal Medicines. New York: American Botanical Council, 1998. (10)Freeman C, Spelman K. A critical evaluation of drug interactions with Echinacea spp. Mol Nutr Food Res. 2008;52(7):789-98.

  9. Saw Palmetto • Berry from dwarf palm tree • German Commission E: “May be useful for sxs of prostatic hypertrophy & irritable bladder”(6) • May ↓ absorption of oral iron • May ↑ bleeds if taken with agents such as aspirin or ibuprofen Serenoa repens (6)Klein S, editor, Rister R, author, Riggins C, editor. The Complete German Commission E Monographs: Therapeutic Guide to Herbal Medicines. New York: American Botanical Council, 1998.

  10. Gingko Biloba • Derived from leaf of gingko tree • German Commission E: “May be useful for ‘organic brain dysfunction’, claudication, tinnitus/ vertigo secondary to vascular disease”(6) • May increase risk of bleeding esp. in pts on anticoagulants or antiplatelet therapies(12) • May increase seizure risk with anticonvulsants such as phenytoin & levetiracetam. May ↑ seizures in pts on bupropion(13) Gingko biloba; gingko leaf extract (6)Klein S, editor, Rister R, author, Riggins C, editor. The Complete German Commission E Monographs: Therapeutic Guide to Herbal Medicines. New York: American Botanical Council, 1998. (12)Spolarich AE, Andrews L. An examination of the bleeding complications associated with herbal supplements, antiplatelet and anticoagulant medications. J Dent Hyg. 207;81(3)30-33. (13)Bressler R. Herb-drug interactions: Interactions between Gingko biloba and prescription medications. Geriatrics. 205;60(4):30-33

  11. Soy • Contains isoflavones – may be useful for hot flashes of menopause – Am College of Obstetrics & Gynecology(1) • May ↓ absorption of oral iron & levothyroxine • May ↑ TSH and ↓ PTH • May accelerate growth of estrogen-dependent tumors(14) Glycine soja/soybean (1)Grossberg GT, Fox B. The Essential Herb-Drug-Vitamin Interaction Guide. New York: Broadway Books, 2007. (14)Bent S. Herbal medicine in the United States: review of efficacy, safety, and regulation: grand rounds at U of California, San Francisco Medical Center, J Gen Int Med. 208;23(6):854-59.

  12. Cranberry • Flavonoid – juice; extract pills/ capsules • Acidifies urine/decreases bacterial adherence to uroepitheleal cells. May ↓ recurrent UTI’s.(16) • Inhibits CYP-2C9, which metabolizes warfarin & may impact INR’s(17) (16)Santillo VM, Lowe FC. Cranberry juice for the prevention and treatment of urinary tract infections. Drugs Today. 2007;43(1):47-54 (17)Pham DQ, Pham AQ. Interaction potential between cranberry juice and warfarin. Am J Health Syst Pharm. 2007;64(5)490-94.

  13. Ginseng • Ginsenosides = active ingredient – has anti-oxidant & anti-inflammatory effects(18) • May ↑ risk of bleeding with anticoagulants & anti-platelet therapies. • May lower blood sugar, esp. with insulin or oral hypoglycemics • MAOI’s + Panax ginseng → headaches/agitation • May augment activity of conjugated estrogen(19) Panax quinquefolius, Panax ginseng, Eluthrococcus senticosus (18)Kiefer D, Pantuso T. Panax ginseng. Am Fam Physician. 2003;68(8):1539-42 (19)Bressler R. Herb-drug interactions: interactions between ginseng and prescription medications. Geriatrics. 2005;60(8):16-17.

  14. Ginseng (cont) • Impact of lab values - ↓ FBS & HbA1C - ↑ PTT + INR levels - May alter digitalis levels

  15. Black Cohosh • Commonly used to treat menstrual/menopausal sxs(20) • May induce labor in 1st trimester(21) • May augment antihypertensive effect of BP meds such as HCTZ, lisinopril, diltiazam. • May ↓ absorption of oral iron • Due to estrogen-like effects, may impact growth of estrogen-dependent tumors(15) Actaea racemosa (15)Haimov-Kochman R, Brzezinski A, Holchner-Celnikier D. Herbal remedies for menopausal symptoms; are we cautious enough? Eur J Contracept Reprod health Care. 208;13(2):133-37. (20)Kligler B. Black Cohosh. Am Fam Physician. 2003;68(1):114-16. (21)Dugoua JJ, Seely D, Perri D, Joren G, etal. Safety and efficacy of black cohosh during pregnancy and lactation. Can J Clin Pharmacol. 2006;13(3):257-61.

  16. St. John’s Wort • Extensively studied • German Commission E: “May be useful for depressed mood, anxiety, skin inflammation/ burns.”(6) • Recent controlled studies – may be useful for low-grade depression • May lower plasma concentration of: digitalis, cyclosporine, simvastatin, warfarin, alprazolam, oral contraceptives. Induces CYP-450-3A4(22,23) Hypericum perforatum (6)Klein S, editor, Rister R, author, Riggins C, editor. The Complete German Commission E Monographs: Therapeutic Guide to Herbal Medicines. New York: American Botanical council, 1998. (22)Izzo AA. Drug interactions with St John’s Wort: a review of the clinical evidence. Int J Clin Pharmacol Ther. 2004;42(3):139-48. (23)Zhou S, Chan E, Pan SQ, Huang M, et al. Pharmacokinetic interactions of drugs with St John’s Wort. J Psychopharmacol. 204;18(2):262-76.

  17. St John’s Wort (cont) • Serotonin syndrome – if combined with SSRI, SNRI’s, buspirone(23) • Increases risk of bleeds in pts on heparin • Increased risk of hypoglycemia with oral hypoglycemics such as glipizide or rosiglitazone(1) • Increases photosensitivity(1) • May cause delirium with loperamide(1) • May trigger mania in bipolar pts & psychosis in schizophrenia(1) (1)Grossberg GT, Fox B. The Essentials Herb-Drug-Vitamin Interaction Guide. New York: Broadway Books, 2007. (23)Zhou S, Chan E, Pan SQ, Huang M, et al. Pharmacokinetic interactions of drugs with St John’s Wort. J Psychopharmacol, 2004;18(2):262-76.

  18. Milk Thistle • German Commission E: May be useful in treating liver & gallbladder sxs & dyspepsia(6) • Relatively safe – no significant interactions • May cause diarrhea with acarbose(1) • May interact with anti-retroviral agents(25) Sylibum marianum (1)Grossberg GT, Fox B. The Essential herb-Drug-Vitamin Interaction Guide. New York: Broadway Books, 2007 (6)Klein S, editor, Rister R, author, Riggins C, editor. The Complete German Commission E Monographs: Therapeutic Guide to Herbal Medicine. New York: American Botanical Council, 1998. (25)Van den Bout-van den Beukel CJ, Koopmans PP, van der Ven AJ, De Smet PA, et al. Drug Metab Rev. 206;38(3):477-514.

  19. Conclusions • The FDA categorizes herbs as foods – not drugs • More than 60 million Americans use herbs and the numbers are growing • Herb-drug interactions are a growing problem – resulting in increase morbidity, hospital-stays, and even mortality

  20. Conclusion (cont) • It is important for physicians to inquire about herbs, supplements, vitamins and OTC remedies • Increased education of physicians relative to the uses and risks of herbs is desirable • Closer FDA scrutiny/regulation of herbs & supplements is needed

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