1. Deadly Mix: Herbs, Supplements, and Drug Interactions Geneva Briggs, Pharm.D., BCPS MedOutcomes, Inc.

2. Objectives b Discuss the alternative medications that are most dangerous. b Identify the most common drug interactions with alternative medications. b List five sources for unbiased information on alternative medications and supplements. 1

3. “Poisons and medicines are oftentimes the same substances given with different intents” Peter Mere Latham (1789-1875) 2

4. Complementary and Alternative Medicine Practices b ~40% of the US population uses dietary supplements often b ~ 50% of people have used herbals b ~ 4% rely exclusively on alternatives b In Germany over 700 herbs are available and prescribed by 70% of physicians NEJM 1993;328:246-52. JAMA 1998;279:1548-53. 3

5. Complementary and Alternative Medicine Practices b <40% of patients inform someone they are taking alternative medications b Most commonly purchased – echinacea, feverfew, garlic, ginseng, ginkgo, goldenseal, kava, St. John’s wort, saw palmetto, and valerian b “Typical” user – female, 35-64, white, college graduate, relatively affluent J Am Diet Assoc 2003;103:1500-5 JAMA 1998;280:1569-75 Pharmacotherapy 2000;20:877-91 4

6. Pharmaceuticals vs Phytomedicines b Must prove efficacy and safety b Mandatory ADE monitoring b Product formulation standards b Consensus for use b Marketing more restricted b Safety & efficacy data may be lacking b ADE monitoring not mandatory b No product standards mandated b Dosing uncertain b No treatment or cure claims on label 5

7. Concerns with Phytomedicine b Variability of active constituents b Misidentification of the plant b Selection of the wrong part of the plant b Inadequate storage b Contamination b Adulteration b Mislabeling of the final product 6

8. Asian or Chinese patent medicines b Of 251 purchased in CA, 24 contained lead, 36 arsenic, 35 mercury b 24% of 2,609 samples of Chinese patent medicines contained pharmaceutical adulterants J Clin Pharmacol 1997; 37: 344­50. BMJ 1994; 308: 1162. N Engl J Med 1998; 339: 847 7

9. Which herbals are most likely to cause significant adverse effects? 8

10. Top 10 Offenders b Kava [Piper methysticum] b Comfrey b Chaparral [Larrea tridentata] b Germander [Teucrium genus] b Aristolochic acid b Germanium dioxide or lactate citrate b Lobelia [Indian tobacco] b Stephania b L-tryptophan b Ephedra (ma-huang) 9

11. Beyond the Top 10 b Pennyroyal oil b Sassafras b Borage b Calamus b Coltsfoot b Life root 10

12. Significant Interactions with Alternative Supplements 11

13. St John’s Wort [Hypericum perforatum] Digoxin Warfarin Theophylline Nefazodone Oral contraceptives Antiretrovirals Cyclosporine Imatinib (Gleevec) b Irinotecan [Camptosar] b Simvastatin b Amitriptyline b SSRI (fluoxetine, sertraline, etc.) Lancet 2000;355:1343-8 Pharmacotherapy 2004;24:1508-14 12

14. Herbal and Supplement Products That Interact with Warfarin b Increased INR Ginkgo Biloba Dong Quai (Angelica sinesis) Danshen (Salvia miltiorrhiza) Vitamin E b Decreased INR St. John’s Wort Coenzyme Q10 American ginseng b Altered Platelets Garlic [Allium sativum] Feverfew Ginseng Turmeric Meadowsweet Willow bark b Contain Coumarins* Horse chestnut Red clover Lancet 2000;355:13438 J Clin Pharm Ther 2002;27:391-401 13

15. Significant Interactions with Alternative Meds and Supplements b Siberian Ginseng (Eleutherococcus senticocous) - Digoxin b Valerian [Valeriana officinalis] – alcohol, benzodiazepines, anticonvulsants, TCA b Licorice - ACE-I, ARB, diuretics, digoxin Lancet 2000;355:13438 14

16. Significant Interactions with Alternative Meds and Supplements b Kava and valerian– alcohol, barbiturates, antispychotic drugs, sedatives, benzodiazepines, b Garlic – saquinavir b Red rice yeast [Chinese red rice]- statins, gemfibrozil, fenofibrate 15

17. Patient Groups Most Likely to have Problems b Multiple medications b HIV/AIDS b Cancer b Transplant b Treated with warfarin, digoxin, or other agents prone to drug interactions b Undergoing surgery Am J Health-Syst Pharm 2004;61:1707-11 16

18. Avoid Recommending Herbals b Pregnant and lactating women b Children 17

19. Problem Products in Surgery b Ginkgo biloba b Saw Palmetto b American Ginseng [Panex quinquefolias] b Kava b St John’s wort b Feverfew 18

20. Problem Products in Cancer Treatment b Garlic b Ginkgo b Echinacea b Panax ginseng b St John’s wort b Kava J Clin Oncol 2004;22:2489-503 19

21. Reasonably Effective Herbals b Aloe Vera (topical) b Arnica (topical) b Black Cohosh b Chamomile tea b Echinacea b Evening primrose oil b Feverfew b Garlic b Ginger b Ginkgo Biloba b Hawthorn b Peppermint tea b Saw Palmetto b Siberian Ginseng b St John’s wort b Valerian 20

22. Reliable Printed Resources b Herbal medicine: Expanded Commission E monographs b Review of Natural Products b Tyler’s Herbs of Choice. The Therapeutic Use of Phytomedicinals b Tyler’s Honest Herbal: A Sensible Guide to the Use of Herbs and Related Products. b Facts and Comparisons: The Review of Natural Products 21

23. Reliable Online Resources b consumerlab.com b herbalgram.com American Botanical Council b nccam.nih.gov NIH’s National Center for Complementary and Alternative Medicine b vm.cfsan.fda.gov Center for Food Safety and Applied Nutrition 22

24. Reliable Online Resources b www.uic.edu/pharmacy/research/diet/con tent/scont_about_evaluations.htm University of Illinois b www.pharmacist.com/pdf/dietary_supple ments.pdf Healthcare Professional’s Guide to Evaluating Dietary Supplements b www.herbalwatch.com 23

25. To Buy Anything and Everything b www.herbalremedies.com Blood Circulator Made of medicinal rhubarb, prepared rehmannia root, common peony root, peach seed, bitter apricot seed, licorice root, scute, dun fly, gadfly, leech, June beetle grub, dried lacquer and ground beetle. 24

26. Patient Counseling b Encourage disclosure of ALL medicinal substances b Discuss available information about alternative medicines b Discuss health risk and self-monitoring b Set objective goals to follow progress b Steer patients seeking to self-treat serious disorders such as depression to a physician 25

27. How to Report an Adverse Effect b Complete the Medwatch form online www.fda.gov/medwatch/report/hcp.htm b Report by telephone (1-800-FDA-1088) b Download a copy of the form and either fax it to 1-800-FDA-0178 or mail it back using the postage-paid addressed form. 26

28. Evaluating Products for Quality b Look for USP standardization –feverfew, ginger, chamomile, cranberry, ginkgo biloba, St John’s wort, saw palmetto, milk thistle, valerian, siberian ginseng, and echinacea Reputable manufacturer Consumerlab.com evaluations 27

29. Conclusion b Current regulation of dietary supplements fails to address substantial risk to public health b Educate patients to give “Full Disclosure” b Know the problem herbs and most common interacting herbs b Report adverse events 28