Deadly Mix: Herbs, Deadly Mix: Herbs, Supplements, and Drug Supplements, and Drug InteractionsInteractions

Geneva Briggs, Pharm.D., BCPSMedOutcomes, Inc.

ObjectivesObjectives

Discuss the alternative medications that are most dangerous.

Identify the most common drug interactions with alternative medications.

List five sources for unbiased information on alternative medications and supplements.

1

“Poisons and medicines are oftentimes the same

substances given with different intents”

Peter Mere Latham (1789-1875)

2

Complementary and Complementary and Alternative Medicine Alternative Medicine Practices Practices

~40% of the US population uses dietary supplements often

~ 50% of people have used herbals ~ 4% rely exclusively on alternatives In Germany over 700 herbs are

available and prescribed by 70% of physicians

NEJM 1993;328:246-52.JAMA 1998;279:1548-53.

3

Complementary and Complementary and Alternative Medicine Alternative Medicine PracticesPractices

<40% of patients inform someone they are taking alternative medications

Most commonly purchased – echinacea, feverfew, garlic, ginseng, ginkgo, goldenseal, kava, St. John’s wort, saw palmetto, and valerian

“Typical” user – female, 35-64, white, college graduate, relatively affluent

J Am Diet Assoc 2003;103:1500-5JAMA 1998;280:1569-75

Pharmacotherapy 2000;20:877-91 4

Pharmaceuticals vs Pharmaceuticals vs PhytomedicinesPhytomedicines

Must prove efficacy and safety

Mandatory ADE monitoring

Product formulation standards

Consensus for use Marketing more

restricted

Safety & efficacy data may be lacking

ADE monitoring not mandatory

No product standards mandated

Dosing uncertain No treatment or

cure claims on label

5

Concerns with Concerns with PhytomedicinePhytomedicine

Variability of active constituents Misidentification of the plant Selection of the wrong part of the

plant Inadequate storage Contamination Adulteration Mislabeling of the final product

6

Asian or Chinese patent Asian or Chinese patent medicinesmedicines

Of 251 purchased in CA , 24 contained lead, 36 arsenic, 35 mercury

24% of 2,609 samples of Chinese patent medicines contained pharmaceutical adulterants

J Clin Pharmacol 1997; 37: 344 50.  BMJ 1994; 308: 1162.

N Engl J Med 1998; 339: 847

7

Which herbals are most Which herbals are most likely to cause significant likely to cause significant

adverse effects?adverse effects?

8

Top 10 OffendersTop 10 Offenders

Kava [Piper methysticum]

Comfrey Chaparral [Larrea

tridentata] Germander

[Teucrium genus] Aristolochic acid Germanium dioxide

or lactate citrate

Lobelia [Indian tobacco]

Stephania L-tryptophan Ephedra (ma-

huang)

9

Beyond the Top 10Beyond the Top 10

Pennyroyal oil Sassafras Borage Calamus Coltsfoot Life root

10

Significant Interactions with Significant Interactions with Alternative SupplementsAlternative Supplements

11

St John’s Wort [St John’s Wort [Hypericum Hypericum perforatumperforatum]]

• Digoxin• Warfarin• Theophylline• Nefazodone• Oral

contraceptives• Antiretrovirals• Cyclosporine• Imatinib (Gleevec)

Irinotecan [Camptosar]

Simvastatin Amitriptyline SSRI (fluoxetine,

sertraline, etc.)

Lancet 2000;355:1343-8

Pharmacotherapy 2004;24:1508-1412

Herbal and Supplement Herbal and Supplement Products That Interact Products That Interact with Warfarin with Warfarin

Increased INR• Ginkgo Biloba• Dong Quai (Angelica

sinesis)• Danshen (Salvia

miltiorrhiza)• Vitamin E

Decreased INR• St. John’s Wort• Coenzyme Q10• American ginseng

Altered Platelets• Garlic [Allium

sativum]• Feverfew• Ginseng• Turmeric• Meadowsweet• Willow bark

Contain Coumarins*• Horse chestnut• Red clover

Lancet 2000;355:13438J Clin Pharm Ther 2002;27:391-40113

Significant Interactions with Significant Interactions with Alternative Meds and Alternative Meds and SupplementsSupplements

Siberian Ginseng (Eleutherococcus senticocous) - Digoxin

Valerian [Valeriana officinalis] – alcohol, benzodiazepines, anticonvulsants, TCA

Licorice - ACE-I, ARB, diuretics, digoxin

Lancet 2000;355:1343814

Significant Interactions with Significant Interactions with Alternative Meds and Alternative Meds and SupplementsSupplements

Kava and valerian– alcohol, barbiturates, antispychotic drugs, sedatives, benzodiazepines,

Garlic – saquinavir Red rice yeast [Chinese red rice]-

statins, gemfibrozil, fenofibrate

15

Patient Groups Most Likely Patient Groups Most Likely to have Problemsto have Problems

Multiple medications HIV/AIDS Cancer Transplant Treated with warfarin, digoxin, or

other agents prone to drug interactions

Undergoing surgeryAm J Health-Syst Pharm 2004;61:1707-11

16

Avoid Recommending Avoid Recommending HerbalsHerbals

Pregnant and lactating women Children

17

Problem Products in Problem Products in SurgerySurgery

Ginkgo biloba Saw Palmetto American Ginseng [Panex

quinquefolias] Kava St John’s wort Feverfew

18

Problem Products in Problem Products in Cancer TreatmentCancer Treatment

Garlic Ginkgo Echinacea Panax ginseng St John’s wort Kava

J Clin Oncol 2004;22:2489-50319

Reasonably Effective Reasonably Effective HerbalsHerbals

Aloe Vera (topical) Arnica (topical) Black Cohosh Chamomile tea Echinacea Evening primrose

oil Feverfew Garlic

Ginger Ginkgo Biloba Hawthorn Peppermint tea Saw Palmetto Siberian Ginseng St John’s wort Valerian

20

Reliable Printed ResourcesReliable Printed Resources

Herbal medicine: Expanded Commission E monographs

Review of Natural Products Tyler’s Herbs of Choice. The Therapeutic

Use of Phytomedicinals Tyler’s Honest Herbal: A Sensible Guide

to the Use of Herbs and Related Products.

Facts and Comparisons: The Review of Natural Products

21

Reliable Online Resources Reliable Online Resources

consumerlab.com herbalgram.com

• American Botanical Council nccam.nih.gov

• NIH’s National Center for Complementary and Alternative Medicine

vm.cfsan.fda.gov• Center for Food Safety and Applied

Nutrition

22

Reliable Online ResourcesReliable Online Resources

www.uic.edu/pharmacy/research/diet/content/scont_about_evaluations.htm• University of Illinois

www.pharmacist.com/pdf/dietary_supplements.pdf• Healthcare Professional’s Guide to

Evaluating Dietary Supplements www.herbalwatch.com 23

To Buy Anything and To Buy Anything and Everything Everything

www.herbalremedies.com

Blood CirculatorMade 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

Patient CounselingPatient Counseling

Encourage disclosure of ALL medicinal substances

Discuss available information about alternative medicines

Discuss health risk and self-monitoring Set objective goals to follow progress Steer patients seeking to self-treat

serious disorders such as depression to a physician

25

How to Report an Adverse How to Report an Adverse EffectEffect

Complete the Medwatch form online• www.fda.gov/medwatch/report/hcp.htm

Report by telephone (1-800-FDA-1088) 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

Evaluating Products for Evaluating Products for QualityQuality

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

ConclusionConclusion

Current regulation of dietary supplements fails to address substantial risk to public health

Educate patients to give “Full Disclosure”

Know the problem herbs and most common interacting herbs

Report adverse events 28