Herbal and Natural Medicines: What You Should Know

1
Herbal and Natural MedicinesWhat You Should Know

• Mandy Leonard, R.Ph., Pharm.D., BCPS
• Drug Information Specialist
• Department of Pharmacy
• The Cleveland Clinic Foundation
• April 2004

2
Objectives

• Review the reasons why people are using herbal/
  alternative medicines.
• Describe risks from the consumption of herbal/
  alternative medicines.
• Describe briefly changes in law regarding dietary
  supplements.
• Discuss commonly used dietary supplements,
  including herbal medicines.
• Review reputable sources of information regarding
  herbal/alternative medicines.

3
Introduction

• Definitions
• Food and Drug Administration (FDA)
• World Health Organization (WHO)
• Homeopathy
• Over 20,000 herbal and other natural products
  available in the United States.
• Economics
• Widespread use

4
(No Transcript)
5
Top-Selling Herbs in Mainstream Market in U.S.
2001

• Gingko (46)
• Echinacea (40)
• Garlic (39)
• Ginseng (31)
• Soy (28)
• Saw Palmetto (25)
• St. Johns wort (24)
• Valerian (12)

• Cranberry (11)
• Black cohosh (10)
• Kava kava ( 9)
• Milk thistle ( 7)
• Evening primrose ( 6)
• Grape seed ( 4)
• Bilberry ( 4)
• Yohimbe ( 2)
• ( in millions Herbalgram 20025560.)

6
Top-Selling Herbs in Mainstream Market in U.S.
2002 (? 13.9)

• Garlic (34)
• Ginkgo (32)
• Echinacea (32)
• Soy (28)
• Saw Palmetto (23)
• Ginseng (21)
• St. Johns wort (15)
• Black cohosh (12)

• Cranberry (11)
• Valerian ( 8)
• Milk thistle ( 7)
• Evening primrose ( 7)
• Kava kava ( 6)
• Bilberry ( 3)
• Grape seed ( 3)
• Yohimbe ( 2)
• ( in millions Herbalgram 20035871.)

7
Herbal versusConventional Medication

• Disappointment with current conventional
  therapies
• Fear of safety and long-term effects
• Lack of effective treatments/cures

8
Herbal versusConventional Medication

• Belief that herbal products are safe because
  derived from nature
• Peer influence
• Desire to have control of ones own health
• False claims from manufacturers

9
Safety Considerations

• Forty to 70 of patients do not inform physicians
  about use of alternative therapies
• Adverse reactions
• One or more chemical component of the plant
• Inappropriate or incorrect manufacturing process
• FDA does not require reporting of adverse
  reactions from alternative therapies (MedWatch
  and SN/AEMS)
• Examples L-tryptophan, ephedra (ma haung)

10
Safety Considerations

• Standardization
• Nomenclature and chemical constituents vary
• Mixtures are NOT standardized
• Lack of Good Manufacturing Practices (GMPs)
• Examples ginseng, ephedra
• Difficult to identify ingredients
• Lack of active ingredient
• Contamination

11
Unsafe Herbal Therapies

• Ephedra (ma haung)
• Ephedra sinica
• Anorexiant, decongestant
• 1 ephedrine
• Palpitations, MIs, death
• Maximum recommended dose 100 mg/24 hours
• Contraindications
• Drug interactions
• Theophylline, digoxin, caffeine

• Licorice
• Glycyrrhiza glabra
• Peptic ulcers
• High doses
• (pseudoaldosteronism)
• Use no longer than 6 weeks
• Contraindications
• Drug interactions
• Digoxin, furosemide

12
Ephedra

• Products containing ephedra account for 64 of
  all adverse reactions to herbs in the US
• Less than 1 of herbal product sales
• FDA announced ban on 12/30/2003
• After Mid-March 2004, illegal to manufacture or
  sell dietary supplements that contain
  ephedrine and related alkaloids
• Does not include teas

13
Kava (Piper methysticum)

• Anxiety, stress, sleep disorders (kavapyrones)
• May be effective for short-term treatment of
  anxiety (similar to Valium and Ativan)
• Hepatoxicity liver failure and liver
  transplantation
• FDA warning Canada and some European countries-
  market removal
• Kava dermopathy
• Use no gt 4 weeks no alcohol/sedating
  medications caution when driving or operating
  heavy machinery

14
FDA Proposed Labeling and Manufacturing Standards

• Designing/construction of physical plants
• Establishing quality control procedures
• Testing manufactured dietary ingredients and
  supplements
• Five out of 18 soy or red clover-containing
  products
• Only 50 to 80 of declared isoflavones
• Niacin
• Almost 10 times more niacin
• Folic acid
• Only 35 of what was stated on label

15
(No Transcript)
16
(No Transcript)
17
United States Pharmacopeia (USP) Dietary
Supplement Verification Program (DSVP)
18
ConsumerLab.com
19
NSF International
20
Potential Warfarin-Herb Interactions

• Feverfew
• Additive effect
• Monitor or avoid
• St. Johns Wort
• Increased metabolism decreased effect of
  warfarin
• Monitor or avoid

• Ginger
• Additive effect
• Avoid supplements, but small amount in diet
  should not be problematic
• Garlic
• Additive effect
• Avoid supplements, but small amount in diet
  should not be problematic

21
Consumer Survey

• Herbal use, products, and willingness to inform
  health care practitioners
• 794/1300 surveys returned
• 42 (n330) Herbal product use
• Common herbal products (aloe, garlic, ginseng,
  echinacea, and St. Johns wort)
• Women (majority)
• Higher education (75)
• Herbal users more prescription medications
• Herbal users negative perception of
  prescription medications
• Pharmacother 200020(1)83-7

22
Laws and Regulations

• 1994- Dietary Supplement Health and Education Act
  (DSHEA)
• Definition (dietary supplements not categorized
  as food additives)
• Premarketing approval
• Burden of proof that product is adulterated or
  unsafe rests on the FDA (e.g., ephedra)
• Third-party Literature
• Balanced view of available data
• Structure/Function Statements

23
Structure/Function Statements

• This product is not intended to diagnose, treat,
  cure or prevent a disease.
• Change in definition of disease
• Examples
• Absentmindedness and hair loss associated with
  aging
• Hot flashes
• Premenstrual syndrome
• Herbalgram 20004832-8

24
Ginkgo (Ginkgo biloba)

• Leaves of the ginkgo biloba tree
• Distinct chemical components
• Work synergistically
• Improves blood flow (brain and heart)
• Protects against oxidative damage from free
  radicals (antioxidant)
• Inhibits effects of platelet activating factor
  (PAF)

25
(No Transcript)
26
Ginkgo Efficacy

• Data demonstrate ginkgo leaf extract can
  stabilize or improve some measures of cognitive
  function and social functioning in patients with
  multiple types of dementia.
• No direct comparisons to conventional medications
  for dementia.
• Modestly improve visual memory and speed of
  cognitive processing in non-demented patients
  with age-related memory impairment.

27
Ginkgo Adverse Effects Drug Interactions

• Adverse Effects
• Hypersensitivity reactions, gastrointestinal
  disturbances
• Spontaneous bleeding (few case reports)
• Drug Interactions
• Anticoagulants (Coumadin)
• Antiplatelets (aspirin, Plavix, Ticlid)
• Insulin

28
Ginkgo Dose and Administration

• Standardized 24 flavone glycosides and 6
  terpenoids (leaf extract)
• Dementia
• 120 to 240 mg ginkgo leaf extract administered
  orally in two or three divided doses

29
Ginkgo Summary

• Mild-to-moderate vasoactive agent
• Data promising in Alzheimers Disease
• Used extensively in Germany
• No comparison to standard of care
• Well-tolerated (weeks to 1 year)
• Potential drug-herb interactions with
  anticoagulants, antiplatelets, and insulin

30
Ginseng

• Each type of ginseng is unique
• Asian or Oriental ginseng (Panax ginseng)
• Siberian ginseng (Eleutherococcus senticosus)
• American ginseng (Panax quinquefolius)
• Active ingredients Root (panaxosides)
• Ginsenoside Rb-1
• Central nervous system depressant
• Lowers blood pressure
• Ginsenoside Rg-1
• Central nervous system stimulant
• Raises blood pressure

31
Panax Ginseng Efficacy

• Data demonstrate possibly effective
• Improving abstract thinking, selective memory,
  and mental arithmetic skills (more effective in
  conjunction with ginkgo biloba leaf extract)
• Improving resistance to stress
• Controlling blood glucose levels in people with
  non-insulin dependent diabetes (Type 2)
• Possibly ineffective for enhancing athletic
  performance in healthy, young adults

32
Panax Ginseng Adverse Effects Drug
Interactions

• Adverse Effects
• Nervousness, insomnia, excitation, palpitations,
  affects blood pressure, lowers blood glucose,
  alters immune functiom
• Ginseng abuse syndrome? (long-term use)
• Drug Interactions
• Antidiabetic agents
• Warfarin (Coumadin)

33
St. Johns Wort (Hypericum perforatum)

• Common forms capsules, tablets, tinctures
• Source
• Flowering tops
• Naphthodianthrones (one of many potential active
  components)
• Hypericin - Inhibits MAOA gt MAOB
• Hyperforin Modulates effects of serotonin
• Serotonin inhibition at high concentrations
• Norepinephrine inhibition
• Catechol-O-methyl-transferase (COMT) inhibition

34
St. Johns Wort Efficacy

• For the treatment of mild-to-moderate depression,
  data demonstrate that St. Johns
  wort is
• Superior to placebo
• As effective as low-dose tricyclic
  antidepressants (TCAs Elavil and Pamelor),
• Possibly as effective as selective serotonin
  reuptake inhibitors (SSRIs Prozac, Zoloft,
  Celexa, and Lexapro)

35
St. Johns Wort Adverse Effects Drug
Interactions

• Adverse Effects
• Sun-exposure Photosensitivity/Phototoxicity
  (hypericin component watch if taking
  antibiotics)
• Insomnia, vivid dreams, headache, dizziness
• Drug Interactions
• MAOIs, selective serotonin reuptake inhibitors
  (SSRIs), Imitrex, tramadol (Ultram) Increased
  serotonin
• Cyclosporine (Neoral) Decreased levels
• Warfarin (Coumadin) Decreased INR (lab test)
• Oral contraceptives or hormone replacement
  therapy Breakthrough bleeding

36
St. Johns Wort Dose and
Administration

• Standardized extract
• 0.3 hypericin
• 5 hyperforin
• Mild-to-moderate depression
• 300 mg
• Administed orally three times a day
• Doses of 1200 mg/day have also been used

37
Echinacea (Echinacea angustifolia, pallida,
purpurea)

• Common Forms tablet, juice, tea
• Purple coneflower
• Source Applicable parts are the roots and above
  ground parts.
• Pharmacologic action constituent(s)?
• Indirect antiviral activity
• Immune system stimulatory effects
• Cytokines, monocytes, natural killer cells

38
Echinacea Efficacy

• Echinacea is possibly effective for
• Reducing symptoms associated with influenza-like
  upper respiratory infections such as the common
  cold and flu.
• Evidence suggests reduction in duration and
  severity of symptoms if started when symptoms are
  first noticed and used for 7 to 10 days.
• Possibly ineffective for preventing the common
  cold or influenza when taken prophylactically.

39
Echinacea Adverse Effects Drug Interactions

• Adverse Effects
• Allergic reactions
• ragweed, daisies, marigolds
• Fever, nausea, vomiting, unpleasant taste, and
  dizziness
• Atopy more likely to experience allergic
  reaction
• Drug Interactions
• Immunosuppressants Interfere with therapy
• Medications used for transplant patients, cancer
  patients, and patients with multiple sclerosis

40
Echinacea Dose and Administration

• Wide variety of doses depending on formulation
• Difficulty in standardization (echinacoside,
  alkamide content)
• Purpurea herb juice 6 to 9 mL for 8 weeks
• Purpurea crude extract 2 tablets administered
  orally three times a day
• Tea 5 to 6 cups on day 1 of symptoms, then 1
  cup/day for 5 days

41
Echinacea Summary

• Formulation/species that offer most benefit is
  unclear.
• E. purpurea pressed juice or E. pallida root
  extracts at first sign of cold
• If taken greater than 8 weeks
• Reduced immunostimulatory effects?
• One week drug holiday (not substantiated)
• Well-tolerated (up to 12 weeks)

42
Dietary SupplementsImmune-Stimulating Properties

• Alfalfa
• Panax ginseng
• Astragalus
• Cats claw
• Coenzyme Q10
• DHEA
• Echinacea
• Garlic

• Goldenseal
• Grape seed extract
• Melatonin
• Siberian ginseng

43
Dietary Supplements-Potential Interaction with
Steroids

• Aloe
• Asian (Panax) ginseng
• Bayberry
• Licorice

44
Herbal Use in Patients Undergoing Surgery

• Approimately 26 of patients scheduled for
  surgery use herbal products
• Cardiovascular instability
• Prolongation of anesthesia/sedation
• Bleeding
• Electrolyte disturbances
• Immunosuppression
• Anaesthesia 200257889-99

45
Discontinuation of Use Before Surgery

• Echinacea
• No data
• Immunosuppression
• Ephedra (ma huang)
• 24 hours
• Cardiac cautions
• Garlic
• 7 days
• Bleeding
• Gingko
• 36 hours
• Bleeding

• Ginseng
• 7 days
• Hypoglycemia Bleeding
• Kava
• 24 hours
• Sedation
• St. Johns Wort
• 5 days
• Drug-herb interactions
• Valerian
• No data
• Sedation
• JAMA 2001286(2)213

46
Herbal References

• Natural Medicines Comprehensive Database
• 92/year (book or web version)
• 132/year (book and web version)
• The Review of Natural Products
• 160/year (bimonthly updates)
• The Professionals Handbook of Complimentary and
  Alternative Medicine
• 40/edition

47
Natural Medicines Comprehensive Database
48
The Review of Natural Products
49
Herbal Medicine Expanded Commission E Monographs
50
PDR for Herbal Medicines
51
American Botanical Council (ABC)
52
Herbal References

• The United States Pharmacopeia and The National
  Formulary (USP-NF)
• 526/edition
• 21 botanical monographs (since 1995)
• Internet Reference
• The Natural Pharmacist (www.tnp.com)
• Conditions
• Drug Interactions
• Review of published articles
• Search

53
Herbal References

• The Herbal Internet Companion
• Herbs and Herbal Medicine Online
• 20 (ISBN 0-7890-1052-6)

54
IBIDS Database

• International Bibliographic Information on
  Dietary Supplements
• Office of Dietary Supplements (ODS) at the NIH
• Published, international, scientific literature
• Vitamins, minerals, and botanicals
• Over 676,000 unique scientific citations
  abstracts
• Three databases
• Full IBIDS database
• Peer-Reviewed Citations Only database
• IBIDS Consumer database

55
CARDS Database

• Computer Access to Research on Dietary
  Supplements
• Office of Dietary Supplements (ODS) at the NIH
• Specific mandates from the DSHEA
• Federally funded research projects pertaining to
  dietary supplements
• Free of charge
• www.ods.od.nih.gov

56
Summary

• Tell physician, nurse, and pharmacist about
  herbal therapy use (documentation)
• Natural does not mean safe
• Herbal-pharmaceutical interactions do occur
• Lack of standardization (variability in herbal
  content and efficacy among manufacturers)
• Lack of quality control and regulation
  (contamination and misidentification)

57
Conclusions

• Because of lack of efficacy and toxicity
  information, patients and clinicians should be
  aware that advice about herbal therapies is not
  absolute and is a matter of judgment.
• Base advice on available knowledge that is
  congruent with your needs and the clinicians
  best judgment
• Majority of recommendations are NOT evidence-based

58
(No Transcript)