Transcript Herbal Medication: Fact and Fiction

Herbal and Natural Medicines:
What You Should Know
Mandy Leonard, R.Ph., Pharm.D., BCPS
Drug Information Specialist
Department of Pharmacy
The Cleveland Clinic Foundation
April 2004
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.
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
Top-Selling Herbs in Mainstream
Market in U.S. 2001
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Gingko
Echinacea
Garlic
Ginseng
Soy
Saw Palmetto
St. John’s wort
Valerian
($46)
($40)
($39)
($31)
($28)
($25)
($24)
($12)
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Cranberry
Black cohosh
Kava kava
Milk thistle
Evening primrose
Grape seed
Bilberry
Yohimbe
($11)
($10)
($ 9)
($ 7)
($ 6)
($ 4)
($ 4)
($ 2)
($ in millions; Herbalgram 2002;55:60.)
Top-Selling Herbs in Mainstream
Market in U.S. 2002 ( 13.9%)
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Garlic
Ginkgo
Echinacea
Soy
Saw Palmetto
Ginseng
St. John’s wort
Black cohosh
($34)
($32)
($32)
($28)
($23)
($21)
($15)
($12)
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Cranberry
($11)
Valerian
($ 8)
Milk thistle
($ 7)
Evening primrose ($ 7)
Kava kava
($ 6)
Bilberry
($ 3)
Grape seed
($ 3)
Yohimbe
($ 2)
($ in millions; Herbalgram 2003;58:71.)
Herbal versus
Conventional Medication
• Disappointment with current
conventional therapies
• Fear of safety and long-term effects
• Lack of effective treatments/cures
Herbal versus
Conventional Medication
• Belief that herbal products are safe because
derived from nature
• Peer influence
• Desire to have control of one’s own health
• False claims from manufacturers
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)
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
Unsafe Herbal Therapies
• Ephedra (ma haung)
• Licorice
– Glycyrrhiza glabra
– Peptic ulcers
– High doses
(pseudoaldosteronism)
– Use no longer than 6 weeks
– Contraindications
– Drug interactions
• Digoxin, furosemide
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Ephedra sinica
Anorexiant, decongestant
1% ephedrine
Palpitations, MIs, death
Maximum recommended
dose: 100 mg/24 hours
– Contraindications
– Drug interactions
• Theophylline, digoxin,
caffeine
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
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 countriesmarket removal
– Kava dermopathy
• Use no > 4 weeks; no alcohol/sedating medications;
caution when driving or operating heavy machinery
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
United States Pharmacopeia (USP)
Dietary Supplement
Verification Program (DSVP)
ConsumerLab.com
NSF International
Potential Warfarin-Herb Interactions
• 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
• Feverfew
– Additive effect
– Monitor or avoid
• St. John’s Wort
– Increased metabolism &
decreased effect of
warfarin
– Monitor or avoid
Consumer Survey
• Herbal use, products, and willingness to inform health care
practitioners
• 794/1300 surveys returned
– 42% (n=330): Herbal product use
– Common herbal products (aloe, garlic, ginseng,
echinacea, and St. John’s wort)
– Women (majority)
– Higher education (75%)
– Herbal users = more prescription medications
– Herbal users = negative perception of prescription
medications
Pharmacother 2000;20(1):83-7
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
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 2000;48:32-8
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)
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.
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
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
Ginkgo: Summary
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Mild-to-moderate vasoactive agent
Data promising in Alzheimer’s 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
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
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
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®)
St. John’s Wort (Hypericum perforatum)
• Common forms: capsules, tablets, tinctures
• Source:
– Flowering tops
– Naphthodianthrones (one of many potential active components)
• Hypericin - Inhibits MAOA > MAOB
• Hyperforin: Modulates effects of serotonin
– Serotonin inhibition at high concentrations
– Norepinephrine inhibition
– Catechol-O-methyl-transferase (COMT) inhibition
St. John’s Wort: Efficacy
• For the treatment of mild-to-moderate
depression, data demonstrate that
St. John’s 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®)
St. John’s 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
St. John’s 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
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
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.
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
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
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)
Dietary Supplements:
Immune-Stimulating Properties
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Alfalfa
Panax ginseng
Astragalus
Cat’s claw
Coenzyme Q10
DHEA
Echinacea
Garlic
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Goldenseal
Grape seed extract
Melatonin
Siberian ginseng
Dietary SupplementsPotential Interaction with Steroids
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Aloe
Asian (Panax) ginseng
Bayberry
Licorice
Herbal Use in Patients
Undergoing Surgery
• Approimately 26% of patients scheduled for
surgery use herbal products
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Cardiovascular instability
Prolongation of anesthesia/sedation
Bleeding
Electrolyte disturbances
Immunosuppression
Anaesthesia 2002;57:889-99
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. John’s Wort
– 5 days
– Drug-herb interactions
• Valerian
– No data
– Sedation
JAMA 2001;286(2):213
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 Professional’s Handbook of
Complimentary and Alternative Medicine
– $40/edition
Natural Medicines
Comprehensive Database
The Review of
Natural Products
Herbal Medicine: Expanded
Commission E Monographs
PDR for Herbal Medicines
American Botanical Council
(ABC)
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)
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Conditions
Drug Interactions
Review of published articles
Search
Herbal References
• The Herbal Internet Companion
– Herbs and Herbal Medicine Online
– $20 (ISBN 0-7890-1052-6)
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
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
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)
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 clinician’s
best judgment
• Majority of recommendations are NOT
evidence-based