Transcript Herbal Medication Update

Herbal Medication Update:
Enhancing Your Herbal IQ
Andrew Burgdorf, PharmD,BCPS
Clinical Pharmacist
Upstate Cancer Center
June 5th, 2015
Disclosure
• I do not have any relevant financial
relationships to disclose
Learning Objectives
• Appreciate the characteristics of patients who use
herbal supplements and the conditions they use
them to treat
• Learn relevant legislation and regulations related to
herbal supplements
• Identify benefits and risk of some popular herbal
supplements
Conference Theme 2015
Nurse Practitioners:
Agents of Change
How does this lecture fit in?
What can you change in your practice related to
herbal medications / dietary supplements?
Herbal Case
• Mr. T is a 64 yo male engineer who arrives
at your primary care office
• cc: Feeling fatigued due to insomnia, lack
of interest in activities he usually likes
• Pmhx: RLE DVT (2 months ago), partial
onset seizures, htn
• Allergies: nkda
• Med List:
– Lacosamide (Vimpat) 200mg po BID
– Rivaroxaban (Xarelto)20mg po qpm w/ dinner
– Hydrochlorthiazide 12.5 mg po qday
Herbal Case
• Your patient asks about treatment
options for depression including
herbal supplements…
• What do you advise?
• Why?
Impact of Herbals on Society
• National Health Statistics Report
– 14.8 Billion dollars were spent on nonvitamin, non-mineral, natural products
(2007)
– 17.7% of American adults had used “natural
products” (other than vitamins/minerals) in
the past 12 months (2012)
– Non-vitamin, non-mineral, natural products
used more commonly than deep breathing,
meditation, chiropractic/osteopathic
intervention, massage and yoga (2012)
Note* CAM portion of NHIS survey done every 5 years
National Center for Complementary &
Integrative Health (NCCIH)
nccih.nih.gov
Impact of Herbals on Society
2015 Survey of National Health Statistics
– Who is using complementary health approaches?
Women > Men
People with higher education levels
 College degree or higher (42.6%)
All different age groups (18-44, 45-64, 65+)
Insured?
 Private (38%), Public (24.8%), Uninsured (22.9%)
Why herbals?
• Herbal products are “natural” and
therefore, “safe”
• Desire for disease prevention – health
maintenance
• Easy access – no office visit, found in
pharmacies, malls and the internet
• No paperwork / insurance issues
• Distrust in conventional medicine
What’s not to trust about
conventional medicine?
Glaxo Agrees to Pay $3 Billion in Fraud
Settlement (Published: NY Times 7/2/2012)
-Largest settlement ever involving a
pharmaceutical company
-Promoting it’s best-selling
antidepressants for unapproved uses
(Paxil in children, Wellbutrin-sexual dysfunction
& weight loss)
-Failing to report safety data about a top diabetes drug
-“Prosecutors said the company had tried to win over
doctors by paying for trips to Jamaica and Bermuda, as
well as spa treatments and hunting excursions”
Top 10 US Dept of Justice / Pharma Settlements
(1991-2012)
Legislation/Regulations
• 1994 “Dietary Supplement Health and
Education Act” (DSHEA)
– Herbal products deemed “Dietary
Supplements” not drugs
– Post marketing surveillance for safety
shifted from manufacturers to FDA
• Products removed if found to be unsafe
– FDA given authority to establish Good
Manufacturing Practices
– Manufacturers should provide evidence to
FDA re: “a reasonable expectation of
safety (Frankly, NOT enforced…)
Legislation/Regulations
• 1994 “Dietary Supplement Health and
Education Act” (DSHEA)
– Formed Commission on Dietary Supplement
Labels and Office of Dietary Supplements
within the NIH
– Specified Labeling Requirements
• “This product is not intended to diagnose, treat,
cure or prevent any disease”
• However, regulations of content and quality are
NOT included
Legislation Updated
• FDA Issues Dietary Supplements
Final Rule, June 2007
– Requires current good manufacturing
practices (cGMP) for dietary supplements
– Ensuring products produced in quality
manner, properly labeled and free from
contaminants and impurities
– Industry will be required to report all
serious adverse events to FDA
Legislation Update
• Final Rule 2007 (Continued)
– Manufacturers will be required to
evaluate the identity, purity,
strength, and composition of their
dietary supplements
– New requirements being phased in
from 2008 to 2010 depending on
size of manufacturer
– Compliance with new regulations
about GMPs = difficult to find…
New FDA proposal - July 2011
• FDA safety evidence evaluation based on 3
key factors
– Documented history of use, formulation and
proposed dosage, recommended duration of
use
• Noted proposal weaknesses
– Historical use vs. experimental data
– Per IOM, historical use doesn’t guarantee
long term safety
• Strong opposition from supplement lobby
Never made into law! Thanks Congress!
Product Quality Issues
• Product labeling and content do not
match!
– Ginseng study showed differences from 11%
to 328% of labeled active ingredient
• Contamination/Adulteration
– Accidental
• Misidentified plants collected
– Purposeful
• Natural sleep remedy contains estazolam
• Swiss “All Natural” Skin Cream has Triamcinolone
– DNA testing found 4 of 5 products didn’t contain
products on the labels
– Unlabeled ingredients found: radish, house plants,
wheat, garlic, legumes, soy / peanut derivatives
– Cease & desist letters sent to GNC, Walgreens,
Walmart & Target
– AG Demanded to know what quality procedures
being used
Independent Quality Programs
• In the US, out of thousands of
manufacturers of herbal products, only
a handful are involved in such programs
• However, look for products from
manufacturers that are forthcoming
with information
– Website discusses quality measures
– Information on testing available upon
request
– Restriction of sales outlets
One example - Dietary Supplement
Verification Program (DSVP)
• Not for profit program of the U.S.
Pharmacopeia
– Thorough manufacturing and quality
control document review
– On-site manufacturing facility audit
• USP standards and FDA GMP standards
– Random off-the-shelf testing
Dietary Supplement Verification Program
(DSVP) - continued
– ~10 manufacturers participate
– The symbol ensures verification of
• What is on the label is in the bottle
• No harmful level of contaminants
• Supplement will break down & release
in the body
• Made according to FDA current GMPs
for sanity & well controlled procedures
Review of some popular herbal
medications / dietary supplements
• Echinacea
• Co-enzyme Q10
• Probiotics
• Glucosamine
• Melatonin
• Fish Oil / Omega 3-FAs
• St. John’s Wort
Echinacea
(purple cone flower)
• Uses
– Traditionally used to fight or prevent colds, flu, or other
infections
– Belief is that it stimulates the immune system
– Less commonly, for wounds and skin issues
(i.e. acne or boils)
• Studies
– Does NOT appear to prevent colds or other infections
– Course of cold or flu NOT shortened (2 NCCAM studies)
• National Library of Medicine, Medline Plus
– Rating “C”, unclear scientific evidence for use
Echinacea
(purple cone flower)
 Warnings
– Limit use to 8 weeks or less
 Avoid
 Using for allergies or asthma
 If taking immunosuppressants (Prednisone, Cyclosporine)
 If patient has transplanted organ
 If patient has autoimmune disorder (Rheumatoid Arthritis,
Lupus)
Melatonin
• Uses
– Insomnia, jet lag
– Usually derived from synthetic or animal sources
• Mechanism
– Produced endogenously by the pineal gland
– Thought to control circadian rhythm & promote
sleep
• Studies
– Some show decreased sleep latency & improved
sleep duration
– Other randomized studies show mixed results
• Side effects
Melatonin
– Altered mental status, disorientation, tachycardia, flushing,
pruritus, abdominal cramps, headache, hypothermia
• Warnings
– Caution related to driving and heavy equipment
– May alter estrogen levels affecting hormone sensitive cancers
• Drug interactions
– Blood thinners – Melatonin may decrease coagulation factors
– Nifedipine + Melatonin may increase BP / HR
– CYP1A2 Inhibitor – May increase fluvoxamine levels
• What are they?
Probiotics
– Microorganisms that have beneficial properties for the host
– Most come from food-derived products such as cultured milk
products
• Common products
– VSL#3 (Bifidobacterium breve, B. longum, B. infantis, Lactobacillus
acidophilus, L. plantarum, L. paracasei, L. bulgaricus, Streptococcus
thermophilus)
– Align (B. infantis)
– Culturelle (L. rhamnosus GG)
– DanActive (L. casei)
– Mutaflor (E. coli Nissle 1917)
– Florastor (S. boulardii)
• Uses
Probiotics
– Constipation, IBS, GI inflammation, allergy/atopic
dermatitis
– Infectious diarrhea (C.Diff – separate story)
(Evidence supports modest reduction in duration of
illness)
• Mechanism(s) of action
– Suppression of growth or epithelial binding/invasion
by pathogenic bacteria
– Improvement of intestinal barrier function
– Modulate the immune system
• Suppress inflammatory cytokines
• Increase protective cytokines
– Modulation of pain perception
Probiotics
• Side effects
– Constipation, flatulence, thirst
– Reports of fungemia
• Warning(s)
– Lactose intolerance, yeast allergy, immunocompromised
– Not all probiotics are alike
• Considerable differences exist in composition, doses, and biologic
activity between various commercial preparations
– Benefits observed clinically with one species (or combination
of species) are not necessarily generalizable to another
Glucosamine Sulfate
• Mechanism
– Lessens inflammation and cartilage
degradation
– Believed to beneficially affect the
imbalance between rates of
synthesis and degradation of
cartilage
• Uses
Glucosamine Sulfate
– Osteoarthritis of the knee
• Can be used with or without chondroitin
• Studies have shown that Glucosamine is as
effective as NSAIDs
• Subgroup analysis of 2006 NEJM study by Clegg et
al. Showed glucosamine/chondroitin may be
effective for moderate to severe knee pain
(p=0.02)
• Osteoarthritis Research Society International
(2008) Guideline for Management of Hip/Knee OA
– Glucosamine +/- chondroitin may provide symptomatic
benefit in Knee OA (Discontinue if no response in 6 months)
– Glucosamine (1500mg/day)& chondroitin in Symptomatic
Knee OA
» May have structure modifying effects
Glucosamine Sulfate
• Uses (Continued)
– Temporomandibular joint disorder (TMJ)
• Studies support Glucosamine/Chondroitin used in
combination
– Efficacy lacking in treatment of back pain
• In general, considered safe and well tolerated
– Multiple 3 year studies exhibit fairly clean safety
profile
• Warnings
– Contraindicated in folks who are allergic to shellfish
– Caution in diabetics
• Glucose metabolism may be altered
Glucosamine
2005 Cochrane Review
Summarizes Glucosamine for OA
– May reduce their pain
– May improve their physical function
– Low likelihood of side effects
– Best effects usually seen within 6 months
Omega 3 Fatty Acids (Fish Oil)
• Uses
– Cardiovascular protection
• Lots of epidemiologic data / clinical trial data
showing reduction in cardiovascular disease –
ideal consumption is unclear
• GISSI-Prevention Study, largest RCT, showing
15% reduction in composite endpoint of death,
non-fatal MI, non-fatal stroke (secondary
prevention trial)
• ORIGIN Trial did NOT demonstrate
cardioprotective effects (NEJM July 2012)
– Hyperlipidemia – HIGH triglycerides
Omega 3 Fatty Acids (Fish Oil)
– Depression
Finnish study shows lack of fish oil linked with
depression
– Cancer Prevention
The role of Omega 3s in cancer prevention is
inconclusive
– Others as well
Omega 3 Fatty Acids
(Fish Oil)
Side Effects
– Fishy taste, loose stools and nausea
– Generally, well tolerated
Warnings
– May increase bleeding time
– May decrease TG, while causing bump in LDL
EPA = eicosapentainoic acid, DHA = docosahexainoic acid
Omega 3 Fatty Acids (Fish Oil)
• 2011 AHA Statement –
Triglycerides and
Cardiovascular
Disease
– Triglyceride lowering is
better with marinederived Omega-3 PUFA
– Non-Marine Omega-3 is
derived from alphalinolenic acid (plant
based)
• Triglyceride
reductions have been
less consistent
Omega 3 Fatty Acids
(Fish Oil)
• The ORIGIN Trial Investigators
(Outcome Reduction with Initial Glargine
Intervention) (NEJM 2012)
• Double blind, 2x2 design, 6.2 yrs follow up
• 12,536 patients (High risk for CV events and
IFG, IGT, or Diabetes) to get…
1-g capsule n-3 fatty acids or placebo daily and
insulin glargine or standard care
• This intervention did NOT reduce the incidence
of CV events in high risk patients
Omega 3 Fatty Acids
(Fish Oil)
• Environmental contaminants
– Some of fish oil excitement
balanced by concerns here
– Found in low levels in fresh water
and in oceans
• PCBs
• Methylmercury
• Dioxin
Lovaza
(Omega -3-acid ethyl ester)
Prescription Medication
– FDA approved in conjunction with diet to reduce
very high triglyceride levels in adult patients (TG
>500 mg/dL)
– Dosing
4g once daily or 2g po bid
Fish/Fish Oil & Chemo Interaction?
• Daenen, et al. JAMA Oncology, April 2, 2015
“Increased plasma levels of ChemoresistanceInducing Fatty Acid 16:4(n-3) After consumption of
Fish and Fish Oil”
– Amsterdam, Netherlands
– Background: Mice model shows protective fatty
acid (16:4) neutralized chemotherapy activity
– Plasma levels of FA (16:4) examined in healthy
volunteers (after fish oil / fish)
– Conclusion
• Avoid fish oil, mackeral & herring fishes the day
before, the day of and the day after chemotherapy
Co-Enzyme Q10 (Co-Q10)
• Most common purported uses
– Angina, cardiovascular disease, congestive heart failure
(Also, Infertility, Migraine prophylaxis, Parkinson's disease, Periodontal
disease, strength and stamina)
• Mechanism of action
– Anti-oxidant & membrane stabilizing capabilities
– Necessary for ATP production
– Scavenges free radicals, reduces mitochondrial damage, &
maintains myocardial calcium channels
(All during times of cardiac ischemia)
Co-Enzyme Q10 (Co-Q10)
• Drug Intxns / Drug-Disease Intxns
– Warfarin
• Co-Q10 antagonizes warfarin
• Co-Q10 structurally similar to vitamin K
– Theophylline
• Co-Q10 reduces clearance of theophylline, risk for
causing persistent vomiting, cardiac arrhythmias
and intractable seizures
– Statins (Lovastatin, Simvastatin,
Atorvastatin)
• May reduce Co-Q10 levels
– Cancer patients
• Due to it’s anti-oxidant properties, it may interfere with radiation
and/or chemotherapy
St. John’s Wort
(Hypericum perforatum)
• Uses
– Mild to moderate depression
– Nerve pain, anxiety, sleep disorders
• Evidence
– Some studies share comparable efficacy
with Imipramine (TCA) and SSRIs in mild
to moderate depression
– 2 Other NCCAM studies – no better than
placebo in major depression of moderate
severity
St. John’s Wort
(Hypericum perforatum)
• Side Effects
– Common: headache, fatigue, GI
– Infrequent: photosensitivity, elevated
LFTs
• Drug Interactions !!!
– Induces CYP 3A4, 1A2,
2C9 & P-glycoprotein
– Additive effects w/ SSRIs
– Wide range of drugs effected
• Warfarin, Digoxin, Cyclosporine,Tacrolimus,
HIV protease inhibitors, oral contraceptives,
anti-convulsants, some chemotherapy
Generalized practice advice
Drug Interaction Concerns
• Practitioners must seriously consider
risk vs. benefit when combining herbals
with
– Blood thinners
• Aspirin, Clopidogrel, Heparin, LMWH, Warfarin
• Dabigatran? Rivaroxaban? Apixaban?
– Narrow therapeutic index drugs
• Levothyroxine, HIV Drugs, Anti-convulsants,
Digoxin, Cyclosporine/Tacrolimus
– Oral contraceptives
– Chemotherapy
https://nccih.nih.gov/health/herbs/understanding-interactions
Special Populations
Elderly
– Increased sensitivity to medications in general
– Likely to be on other prescription medications
(drug interaction potential)
– Bleeding risk with some herbals
• Pediatrics, pregnant/lactating, & end organ
dysfunction
Food for Thought
• What patients are good candidates for
herbal supplements?
• Who should you discourage from
using herbals?
• How will you manage patients who
take herbal supplements? What
questions will you ask?
• Did you document your advice to use
caution with herbal supplements?
Advice for Patients
• Communication is the key
– NCCAM/AARP Survey - Respondents
>50yoa, 69% of those who use CAM do
not discuss it with their doctors
• Peri-Operatively
– Discontinue herbal supplements 2 weeks
prior to surgery
• Bleeding risk
• May effect anesthesia
Advice for Patients
• Before taking herbal supplements it is best to
consult with your healthcare provider
• Some herbals can be helpful, some herbals
can be harmful…
– Discontinue if you notice adverse effects and
contact your healthcare provider
– Consider contraindications and potential drug
interactions
– Beware of biased information on safety and efficacy
of herbal supplements
– Avoid multi-supplement combination products
Advice for Patients
FDA’s “6 Tip-offs to Rip-offs”
• Disease-related claims
that are…
“not worth the risk”
• Tip Offs
– Weight loss
– One product does it all!
– Memory loss
– Personal testimonials
– Sexual performance
– Quick fixes
– Serious diseases
– Miracle cure
(Cancer, DM, Heart Disease,
Alzheimers)
– Conspiracy theories
www.fda.gov/ForConsumers/ConsumerUpdates/ucm341344.htm
Herbal Case
• Mr. T is a 64 yo male engineer who arrives
at your primary care office
• cc: Feeling fatigued due to insomnia, lack
of interest in activities he usually likes
• Pmhx: RLE DVT (2 months ago), partial
onset seizures, htn
• Allergies: nkda
• Med List:
– Lacosamide (Vimpat) 200mg po BID
– Rivaroxaban (Xarelto)20mg po qpm w/ dinner
– Hydrochlorthiazide 12.5 mg po qday
Herbal Case
• Your patient asks about treatment
options for depression including
herbal supplements…
• What do you advise?
• Why?
Resources
• nccih.nih.gov
– National Center for Complementary and
Integrative Health
• mskcc.org/aboutherbs
– Memorial Sloan Kettering Cancer Center,
About Herbs
Questions?
Thank you…
References
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Centers for Medicare & Medicaid Services. 1997 National Health Expenditures
Survey. www.cms.hhs.gov/statistics/nhe
Clarke, T, et al. "National Health Statistics Reports: Trends in the Use of Complementary Health
Approaches Among Adults: United States, 2002-2012." US Department of Health and Human
Services, 10 Feb. 2015. Web.
Clegg, et al. Glucosamine, Chondroitin Sulfate and the Two in combination for
Painful Knee Arthritis, NEJM, 2006: 354(8): 795-808
Daenen, L, et al. "Increased Plasma Levels of Chemoresistance-Inducing Fatty Acid (16:4) After
Consumption of Fish and Fish Oil." JAMA Oncol (2015): E1-E9. 2 Apr. 2015. Web.
Eisenberg DM, Davis RB, Ettner SL, et al. Trends in alternative medicine use in
the United States, 1990-1997: results of a follow-up national survey JAMA.
1998;280(18):1569-1575.
Kris-Etherton, Penny, William S. Harris, and William J. Appel. "Fish Consumption,
Fish Oil, Omega 3 Fatty Acids and Cardiovascular Disease." Circulation 106:
2747-757.
McQueen, Cydney E., ed. Pharmaceutical Care with Dietary Supplements,
Concepts and Common Sense. Bethesda: American Society of Health System
Pharmacists, 2007
Memorial Sloan-Kettering Cancer Center. 12 May 2015
<www.mskcc.org/aboutherbs>
National Center for Complementary and Integrative Health NIH. 30 May 2015
<nccih.nih.gov>
References
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Schneiderman, Eric T., Attorney General, and Martin J. Mack, Executive Assistant
Attorney General. "Cease and Desist Notification." Letter to Alexander Gourlay,
President. 2 Feb. 2015.
Schneiderman, Eric T., Attorney General, and Martin J. Mack, Executive Assistant
Attorney General. "Cease and Desist Notification." Letter to Brian C. Cornell, CEO. 2
Feb. 2015.
Schneiderman, Eric T., Attorney General, and Martin J. Mack, Executive Assistant
Attorney General. "Cease and Desist Notification." Letter to Doug McMillan,
President/CEO. 2 Feb. 2015.
Schneiderman, Eric T., Attorney General, and Martin J. Mack, Executive Assistant Attorney
General. "Cease and Desist Notification." Letter to Michael G Archbold, CEO. 2 Feb. 2015.