CP111_18Nov14
Distinguish between complimentary medicine and alternative medicine.
"Complementary" means using together with western medicine. "Alternative" means in place of the western medicine.
What is the standard legal disclaimer for a structure-function claim? What is the only exception?
"This product has not been evaluated by the FDA. This product is not intended to diagnose, treat, cure or prevent any disease." Exception: Can describe benefits related to a nutrient deficiency disease as long it qualifies how widespread the disease is in the U.S.Vitamin C may reduce the risk of scurvy which affects less than 1% of the U.S. population
What is the list of (seven) DSHEA labeling requirements for a dietary supplement?
1) Name of product 2) Net quantity of contents (i.e. how many capsules) 3) Non dietary fillers, colors, sweeteners, and binders by weight (most prevalent to least) active ingredients and inactive ingredients. 4) Name and place of business of manufacturer 5) Directions for use 6) The wording "Dietary Supplement" 7) ***Cautionary statements ARE NOT REQUIRED*** -Doesn't have to list side effects, drug interactions, contraindications. -But "may" list -Lack of such a statement does not imply safety
What items must be listed on the supplement facts panel of a dietary supplement?
1) Serving size (e.g. how many capsules) 2) Dietary ingredients (per serving size) 3) Amount per serving (by weight) 4) % Daily value (if established) 5) If plant based, name of plant and plant part used 6) If blend is PROPRIETARY (exclusive to manufacturer), total weight of blend and it's components
What law regulates dietary supplements as foods?
1994 DSHEA - Dietary Supplement Health and Education Act
Why do people use dietary supplements?
45% reported use to "improve" overall health 33% to "maintain" overall health OTHER REASONS PATIENTS USE DS "Natural" implies safe and healthy Desire to heal one's self, active participant in your treatment plan Dissatisfaction with western physicians, medication side effects, costs Desire to treat whole person not just a part Easy access Focus on prevention Immigration from non-western culture
What proportion of supplement users informed their HCP of the fact?
57.6% of supplement users did not tell their HCP 69% of persons using a supplement and a prescription drug did not discuss this use with their HCP
What are the top 2 areas of natural product drug development?
Anti-cancer Anti-infective
How does the FDA announce information about recalls and warnings? What classes of drugs tend to be the biggest offenders?
Any HCP can sign up for email updates from FDA website Products for sexual performance and weight-loss supplements tend to be the biggest offenders.
Approximately what proportion of drugs come from natural resources? From plants specifically?
Approximately 50% of drugs come from natural resources of which 25% are plants
What does "Integrative health care" mean?
CAM is classified by NCCAM Alternative Medical systems -TCM, Ayuverdic, Homeopathy, Naturopathy Mind/Body → using the mind to control the body -Meditation, Acupuncture, Tai Chi, yoga -Chiropractic and Osteopathic manipulation, massage, movement therapies (Pilates). CAM encompasses Biological Therapies (botanicals, dietary, minerals, vitamins), and Energy Therapies ( Energy fields, magnets, electromagnetic field devices, manipulation of energy fields through Reiki).
As a pharmacist, if someone walks up to you with a supplement and asks you about it, what do you do?
CHECK LABEL if you have one What if you don't have the bottle? -Google product ingredients if you know the name of the product and the manufacturer -National Institute of Health - DS Labels Database -DS content ~6,000 products -Can search by product name or a specific ingredient
What defines a "nutrient content claim?"
Characterize the level of a nutrient in a food or supplement and are FDA pre-approved terms -Typically involve nutrients or dietary substances that have established daily values or % claims for dietary ingredients. There are criteria for these claims. Examples: -"High Potency" - OK if product has 100% or more of the dietary reference intake (DRI) for at least 2/3 of the vitamins and minerals -"Good Source" - OK if product contains at least 20% of the DRI for the nutrient described
Define the term "CAM."
Complimentary and Alternative medicine
How does the DSHEA define a dietary supplement?
Defines dietary supplements as any: vitamin, mineral, herb, amino acid, extract or concentrate, and other substances (e.g. enzymes, metabolites) used to supplement the diet
What law regulates reporting of adverse drug effects associated with dietary supplements?
Dietary Supplement and Non-Prescription Drug Consumer Protection Act → Went into effect in December of 2007 -This came out of a supplement called "metabolife" that was causing many many strokes, but the manufacturer had no responsibility to report it and the problem just got worse. This introduces some "post-marketing surveillance" in the hands of the manufacturer.
Even if no contamination exists, what are other possible hazards of dietary supplements?
Direct Toxicity -Irreversible blu-grey skin discoloration from colloidal silver (picture of Paul Karason aka Smurf man) -Cases of liver dysfunction green tea extract prompt USP to propose new warning labels in 2007 - catechin in extract likely causal factor Drug interactions -Metabolic Effects: St John's wort affects enzymes that metabolize medications (can decrease effect of birth control pills, cyclosporine, antiretrovirals, digoxin and others) -Additive or Opposing Effects: Supplements with similar or opposing pharmacology to OTC/Rx drugs (e.g. opposing effect = where drug has opposite effect of what you want to happen. so echinacea with immunosuppression) Hazards introduced by the consumer -Intended or accidental over supplementation (e.g. "smurf man") -Use of supplements in lieu of more proven effective therapies
What is the distinction between a disease claim and a structure-function claim?
Disease claims mention a disease, a class of diseases, or a sign or symptom characteristic of a disease
What are some tips for providers of DSs?
Educate yourself -20 products comprise 85% of DS sales Pharmacists should report any side effects, since manufacturers are not required to do so and FDA functions on post marketing surveillance -Med-Watch at 800-FDA-1088 -800-4USP-PRN As part of medication history ask about any dietary supplements or herbs - give examples so patients know what you are talking about Do not recommend in children or during pregnancy and lactation Do not recommend if patient is already taking a prescription product for the same problem unless they consult with a doctor Do not recommend using more than directed on the label
What populations may be particularly susceptible to adverse events caused by dietary supplements?
Elderly and Children -Elderly especially susceptible to exorbitant claims and are likely to be on more prescription drug products -Supplement use in children is poorly studied -Children and elderly may be more susceptible to adverse effects
What agency regulates claims on product labels and packaging?
FDA
What are the three types of claims that can be made on dietary supplement labels?
FDA Approved Health Claims FDA Approved Nutrient Content Claims Structure Function Claims → Not FDA Approved -only health claims and nutrient content claims are FDA-approved, not structure-function claims. And this last kind is most of what we see.
What agency regulates claims on advertisements (broadcast/print)?
FTC
For what class of supplements are International Units (IUs) used?
For Fat-soluble vitamins, you'll see International Units (IU), e.g. Vit A,D,E
Can structure-function claims be made about pregnancy?
For a while manufacturers were trying to market products specifically for pregnancy, without any idea of the fetal risk or tests. It has since been removed.
Why would pharmacies want to stock a large supply of dietary supplemetns?
Generally high profit margins - can make up for income lost from lack of reimbursement Boost revenue for pharmacies because direct cash sale. -Patients may not be reimbursed by their insurance company for use of CAM therapies or Dietary Supplements
What is the legal definition of a "health claim?"
Health claims link a food, food component or dietary supplement ingredient and reducing risk of a disease or health-related condition -It links the supplement to a disease, but it MUST be FDA approved. The manufacturer sends proof to the FDA. -There are pre-approved examples anyone can use, like "A diet rich in calcium may decrease the risk of osteoporosis" or, "A diet rich in folate may reduce the risk of neural tube defects," A diet low in sodium may decrease the risk of high blood pressure."
What are two challenges to drug discovery from natural sources?
Identification process is slow, need for "blockbuster drugs" Isolation of a lead compound, complexity of synthesis
What four things does Consumer Lab test?
Identity: Does the product meet recognized standards of quality and does the product meet the level of quality claimed on the label? Strength (quantity): Does the product contain the amount of ingredient claimed on the label? Purity: Is the product free of common contaminants? Availability: Does the product break apart properly so that it may be used by the body?
Which of these are disease claims an which are structure function claims? Improves absent mindedness Improves memory loss associated with aging Improves senile dementia Reduces cholesterol Maintains normal cholesterol Relieves stress and frustration Relieves cramps and edema associated with menstruation
Improves absent mindedness → structure-function claim Improves memory loss associated with aging → structure-function Improves senile dementia → disease claim Reduces cholesterol → disease claim (infers benefit for hyperlipidemia/ cardiovascular disease) Maintains normal cholesterol → structure-function Relieves stress and frustration → structure-function Relieves cramps and edema associated with menstruation → structure-function
What governs the purity and potency of dietary supplements?
Industry guidance released by FDA in 2007 → Good Manufacturing Practices supplement standards require manufacturers to ensure their products are pure, free of contaminants and contain the type and amount of ingredients indicated on the label *Can consumers be assured that all supplements will meet these new content guidelines? Nope, there is no guarantee.*
What are two possible contaminating hazards in DSs?
Look-alike plants -Case reports digitalis poisoning - mistaking foxglove for other plant species -Liver toxicity - mistaking mushroom species Prescription Drugs and Heavy Metals -Survey of 260 Asian patent medicines from CA retail herbal stores; 32% with undeclared pharmaceuticals or heavy metals. -Not all manufacturers are honest about what is in the supplement.
Why would a manufacturer choose to standardize their product?
Manufacturer decides if they want to standardize their product if one or more active ingredients are known -Examples: Garlic may be standardized to 1.3% alliin or 0.6% allicin, Saw palmetto to 85-95% fatty acids and sterols -Gives better batch to batch quality & improves quality control -May improve chances of efficacy
What defines a proprietary blend?
Manufacturers have the "Secret recipes," and they don't have to tell you exactly what is in it, in what concentrations. All you have is the list that have the most highly concentrated ingredients listed first. In this case, they only tell you the total weight. How do you know exactly how much you are getting?
Why do DSs pose a challenge to HCPs?
Many scientific studies are of poor quality, small sample size and short duration -Structure/function claims can be vague -"Helps to maintain a healthy circulatory system" -European products may not be available in U.S., a lot of studies are not done in US. -Limited training on DS in schools
What are two reliable sources for information about DSs?
Natural Medicines Comprehensive Database Available on-line and in book format Covers herbs and supplements -Ranks effectiveness of efficacy claims in terms of likely effective, possibly effective or possibly ineffective -Rated #1 reliable resource in two recent studies DS information resources Natural Standard Website or Handbook→ www.naturalstandard.com -Includes both herbs and supplements -Balanced, unbiased reviews categorize claims of efficacy on scale of A (strong) to F (evidence against its use) -Includes reviewers from all disciplines -Only available for institutional subscriptions NCCAM (NIH website) -http://nccam/nih.gov -Provides information on clinical trials involving CAM therapies -DS monographs very evidence based US Food and Drug Administration -http://www.fda.gov/food/dietarysupplements/ -Covers legislative issues, press releases regarding products with problems
Can melatonin or coenzyme Q10 be standardized?
No, they are 100% of what they are already. They don't have any other plant chemicals in them
How are DSs generally considered by HCPs?
Often forget DS as part of a med history -Survey of 250 consumers from Virginia -"Does your pharmacist ever ask if you are taking DS" - 75% said "never" -"Does your health-care provider ask you if you are taking DS before prescribing medication" → 58% said "never" Fail to counsel or advise against product use due to inadequate knowledge, doubts regarding product quality and fear of legal ramifications (e.g. malpractice)
What are some of the most common conditions for which people use DSs?
Pain - back, neck, joint, arthritis Anxiety Cholesterol Head or chest cold Headache/migraine Insomnia/trouble sleeping
What four factors influence clinical effects of a plant-based medicine?
Plant part → Different chemicals are found in roots, stems, flowers, etc... -E.g. root of dandelion is a laxative, but the flower is a diuretic. Age of plant -Something like a ginseng root; the active ingredients become more concentrated with age. Growing conditions....soil, climate Method of preparation -E.g soaking in water vs oil.
Define "standardization" of a product
Products may be standardized to a particular chemical or marker, especially if the chemical is thought to contribute to the pharmacological effect Some products have no standardization as the active chemical markers are unclear (e.g. echinacea)
What is the RTA framework?
R.T.A - Recommend, Tolerate, Avoid E.g. "Tolerate" Milk thistle for liver, associate with liver protection, but the bulk of the literature doesn't have a strong support. So look to see if there are any harmful side effects or drug interactions. Not going to negatively impact health condition. We cannot promise that it will have a benefit, but it should not harm.
What are the four classes of Dietary Reference Intakes?
RDA = Recommended Dietary Allowance -Average daily intake needed to meet the needs of 97.5% of healthy people, usually in association with a vitamin or mineral. AI = Adequate Intake -Daily intake needed to ensure nutritional adequacy in healthy people -Used when RDA value not established. meets the needs of almost all healthy people. UL = Tolerable Upper Level -Maximum daily intake unlikely to produce adverse effects -E.g. for vitamin C, the upper limit is 2g / day. If you go over this, you will develop side effects. -Upper limit for vitamins and minerals, MTC. DV = Daily value -Developed to help consumers determine the level of various nutrients in a standard serving of food in relation to their approximate requirement for it -Some nutrients (e.g. choline, inositol) have no established % DV, for vitamins and minerals the % DV is based on the RDA -For people 4 yo or older on a diet of 2000 calories a day.
List some flaws in the current regulation of dietary supplements.
Regulated as "foods" not "drugs" by the FDA -Drugs (OTC/Rx) require proof of safety and efficacy prior to being marketed to the public -DS manufacturers do not have to submit proof of efficacy to the FDA prior to marketing -DS manufacturers do not have to submit safety data to FDA prior to marketing unless the product contains a new dietary ingredient not previously marketed prior to Oct 1994 in which case must notify FDA 75 days in advance of marketing with data showing safety in humans when used as directed -Assumed safe if contains ingredients marketed prior to Oct 1994 based on history of use in humans
What government branch regulates dietary supplements?
Regulation of dietary supplements falls under the FDA's Center for Food Safety and Applied Nutrition (CFSAN)
What factors would indicate a quality DS?
Reputable distributor -Manufacturers: drug companies/largercompanies (e.g. Nature's way) -Avoid products with multiple ingredients (proprietary blends) Labeling should include: -Labeling requirements of DSHEA -lot number, expiration date
What does the Dietary Supplement and Non-Prescription Drug Consumer Protection Act require of manufacturers?
Requires mandatory reporting to FDA of serious ADEs → Death, life threatening experience, hospital admit, disability, birth defect or medical/surgical intervention required Manufacturers must keep records of all consumer complaints over last 6 years and how they were handled
What types of groups do product testing?
Some Independent Testing Labs -Consumer Lab randomly tests products and reports results -Manufacturers can also pay to have their products tested so they can put a certification mark on the product NSF Consumer Affairs Office -manufacturers can put the NSF label on their product United States Pharmacopoeia -This means that the supplement has been tested for purity, potency content.
What must be true of a statement made on a dietary supplement? Who regulates this?
Statements must be accurate, true and not misleading FTC (Federal Trade commision) oversees DS advertisements
What authority does the FDA have over structure-function claims on dietary supplements?
Structure-function claims do not require FDA review or authorization but manufacturers must notify FDA within 30 days after marketing the product of the text of the claim -These claims link a food, food component or dietary supplement ingredient to maintaining normal healthy structure or function of the body e.g) "Antioxidants maintain cell integrity," "Glucosamine supports healthy joint function and cartilage"
How widespread is knowledge of DSs among pharmacists?
Survey of 800 pharmacists -rated knowledge of herbs, homeopathic products and neutracueticals on a scale of 1 (least) to 5 (extremely knowledgeable) -Average score of 2 -"We are relatively ignorant in this area. Many of our consumers know more than we do" Consumer Reports undercover operation -Surveyed 25 pharmacists in 6 states on purchase of ginkgo with prescription for warfarin -No pharmacist cautioned against concomitant use
In what circumstances can the FDA pull a dietary supplement from the shelves?
The FDA can only pull a product if it is proven unsafe, or proven to be misbranded. This can take a while. -Product can only be removed from the market if 31 proven unsafe by FDA (e.g. ephedra)
How does the FDA define dietary supplements?
The Food and Drug Administration (FDA) defines dietary supplements (DS) as vitamins, minerals, herbs or other botanicals, amino acids; dietary substances used to supplement the diet by increasing dietary intake or concentrates, metabolites
What is a major issue with the structure-function claims laws?
The manufacturer can decide what the structure-function claim is, without review form an outside source, and then it's in the market for quite a while before the FDA is notified.
Who is responsible for ensuring that a supplement is safe for use as directed?
The manufacturer is responsible for ensuring that the supplement is safe when used as directed.
What is the entymology of the word "drug?"
The word "drug" comes from the Middle English word "drogges" which means "to dry" referring to first drugs which were dried plants
How do you read a supplement label?
Too much to list; available in page 8 of notes
What ecosystem is the best source for new plant-based medicines?
Tropical rain forests are the richest source of new plant based medicines, but only 1% of plants have been thoroughly tested with 0.5% yielding 25% of the drugs we use today. ~130 plant/animal/microorganisms lost per day due to deforestation (~50,000 species/year)
What is the public perception of DSs and, in particular, their HCP's view of DSs?
Users believed in product usefulness irrespective of scientific data -It's not about efficacy, it's about consumers wanting access. -71% would continue use even if government said it was ineffective Confidence in physician's openness and knowledge -49% felt their physician was prejudiced against DS use -44% felt their physician knew little or nothing about DS
What three properties do products require to have the NSF and USP symbols?
Verified for content and quantity of ingredients Contain no undeclared ingredients or contaminants Demonstrate conformance with good manufacturing practices for DS (USP also tests for product dissolution)
What limits servign size in supplements?
While the manufacturer is responsible for ensuring safety, there is no rule limiting serving size or the amount of a nutrient in any form of dietary supplements Serving size does not require FDA review or approval, it is up to the manufacturer.