ate to establish the Advisory Panel on Natural Health in 1997. After consultations with interested stakeholders, the Minister of Health tabled Natural Health Products: A New Vision, which provided the framework for the development of the Office of Natural Health Products. This office would later be renamed the Natural Health Products Directorate (NHPD). The NHPD’s role is “to ensure that Canadians have ready access to natural health products that are safe, effective and of high qual- ity while respecting freedom of choice and philosoph- ical and cultural diversity”(NHPD, 2009). In 2004, the Natural Health Products Regulations came into effect. Manufacturers must obtain a product license from Health Canada to sell their products in Canada. If the product meets the NHPD criteria, then a Natural Prod- uct Number will be issued. The Licensed Natural Health Products Database (LNHPD), managed by Health Can- ada, provides information on licensed natural health products. These include vitamin and mineral supple- ments, herb and plant-based remedies, traditional medicines (such as traditional Chinese medicines or Ayurvedic [Indian] medicines), omega-3 and essential fatty acids, probiotics and homeopathic medicines, and many everyday consumer products, such as certain tooth- pastes, antiperspirants, shampoos, facial products, and mouthwashes. This database can be accessed at http:// www.hc-sc.gc.ca/dhp-mps/prodnatur/applications/ licen-prod/lnhpd-bdpsnh-eng.php.
Homeopathic medicines (HMs) receive a Drug Identifica- tion Number (DIN)-HM followed by a product number. Extensive product labelling must meet specific require- ments regarded as essential to risk management. On the basis of information from the World Health Organization, the European Scientific Cooperative on Phytotherapy, and the German Commission E, the NHPD developed the Compendium of Monographs. The NHPD classi- fies natural health products into six risk categories from highest to lowest (see Box 7-3). The risk classification scheme is an “evidence-based approach that classifies a product into a level of risk based on relevant information from published and unpublished sources such as, but not limited to, journals, textbooks, or reports from regula- tory bodies” (Health Canada, 2007). The regulations also impose standard labelling requirements to ensure that consumers can make informed choices about natural health products. Labels contain such things as the prod- uct name, the quantity of the product in the bottle, and the recommended conditions for use, which include rec- ommended use or purpose and dose, warnings, caution- ary statements, contraindications, and possible adverse reactions. With such regulations, Canada, like Germany, France, and the United Kingdom, enforces standards for the assessment of natural-product quality and safety.
Consumer Use of Natural Health Products
A 2005 Health Canada survey showed that 71% of Can- adians regularly take NHPs in the forms of vitamins and
Risk Classification of
Natural Health Products
BOX 7-3
High Risk
Level 1: Natural health products on the Therapeutic Products Directorate’s listing of drugs currently regulated as new drugs
Level 2: Isolates, amino acids, fatty acids, concen- trated volatile (essential) oils indicated for internal use, and extracts other than those prepared by traditional methods
Level 3: Algal, bacterial, probiotic, fungal, and non- human animal materials
Level 4: Plants, plant materials, extracts prepared by traditional methods, and volatile (essential) oils other than those concentrated and indicated for internal use
Level 5: Vitamins and minerals Level 6: Homeopathic medicines
Low Risk
Source: Health Canada (2003b). Natural health products regu- lations. Note: Review of risk classification to be finalized pending revisions from the HPFB (Risk Classification) Working Group.
Over-the-Counter Drugs and Natural Health Products CHAPTER 7
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had more than one pair of possible medication–NHP or NHP–NHP interactions.
Although still in the beginning stages, there is a body of evidence on NHP–medication interactions that is rapidly developing. The Canadian Interdisciplinary Network for CAM Research (IN-CAM) is a new research commun- ity established by Dr. Heather Boon, a pharmacist and medical sociologist at the University of Toronto’s Faculty of Pharmacy with an interest in CAM, and Dr. Marja Verhoef, a social scientist and epidemiologist who holds a Canada Research Chair in Complementary Medicine at the University of Calgary’s Department of Community Health Sciences. To address the gaps that exist in the CAM evidence base, IN-CAM’s mission is to “create a sustain- able, well-connected, highly trained Complementary and Alternative Medicine (CAM) research community in Can- ada that is internationally recognized and known for both its excellence in research and its contributions to under- standing CAM and its use” (Canadian Interdisciplinary Network for Complementary & Alternative Medicine Research, 2009). The National Center for Complementary and Alternative Medicine/National Institutes of Health (NCCAM/NIH) and the International Society for Comple- mentary Medicine Research (ISCMR) are other organ- izations involved in generating high-quality research. In Some herbs have been shown to have possible muta-
genic effects and to interact with drugs (see Natural Health Products and Their Possible Drug Interactions). Recent examples of some of the growing concerns with herbal remedies include Health Canada warnings about possible liver toxicity with the use of kava and possible cardiovascular and stroke risks with the use of ephedra. In July 2005, Health Canada warned con- sumers to avoid the use of certain Ayurvedic medicinal products because they contain high levels of heavy metals such as lead, mercury, and arsenic. As a result, of knowing that there are potential risks associated with the use of natural health products, the public atti- tude is beginning to change.
Goldman, Rogovik, Lai, and Vohra (2008) investi- gated the use of NHPs with medications in children arriving at an emergency department of a large chil- dren’s hospital in Canada. The researchers interviewed 1804 families and found that one in five children was administered medications concurrent with NHPs and 15% were receiving more than one NHP simul- taneously. The researchers estimated that 16% of the children had taken a combination of medication and NHP that could result in pharmacodynamic or phar- macokinetic interactions. Eight percent of the cohort
NATURAL HEALTH PRODUCTS AND THEIR POSSIBLE DRUG INTERACTIONS
Natural Health Product Possible Drug Interaction
Chamomile Increased risk for bleeding with anticoagulants
Cranberry Decreased elimination of many drugs excreted by the kidneys
Echinacea Possible interference with or counteraction to immunosuppressant drugs Evening primrose Possible interaction with antipsychotic drugs
Garlic Possible interference with hypoglycemic therapy Alters bleeding time of warfarin
Ginger root At high dosages, possible interference with heart, antidiabetic, or anticoagulant drugs
Grapefruit Increases blood levels of some calcium channel blockers (e.g., felodipine, nimodipine, verapamil), which can result in an increase in the effect and adverse effects of these drugs
Increases blood levels and absorption of some statins (atorvastatin, lovastatin and simvastatin, and ezetimibe/simvastatin)
Decreases metabolism of drugs used for erectile dysfunction
Decreases metabolism of estrogens, some psychotherapeutic drugs (sertraline)
Increases risk of toxicity of immunosuppressants and of some psychotherapeutic drugs (pimozide, escitalopram)
Increases intensity and duration of effects of caffeine Hawthorn May lead to toxic levels of cardiac glycosides (e.g., digitalis) Kava May increase the effect of barbiturates and alcohol
Saw palmetto May change the effects of hormones in oral contraceptive drugs, patches, or hormonal replace- ment therapies
St. John’s wort If other serotonergic drugs are also used (such as selective serotonin reuptake inhibitors), may lead to serotonin syndrome
Valerian Increases central nervous system depression if used with sedatives
Modified from Mertens-Talcott, S. U., Zadezensky, I., De Castro, W. V., Derendorf, H., & Butterweck, V. (2006). Grapefruit–drug interactions: Can interactions with drugs be avoided? Journal of Clinical Pharmacology, 46(12), 1390–1416; Skalli, S., Zaid, A., & Soulaymani, R. (2007). Drug interactions with herbal medicines. Therapeutic Drug Monitoring, 29(6), 679–686; McCloskey, W. W., Zaiken, K., & Couris, R. R. (2008). Clinically significant grapefruit juice–drug interactions. Nutrition Today, 43(1), 19–28.
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PART ONE Pharmacology BasicsCanada maintains a public information Web site, It’s Your Health, to reinforce the safe use of natural health prod- ucts. Specific natural health products are discussed in greater detail in the Natural Health Products boxes that appear in various chapters on specific drugs (see the inside back cover for a complete listing of these special- feature boxes with page numbers).
Medical Use of Marihuana
Marihuana is an herb with a long history of use for its therapeutic and medicinal qualities. In Canada, mari- huana remains an illegal and controlled substance. In 2003, Health Canada implemented the Marihuana Medical Access Regulations to allow access to and possession of marihuana for individuals suffering from specific grave and debilitating illnesses. Marihuana seeds and dried product are made available to those authorized to use marihuana for medicinal purposes from a company under contract to Health Canada. Marihuana is produced for clinical trials to determine the safety and efficacy of marihuana for medical pur- poses. However, in January 2008, a Federal Court judge declared the Marihuana Medical Access Regulations invalid because they limited licensed producers to growing marihuana for only one patient. This was deemed a violation of the charter rights of patients and their ability to rightfully access the drug. In April 2009, Health Canada appealed the ruling but this was denied. See Box 7-4 for discussion of the use of marihuana (also known as cannabis) for medical purposes.
addition, journals such as Evidence-Based Complementary and Alternative Medicine (eCAM) and The Journal of Alterna- tive and Complementary Medicine provide researchers with a peer-reviewed forum in which to publish their findings. It is important that this trend continue, as one of the criti- cisms levelled at CAM is the lack of evidence for efficacy. Health care providers should be aware of literature about the safe and effective use of herbal remedies and reported adverse effects. For some herbal remedies the risk may be less than that for conventional drugs. The discriminate and proper use of some herbal products is safe and may provide some therapeutic benefits, but the indiscriminate or excessive use of herbs can be unsafe and even dangerous. In order to improve the NHP vigi- lance system, several initiatives have been put in place by Health Canada that are available to both consumers and health care providers. The Canada Vigilance Pro- gram maintains an online database of suspected adverse reactions submitted by both consumers and health care providers. The database provides information only. MedEffect e-Notice is a free e-mail service that provides advisories, warnings, and recalls for health products that Canadians use. Also available is the Canadian Adverse Reaction Newsletter, published quarterly, with facts and safety information about marketed health products and reported adverse reactions that are suspected to be asso- ciated with specific health products. To identify and track serious and life-threatening reactions associated with natural health products in children there is a Can- adian pediatric surveillance program. In addition, Health
Cannabis sativa, or cannabis from the hemp plant, is
widely used for recreational purposes. After tobacco, it is the most frequently smoked substance worldwide. Cannabinoids are the psychoactive ingredients of mari- huana, of which 1-Δ9-trans-tetrahydrocannabinol (THC),
concentrated in the bud of the female plant, is the main psychoactive substance. When marihuana is smoked, the effect is almost immediate and lasts for 1 to 3 hours. THC is absorbed by most tissues and organs in the body; however, it is primarily found in fat tissues. The body attempts to eliminate the foreign chemical by chemically transforming THC into metabolites. THC metabolites can be found in the urine for up to 1 week after smoking mari- huana. THC acts on cannabinoid receptors on brain cells and triggers a series of chemical reactions that ultimately lead to the “high” that users experience. Cannabinoid receptors are found in areas of the brain that influence pleasure, memory, thought, concentration, sensory and time perception, and coordinated movement. There is evidence that THC acts on neurotransmitters and exerts either excitatory or inhibitory effects.
While there is sociopolitical concern around the med- ical use of marihuana and the clinical therapeutic potential
for marihuana has not yet been proven in controlled clin- ical trials beyond 6 weeks, there is anecdotal evidence that marihuana may be beneficial in a variety of disorders. In Canada, there are four cannabinoid products available for medical use. Three cannabinoids are available by prescription. One product is Cannabis sativa L. extract (Sativex), a buccal spray, which has been issued marketing authorization on the basis of promising clinical evidence for use as an adjunctive treatment for neuropathic pain in adults with multiple sclerosis and as adjunctive anal- gesic treatment in adult patients with advanced cancer. A synthetic derivative of dronabinol (Marinol) is available in capsules for AIDS-related anorexia associated with weight loss, as well as for severe nausea and vomiting associated with cancer chemotherapy. The third product, nabilone (Cesamet), is a synthetic derivative of THC and is available in capsules for severe nausea and vomiting associated with chemotherapy. The medical use of the herbal form of cannabis for smoking is available through the Medical Marihuana Access Regulations. It is estimated that over 2200 patients are legally authorized to use herbal can- nabis for medical purposes; however, only approximately 20% access the government-endorsed supplier.