- Email: [email protected]
Over-the-Counter Medicines and Diabetes Care
Can J Diabetes 41 (2017) 551–557
Contents lists available at ScienceDirect
Canadian Journal of Diabetes journal homepage: w w w. c a n a d i a n j o u r n a l o f d i a b e t e s . c o m
Practical Diabetes
Over-the-Counter Medicines and Diabetes Care Jeff Taylor BSP, PhD * College of Pharmacy, University of Saskatchewan, Saskatoon, Saskatchewan, Canada
Key Messages
• • •
As agents often used by people with diabetes, health-care providers have devoted a lot of attention assessing the impact overthe-counter medicines have on blood sugar. This article looks at some of the more relevant ones. The evidence seems to suggest most do not alter blood sugar to any significant extent. More deserving of our attention is the safety of nonsteroidal anti-inflammatory drugs (NSAIDs), even at over-the-counter doses, within this group of patients.
a r t i c l e i n f o
a b s t r a c t
Article history: Received 1 May 2017 Received in revised form 28 June 2017 Accepted 28 June 2017
Objectives: People with diabetes turn to over-the-counter (OTC) medicines for many ailments. The focus of this brief review is the impact common OTC medicines might have on this group of patients. Methods: Three types of OTC medicines were selected as most deserving of attention: 3 herbal agents, nonsteroidal anti-inflammatory drugs (NSAIDs) and cough/cold products. Existing literature was used to determine precautions that might be in order. Results: Herbal/natural agents with the potential to impact blood sugar have been identified in various reports. In discussing 3, glucosamine and cinnamon (at doses recommended on commercial products) should have minimal impact on diabetic management, whereas St. John’s wort is a concern involving potential drug interactions. For colds, of about 11 active ingredients, only decongestants (primarily oral) need be considered for their possible effects on blood sugar. Finally, NSAIDs (even at OTC doses) must be used with caution, given their cardiovascular, renal and gastrointestinal risks. Care guidelines do encourage patients to take ownership of their condition. Yet the ability to self-medicate safely is not a certainty. In spite of easy access and a reasonable level of safety, OTC medicines still can negatively impact a user. NSAIDs available without prescription continue to cause concern. Conclusions: Before the use of any medicine, a person must ensure it will be safe. A health-care provider can be asked for assistance, but that option may not always be employed. Package information is there to provide critical information in lieu of that, something the self-medicating patient will, it is hoped, embrace. © 2017 Canadian Diabetes Association.
Keywords: over-the-counter medicines self-medication safety herbals cough and cold medicines OTC NSAIDs
r é s u m é Mots clés : médicaments en vente libre automédication innocuité agents à base de plantes médicaments contre la toux et le rhume MVL AINS
Objectifs : Les personnes diabétiques se tournent vers les médicaments en vente libre (MVL) pour traiter de nombreuses affections. Cette brève étude porte principalement sur les répercussions fréquentes que peuvent avoir les MVL sur ce groupe de patients. Méthodes : Trois types de MVL méritent que l’on s’y attarde plus particulièrement : 3 agents à base de plantes, les anti-inflammatoires non stéroïdiens (AINS) et les produits contre la toux et le rhume. Nous avons consulté la littérature actuelle pour déterminer les précautions à prendre.
* Address for correspondence: Jeff Taylor, BSP, PhD, College of Pharmacy, University of Saskatchewan, 110 Science Place, Saskatoon, Saskatchewan S7N 5C9, Canada. E-mail address: [email protected] 1499-2671 © 2017 Canadian Diabetes Association. The Canadian Diabetes Association is the registered owner of the name Diabetes Canada. https://doi.org/10.1016/j.jcjd.2017.06.015
552
J. Taylor / Can J Diabetes 41 (2017) 551–557
Résultats : Nous avons relevé dans divers rapports des agents à base de plantes et des produits naturels qui peuvent agir sur la glycémie. Nous traitons de questions relatives aux 3 produits suivants : la glucosamine et la cannelle (selon la posologie recommandée sur le produit) devraient avoir des effets minimes sur la prise en charge du diabète, tandis que le millepertuis suscite des inquiétudes en raison de ses possibles interactions médicamenteuses. En ce qui concerne les rhumes, parmi les 11 ingrédients actifs, seuls les décongestionnants (par voie orale principalement) doivent être pris en considération en raison de leurs effets possibles sur la glycémie. Finalement, les AINS (même selon la posologie des MVL) doivent être utilisés avec précaution, étant donné les risques qu’ils posent sur les plans cardiovasculaire, rénal et gastro-intestinal. Les lignes directrices en matière de soins incitent les patients à prendre en charge leur état de santé. Néanmoins, la capacité de recourir de façon sûre à l’automédication n’est pas infaillible. En dépit de leur accessibilité facile et de leur niveau d’innocuité raisonnable, les MVL peuvent tout de même avoir des effets néfastes sur la santé des utilisateurs. Les AINS en vente libre continuent de susciter des inquiétudes. Conclusions : Avant l’utilisation d’un médicament, la personne doit s’assurer de son innocuité. Les utilisateurs peuvent consulter les prestataires de soins de santé pour obtenir de l’aide, mais n’y recourent pas toujours. Les renseignements qui figurent sur l’emballage sont destinés à fournir des informations importantes qui, espérons-le, seront comprises par le patient qui a recours à l’automédication. © 2017 Canadian Diabetes Association.
Introduction Minor ailments are a common part of life. Most of us can likely attest to having had dry skin, a sore back, some heartburn or a few days in the bathroom with stomach flu. For perspective, Canadian adults experienced an estimated 82 million headaches, 85 million colds or flu and 46 million episodes of indigestion during a recent year (1). Over a shorter timeframe (2 weeks), 41.3% of citizens in the United Kingdom complained of feeling tired or rundown, 38.7% had headaches and 31.2% experienced some joint pain (2). The public often turn to over-the-counter (OTC) medicines for such situations. There were approximately 3000 OTC products available in Canada (circa 2012) for this purpose (3), with the majority being sold by pharmacies. This is big business. The self-care product industry generated $5.6 billion in sales in 2014 (4), and a few years earlier, OTC medicines/personal health supplies represented 16% of all drug expenditures in Canada (5). By category, some of the main areas have been analgesics ($530.0 million), vitamins ($356.6 million) cough/cold remedies ($218.8 million), allergy/sinus medications ($171.3 million), upset stomach remedies ($138.8 million), first aid ($110.5 million) and laxatives ($104.8 million) (6). People with diabetes will undoubtedly be users of these products. In Australia, a survey found an average of 1.2 OTCs used within a 2-week period. Approximately 59% had used at least 1 agent and (uncovering some concern), about 41% had used a medicine that was deemed to be unsafe (7). Of 502 Canadians with diabetes, 44% were using OTC agents, and 31% were taking alternative medicines (8). The former figure would undoubtedly have been higher had all common OTCs (such as antihistamines, analgesics and laxatives) been included in the tally; the study focus, instead, was on vitamins and minerals. These subjects spent almost as much on OTCs ($9.98 per month) and alternative medicines ($13.55 per month) as they did on prescribed medications. The focus of this review is the impact common OTC medicines might have on this group of patients.
Relevant Consumer Behaviour In spite of easy access and a reasonable level of safety, OTCs can still impact users negatively (9). Nonsteroidal anti-inflammatory drugs (NSAIDs) available without prescription, in particular, continue to garner a lot of attention (10–13). Before the purchase of an NSAID, or any other medicine for that matter, people must ensure that it will be safe to use. A health-care provider can be asked for assistance, but that may not always be practical or in line with
patients’ perceived needs. Package information is there to provide critical information in lieu of that. In most countries, a medicine that cannot be taken safely and effectively via those directions (either on or in the package) is likely to remain prescription only. Accordingly, much interest has been shown in the readability of such information and the propensity of the public to read it. This includes concerns about literacy and numeracy skills. Industry-based data indicated that 91% of Canadians claimed to read labels carefully before using a product for the first time (14), and they appeared to be satisfied with the information provided (15). A survey of 805 Canadians found that 88% followed the manufacturer’s directions when last using an OTC (16). Among the 5% who were noncompliant with those directions, 31% took a dose larger than directed 19% took another dose sooner than directed, and 11% exceeded the maximum daily dosage. This was usually motivated by symptoms that were serious or a perceived lack of efficacy of the agent. Interestingly, 16% of noncompliers stated they were actually following directions from a health-care professional that had been given to them at a different time. On the other hand, there have also been less positive results. Canadian government data found that 62% of participants stated that they always read labels, 16% often read them, 9% reported sometimes reading them, 6% seldom read them and 7% never read them (17). National consumer surveys in the United States and Canada have suggested that most, at the time of first purchase, do not read the full information provided (18,19). Only 40% of Canadians read about active ingredients when buying a product for the first time, followed by the dosage level (34%), the symptom it treats (26%), the possible side effects (23%), the directions for usage (18%) and the warnings (10%) (19). Concern about the public’s ability to self-medicate is real. In the United States, 334 of 1011 responders indicated they had taken more than the recommended dose of an OTC (20). Of that subset, 69% said this would manifest as taking more than the recommended number of pills at a single time, while 63% reported it could mean taking the next dose sooner than directed. The BeMedWise campaign in Canada found that 13% took 2 products simultaneously to treat the same symptoms (21). At 1 point, half of a sample could not name the active ingredient in the headache medication they used most often (19). In the United States, 66% could not do the same (20), although follow up in 2003 suggested that some improvement had occurred (22). Internet sites for health- and medicine-related information are growing in importance. A keyword search of health in 2005 netted 473 000 000 hits (23). Many in health-care will undoubtedly question the Internet’s value at times, but at least 1 review has suggested that, generally, it has had a positive impact on consumer
J. Taylor / Can J Diabetes 41 (2017) 551–557
health (24). On one front, symptom-checker sites are growing in popularity as a means of self-diagnosis (25). Herbal and natural products Some of the most commonly used herbal and natural products today are multivitamins, vitamin D, omega-3 fatty acids, glucosamine/chondroitin, echinacea, turmeric, probiotics and melatonin. Of the nonvitamins, omega-3s and glucosamine sit near the top in sales. Nearly 6% of Canadians with diabetes, according to 1 report, were taking glucosamine, while about 12% were using garlic (8). Herbal and natural agents with potential for aiding in bloodsugar management have been nicotinamide, ginseng, fenugreek, vitamin D, chromium and cinnamon (26). A review focused solely on spices added ginger, cumin, tumeric, coriander, anise, garlic, onion, cloves, mustards, black pepper and curry leaves to that list (27). During a look at possible future therapeutic entities, a review in Canadian Journal of Diabetes identified 11 entities that had lowered glycated hemoglobin (A1C) levels by 0.5% or more in trials lasting at least 3 months, concluding that they merited further research (28). To focus on a few agents, headlines were made in 2010 regarding the potential effect of glucosamine on diabetes (29). Researchers determined that high (or prolonged) doses of this antiarthritis agent caused the death of pancreatic cells (during in vitro testing) and, thus, could increase the risk for developing diabetes (30). Dosages studied were 5 to 10 times higher than the recommended amount of 1500 mg per day. This amounted to another example in a long list of ongoing research showing that herbals can have negative effects. A review of this agent at about the same time concluded that glucosamine did not have any impact on blood glucose, glucose metabolism or insulin sensitivity either in healthy people or in those with diabetes (31). Cinnamon is often mentioned in lay circles as a way to help attain glycemic control. It obviously comes as the raw spice for food preparation or as capsules from pharmacies and natural food stores. A health-based website concluded that it was unlikely that a person could get enough of the spice during cooking or baking to make a significant difference in blood sugar levels (32). This same website stated that dosages vary from 1 to 2 grams per day, then cited a prominent resource indicating that most people can safely take up to 6 grams per day (for up to 6 weeks) without having major side effects. A review of cinnamon in 2016 concluded that when used by patients taking standard hypoglycemic agents, or in addition to lifestyle modifications, it had only modest effects on fasting blood glucose or A1C levels (33). Canadian guidelines supported that position, stating that the spice has failed to lower A1C levels by 0.5% or more in trials lasting at least 3 months in adults with type 2 diabetes (28). The Xinyan et al review of spices concluded that those they listed are considered to have well-recognized antidiabetic actions, seemingly mediated by stimulation of the pancreas to secrete insulin, alter glucose absorption or induce insulin-sparing activity (27). Most of the research, however, had been done at the level of cell cultures and animal models. Critical to any potential impact during human use, then, will be the dosage. Whether taken as a raw spice or an extract is a factor in determining any impact, as is the preparation technique used in its manufacture. For perspective on studied dosages versus commercial products that are currently available, let’s consider 2 agents. Cinnamon has been assessed at 1 to 6 grams per day, while ginger has been studied at 3 grams per day. At the store level, a Canadian cinnamon product contains 150 mg (of a 20:1 extract derived from 3000 mg of cinnamon bark) per capsule, with the indication “healthy glucose metabolism” prominently displayed on the package (34).
553
At a dosage of 1 or 2 capsules a day, the resultant exposure might be less than the amounts cited above. Conversely, Gravol Natural Source ginger tablets are the equivalent of 500 mg of dried ginger root, with the labelled directions of 2 tablets, 1 to 3 times a day (up to a maximum of 6 tablets a day) (35). Use of the daily maximum of this product would allow this agent to reach that 3 gram level. One of the more efficient ways to check the potential impact of any herbal agent is the Natural Medicines Comprehensive Database. Regarding cinnamon (using Cassia cinnamon as the reference point), this resource concluded that the spice may lower blood glucose levels and/or have an additive effect on other antidiabetic agents (36). On a scale of minor, moderate or major, this drugherbal interaction was ranked as moderate. “Use with caution” was recommended for patients with type 2 diabetes, specifically, and dose adjustments may be warranted. The actual impact on fasting blood glucose was quantified in the monograph (24.6 mg/dL), which was based on a wide range of dosages, from 120 mg to 6 grams daily. For glucosamine sulfate (the more commonly seen salt), the Natural Medicines Comprehensive Database concluded that the agent, used for up to 3 months, is unlikely to affect A1C or blood glucose levels in those with type 2 diabetes; any interactions with antidiabetes agents were described as minor (37). A third herbal agent one should consider during medication assessment is St. John’s wort. It is used primarily for depression and is described as being well tolerated (perhaps more so than tricyclic antidepressants) by users, although neuropathy has been reported (38). The significant downside of this agent is a propensity to interact extensively with other medicines. CYP2C9 substrates (glipizide) are mentioned, as is gliclazide, with both rated as having moderate interactions. The net result in both cases would be that blood sugar-lowering effects may be reduced, with a conclusion to not use this particular antidepressant.
Coughs and colds Adults experience about 1 to 3 colds per year (39). The Canadian Medical Association Journal cited data showing that 7% to 17% of adults and 33% of children see physicians because of upper respiratory tract infections (39). Although generally described as mild, such infections make life rather miserable for about a week. Patients with diabetes will be trained to shift into sick-day management. The first cold symptom is usually throat discomfort. Various degrees of nasal congestion and rhinorrhea follow. Nasal discharge is at first clear and watery, becoming more tenacious as the infection progresses. Breathing through the nose eventually becomes difficult. This congestion may lead to sinus headaches and perhaps a muffled sensation with regard to hearing. Postnasal drip can further irritate a throat. Significant fever is seldom evident, but chill sensations are common. Colds rarely cause serious consequences. If a cough occurs, it usually starts as dry and unproductive, becoming productive as the cold progresses (bronchial secretions and cellular debris increase). With the appearance of coughing, it is then deemed a chest cold, and that may be more concerning than a simple head cold. The typical causes of coughs at the primary care level are depicted in Figure 1 (40,41). Coughing tends to be 1 of the more persistent symptoms (42). On average, a cough lasts about 18 days, but sufferers tend to think it should be finished in 1 week (43). This mismatch of expectations and reality can lead to inappropriate use of antibiotics. The common cold differs from influenza by being far milder, having no sudden onset of a spiking fever, less severe coughing and an absence of substantial body aches and pains (44). Generally, a cold simply runs its course, in spite of efforts to combat it. There is no cure, but general measures can provide some
554
J. Taylor / Can J Diabetes 41 (2017) 551–557
Figure 1. Distribution of causes of acute cough in adults found in typical general practice. COPD, chronic obstructive pulmonary disease. Note: Used with permission from Canadian Family Physician.
comfort. Getting some rest and fluids, such as orange juice, are often tried (45). The public continues to turn to OTC medicines for some semblance of relief, although large reviews have not shown the benefit (especially for pediatric use) of these products (46–48). About 100 different entities can be found in larger pharmacies. The actual number of active agents within them, however, is quite small. About 11 chemicals make up the vast majority of active ingredients across those 100 products: analgesics (acetaminophen, ibuprofen); nasal decongestants (phenylephrine, pseudoephedrine, oxymetazoline, xylometazoline); cough suppressants (diphenhydramine, dextromethorphan); an expectorant (guaifenesin); and antihistamines (diphenhydramine, chlorpheniramine). Combinations are common. Of these ingredients, only decongestants need be considered for their possible effects on blood sugar levels; the other products do not alter them. A health-care professional would have to consider only whether the calories in a liquid or lozenge formulation might be an issue (which generally is not the case). The alcohol content of modern syrups is very low. Nasal decongestants fall into 2 camps: oral and topical. Topical entities, such as xylometazoline and oxymetazoline, act faster than oral agents. If they are not washed away by nasal secretions, they will relieve congestion for up to 10 and 12 hours, respectively. They are available only as single-agent products. The incidence of adverse effects is low, given that absorption from the application site tends to be minimal. Generally, labelled warnings applicable to oral decongestants (see below) do not apply to topically applied entities. Thus, they have a high safety factor in diabetes and should not influence blood sugar. Their overuse, however, can produce a rebound effect, wherein the drug originally used to combat the congestion is now itself responsible for continued congestion. Periods of use shorter than 7 days will avoid that issue, although some authors have questioned whether rebound congestion occurs at all (49). Oral agents share many of the same structure-activity properties as amphetamines and, by extension, a similar (but milder) side-effect profile. Aside from relieving some of the congestion, oral agents possess the negative potential for cardiovascular effects, blood sugar changes, prostatic hypertrophy, drug interactions and
CNS effects (especially in the elderly). It is probably prudent to avoid oral decongestant use by people with diabetes and hypertension. The stimuli that control blood sugar are complex, but such sympathomimetic agents tend to increase glucose levels. This effect is far more pronounced with something like epinephrine than with oral decongestants, but precautions should still be considered for people with type 1 diabetes. Practically speaking, their use should amount to only about 3 or 4 days of exposure, for which the cold itself will increase blood sugar to a greater extent than any drug. Of the oral agents, phenylephrine (PE) was minimally used commercially until, that is, pseudoephedrine (PSE) started being diverted for clandestine use in crystal meth labs. At that point, more manufacturers turned to PE. This is unfortunate because PE is a less reliable agent than PSE in terms of bioavailability (50). Coughs have been typically described as dry or wet, although some authors have questioned this designation (51). Accordingly, patients with coughs depicted as dry but congested are commonly given an expectorant to help loosen them up. Coughs that are already productive need not be suppressed, unless some relief is needed in the short term. Either way, doubt continues to be cast on whether any benefit is seen from their use (47). The syrup base of any product might be something to consider. To use Robitussin products just as an example, the caloric content of some of their common syrups can range from 1.2 and 3.0 kcal up to 11.7 kcal per 5 mL. Even at this higher level, the impact of 4 times a day dosing on caloric intake would be minimal. Regarding another of their products, Robitussin Cough Control for People with Diabetes uses sorbitol and sucralose in its formulation, resulting in 23 kcal per 15 mL. At a maximum of 4 doses per day, this would lead to a 92 kcal spread over a 24-hour period for about 7 days. Obviously, there is no guarantee of that timeline, given that coughs often last longer. More important than its caloric load (in the opinion of the author) is that it contains a cough suppressant and an expectorant. First, will that be useful for a patients’ symptoms, given the evidence? Is the combination rational? Another issue is whether there is a possibility that some people with diabetes will choose this product for all their upper respiratory tract infections, based on a sense of security in seeing mention of diabetes on the label. While being safe in terms of blood sugar, as noted in its name, it is designed only for coughs. An impact of a Health Canada ruling on cough/cold product use in children younger than 6 years of age was parents’ shifting to “safer” products. This led to a rise in homeopathic products and honey. A Cochrane review concluded there was no strong evidence for or against the use of honey for coughs (52). An article in Canadian Family Physician went a bit further, stating that honey can be recommended at a “dose” of 2.5 mL before bedtime for coughing children older than 1 year of age (53). A teaspoon of honey has 22 kcal (versus 16 kcal found in 1 teaspoon of table sugar) (54). To tap into the interest shown in honey, several cough syrups also mention honey on the package. But they would not be formulations in the same vein as pure honey. Rather, the honey is likely to be just 1 of the ingredients in a syrup base. As another formulation example, there are sugar-free lozenges on the market, several of them low in calories. NSAIDs OTC versions of ibuprofen (up to 1200 mg) and naproxen (up to 400 mg base) are lower in daily dosage than their prescription counterparts, with labelled directions calling for shorter periods of use if medical care is not in place. Reviews, thus, tend to indicate a lower incidence of side effects at so-called OTC levels of use (55–59). Be that as it may, the cardiovascular, renal and gastrointestinal risks of NSAIDs are well known and can be significant (60). These
J. Taylor / Can J Diabetes 41 (2017) 551–557
issues have to be considered with serious conviction prior to use in persons with diabetes (who are at greater risk). American Family Physician calls for the avoidance of NSAIDs in patients with hypertension, heart failure or chronic kidney disease of all causes, including diabetes (61). Canadian guidelines state that during sick-day management, NSAIDs can further reduce renal blood flow, and patients should withhold use if they feel they are becoming dehydrated (62). Further, it is not just greater duration of use that is of concern; even short-term use has implications (63–65). A look at how pervasive their use is, and the extent to which liberties might be taken, could be helpful in this discussion. Analgesic use has been described as extremely high among American adults (66). An estimated 147 million adults used them monthly. Prescription analgesic use was determined to be 9%, while OTC use was 76%. Approximately 30% used multiple agents over a 1-month period. Another report found that acetaminophen was used 1 day a week or more often by more than 20% of American women, and 42% report similar usage of NSAIDs (67). Based on concerns from many sources, the United States Food and Drug Administration engaged in a campaign to promote safe use of OTC analgesics, stressing the importance of following label directions carefully (68). Other experts have even called for a reassessment of the OTC status of such agents (69,70). In Canada, appropriate use of acetaminophen is being promoted by a campaign (71). A survey found that 37% of citizens admitted to taking more than the recommended amount of OTC pain killers, either by taking the next dose sooner than directed on the label, by taking more pills at a single time than recommended or by exceeding the daily dosage (72). Although most said they read the label (during first-time use) to see how many pills to take and how often (91%), which symptoms the agent would treat (85%) and possible side effects (77%), some (27%) did not read warnings about use with other OTCs or determine the active ingredient (48%). Approximately 29% said they did not worry about how long or how often they take an agent, as long as it manages their pain, and 12% noted that they sometimes add an OTC pain killer to a prescriptive agent, believing they would get more pain relief without increasing the potential for side effects. Just over 4 in 10 (41%) were not very or not at all concerned about potential side effects. This apparent lack of concern for side effects has been seen elsewhere. Two surveys constituting a total of 9062 respondents were carried out on a national sample of Americans regarding OTC NSAID use (73). In the first survey, exclusive OTC users were neither aware of (60%), nor believed they were at risk for (29%), side effects from NSAIDs, while 22% believed warning symptoms would always precede any NSAID-induced complication. In the second survey, 49% were not concerned about potential side effects, and 30% believed there was less risk with OTC analgesics than with their prescription counterparts. It was concluded that OTC NSAIDs are widely used and are frequently taken inappropriately, with potentially dangerous results. In a survey from Finland, 44% had used analgesics (OTC or prescribed) within the previous week. Users reported doctors (35%), information leaflets (33%) and pharmacists (33%) as the most common sources for information. In spite of that, it was concluded analgesic users do not receive much information from healthcare providers, which may put self-medicators at risk (74). Along the same lines, another Scandinavian report revealed substantial regular use of analgesics in several situations of contraindications, including 8% in patients with chronic kidney disease (75). About 4% demonstrated at least 1 potential drug interaction. OTC analgesic use in 1500 Scottish subjects was assessed (11). More than 500 had used an agent in the previous 2 weeks. Potential inappropriate use was identified in 115 (n=21%) of the OTC analgesic users, including use of multiple analgesics (n=67), use in
555
conditions in which caution applied (n=51), and potential drugdrug interactions (n=15). The authors concluded there is a high level of OTC analgesic use by the general public and significant potential for inappropriate use. Dozens of similar reports exists. To provide a degree of balance, not all the evidence points to dangerous use. In 1 study, community pharmacists in the United Kingdom recruited users and purchasers of ibuprofen. Most participants had not sought medical advice for their symptoms or asked questions during the purchase. A small proportion of participants reported ingesting higherthan-recommended doses (>1200 mg) or prolonged use (>20 weeks), but no symptoms of potentially serious adverse events were reported (although that may have been due to the small numbers). It was concluded that greater vigilance was required for adverse events potentially related to ibuprofen use, but overall, it appeared to be used safely and effectively (76). In Norway, participants were recruited from consumers presenting at 62 community pharmacies after purchasing low-dose OTC diclofenac. The directions were followed with regard to recommended indications, contraindications and maximum dosage but less so with respect to recommended duration of use and concurrent medications. Overall, the use of the agent was described as efficacious, safe and commonly used in accordance with directions for use (77). In another, Canadians with a different chronic condition, arthritis, were surveyed. Their key information sources were doctors, followed by the Internet and friends or family, then pharmacists. When they had experienced their most recent flare-ups, 46% had turned to an OTC medicine for relief, about 16% arranged to see a doctor, while 6% consulted a pharmacist. Of the respondents, 70% felt confident in managing and treating minor ailments themselves, yet many felt it was also important to speak to a healthcare provider before taking an OTC medicine (59%) or a natural health product (54%) for the first time (78).
Conclusions Three main areas of OTC medicines were the focus of this study; they were selected as being deserving of the most attention by practitioners. It is this author’s opinion that although use of herbal and natural products should, indeed, be considered by health-care providers during medication assessments, the actual effects they will have on other medicines, or on the course of diabetic illness, should be minimal if used according to package instructions. Instead, more in need of our attention is whether a herbal entity will actually help what it is being used for (e.g. salmon oil for cardioprotection, melatonin for insomnia, ginger for motion sickness, saw palmetto for prostate enlargement and so on). Advice on this front could likely save people money and some frustration, even though many consumers will swear by the agents they use. As part of that assessment, consideration should also be given to whether medical care is being delayed as a result of such use. Input into these 2 issues could produce bigger dividends than a singular focus on blood sugar changes. The exception to this suggestion, however, might be St. John’s wort, for which the potential for drug interactions is so extensive that use should probably be avoided. Contingent with this opinion is that any herbal dose is not extreme, for it is likely that as ingested amounts rise, an agent will move from being a simple spice or herbal remedy on through functional food status and up to eventually having potential for adverse drug reactions. From the perspective of cough and cold products, oral decongestants are the only concern regarding blood glucose levels. It is this author’s opinion that their impact on type 1 diabetes would
556
J. Taylor / Can J Diabetes 41 (2017) 551–557
be minimal and would be even less so for type 2 diabetes. In a rather scathing report on the safety of such agents (primarily cardiovascular) and concern for their widespread availability, specialists did not even mention blood sugar change as a danger with their use (79). Tablet and caplet forms of these agents have negligible caloric content. Of syrups, many are sweetened with sucrose, but the caloric load is low. Alcohol content is of almost no consequence for the vast majority of products. OTC NSAIDs can be effective for pain (so common in our seniors), are widely used and are easily accessible by the public. Considering all these dynamics, it may prove difficult to reduce their use, although efforts must continue on this front. A key point is that selfmedication is possible, and that is unlikely to change in the foreseeable future. Care guidelines, in fact, encourage patients to take ownership of their conditions and participate in self-monitoring and decision making (80). Unfortunately, in the case of diabetes and OTC NSAID use (or potentially any high-risk group, for that matter), a degree of disconnect is evident. OTC NSAIDs are commonly taken without the knowledge of prescribers (81). A tenet of self-care and self-medication is that in lieu of getting advice, the users must themselves undertake the reading about and research into the medication they intend to use. To the extent that that goal is not met, any opportunity for self-medicating patients to let their physicians know what they are taking and how they are taking it would, at least, enable monitoring to take place. Pharmacists can also monitor and convey any risks to users. For patients who choose not to put in the effort, less emphasis on the self in self-medication might prove prudent.
18.
19. 20.
21. 22.
23. 24. 25. 26. 27. 28. 29. 30.
31.
32. 33.
References 1. Willemsen KR, Harrington G. From patient to resource: The role of self-care in patient-centered care of minor ailments. Self Care 2012;3:43–55. 2. McAteer A, Elliott AM, Hannaford PC. Ascertaining the size of the symptom iceberg in a UK-wide community-based survey. Br J Gen Pract 2011;61:e22–30. 3. Harrington G. Director of Public Affairs, Consumer Health Products Canada. Personal communication. September 11, 2012. 4. Macdonald A, Stewart M. Healthy growth: Estimating the economic footprint of the fast-growing consumer health products industry. 2015. http://www .chpcanada.ca/sites/default/files/healthy_growth_final_report.pdf. Accessed June 27, 2016. 5. Canadian Institute for Health Information. Drug expenditure: Prescribed and non-prescribed drugs. Outlook:2010 and 2011. In: Drug expenditure in Canada, 1985 to 2011. Ottawa: CIHI, 2011. 6. Wood V. 2011 OTC market report: Non-prescription sales hold steady. Drugstore Can 2011;4:13–21. 7. Gattera JA, Stewart K, Benrimoj SI, Williams GM. Usage of nonprescription medication by people with diabetes. J Soc Admin Pharm 1992;9:66–74. 8. Ryan EA, Pick ME, Marceau C. Use of alternative medicines in diabetes mellitus. Diabet Med 2001;18:242–5. 9. Schmiedl S, Rottenkolber M, Hasford J, et al. Self-medication with over-thecounter and prescribed drugs causing adverse-drug-reaction-related hospital admissions: Results of a prospective, long-term multi-center study. Drug Saf 2014;37:225–35. 10. Ipsos Reid. Many Canadians take risks with OTC pain medications. Toronto: Ipsos Reid, 2006. 11. Porteous T, Bond C, Hannaford P, Sinclair H. How and why are non-prescription analgesics used in Scotland? Fam Pract 2005;22:78–85. 12. Castelli G, Petrone A, Xiang J, et al. Rates of nonsteroidal anti-inflammatory drug use in patients with established cardiovascular disease: A retrospective, crosssectional study from NHANES 2009–2010. Am J Cardiovasc Drugs 2017;17:243– 9. 13. Lawson B, Putnam W, Nicol K, et al. Managing osteoarthritis: Medication use among seniors in the community. Can Fam Physician 2004;50:1664–70. 14. Canadian Facts. Consumer usage and attitude study, vol. I. Toronto: Canadian Facts, 1991. 15. Consumer Health Products Canada. HealthVision 1999/2000. Ottawa: Nonprescription Drug Manufacturers Association of Canada, www.chpcanada.ca. Accessed December 2, 2009. 16. Responsible use of nonprescription medications in Canada: A research report to Nonprescription Drug Manufacturers Association of Canada. Ottawa, Ontario, Canada: Martin Redfern, 2007. 17. Attitudes, perceptions and behaviour relating to ethical medicines: A research report to the Department of National Health and Welfare. Ottawa, Ontario,
34. 35. 36. 37. 38. 39. 40. 41.
42.
43.
44.
45.
46. 47.
48. 49.
50.
51. 52.
Canada: Decima Research, 1990 http://dsp-psd.pwgsc.gc.ca/Collection/H42-243-1990E.pdf. Accessed December 2, 2009. Harris Interactive, National Council on Patient Information and Education. Attitudes and beliefs about the use of over-the-counter medicines: A dose of reality: A national survey of consumers and health professionals. 2002 www.bemedwise .org/survey/final_survey.pdf. Accessed December 1, 2009. OTC habits and practices: BeMedWise survey. Toronto: Drug Information and Research Centre (DIRC), 2002. National Council on Patient Information and Education. Attitudes and beliefs about the use of over-the-counter medicines: A dose of reality: A national survey of consumers and health professionals. Harris Interactive, January, 2002. Drug Information and Research Centre. Survey on Canadians’ use of OTC medications: The BeMedWise survey 2004. Toronto, Ontario: 2004. National Council on Patient Information and Education. Uses and attitudes about taking over-the-counter medicines: Findings of a 2003 national opinion survey. Harris Interactive. 2003. Ybarra ML, Suman M. Help-seeking behavior and the Internet: A national survey. Int J Med Inform 2006;75:29–41. Renahy E, Chauvin P. Internet uses for health information seeking: A literature review. Rev Epidemiol Sante Publique 2006;54:263–75. Semigran HL, Linder JA, Gidengil C, Mehrotra A. Evaluation of symptom checkers for self-diagnosis and triage: Auditstudy. BMJ 2015;351:h3480. Yilmaz Z, Piracha F, Anderson L, Mazzola N. Supplements for diabetes mellitus: A review of the literature. J Pharm Pract 2016;1–8. Xinyan B, Joseph L, Christiani Jeyakumar H. Spices in the management of diabetes mellitus. Food Chem 2017;217:281–93. Clinical Practice Guidelines. Natural health products. Can J Diabetes 2013;37:S97–9. Université Laval. Too much glucosamine can cause the death of pancreatic cells, increase diabetes risk, researchers find. Science Daily, October 27, 2010. Lafontaine-Lacasse M, Dore G, Picard F. Hexosoamines stimulate apoptosis by altering Sirt1 action and levels in rodent pancreatic β-cells. J Endocrinol 2011;208:41–9. Simon RR, Marks V, Leeds AR, Anderson JW. A comprehensive review of oral glucosamine use and effects on glucose metabolism in normal and diabetic individuals. Diabetes Metab Res Rev 2011;27:14–27. Can cinammon ease diabetes symptoms? www.healthline.com/health/cancinammon-ease-diabetes-symptoms. Accessed April 17, 2017. Costello RB, Dwyer JT, Saldanha L, et al. Do cinnamon supplements have a role in glycemic control in type 2 diabetes? A narrative review. J Acad Nutr Diet 2016;116:1794–802. Webber Naturals. www.webbernaturals.com. Accessed April 17, 2017. Gravol Natural Source ginger tablets. www.gravol.ca. Accessed April 18, 2017. Natural Medicines Comprehensive Database. Cassia cinnamon. www.naturaldatabase.therapeuticresearch.com. Accessed April 24, 2017. Natural Medicines Comprehensive Database. Glucosamine sulfate. www.naturaldatabase.therapeuticresearch.com. Accessed April 24, 2017. Natural Medicines Comprehensive Database. St. John’s wort. www.naturaldatabase .therapeuticresearch.com. Accessed April 24, 2017. Allan GM, Arroll B. Prevention and treatment of the common cold: Making sense of the evidence. Can Med Assoc J 2014;186:190–9. Worrall G. Acute coughs in adults. Can Fam Physician 2011;57:48–51. McCormick A, Fleming D, Charlton C. Morbidity statistics from general practice: Fourth national morbidity survey, 1991–92. London: HMSO, Office for National Statistics, 1995. Eccles R, Dicpinigaitis P, Turner RB, et al. Characterization of urge to cough and cough symptoms associated with the common cold: Results of a US internet study. Postgrad Med 2016;128:485–91. Ebell MH, Lundgren J, Youngpairoj S. How long does a cough last? Comparing patients’ expectations with data from a systematic review of the literature. Ann Fam Med 2013;11:5–13. Thirion DJG. Assessment of patients with upper respiratory tract symptoms. In: Jovaisas B, ed. Compendium of therapeutics for minor ailments. Ottawa: Canadian Pharmacists Association, 2016, pg. 245–9. Thielmann A, Gerasimovska-Kitanovska B, Buczkowski K, et al. Self-care for common colds by primary care patients: A European multicenter survey on the prevalence and patterns of practices: The COCO study. Evid Based Complement Alternat Med 2016;2016:6949202. Deckx L, De Sutter AI, Guo L, et al. Nasal decongestants in monotherapy for the common cold. Cochrane Database Syst Rev 2016;(10):CD009612. Smith SM, Schroeder K, Fahey T. Over-the-counter (OTC) medications for acute cough in children and adults in community settings. Cochrane Database Syst Rev 2014;(11):CD001831. Yang M, So T-Y. Revisiting the safety of over-the-counter cough and cold medications in the pediatric population. Clin Pediatr (Phila) 2014;53:326–30. Mortuaire G, de Gabory L, François M, et al. Rebound congestion and rhinitis medicamentosa: Nasal decongestants in clinical practice: Critical review of the literature by a medical panel. Eur Ann Otorhinolaryngol Head Neck Dis 2013;130:137–44. Eccles R. Substitution of phenylephrine for pseudoephedrine as a nasal decongestant: An illogical way to control methamphetamine abuse. Br J Clin Pharmacol 2006;63:10–14. Morice AH, Kantar A, Dicpinigaitis PV, et al. Treating acute cough, wet versus dry: Have we got the paradigm wrong? ERS Open Res 2015;1:00055-2015. Oduwole O, Meremikwu MM, Oyo-Ita A, Udoh EE. Honey for acute cough in children. Cochrane Database Syst Rev 2014;(12):CD007094.
J. Taylor / Can J Diabetes 41 (2017) 551–557
53. Goldman RD. Honey for treatment of cough in children. Can Fam Physician 2014;60:1107–11. 54. Amount of calorie in honey. www.benefits-of-honey.com. Accessed April 18, 2017. 55. Bjarnason I. Gastrointestinal safety of NSAIDs and over-the-counter analgesics. Int J Clin Pract 2013;178(Suppl.):37–42. 56. Moore N, Salvo F, Duong M, et al. Cardiovascular risks associated with lowdose ibuprofen and diclofenac as used OTC. Expert Opin Drug Saf 2014;13:167– 79. 57. Angiolillo DJ, Weisman SM. Clinical pharmacology and cardiovascular safety of naproxen. Am J Cardiovasc Drugs 2017;17:97–107. 58. Moore RA. Analgesic safety: Myths, mysteries and misconceptions. Int J Clin Pract 2015;69(Suppl. 182):24–7. 59. Moore N, Pollack C, Butkerait P. Adverse drug reactions and drug-drug interactions with over-the-counter NSAIDs. Ther Clin Risk Manag 2015;11:1061– 75. 60. Davis A, Robson J. The dangers of NSAIDs: Look both ways. Br J Gen Pract 2016;66:172–3. 61. Choosing wisely. www.aafp.org. Accessed April 27, 2017. 62. McFarlane P, Gilbert RE, MacCallum L, et al. Clinical practice guidelines: Chronic kidney disease in diabetes. Can J Diabetes 2013;37(Suppl. 1):S129–36. 63. Lapi F, Azoulay L, Yin H, et al. Concurrent use of diuretics, angiotensin converting enzyme inhibitors, and angiotensin receptor blockers with non-steroidal antiinflammatory drugs and risk of acute kidney injury: Nested case-control study. BMJ 2013;346:e8525. 64. Schjerning Olsen AM, Fosbøl EL, Lindhardsen J, et al. Duration of treatment with nonsteroidal anti-inflammatory drugs and impact on risk of death and recurrent myocardial infarction in patients with prior myocardial infarction: A nationwide cohort study. Circulation 2011;123:2226–35. 65. Schjerning Olsen AM, Gislason GH, McGettigan P, et al. Association of NSAID use with risk of bleeding and cardiovascular events in patients receiving antithrombotic therapy after myocardial infarction. JAMA 2015;313:805– 14. 66. Paulose-Ram R, Hirsch R, Dillon C, et al. Prescription and non-prescription analgesic use among the US adult population: Results from the third National Health and Nutrition Examination Survey (NHANES III). Pharmacoepidemiol Drug Saf 2003;12:315–26. 67. Curhan GC, Bullock AJ, Hankinson SE, et al. Frequency of use of acetaminophen, nonsteroidal anti-inflammatory drugs, and aspirin in US women. Pharmacoepidemiol Drug Saf 2002;11:687–93.
557
68. Anonymous. FDA launches campaign on OTC pain relief products. FDA Consum 2004;38:8. 69. Fosbøl EL, Køber L, Torp-Pedersen C, Gislason GH. Cardiovascular safety of nonsteroidal anti-inflammatory drugs among healthy individuals. Expert Opin Drug Saf 2010;9:893–903. 70. Tielemans MM, van Rossum LG, Focks JJ, et al. Gastrointestinal symptoms are increased in both prescribed and over-the-counter NSAID users compared to non users in the community. In: Digest Disease Week 2012; San Diego, CA, May 2012. 2012. 71. Spotlight on acetaminophen. https://safemedicationuse.ca/tools_resources/ tips_acetaminophen.html. Accessed April 21, 2017. 72. Ipsos Reid. Many Canadians take risks with OTC pain medications. Toronto: Ipsos Reid, 2006. 73. Wilcox CM, Cryer B, Triadafilopoulos G. Patterns of use and public perception of over-the-counter pain relievers: Focus on nonsteroidal antiinflammatory drugs. J Rheumatol 2005;32:2218–24. 74. Närhi U, Helakorpi S. Analgesic users’ sources of medicine information. Int J Pharm Pract 2007;15:251–3. 75. Samuelsen PJ, Slordal L, Mathisen UD, Eggen AE. Analgesic use in a Norwegian general population: Change over time and high-risk use: The Tromso Study. BMC Pharmacol Toxicol 2015;16:16. 76. Layton D, Sinclair HK, Bond CM, et al. Pharmacovigilance of over-the-counter products based in community pharmacy: Methodological issues from pilot work conducted in Hampshire and Grampian, UK. Pharmacoepidemiol Drug Saf 2002;11:503–13. 77. Hasford J, Moore N, Hoye K. Safety and usage pattern of low-dose diclofenac when used as an over-the-counter medication: Results of an observational cohort study in a community-based pharmacy setting. Int J Clin Pharmacol Ther 2004;42:415–22. 78. Arthritis: Consumer behaviour and attitudes. Consumer Health Products Canada, Redfern Research, August 2011. 79. Laccourreye O, Werner A, Giroud J-P, et al. Benefits, limits and danger of ephedrine and pseudoephedrine as nasal decongestants. Eur Ann Otorhinolaryngol Head Neck Dis 2015;132:31–4. 80. Canadian Diabetes Association Clinical Practice Guidelines Expert Committee, Jones H, Berard LD, et al. Clinical Practice Guidelines: Self-Management Education. Can J Diabetes 2013;37(Suppl. 1):S26–30. 81. Hamilton K, Davis C, Falk J, et al. High risk use of OTC NSAIDs and ASA in family medicine: A retrospective chart review. Int J Risk Saf Med 2015;27:191–9.
Contents lists available at ScienceDirect
Canadian Journal of Diabetes journal homepage: w w w. c a n a d i a n j o u r n a l o f d i a b e t e s . c o m
Practical Diabetes
Over-the-Counter Medicines and Diabetes Care Jeff Taylor BSP, PhD * College of Pharmacy, University of Saskatchewan, Saskatoon, Saskatchewan, Canada
Key Messages
• • •
As agents often used by people with diabetes, health-care providers have devoted a lot of attention assessing the impact overthe-counter medicines have on blood sugar. This article looks at some of the more relevant ones. The evidence seems to suggest most do not alter blood sugar to any significant extent. More deserving of our attention is the safety of nonsteroidal anti-inflammatory drugs (NSAIDs), even at over-the-counter doses, within this group of patients.
a r t i c l e i n f o
a b s t r a c t
Article history: Received 1 May 2017 Received in revised form 28 June 2017 Accepted 28 June 2017
Objectives: People with diabetes turn to over-the-counter (OTC) medicines for many ailments. The focus of this brief review is the impact common OTC medicines might have on this group of patients. Methods: Three types of OTC medicines were selected as most deserving of attention: 3 herbal agents, nonsteroidal anti-inflammatory drugs (NSAIDs) and cough/cold products. Existing literature was used to determine precautions that might be in order. Results: Herbal/natural agents with the potential to impact blood sugar have been identified in various reports. In discussing 3, glucosamine and cinnamon (at doses recommended on commercial products) should have minimal impact on diabetic management, whereas St. John’s wort is a concern involving potential drug interactions. For colds, of about 11 active ingredients, only decongestants (primarily oral) need be considered for their possible effects on blood sugar. Finally, NSAIDs (even at OTC doses) must be used with caution, given their cardiovascular, renal and gastrointestinal risks. Care guidelines do encourage patients to take ownership of their condition. Yet the ability to self-medicate safely is not a certainty. In spite of easy access and a reasonable level of safety, OTC medicines still can negatively impact a user. NSAIDs available without prescription continue to cause concern. Conclusions: Before the use of any medicine, a person must ensure it will be safe. A health-care provider can be asked for assistance, but that option may not always be employed. Package information is there to provide critical information in lieu of that, something the self-medicating patient will, it is hoped, embrace. © 2017 Canadian Diabetes Association.
Keywords: over-the-counter medicines self-medication safety herbals cough and cold medicines OTC NSAIDs
r é s u m é Mots clés : médicaments en vente libre automédication innocuité agents à base de plantes médicaments contre la toux et le rhume MVL AINS
Objectifs : Les personnes diabétiques se tournent vers les médicaments en vente libre (MVL) pour traiter de nombreuses affections. Cette brève étude porte principalement sur les répercussions fréquentes que peuvent avoir les MVL sur ce groupe de patients. Méthodes : Trois types de MVL méritent que l’on s’y attarde plus particulièrement : 3 agents à base de plantes, les anti-inflammatoires non stéroïdiens (AINS) et les produits contre la toux et le rhume. Nous avons consulté la littérature actuelle pour déterminer les précautions à prendre.
* Address for correspondence: Jeff Taylor, BSP, PhD, College of Pharmacy, University of Saskatchewan, 110 Science Place, Saskatoon, Saskatchewan S7N 5C9, Canada. E-mail address: [email protected] 1499-2671 © 2017 Canadian Diabetes Association. The Canadian Diabetes Association is the registered owner of the name Diabetes Canada. https://doi.org/10.1016/j.jcjd.2017.06.015
552
J. Taylor / Can J Diabetes 41 (2017) 551–557
Résultats : Nous avons relevé dans divers rapports des agents à base de plantes et des produits naturels qui peuvent agir sur la glycémie. Nous traitons de questions relatives aux 3 produits suivants : la glucosamine et la cannelle (selon la posologie recommandée sur le produit) devraient avoir des effets minimes sur la prise en charge du diabète, tandis que le millepertuis suscite des inquiétudes en raison de ses possibles interactions médicamenteuses. En ce qui concerne les rhumes, parmi les 11 ingrédients actifs, seuls les décongestionnants (par voie orale principalement) doivent être pris en considération en raison de leurs effets possibles sur la glycémie. Finalement, les AINS (même selon la posologie des MVL) doivent être utilisés avec précaution, étant donné les risques qu’ils posent sur les plans cardiovasculaire, rénal et gastro-intestinal. Les lignes directrices en matière de soins incitent les patients à prendre en charge leur état de santé. Néanmoins, la capacité de recourir de façon sûre à l’automédication n’est pas infaillible. En dépit de leur accessibilité facile et de leur niveau d’innocuité raisonnable, les MVL peuvent tout de même avoir des effets néfastes sur la santé des utilisateurs. Les AINS en vente libre continuent de susciter des inquiétudes. Conclusions : Avant l’utilisation d’un médicament, la personne doit s’assurer de son innocuité. Les utilisateurs peuvent consulter les prestataires de soins de santé pour obtenir de l’aide, mais n’y recourent pas toujours. Les renseignements qui figurent sur l’emballage sont destinés à fournir des informations importantes qui, espérons-le, seront comprises par le patient qui a recours à l’automédication. © 2017 Canadian Diabetes Association.
Introduction Minor ailments are a common part of life. Most of us can likely attest to having had dry skin, a sore back, some heartburn or a few days in the bathroom with stomach flu. For perspective, Canadian adults experienced an estimated 82 million headaches, 85 million colds or flu and 46 million episodes of indigestion during a recent year (1). Over a shorter timeframe (2 weeks), 41.3% of citizens in the United Kingdom complained of feeling tired or rundown, 38.7% had headaches and 31.2% experienced some joint pain (2). The public often turn to over-the-counter (OTC) medicines for such situations. There were approximately 3000 OTC products available in Canada (circa 2012) for this purpose (3), with the majority being sold by pharmacies. This is big business. The self-care product industry generated $5.6 billion in sales in 2014 (4), and a few years earlier, OTC medicines/personal health supplies represented 16% of all drug expenditures in Canada (5). By category, some of the main areas have been analgesics ($530.0 million), vitamins ($356.6 million) cough/cold remedies ($218.8 million), allergy/sinus medications ($171.3 million), upset stomach remedies ($138.8 million), first aid ($110.5 million) and laxatives ($104.8 million) (6). People with diabetes will undoubtedly be users of these products. In Australia, a survey found an average of 1.2 OTCs used within a 2-week period. Approximately 59% had used at least 1 agent and (uncovering some concern), about 41% had used a medicine that was deemed to be unsafe (7). Of 502 Canadians with diabetes, 44% were using OTC agents, and 31% were taking alternative medicines (8). The former figure would undoubtedly have been higher had all common OTCs (such as antihistamines, analgesics and laxatives) been included in the tally; the study focus, instead, was on vitamins and minerals. These subjects spent almost as much on OTCs ($9.98 per month) and alternative medicines ($13.55 per month) as they did on prescribed medications. The focus of this review is the impact common OTC medicines might have on this group of patients.
Relevant Consumer Behaviour In spite of easy access and a reasonable level of safety, OTCs can still impact users negatively (9). Nonsteroidal anti-inflammatory drugs (NSAIDs) available without prescription, in particular, continue to garner a lot of attention (10–13). Before the purchase of an NSAID, or any other medicine for that matter, people must ensure that it will be safe to use. A health-care provider can be asked for assistance, but that may not always be practical or in line with
patients’ perceived needs. Package information is there to provide critical information in lieu of that. In most countries, a medicine that cannot be taken safely and effectively via those directions (either on or in the package) is likely to remain prescription only. Accordingly, much interest has been shown in the readability of such information and the propensity of the public to read it. This includes concerns about literacy and numeracy skills. Industry-based data indicated that 91% of Canadians claimed to read labels carefully before using a product for the first time (14), and they appeared to be satisfied with the information provided (15). A survey of 805 Canadians found that 88% followed the manufacturer’s directions when last using an OTC (16). Among the 5% who were noncompliant with those directions, 31% took a dose larger than directed 19% took another dose sooner than directed, and 11% exceeded the maximum daily dosage. This was usually motivated by symptoms that were serious or a perceived lack of efficacy of the agent. Interestingly, 16% of noncompliers stated they were actually following directions from a health-care professional that had been given to them at a different time. On the other hand, there have also been less positive results. Canadian government data found that 62% of participants stated that they always read labels, 16% often read them, 9% reported sometimes reading them, 6% seldom read them and 7% never read them (17). National consumer surveys in the United States and Canada have suggested that most, at the time of first purchase, do not read the full information provided (18,19). Only 40% of Canadians read about active ingredients when buying a product for the first time, followed by the dosage level (34%), the symptom it treats (26%), the possible side effects (23%), the directions for usage (18%) and the warnings (10%) (19). Concern about the public’s ability to self-medicate is real. In the United States, 334 of 1011 responders indicated they had taken more than the recommended dose of an OTC (20). Of that subset, 69% said this would manifest as taking more than the recommended number of pills at a single time, while 63% reported it could mean taking the next dose sooner than directed. The BeMedWise campaign in Canada found that 13% took 2 products simultaneously to treat the same symptoms (21). At 1 point, half of a sample could not name the active ingredient in the headache medication they used most often (19). In the United States, 66% could not do the same (20), although follow up in 2003 suggested that some improvement had occurred (22). Internet sites for health- and medicine-related information are growing in importance. A keyword search of health in 2005 netted 473 000 000 hits (23). Many in health-care will undoubtedly question the Internet’s value at times, but at least 1 review has suggested that, generally, it has had a positive impact on consumer
J. Taylor / Can J Diabetes 41 (2017) 551–557
health (24). On one front, symptom-checker sites are growing in popularity as a means of self-diagnosis (25). Herbal and natural products Some of the most commonly used herbal and natural products today are multivitamins, vitamin D, omega-3 fatty acids, glucosamine/chondroitin, echinacea, turmeric, probiotics and melatonin. Of the nonvitamins, omega-3s and glucosamine sit near the top in sales. Nearly 6% of Canadians with diabetes, according to 1 report, were taking glucosamine, while about 12% were using garlic (8). Herbal and natural agents with potential for aiding in bloodsugar management have been nicotinamide, ginseng, fenugreek, vitamin D, chromium and cinnamon (26). A review focused solely on spices added ginger, cumin, tumeric, coriander, anise, garlic, onion, cloves, mustards, black pepper and curry leaves to that list (27). During a look at possible future therapeutic entities, a review in Canadian Journal of Diabetes identified 11 entities that had lowered glycated hemoglobin (A1C) levels by 0.5% or more in trials lasting at least 3 months, concluding that they merited further research (28). To focus on a few agents, headlines were made in 2010 regarding the potential effect of glucosamine on diabetes (29). Researchers determined that high (or prolonged) doses of this antiarthritis agent caused the death of pancreatic cells (during in vitro testing) and, thus, could increase the risk for developing diabetes (30). Dosages studied were 5 to 10 times higher than the recommended amount of 1500 mg per day. This amounted to another example in a long list of ongoing research showing that herbals can have negative effects. A review of this agent at about the same time concluded that glucosamine did not have any impact on blood glucose, glucose metabolism or insulin sensitivity either in healthy people or in those with diabetes (31). Cinnamon is often mentioned in lay circles as a way to help attain glycemic control. It obviously comes as the raw spice for food preparation or as capsules from pharmacies and natural food stores. A health-based website concluded that it was unlikely that a person could get enough of the spice during cooking or baking to make a significant difference in blood sugar levels (32). This same website stated that dosages vary from 1 to 2 grams per day, then cited a prominent resource indicating that most people can safely take up to 6 grams per day (for up to 6 weeks) without having major side effects. A review of cinnamon in 2016 concluded that when used by patients taking standard hypoglycemic agents, or in addition to lifestyle modifications, it had only modest effects on fasting blood glucose or A1C levels (33). Canadian guidelines supported that position, stating that the spice has failed to lower A1C levels by 0.5% or more in trials lasting at least 3 months in adults with type 2 diabetes (28). The Xinyan et al review of spices concluded that those they listed are considered to have well-recognized antidiabetic actions, seemingly mediated by stimulation of the pancreas to secrete insulin, alter glucose absorption or induce insulin-sparing activity (27). Most of the research, however, had been done at the level of cell cultures and animal models. Critical to any potential impact during human use, then, will be the dosage. Whether taken as a raw spice or an extract is a factor in determining any impact, as is the preparation technique used in its manufacture. For perspective on studied dosages versus commercial products that are currently available, let’s consider 2 agents. Cinnamon has been assessed at 1 to 6 grams per day, while ginger has been studied at 3 grams per day. At the store level, a Canadian cinnamon product contains 150 mg (of a 20:1 extract derived from 3000 mg of cinnamon bark) per capsule, with the indication “healthy glucose metabolism” prominently displayed on the package (34).
553
At a dosage of 1 or 2 capsules a day, the resultant exposure might be less than the amounts cited above. Conversely, Gravol Natural Source ginger tablets are the equivalent of 500 mg of dried ginger root, with the labelled directions of 2 tablets, 1 to 3 times a day (up to a maximum of 6 tablets a day) (35). Use of the daily maximum of this product would allow this agent to reach that 3 gram level. One of the more efficient ways to check the potential impact of any herbal agent is the Natural Medicines Comprehensive Database. Regarding cinnamon (using Cassia cinnamon as the reference point), this resource concluded that the spice may lower blood glucose levels and/or have an additive effect on other antidiabetic agents (36). On a scale of minor, moderate or major, this drugherbal interaction was ranked as moderate. “Use with caution” was recommended for patients with type 2 diabetes, specifically, and dose adjustments may be warranted. The actual impact on fasting blood glucose was quantified in the monograph (24.6 mg/dL), which was based on a wide range of dosages, from 120 mg to 6 grams daily. For glucosamine sulfate (the more commonly seen salt), the Natural Medicines Comprehensive Database concluded that the agent, used for up to 3 months, is unlikely to affect A1C or blood glucose levels in those with type 2 diabetes; any interactions with antidiabetes agents were described as minor (37). A third herbal agent one should consider during medication assessment is St. John’s wort. It is used primarily for depression and is described as being well tolerated (perhaps more so than tricyclic antidepressants) by users, although neuropathy has been reported (38). The significant downside of this agent is a propensity to interact extensively with other medicines. CYP2C9 substrates (glipizide) are mentioned, as is gliclazide, with both rated as having moderate interactions. The net result in both cases would be that blood sugar-lowering effects may be reduced, with a conclusion to not use this particular antidepressant.
Coughs and colds Adults experience about 1 to 3 colds per year (39). The Canadian Medical Association Journal cited data showing that 7% to 17% of adults and 33% of children see physicians because of upper respiratory tract infections (39). Although generally described as mild, such infections make life rather miserable for about a week. Patients with diabetes will be trained to shift into sick-day management. The first cold symptom is usually throat discomfort. Various degrees of nasal congestion and rhinorrhea follow. Nasal discharge is at first clear and watery, becoming more tenacious as the infection progresses. Breathing through the nose eventually becomes difficult. This congestion may lead to sinus headaches and perhaps a muffled sensation with regard to hearing. Postnasal drip can further irritate a throat. Significant fever is seldom evident, but chill sensations are common. Colds rarely cause serious consequences. If a cough occurs, it usually starts as dry and unproductive, becoming productive as the cold progresses (bronchial secretions and cellular debris increase). With the appearance of coughing, it is then deemed a chest cold, and that may be more concerning than a simple head cold. The typical causes of coughs at the primary care level are depicted in Figure 1 (40,41). Coughing tends to be 1 of the more persistent symptoms (42). On average, a cough lasts about 18 days, but sufferers tend to think it should be finished in 1 week (43). This mismatch of expectations and reality can lead to inappropriate use of antibiotics. The common cold differs from influenza by being far milder, having no sudden onset of a spiking fever, less severe coughing and an absence of substantial body aches and pains (44). Generally, a cold simply runs its course, in spite of efforts to combat it. There is no cure, but general measures can provide some
554
J. Taylor / Can J Diabetes 41 (2017) 551–557
Figure 1. Distribution of causes of acute cough in adults found in typical general practice. COPD, chronic obstructive pulmonary disease. Note: Used with permission from Canadian Family Physician.
comfort. Getting some rest and fluids, such as orange juice, are often tried (45). The public continues to turn to OTC medicines for some semblance of relief, although large reviews have not shown the benefit (especially for pediatric use) of these products (46–48). About 100 different entities can be found in larger pharmacies. The actual number of active agents within them, however, is quite small. About 11 chemicals make up the vast majority of active ingredients across those 100 products: analgesics (acetaminophen, ibuprofen); nasal decongestants (phenylephrine, pseudoephedrine, oxymetazoline, xylometazoline); cough suppressants (diphenhydramine, dextromethorphan); an expectorant (guaifenesin); and antihistamines (diphenhydramine, chlorpheniramine). Combinations are common. Of these ingredients, only decongestants need be considered for their possible effects on blood sugar levels; the other products do not alter them. A health-care professional would have to consider only whether the calories in a liquid or lozenge formulation might be an issue (which generally is not the case). The alcohol content of modern syrups is very low. Nasal decongestants fall into 2 camps: oral and topical. Topical entities, such as xylometazoline and oxymetazoline, act faster than oral agents. If they are not washed away by nasal secretions, they will relieve congestion for up to 10 and 12 hours, respectively. They are available only as single-agent products. The incidence of adverse effects is low, given that absorption from the application site tends to be minimal. Generally, labelled warnings applicable to oral decongestants (see below) do not apply to topically applied entities. Thus, they have a high safety factor in diabetes and should not influence blood sugar. Their overuse, however, can produce a rebound effect, wherein the drug originally used to combat the congestion is now itself responsible for continued congestion. Periods of use shorter than 7 days will avoid that issue, although some authors have questioned whether rebound congestion occurs at all (49). Oral agents share many of the same structure-activity properties as amphetamines and, by extension, a similar (but milder) side-effect profile. Aside from relieving some of the congestion, oral agents possess the negative potential for cardiovascular effects, blood sugar changes, prostatic hypertrophy, drug interactions and
CNS effects (especially in the elderly). It is probably prudent to avoid oral decongestant use by people with diabetes and hypertension. The stimuli that control blood sugar are complex, but such sympathomimetic agents tend to increase glucose levels. This effect is far more pronounced with something like epinephrine than with oral decongestants, but precautions should still be considered for people with type 1 diabetes. Practically speaking, their use should amount to only about 3 or 4 days of exposure, for which the cold itself will increase blood sugar to a greater extent than any drug. Of the oral agents, phenylephrine (PE) was minimally used commercially until, that is, pseudoephedrine (PSE) started being diverted for clandestine use in crystal meth labs. At that point, more manufacturers turned to PE. This is unfortunate because PE is a less reliable agent than PSE in terms of bioavailability (50). Coughs have been typically described as dry or wet, although some authors have questioned this designation (51). Accordingly, patients with coughs depicted as dry but congested are commonly given an expectorant to help loosen them up. Coughs that are already productive need not be suppressed, unless some relief is needed in the short term. Either way, doubt continues to be cast on whether any benefit is seen from their use (47). The syrup base of any product might be something to consider. To use Robitussin products just as an example, the caloric content of some of their common syrups can range from 1.2 and 3.0 kcal up to 11.7 kcal per 5 mL. Even at this higher level, the impact of 4 times a day dosing on caloric intake would be minimal. Regarding another of their products, Robitussin Cough Control for People with Diabetes uses sorbitol and sucralose in its formulation, resulting in 23 kcal per 15 mL. At a maximum of 4 doses per day, this would lead to a 92 kcal spread over a 24-hour period for about 7 days. Obviously, there is no guarantee of that timeline, given that coughs often last longer. More important than its caloric load (in the opinion of the author) is that it contains a cough suppressant and an expectorant. First, will that be useful for a patients’ symptoms, given the evidence? Is the combination rational? Another issue is whether there is a possibility that some people with diabetes will choose this product for all their upper respiratory tract infections, based on a sense of security in seeing mention of diabetes on the label. While being safe in terms of blood sugar, as noted in its name, it is designed only for coughs. An impact of a Health Canada ruling on cough/cold product use in children younger than 6 years of age was parents’ shifting to “safer” products. This led to a rise in homeopathic products and honey. A Cochrane review concluded there was no strong evidence for or against the use of honey for coughs (52). An article in Canadian Family Physician went a bit further, stating that honey can be recommended at a “dose” of 2.5 mL before bedtime for coughing children older than 1 year of age (53). A teaspoon of honey has 22 kcal (versus 16 kcal found in 1 teaspoon of table sugar) (54). To tap into the interest shown in honey, several cough syrups also mention honey on the package. But they would not be formulations in the same vein as pure honey. Rather, the honey is likely to be just 1 of the ingredients in a syrup base. As another formulation example, there are sugar-free lozenges on the market, several of them low in calories. NSAIDs OTC versions of ibuprofen (up to 1200 mg) and naproxen (up to 400 mg base) are lower in daily dosage than their prescription counterparts, with labelled directions calling for shorter periods of use if medical care is not in place. Reviews, thus, tend to indicate a lower incidence of side effects at so-called OTC levels of use (55–59). Be that as it may, the cardiovascular, renal and gastrointestinal risks of NSAIDs are well known and can be significant (60). These
J. Taylor / Can J Diabetes 41 (2017) 551–557
issues have to be considered with serious conviction prior to use in persons with diabetes (who are at greater risk). American Family Physician calls for the avoidance of NSAIDs in patients with hypertension, heart failure or chronic kidney disease of all causes, including diabetes (61). Canadian guidelines state that during sick-day management, NSAIDs can further reduce renal blood flow, and patients should withhold use if they feel they are becoming dehydrated (62). Further, it is not just greater duration of use that is of concern; even short-term use has implications (63–65). A look at how pervasive their use is, and the extent to which liberties might be taken, could be helpful in this discussion. Analgesic use has been described as extremely high among American adults (66). An estimated 147 million adults used them monthly. Prescription analgesic use was determined to be 9%, while OTC use was 76%. Approximately 30% used multiple agents over a 1-month period. Another report found that acetaminophen was used 1 day a week or more often by more than 20% of American women, and 42% report similar usage of NSAIDs (67). Based on concerns from many sources, the United States Food and Drug Administration engaged in a campaign to promote safe use of OTC analgesics, stressing the importance of following label directions carefully (68). Other experts have even called for a reassessment of the OTC status of such agents (69,70). In Canada, appropriate use of acetaminophen is being promoted by a campaign (71). A survey found that 37% of citizens admitted to taking more than the recommended amount of OTC pain killers, either by taking the next dose sooner than directed on the label, by taking more pills at a single time than recommended or by exceeding the daily dosage (72). Although most said they read the label (during first-time use) to see how many pills to take and how often (91%), which symptoms the agent would treat (85%) and possible side effects (77%), some (27%) did not read warnings about use with other OTCs or determine the active ingredient (48%). Approximately 29% said they did not worry about how long or how often they take an agent, as long as it manages their pain, and 12% noted that they sometimes add an OTC pain killer to a prescriptive agent, believing they would get more pain relief without increasing the potential for side effects. Just over 4 in 10 (41%) were not very or not at all concerned about potential side effects. This apparent lack of concern for side effects has been seen elsewhere. Two surveys constituting a total of 9062 respondents were carried out on a national sample of Americans regarding OTC NSAID use (73). In the first survey, exclusive OTC users were neither aware of (60%), nor believed they were at risk for (29%), side effects from NSAIDs, while 22% believed warning symptoms would always precede any NSAID-induced complication. In the second survey, 49% were not concerned about potential side effects, and 30% believed there was less risk with OTC analgesics than with their prescription counterparts. It was concluded that OTC NSAIDs are widely used and are frequently taken inappropriately, with potentially dangerous results. In a survey from Finland, 44% had used analgesics (OTC or prescribed) within the previous week. Users reported doctors (35%), information leaflets (33%) and pharmacists (33%) as the most common sources for information. In spite of that, it was concluded analgesic users do not receive much information from healthcare providers, which may put self-medicators at risk (74). Along the same lines, another Scandinavian report revealed substantial regular use of analgesics in several situations of contraindications, including 8% in patients with chronic kidney disease (75). About 4% demonstrated at least 1 potential drug interaction. OTC analgesic use in 1500 Scottish subjects was assessed (11). More than 500 had used an agent in the previous 2 weeks. Potential inappropriate use was identified in 115 (n=21%) of the OTC analgesic users, including use of multiple analgesics (n=67), use in
555
conditions in which caution applied (n=51), and potential drugdrug interactions (n=15). The authors concluded there is a high level of OTC analgesic use by the general public and significant potential for inappropriate use. Dozens of similar reports exists. To provide a degree of balance, not all the evidence points to dangerous use. In 1 study, community pharmacists in the United Kingdom recruited users and purchasers of ibuprofen. Most participants had not sought medical advice for their symptoms or asked questions during the purchase. A small proportion of participants reported ingesting higherthan-recommended doses (>1200 mg) or prolonged use (>20 weeks), but no symptoms of potentially serious adverse events were reported (although that may have been due to the small numbers). It was concluded that greater vigilance was required for adverse events potentially related to ibuprofen use, but overall, it appeared to be used safely and effectively (76). In Norway, participants were recruited from consumers presenting at 62 community pharmacies after purchasing low-dose OTC diclofenac. The directions were followed with regard to recommended indications, contraindications and maximum dosage but less so with respect to recommended duration of use and concurrent medications. Overall, the use of the agent was described as efficacious, safe and commonly used in accordance with directions for use (77). In another, Canadians with a different chronic condition, arthritis, were surveyed. Their key information sources were doctors, followed by the Internet and friends or family, then pharmacists. When they had experienced their most recent flare-ups, 46% had turned to an OTC medicine for relief, about 16% arranged to see a doctor, while 6% consulted a pharmacist. Of the respondents, 70% felt confident in managing and treating minor ailments themselves, yet many felt it was also important to speak to a healthcare provider before taking an OTC medicine (59%) or a natural health product (54%) for the first time (78).
Conclusions Three main areas of OTC medicines were the focus of this study; they were selected as being deserving of the most attention by practitioners. It is this author’s opinion that although use of herbal and natural products should, indeed, be considered by health-care providers during medication assessments, the actual effects they will have on other medicines, or on the course of diabetic illness, should be minimal if used according to package instructions. Instead, more in need of our attention is whether a herbal entity will actually help what it is being used for (e.g. salmon oil for cardioprotection, melatonin for insomnia, ginger for motion sickness, saw palmetto for prostate enlargement and so on). Advice on this front could likely save people money and some frustration, even though many consumers will swear by the agents they use. As part of that assessment, consideration should also be given to whether medical care is being delayed as a result of such use. Input into these 2 issues could produce bigger dividends than a singular focus on blood sugar changes. The exception to this suggestion, however, might be St. John’s wort, for which the potential for drug interactions is so extensive that use should probably be avoided. Contingent with this opinion is that any herbal dose is not extreme, for it is likely that as ingested amounts rise, an agent will move from being a simple spice or herbal remedy on through functional food status and up to eventually having potential for adverse drug reactions. From the perspective of cough and cold products, oral decongestants are the only concern regarding blood glucose levels. It is this author’s opinion that their impact on type 1 diabetes would
556
J. Taylor / Can J Diabetes 41 (2017) 551–557
be minimal and would be even less so for type 2 diabetes. In a rather scathing report on the safety of such agents (primarily cardiovascular) and concern for their widespread availability, specialists did not even mention blood sugar change as a danger with their use (79). Tablet and caplet forms of these agents have negligible caloric content. Of syrups, many are sweetened with sucrose, but the caloric load is low. Alcohol content is of almost no consequence for the vast majority of products. OTC NSAIDs can be effective for pain (so common in our seniors), are widely used and are easily accessible by the public. Considering all these dynamics, it may prove difficult to reduce their use, although efforts must continue on this front. A key point is that selfmedication is possible, and that is unlikely to change in the foreseeable future. Care guidelines, in fact, encourage patients to take ownership of their conditions and participate in self-monitoring and decision making (80). Unfortunately, in the case of diabetes and OTC NSAID use (or potentially any high-risk group, for that matter), a degree of disconnect is evident. OTC NSAIDs are commonly taken without the knowledge of prescribers (81). A tenet of self-care and self-medication is that in lieu of getting advice, the users must themselves undertake the reading about and research into the medication they intend to use. To the extent that that goal is not met, any opportunity for self-medicating patients to let their physicians know what they are taking and how they are taking it would, at least, enable monitoring to take place. Pharmacists can also monitor and convey any risks to users. For patients who choose not to put in the effort, less emphasis on the self in self-medication might prove prudent.
18.
19. 20.
21. 22.
23. 24. 25. 26. 27. 28. 29. 30.
31.
32. 33.
References 1. Willemsen KR, Harrington G. From patient to resource: The role of self-care in patient-centered care of minor ailments. Self Care 2012;3:43–55. 2. McAteer A, Elliott AM, Hannaford PC. Ascertaining the size of the symptom iceberg in a UK-wide community-based survey. Br J Gen Pract 2011;61:e22–30. 3. Harrington G. Director of Public Affairs, Consumer Health Products Canada. Personal communication. September 11, 2012. 4. Macdonald A, Stewart M. Healthy growth: Estimating the economic footprint of the fast-growing consumer health products industry. 2015. http://www .chpcanada.ca/sites/default/files/healthy_growth_final_report.pdf. Accessed June 27, 2016. 5. Canadian Institute for Health Information. Drug expenditure: Prescribed and non-prescribed drugs. Outlook:2010 and 2011. In: Drug expenditure in Canada, 1985 to 2011. Ottawa: CIHI, 2011. 6. Wood V. 2011 OTC market report: Non-prescription sales hold steady. Drugstore Can 2011;4:13–21. 7. Gattera JA, Stewart K, Benrimoj SI, Williams GM. Usage of nonprescription medication by people with diabetes. J Soc Admin Pharm 1992;9:66–74. 8. Ryan EA, Pick ME, Marceau C. Use of alternative medicines in diabetes mellitus. Diabet Med 2001;18:242–5. 9. Schmiedl S, Rottenkolber M, Hasford J, et al. Self-medication with over-thecounter and prescribed drugs causing adverse-drug-reaction-related hospital admissions: Results of a prospective, long-term multi-center study. Drug Saf 2014;37:225–35. 10. Ipsos Reid. Many Canadians take risks with OTC pain medications. Toronto: Ipsos Reid, 2006. 11. Porteous T, Bond C, Hannaford P, Sinclair H. How and why are non-prescription analgesics used in Scotland? Fam Pract 2005;22:78–85. 12. Castelli G, Petrone A, Xiang J, et al. Rates of nonsteroidal anti-inflammatory drug use in patients with established cardiovascular disease: A retrospective, crosssectional study from NHANES 2009–2010. Am J Cardiovasc Drugs 2017;17:243– 9. 13. Lawson B, Putnam W, Nicol K, et al. Managing osteoarthritis: Medication use among seniors in the community. Can Fam Physician 2004;50:1664–70. 14. Canadian Facts. Consumer usage and attitude study, vol. I. Toronto: Canadian Facts, 1991. 15. Consumer Health Products Canada. HealthVision 1999/2000. Ottawa: Nonprescription Drug Manufacturers Association of Canada, www.chpcanada.ca. Accessed December 2, 2009. 16. Responsible use of nonprescription medications in Canada: A research report to Nonprescription Drug Manufacturers Association of Canada. Ottawa, Ontario, Canada: Martin Redfern, 2007. 17. Attitudes, perceptions and behaviour relating to ethical medicines: A research report to the Department of National Health and Welfare. Ottawa, Ontario,
34. 35. 36. 37. 38. 39. 40. 41.
42.
43.
44.
45.
46. 47.
48. 49.
50.
51. 52.
Canada: Decima Research, 1990 http://dsp-psd.pwgsc.gc.ca/Collection/H42-243-1990E.pdf. Accessed December 2, 2009. Harris Interactive, National Council on Patient Information and Education. Attitudes and beliefs about the use of over-the-counter medicines: A dose of reality: A national survey of consumers and health professionals. 2002 www.bemedwise .org/survey/final_survey.pdf. Accessed December 1, 2009. OTC habits and practices: BeMedWise survey. Toronto: Drug Information and Research Centre (DIRC), 2002. National Council on Patient Information and Education. Attitudes and beliefs about the use of over-the-counter medicines: A dose of reality: A national survey of consumers and health professionals. Harris Interactive, January, 2002. Drug Information and Research Centre. Survey on Canadians’ use of OTC medications: The BeMedWise survey 2004. Toronto, Ontario: 2004. National Council on Patient Information and Education. Uses and attitudes about taking over-the-counter medicines: Findings of a 2003 national opinion survey. Harris Interactive. 2003. Ybarra ML, Suman M. Help-seeking behavior and the Internet: A national survey. Int J Med Inform 2006;75:29–41. Renahy E, Chauvin P. Internet uses for health information seeking: A literature review. Rev Epidemiol Sante Publique 2006;54:263–75. Semigran HL, Linder JA, Gidengil C, Mehrotra A. Evaluation of symptom checkers for self-diagnosis and triage: Auditstudy. BMJ 2015;351:h3480. Yilmaz Z, Piracha F, Anderson L, Mazzola N. Supplements for diabetes mellitus: A review of the literature. J Pharm Pract 2016;1–8. Xinyan B, Joseph L, Christiani Jeyakumar H. Spices in the management of diabetes mellitus. Food Chem 2017;217:281–93. Clinical Practice Guidelines. Natural health products. Can J Diabetes 2013;37:S97–9. Université Laval. Too much glucosamine can cause the death of pancreatic cells, increase diabetes risk, researchers find. Science Daily, October 27, 2010. Lafontaine-Lacasse M, Dore G, Picard F. Hexosoamines stimulate apoptosis by altering Sirt1 action and levels in rodent pancreatic β-cells. J Endocrinol 2011;208:41–9. Simon RR, Marks V, Leeds AR, Anderson JW. A comprehensive review of oral glucosamine use and effects on glucose metabolism in normal and diabetic individuals. Diabetes Metab Res Rev 2011;27:14–27. Can cinammon ease diabetes symptoms? www.healthline.com/health/cancinammon-ease-diabetes-symptoms. Accessed April 17, 2017. Costello RB, Dwyer JT, Saldanha L, et al. Do cinnamon supplements have a role in glycemic control in type 2 diabetes? A narrative review. J Acad Nutr Diet 2016;116:1794–802. Webber Naturals. www.webbernaturals.com. Accessed April 17, 2017. Gravol Natural Source ginger tablets. www.gravol.ca. Accessed April 18, 2017. Natural Medicines Comprehensive Database. Cassia cinnamon. www.naturaldatabase.therapeuticresearch.com. Accessed April 24, 2017. Natural Medicines Comprehensive Database. Glucosamine sulfate. www.naturaldatabase.therapeuticresearch.com. Accessed April 24, 2017. Natural Medicines Comprehensive Database. St. John’s wort. www.naturaldatabase .therapeuticresearch.com. Accessed April 24, 2017. Allan GM, Arroll B. Prevention and treatment of the common cold: Making sense of the evidence. Can Med Assoc J 2014;186:190–9. Worrall G. Acute coughs in adults. Can Fam Physician 2011;57:48–51. McCormick A, Fleming D, Charlton C. Morbidity statistics from general practice: Fourth national morbidity survey, 1991–92. London: HMSO, Office for National Statistics, 1995. Eccles R, Dicpinigaitis P, Turner RB, et al. Characterization of urge to cough and cough symptoms associated with the common cold: Results of a US internet study. Postgrad Med 2016;128:485–91. Ebell MH, Lundgren J, Youngpairoj S. How long does a cough last? Comparing patients’ expectations with data from a systematic review of the literature. Ann Fam Med 2013;11:5–13. Thirion DJG. Assessment of patients with upper respiratory tract symptoms. In: Jovaisas B, ed. Compendium of therapeutics for minor ailments. Ottawa: Canadian Pharmacists Association, 2016, pg. 245–9. Thielmann A, Gerasimovska-Kitanovska B, Buczkowski K, et al. Self-care for common colds by primary care patients: A European multicenter survey on the prevalence and patterns of practices: The COCO study. Evid Based Complement Alternat Med 2016;2016:6949202. Deckx L, De Sutter AI, Guo L, et al. Nasal decongestants in monotherapy for the common cold. Cochrane Database Syst Rev 2016;(10):CD009612. Smith SM, Schroeder K, Fahey T. Over-the-counter (OTC) medications for acute cough in children and adults in community settings. Cochrane Database Syst Rev 2014;(11):CD001831. Yang M, So T-Y. Revisiting the safety of over-the-counter cough and cold medications in the pediatric population. Clin Pediatr (Phila) 2014;53:326–30. Mortuaire G, de Gabory L, François M, et al. Rebound congestion and rhinitis medicamentosa: Nasal decongestants in clinical practice: Critical review of the literature by a medical panel. Eur Ann Otorhinolaryngol Head Neck Dis 2013;130:137–44. Eccles R. Substitution of phenylephrine for pseudoephedrine as a nasal decongestant: An illogical way to control methamphetamine abuse. Br J Clin Pharmacol 2006;63:10–14. Morice AH, Kantar A, Dicpinigaitis PV, et al. Treating acute cough, wet versus dry: Have we got the paradigm wrong? ERS Open Res 2015;1:00055-2015. Oduwole O, Meremikwu MM, Oyo-Ita A, Udoh EE. Honey for acute cough in children. Cochrane Database Syst Rev 2014;(12):CD007094.
J. Taylor / Can J Diabetes 41 (2017) 551–557
53. Goldman RD. Honey for treatment of cough in children. Can Fam Physician 2014;60:1107–11. 54. Amount of calorie in honey. www.benefits-of-honey.com. Accessed April 18, 2017. 55. Bjarnason I. Gastrointestinal safety of NSAIDs and over-the-counter analgesics. Int J Clin Pract 2013;178(Suppl.):37–42. 56. Moore N, Salvo F, Duong M, et al. Cardiovascular risks associated with lowdose ibuprofen and diclofenac as used OTC. Expert Opin Drug Saf 2014;13:167– 79. 57. Angiolillo DJ, Weisman SM. Clinical pharmacology and cardiovascular safety of naproxen. Am J Cardiovasc Drugs 2017;17:97–107. 58. Moore RA. Analgesic safety: Myths, mysteries and misconceptions. Int J Clin Pract 2015;69(Suppl. 182):24–7. 59. Moore N, Pollack C, Butkerait P. Adverse drug reactions and drug-drug interactions with over-the-counter NSAIDs. Ther Clin Risk Manag 2015;11:1061– 75. 60. Davis A, Robson J. The dangers of NSAIDs: Look both ways. Br J Gen Pract 2016;66:172–3. 61. Choosing wisely. www.aafp.org. Accessed April 27, 2017. 62. McFarlane P, Gilbert RE, MacCallum L, et al. Clinical practice guidelines: Chronic kidney disease in diabetes. Can J Diabetes 2013;37(Suppl. 1):S129–36. 63. Lapi F, Azoulay L, Yin H, et al. Concurrent use of diuretics, angiotensin converting enzyme inhibitors, and angiotensin receptor blockers with non-steroidal antiinflammatory drugs and risk of acute kidney injury: Nested case-control study. BMJ 2013;346:e8525. 64. Schjerning Olsen AM, Fosbøl EL, Lindhardsen J, et al. Duration of treatment with nonsteroidal anti-inflammatory drugs and impact on risk of death and recurrent myocardial infarction in patients with prior myocardial infarction: A nationwide cohort study. Circulation 2011;123:2226–35. 65. Schjerning Olsen AM, Gislason GH, McGettigan P, et al. Association of NSAID use with risk of bleeding and cardiovascular events in patients receiving antithrombotic therapy after myocardial infarction. JAMA 2015;313:805– 14. 66. Paulose-Ram R, Hirsch R, Dillon C, et al. Prescription and non-prescription analgesic use among the US adult population: Results from the third National Health and Nutrition Examination Survey (NHANES III). Pharmacoepidemiol Drug Saf 2003;12:315–26. 67. Curhan GC, Bullock AJ, Hankinson SE, et al. Frequency of use of acetaminophen, nonsteroidal anti-inflammatory drugs, and aspirin in US women. Pharmacoepidemiol Drug Saf 2002;11:687–93.
557
68. Anonymous. FDA launches campaign on OTC pain relief products. FDA Consum 2004;38:8. 69. Fosbøl EL, Køber L, Torp-Pedersen C, Gislason GH. Cardiovascular safety of nonsteroidal anti-inflammatory drugs among healthy individuals. Expert Opin Drug Saf 2010;9:893–903. 70. Tielemans MM, van Rossum LG, Focks JJ, et al. Gastrointestinal symptoms are increased in both prescribed and over-the-counter NSAID users compared to non users in the community. In: Digest Disease Week 2012; San Diego, CA, May 2012. 2012. 71. Spotlight on acetaminophen. https://safemedicationuse.ca/tools_resources/ tips_acetaminophen.html. Accessed April 21, 2017. 72. Ipsos Reid. Many Canadians take risks with OTC pain medications. Toronto: Ipsos Reid, 2006. 73. Wilcox CM, Cryer B, Triadafilopoulos G. Patterns of use and public perception of over-the-counter pain relievers: Focus on nonsteroidal antiinflammatory drugs. J Rheumatol 2005;32:2218–24. 74. Närhi U, Helakorpi S. Analgesic users’ sources of medicine information. Int J Pharm Pract 2007;15:251–3. 75. Samuelsen PJ, Slordal L, Mathisen UD, Eggen AE. Analgesic use in a Norwegian general population: Change over time and high-risk use: The Tromso Study. BMC Pharmacol Toxicol 2015;16:16. 76. Layton D, Sinclair HK, Bond CM, et al. Pharmacovigilance of over-the-counter products based in community pharmacy: Methodological issues from pilot work conducted in Hampshire and Grampian, UK. Pharmacoepidemiol Drug Saf 2002;11:503–13. 77. Hasford J, Moore N, Hoye K. Safety and usage pattern of low-dose diclofenac when used as an over-the-counter medication: Results of an observational cohort study in a community-based pharmacy setting. Int J Clin Pharmacol Ther 2004;42:415–22. 78. Arthritis: Consumer behaviour and attitudes. Consumer Health Products Canada, Redfern Research, August 2011. 79. Laccourreye O, Werner A, Giroud J-P, et al. Benefits, limits and danger of ephedrine and pseudoephedrine as nasal decongestants. Eur Ann Otorhinolaryngol Head Neck Dis 2015;132:31–4. 80. Canadian Diabetes Association Clinical Practice Guidelines Expert Committee, Jones H, Berard LD, et al. Clinical Practice Guidelines: Self-Management Education. Can J Diabetes 2013;37(Suppl. 1):S26–30. 81. Hamilton K, Davis C, Falk J, et al. High risk use of OTC NSAIDs and ASA in family medicine: A retrospective chart review. Int J Risk Saf Med 2015;27:191–9.