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Regulation of Over-The-Counter Drugs
Technicians and pharmacists are well aware that medications are generally classified as either requiring a prescription or available without a prescription (over-the-counter [OTC]). It is estimated that there are over 800 active ingredients available over the counter for 1400 different uses and these ingredients can be found in over 300,000 different products sold in more than 750,000 retail outlets including not only pharmacies, but other establishments, such as convenience stores, groceries and mass merchandise stores.1,2 Such an enormous volume of products provides the consumer with many options for self-care, but a lack of knowledge and awareness can lead to unintended consequences. While OTC drugs do have such widespread distribution – and do not require a prescription – this does not mean that they are completely unregulated. OTC drugs must obtain approval from the U.S. Food and Drug Administration (FDA) and Federal and state regulatory agencies can further restrict sales in a number of ways, including marketing and advertising, labelling, age restrictions, quantity restrictions and other means. However, even in the absence of strict regulatory control, pharmacy personnel should be vigilant to spot misuse or abuse of OTC products. This manuscript will highlight the regulatory difference between prescription and OTC drugs and examine some of the circumstances where heightened oversight is necessary.
PRESCRIPTION v. OTC DRUGS
Traditionally drugs fall into one of two classes, those that require a prescription (Rx) and those that do not (OTC). Both Rx and OTC drugs have to undergo FDA review and oversight, but are subject to different criteria for approval and labelling.1 [Controlled substances are a separate category subject to regulation by the Drug Enforcement Agency (DEA) and will not be considered here (see3 for more information).]
Prior to 1951, there was no formal distinction between Rx and OTC drugs and the same drug was often marketed as both. In 1951, the Durham-Humphrey Amendment to the Federal Food, Drug and Cosmetic Act of 1938 (FDCA, the law which regulates the approval and marketing of drugs), established a legal framework to differentiate prescription and non-prescription drugs and authorized the FDA to make the distinction.4 The FDA makes the determination whether a drug will be marketed as Rx-only or OTC at the time that the manufacturer seeks approval to market the drug by filing a New Drug Application (NDA). Prior to 1951, the manufacturer could decide if a drug was going to be marketed as Rx or OTC.4 The FDA is given considerable latitude in making its decision. The Durham-Humphrey Amendment also prohibited a drug from being marketed as both an OTC and Rx drug at the same dose and indication, although there can be both an OTC and Rx version of a drug if they have different doses or indications (e.g., Nexium). The FDA defines OTC drugs as “drugs that are safe and effective for use by the general public without seeking treatment by a health professional”5.
In essence the differentiation between drug classes is based upon the potential dangers associated with the drug and the degree of supervision needed to safely use the drug, taking into consideration both the nature of the drug and the risks of self-diagnosis by the patient1. In addition, the information on a drug label differs for Rx and OTC drugs; the OTC label contains information for the benefit of the purchaser (e.g., directions for use, warnings).
OTC Regulatory Review
Regulatory review of OTC drugs is conducted by the Center for Drug Evaluation and Research (CDER) within the FDA6. The CDER was established in 1972 and ensures that available products, including prescription and OTC drugs and other products (e.g., sunscreens, dandruff shampoo, antiperspirants) are safe and effective1.
An important development in the FDA’s drug oversight occurred in 1962 with the enactment of the Kefauver-Harris Amendment to the FDCA .7 The main provisions of the Amendment were to require drug manufacturers to provide proof of efficacy for their intended use before the drug (Rx or OTC) could be marketed (proof of safety had already been required by an earlier provision of the law); to permit withdrawal of approval of a drug if there was substantial doubt about its safety or efficacy; and to require that manufacturers report information bearing on safety or efficacy to the FDA. The Amendment also required a retrospective review of safety and efficacy of drugs approved between 1938 and 1962. The retrospective review included OTC drugs in addition to prescription products. The FDA faced the daunting task of reviewing more than 100,000 then-existing approved OTC products.6
The FDA recognized that requiring the submission of over 100,000 product-specific New Drug Applications (NDA’s) would severely disrupt the availability of self-care products. Instead, the FDA designed a system of active-ingredient-specific OTC monographs (a rulemaking process that establishes drug standards).5,8 An expert advisory panel meets to assess whether the active ingredient(s) meet the standard of “generally recognized as safe and effective” (GRASE) and sets criteria for safety and efficacy and the risk-benefit ratio. The resulting monograph specifies the self-care indications and allowable dosage/concentration for that ingredient. Existing drugs which did not meet these criteria were removed from the market.
The FDA refers to the monographs as analogous to a “recipe book” covering acceptable ingredients, formulations and labelling which are updated as needed.5 For each category, an OTC drug monograph is developed and published in the Federal Register. If a new product conforms to the monograph (i.e., meets the criteria for GRASE), it may be marketed without further FDA clearance. If it does not, the drug is considered a “new drug” and must go through the standard, more burdensome review and approval process required for new drugs.8
LIMITATIONS ON OTC DRUGS
Despite these efforts to minimize risks, experience with drugs after their approval may sometimes necessitate additional safeguards. While safety and self-treatment (use without supervision by a health care practitioner) are the foundation for granting a drug non-prescription status, problems are nevertheless associated with the misuse of OTC products. In particular, two issues that can warrant increased scrutiny will be discussed – safety and abuse.
A recent study found that only 41 percent of consumers read the ingredients on drug labels and most could not identify the names of the main ingredient in OTC pain relievers.9 These results show that there is a lack of consumer knowledge about and appreciation of the risks associated with the use of OTC medications which can lead to harm, despite the presence of warnings and precautions on labels. These risks may lead to increased attention from regulatory agencies. Some relevant examples will be discussed.
An example of subtle restrictions aimed at improving the safety of OTC products can be shown by some recent changes by the FDA regarding acetaminophen. As technicians and pharmacists are aware, acetaminophen is a common ingredient in OTC medications for pain, colds and fever.
High doses of acetaminophen can produce liver and kidney damage and is a leading cause of liver failure in the U.S., accounting for approximately 300 deaths per year.10 The recommended daily maximum dose of acetaminophen is 4000 mg, although toxicity has been observed with lower doses. 10 The toxicity is enhanced by co-ingestion of ethanol. 10 In recognition of these risks, the FDA has issued multiple guidelines to reduce the risk of overdose, especially in formulations intended for use by infants and children.
One concern that the FDA had was the risk of overdoses resulting from confusion over different pediatric formulations; the oral liquid intended for children contained 160 mg/5 ml (teaspoon), while concentrated solutions primarily intended for use in infants through a dropper contained 80 mg/0.8 mL or 80 mg/ml (400-500 mg/5 ml). In addition to overdoses due to dosing errors, there have been reports of overdose from accidental ingestion by children, especially the more concentrated forms. The FDA recommended11 moving to a single, standardized acetaminophen concentration for OTC pediatric oral liquid drug products (160 mg/5ml) in order to minimize the risk of confusion caused by multiple concentrations. The FDA guidelines also recommended that an appropriate dosage delivery device (e.g., oral cup or syringe) be included with the product and that the dosing recommendations be stated in ml instead of mg in order to minimize dosing errors.
In addition to pediatric formulations, the FDA has considered changes in acetaminophen products intended for adults. Outside experts convened by the FDA recommended placing a limit of 325 mg of acetaminophen per adult dosage unit in order to reduce hepatic toxicity as far back as 1977.12 Despite these recommendations, formulations containing as much as 500-650 mg per tablet were permitted to remain available to the public over the counter. An FDA review in 2008 found that there was little, if any, evidence to support the effectiveness of higher doses and that the use of 1000 mg four times a day approached, and may exceed, the level considered safe. The FDA also noted that acetaminophen has a narrow margin of safety.12
In 2009, an FDA advisory panel recommended limits on prescription and OTC acetaminophen, a move that was resisted by OTC manufacturers.13 In 2011, the FDA asked manufacturers to limit the amount of acetaminophen in prescription products to 325 mg/dosage unit, and in 2014 they recommended that health care professionals stop prescribing or dispensing products containing more than 325 mg/dose unit.14,15 For OTC acetaminophen products, the FDA issued guidelines for labels with stronger warnings, including warning of severe liver damage if recommended daily limits were exceeded as well as warnings if alcohol was consumed, but no limits were placed on OTC dose units. Dosage forms containing 500 or 650 mg of acetaminophen are still available OTC. The problem is compounded by the fact that acetaminophen is found in over 600 products and the average consumer is not aware of the ingredients listed on the label, raising the risk of accidental overdose. Pharmacy personnel should be concerned about the dilemma that consumers can self-select a product containing higher amounts of acetaminophen than would be available in prescription products, which require oversight by health care professionals.
When drug abuse is mentioned, one typically conjures up images of “street” drugs like heroin or prescription drugs like oxycodone. However, OTC drugs are also subject to abuse, but are not as well appreciated.16,17 The full extent of the problem is not readily apparent and usually focuses on cough and cold products containing dextromethorphan (discussed below). Relatively little research is available on OTC abuse and what is available is hindered by the variety and accessibility of OTC drugs and lack of surveillance mechanisms.16
Data on drug abuse provided by the National Institute on Drug Abuse (NIDA)18 does not separate OTC drugs into a distinct category, but the 2015 survey indicated that 4.1% of 12th graders used cough syrups non-medically in the previous year (however, this includes both OTC, [largely dextromethorphan] and Rx [largely codeine] containing products). Survey data examining the perception of pharmacists in Great Britain has found that nearly 70% of pharmacists have a “belief” that OTC drugs are being abused.19 Similarly a study in California found that OTC abuse, while relatively low, is highest in the adolescent age group, but the study was limited by methodological concerns.19 An older study from Utah showed that during the decade of the 1990’s, 38 percent of illicit drug use among children and teens involved OTC drugs.16 While the total impact of OTC is likely much lower than prescription drug abuse, it is nevertheless a factor of concern; a 2006 survey noted that more that 3 million individuals aged 12 to 25 used cough and cold preparations to get high, with a trend towards increased admissions to emergency rooms, drug treatment centers, and poison control center reports.16.17 Between 2004 and 2008, OTC-related emergency room visits increased by 70%.20 The incidence of OTC abuse is higher in adolescents who are also abusing other drugs such as alcohol, marijuana or prescription drugs.17,20
One researcher20 has identified five key groups of non-prescription medicines that are implicated in OTC abuse. These are: sympathomimetic decongestants, cough products, analgesics, antihistamines and laxatives. A more complete list of the likely top ten abused OTC drug categories is shown in Table 1.
|Table 1: Top 10 Abused OTC Drug Categories*
Caffeine and energy drinks
Laxatives and herbal diuretics
Motion sickness drugs
Sexual performance enhancing drugs
Herbal hallucinogens and stimulants
|*Adapted from (40)
The nonmedical use of non-prescription medications may be associated with dangerous consequences. These can include serious adverse health effects including potentially life-threatening complications, dependence and withdrawal syndromes.21 Some serious medical problems associated with the misuse of OTC drugs include psychosis, tachycardia, seizures, and agitation.20 Morbidity may be exacerbated by combined use of these drugs with alcohol or illicit drugs, as is commonly encountered, and by the presence of other substances found in the OTC product in addition to the drug that is the source of the abuse (e.g., acetaminophen, sympathomimetics, NSAID’s, etc.). The drugs also pose a risk for suicide; a 2004 national survey demonstrated that suicide-prone patients with a diagnosis of substance abuse are more likely to overdose on OTC medications.22
Most teens who misuse OTC medications are unaware of the potential risks. Because these drugs can be legally obtained and may have been given to them by their parents to treat an illness, adolescents often believe them to be safer than illegal drugs.16,23 This misconception may produce a false sense of security.17 In addition, OTC drugs are abused because they are relatively inexpensive and easily accessible (in many types of retail outlets and over the internet), are more socially accepted, and there is less risk of criminal penalties.16,17 Unlike alcohol or cigarettes, they can usually be purchased by adolescents without proof of age (see pseudoephedrine below as an exception).
Many adolescents start experimenting with OTC drugs for a variety of reasons, including to get “high”, relieve stress or anxiety, increase alertness while studying, or to fit in socially. In addition to the primary goal of obtaining rewarding or beneficial effects from the drug itself, abuse of OTC drugs may involve other features such as22:
- As a substitute for a preferred drug when it becomes temporarily unavailable or is difficult to obtain.
- As a substitute for the user’s drug of choice if faced with a drug test.
- In order to intensify the effects of another drug or to lessen the adverse effects of the user’s drug of choice.
Pharmacy personnel should be aware of the risk of OTC abuse and misuse. Many OTC products contain multiple ingredients which increase the risks (e.g., cough syrups) and an overdose may occur with combinations of OTC products or products combined with prescription drugs, alcohol, or street drugs.16Some examples of abused OTC drugs will be provided.
One of the most highly regulated OTC drugs in the U.S. is the decongestant pseudoephedrine (PSE). In this unusual case, the reason for the more stringent control is not due to the pharmacological effects of PSE itself, but due to the widespread use of PSE as a precursor in the chemical synthesis of methamphetamine. Methamphetamine is a widely abused stimulant drug which produces a brief, intense sensation, or rush, in those who smoke or inject it intravenously and which can produce dangerous adverse effects.
Restrictions were placed on retail sales of PSE as a result of Congressional passage of the Combat Methamphetamine Epidemic Act (CMEA) which became effective in 2006.24 The Act covers sales of phenylpropanolamine and ephedrine in addition to PSE, but since the first two decongestants were subsequently withdrawn by the FDA due to safety concerns, the Act now applies only to PSE.
Under the Act, purchasers are limited to 3.6 grams of pseudoephedrine base per day (not per transaction), and a total of 9 grams per month [7.5 grams for mail order] 24. Included in the provisions of the act are requirements that each seller subject to regulation (usually a pharmacy) must ensure that:
- Purchasers do not have direct access to the product before the sale is made, meaning that products must be placed in a secure location not ordinarily accessible to the general public. Most pharmacies place them behind the prescription counter, but other storage locations are permitted.
- A photo identification card issued by the State or the Federal Government or a document that is considered acceptable by the seller is presented.
- Must be 16 years old or older (most states raise this requirement to 18).
- A printed or electronic logbook listing sales is kept. Information must be kept for at least 2 years.
- The logbook for retail PSE purchases must contain the following information for each sale:
- Purchaser’s name and address
- Date and time of sale
- Name of product sold
- Quantity sold
- Purchaser’s signature
PSE represents a relevant example of the types of severe, restrictive conditions that can be placed on a drug despite the fact that it is OTC.
As noted above, dextromethorphan (DXM) is recognized as a major factor in OTC abuse; one recent study25 has observed that the most commonly abused drug among adolescents 13-19 years of age in the U.S. was DXM combined with an antihistamine or decongestant. Abuse is most common in males.25 The incidence of DXM abuse showed a steady increase in the first part of the 21st century but appears to have plateaued since 2006 at about 3% of teens, possibly as a result of legislative and educational initiatives.25
DXM is a widely used drug for the suppression of cough and is found in well over 100 OTC cough and cold products. 24 DXM is structurally related to the hallucinogenic street drug phencyclidine (PCP, “Angel Dust”) and has similar effects. DXM is often abused by adolescents in high doses to produce a feeling of euphoria and visual and auditory hallucinations. Illicit use of DXM is referred to on the street as “Robo-tripping”.21 Experienced users describe the effects of DXM as four dose-dependent tiers or “plateaus”.21,26
The first Plateau, occurring at 100-200 mg, is characterized by a mild inebriation with stimulation and mild hyperexcitability. The second Plateau (200-400 mg) results in an effect similar to alcohol intoxication, occasionally with mild hallucinations. The abuser's speech can become slurred, and short-term memory may be temporarily impaired. The third Plateau (300-600 mg) produces an altered state of consciousness in which the abuser's senses, particularly vision, can become impaired. In the fourth Plateau (500-1500 mg), the abuser experiences mind and body dissociation or an "out-of-body" experience and can lose some or all contact with his or her senses. The effects at this plateau are comparable to the effects caused by ketamine or PCP. High doses of DXM are metabolized through CYP2D6 to dextrorphan, which is the active form responsible for the hallucinogenic effects 27; peak levels of dextrorphan are achieved approximately 1.5 hours after ingestion. Some users may not experience the dissociative effects of DXM due to difficulty in metabolizing the drug to its active form; approximately 10% of the Caucasian population is believed to have such a genetic metabolic enzyme polymorphism.21
Note that the normal therapeutic dose for cough suppression is 15–30 mg. Thus, the plateaus described by users occur at doses 4–100 fold higher than the normal recommended dose. Experienced users report tolerance to the drug, as well as cravings for repeated use. An abstinence syndrome has also been reported and is associated with dysphoria and intense cravings.21
The clinical presentation of DXM intoxication depends on the ingested dose27. Mild intoxication produces tachycardia, hypertension, vomiting, mydriasis, diaphoresis, nystagmus, euphoria, loss of motor coordination, and giggling or laughing. Moderate intoxication may result in hallucinations and a distinctive, plodding ataxic gait that has been compared with “zombie-like” walking. Severely intoxicated individuals in a dissociated state may become agitated or somnolent. In agitated patients, hyperthermia and metabolic acidosis may develop. In addition, subjects consuming DXM cough preparations containing antihistamines may show anti-cholinergic effects.27
In response to the concern over the growing problem of abuse, at least 12 states28, (Alaska, Arizona, California, Delaware, Florida, Kentucky, Louisiana, New Jersey, New York, Tennessee, Virginia, and Washington) have enacted legislation to control the sale of dextromethorphan-containing products to minors. California became the first state to restrict sales of DXM in 2012 by requiring a prescription for purchases by individual under the age of 18. Tennessee and New Jersey are the most recent states, enacting regulations in 2016. At the Federal level, a bill was introduced in Congress in 2015 (DXM Abuse Prevention Act), but not yet enacted, which would restrict OTC sales of DXM to individuals 18 years of age or older.29
In addition to DXM, antihistamines which are also found in many cough and cold preparations, have a long history of abuse, especially among minors.30 Antihistamines reportedly produce sedative or hallucinogenic effects and are also abused by psychiatric patients because of their anti-anxiety effects.23,30
Some opiate addicts are turning to the anti-diarrheal drug, loperamide (Imodium), as an alternative to prescription opiates like oxycontin.31This drug was originally approved by the FDA as a prescription drug in 1976, and became an OTC drug in 1988. Loperamide has opiate-like properties in the GI tract, but poor oral bioavailability and minimal CNS penetration across the blood-brain barrier limits any CNS opiate effects after therapeutic oral dosing. However, central nervous system opioid effects do occur after supratherapeutic oral doses31 (anecdotally, as many as 100-200 tablets are taken at one time by abusers). Consequently, patients may resort to using the drug to get high or to reduce the symptoms of opiate withdrawal. National poison reporting data revealed a 71 percent increase in calls related to intentional loperamide exposure between 2011 and 2014, while the Upstate New York Poison Center experienced a seven-fold increase in calls related to loperamide abuse or misuse between 2011 and 2015.31
In cases of abuse, individuals often attempt to increase loperamide absorption and CNS penetration or inhibit its metabolism by combining it with other drugs in an effort to enhance its euphoric effects.32 Anecdotally, these include inhibition of efflux transport mediated by p-glycoprotein or the use of CYP3A4 inhibitors (e.g., cimetidine, black pepper).
Concern over the problem of loperamide abuse led the FDA to issue a warning that high doses could result in potentially fatal cardiac adverse events, including QT interval prolongation, Torsades de Pointes or other ventricular arrhythmias, syncope, and cardiac arrest.32
Abuse of laxatives has been characterized as falling into four demographic groups.33 One particularly significant group encompasses patients suffering from an eating disorder, such as anorexia nervosa or bulimia nervosa, who are concerned with body weight and shape and who may also abuse ipecac. Estimates of abuse in this patient group range between 10 – 60%.33,34 The other three groups are middle aged and elderly patients who began by treating constipation and who, over time, became tolerant to the effects; athletes in events where there are weight limits; and surreptitious users trying to maintain a fictitious bowel disorder.33
Abuse of laxatives often results in a vicious cycle of misuse, especially in the eating disorder group. Fluid loss results in dehydration and a compensatory activation of the renin-angiotensin system resulting in fluid retention and weight gain. These consequences lead to increased use of laxatives to eliminate the excess fluid weight.33 In all groups, the GI tract can become tolerant to the laxative effect and results in excessive use of laxatives to overcome the tolerance and achieve the desired effect. 33
Adverse effects of laxative use include diarrhea, GI cramping and pain, severe electrolyte disturbances especially hypokalemia, muscle weakness, cardiac arrhythmias and hemorrhagic and ischemic stroke, acid-base disturbances, renal and hepatic disorders, dehydration and death33,34
California has become sufficiently concerned with laxative abuse to enact a regulation making it a misdemeanor for an athletics coach to give laxatives to a minor for nonmedical purpose, such as to lose weight related to participation in a sport.34
In addition to laxatives, abuse of other OTC weight reduction products has emerged, including diet pills and supplements. It is estimated that 4% of adolescent boys and 6% of adolescent girls use diet products without the advice of a health care practitioner.34
Many pharmacies, as well as other retail outlets, sell e-cigarettes, electronic devices that deliver nicotine as a vapor through a container that resembles a tobacco cigarette. Many questions have been raised about e-cigarettes, including the long-term health effects of inhaling nicotine; the risks associated with their use by adolescents, including the possibility that using them may serve as a gateway to tobacco cigarettes; the health effects of inhaling propylene glycol which is vaporized during the “smoking” process; the health effects of flavorings often added to the mixture (which may also increase their appeal to youths); the health effects of toxic contaminants sometimes found in the device; concern about smoking becoming more socially acceptable; and the critical question of what effect they have (increase or reduce) on the smoking of conventional tobacco cigarettes.
In 2016, the FDA enacted regulations that place restrictions on e-cigarettes.35 Prior to 2009, the FDA had essentially no authority over any tobacco product, until Congress enacted the Tobacco Control Act (Family Smoking Prevention and Tobacco Control Act)36 which authorized the FDA to regulate the manufacture, distribution and marketing of tobacco products and covered cigarettes, cigarette tobacco and smokeless tobacco. For other products, the law authorized the FDA to “deem” them subject to regulations if the FDA determines it will be protective of the public health.36
In its new rule, the FDA deemed cigars, pipe tobacco, waterpipe tobacco and other products including electronic nicotine delivery systems (ENDS) subject to regulation.35 In essence these other products are subject to the same restrictions that the FDA may place on traditional tobacco cigarettes. In contrast, conventional products specifically intended for smoking cessation are generally subject to the FDA’s usual drug approval process for therapeutic agents.
In enacting the deeming provision, the FDA expressed concern over the “alarming” increase in the use of e-cigarettes by middle school and high school students. The FDA also noted that ENDS may deliver as much nicotine as traditional tobacco cigarettes and that the Surgeon General had stated that the adolescent central nervous system may be particularly vulnerable to the effects of nicotine. The FDA also cited the conclusion that “inhaled nicotine from a non-combustible product may be as addictive as inhaled nicotine delivered by combusted tobacco products.”35 In addition, accidental poisonings from children consuming the high concentrations of nicotine found in e-cigarette replacement cartridges are on the rise. The FDA concluded that benefits from adopting regulations include being able to better regulate the distribution of products which now can be readily found in mall kiosks and the internet; monitor individual products which may have distinct risks, including being more attractive to adolescents; improving quality control; and being able to regulate future products that may be promoted as “modified risk tobacco products.”35
Some key features of the e-cigarette regulations are age restrictions on sales, health warnings on product packages (‘‘WARNING: This product contains nicotine. Nicotine is an addictive chemical’’ or ‘‘This product is made from tobacco’’ if it does not contain detectable nicotine), prohibition of vending machine sales and distribution of free samples, and submission of ingredients to the FDA for review.35 Many independent and chain pharmacies have stopped selling traditional tobacco products; for an interesting discussion from the United Kingdom on the pros and cons of selling e-cigarettes in pharmacies, see reference 37.
Changes to FDA Regulations
The FDA is reconsidering how it regulates OTC drugs, recognizing that the current monograph system, enacted more than 50 years ago, is too cumbersome to adjust to emerging issues of safety and oversight and sought public input in 2014.38 Among the problems cited by the FDA are that there are many products for which there are no final monographs, some existing monographs may lack sufficient data for the FDA to determine safety and efficacy, and there are limitations on the ability of the FDA to quickly require new warnings or other labelling changes when new information on safety or efficacy emerge. The FDA has not announced what changes, if any, will be proposed and it has been noted that the FDA may require clear statutory authority from Congress to enact the most meaningful improvements.39 Technicians and pharmacists should anticipate that there will be changes in how OTC drugs are regulated, but the impact is unknown at this time.
SUMMARY AND CONCLUSIONS
OTC products are expected to be used by the consumer without the supervision of a health care practitioner and the consumer generally assumes that they are safer than prescription drugs. However, as noted in this manuscript, some OTC products present an unacceptably high risk of toxicity or are subject to abuse. The pharmacy technician and the pharmacist are at the front line of contact with the consumer and should be able to spot and prevent some types of misuse and abuse.
Pharmacy personnel should be mindful of regulatory changes at the Federal, State and Local level that would place limits on the distribution of OTC products. Some of the changes noted above include stricter warnings on labels, reductions in the amount of active ingredient contained in a dosage form or package, and age-related sales restrictions. Pseudoephedrine is a prime example of the restrictive steps a regulatory agency can undertake, short of reclassifying an OTC drug as a prescription product, when a problem with an OTC is identified. Since the restrictions on PSE are mandated by a Federal statute, the regulations are uniformly applied to all 50 states, although individual states can place additional restrictions (e.g., require a prescription for the drug) if desired. On the other hand, DXM represents an example where there are inconsistencies among states, since there may be age restrictions in one state but not in a neighboring state and the age restrictions could also vary among the states.
Pharmacies should recognize that an OTC designation is not a guarantee of safety and may consider being proactive, especially if they are faced with local problems that disproportionally occur in their community, and can take steps without waiting for the often cumbersome drawn out response by regulatory agencies. Some steps that pharmacies can take to prevent OTC drug misuse and abuse are listed in Table 2.
|Table 2: Steps Pharmacies Can Take to Address Suspected Problems of Misuse or Abuse of OTC Products.
|Counseling on OTC products
Expanded Warnings (written or verbal)
Requiring an ID
Pharmacist Only Sales/Behind the Counter
Limitations on Purchase Quantities
Refusal to Stock Certain Products (e.g., cigarettes).
|*Adapted from (40)
- U.S. Food and Drug Administration. Drug applications for over-the-counter (OTC) drugs. http://www.fda.gov/drugs/developmentapprovalprocess/howdrugsaredevelopedandapproved/approvalapplications/over-the-counterdrugs/default.htm
- Consumer Healthcare Products Association. FAQ's about the regulation of OTC medicines. http://www.chpa.org/FAQsRegOTCs.aspx
- Gianutsos G. Drug rescheduling and controlled substances. U.S. Pharmacist. 2013;38(10):49-56. http://bt.e-ditionsbyfry.com/publication/?i=178277
- Juhl RP. Prescription to over-the-counter switch: a regulatory perspective. Clin Ther. 1998; 20 (Supp. 3): C111-C117.
- U.S. Food and Drug Administration. What are over-the-counter (OTC) drugs and how are they approved? http://www.fda.gov/AboutFDA/Transparency/Basics/ucm194951.htm
- Woodcock J. Modernizing the other side of the counter: FDA oversight of non-prescription drugs. Health Affairs Blog. June 9, 2016. http://healthaffairs.org/blog/2016/06/09/modernizing-the-other-side-of-the-counter-fda-oversight-of-nonprescription-drugs/
- U.S. Food and Drug Administration. About the Center for Drug Evaluation and Research. http://www.fda.gov/AboutFDA/CentersOffices/OfficeofMedicalProductsandTobacco/CDER/
- U.S. Food and Drug Administration. Over-the-Counter Drug Approval Process. http://www.fda.gov/Drugs/DevelopmentApprovalProcess/HowDrugsareDevelopedandApproved/ucm317137.htm
- King JP, Davis TC, Cooper Bailey S, et al. Developing Consumer-Centered, Nonprescription Drug Labeling. Am J Prev Med. 2011; 40(6): 593-598.
- Yoon E, Babar A, Choudhary M, et al. Acetaminophen-Induced Hepatotoxicity: a Comprehensive Update, J Clin Trans Hepatology. 2016; 4(2): 131-142.
- U.S. Food and Drug Administration. Over-the-Counter Pediatric Oral Liquid Drug Products Containing Acetaminophen Guidance for Industry. August 2015. http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM417568.pdf
- Miller TC, Gerth J. FDA Opens Review of Rules for Over-the-Counter Drugs, Including Acetaminophen. ProPublica Feb. 27, 2014. https://www.propublica.org/article/fda-opens-review-of-rules-for-over-counter-drugs-including-acetaminophen
- Gerth J, Miller TC. Over-the-counter Pills left out of FDA Acetaminophen Limits. ProPublica Jan. 16, 2014. https://www.propublica.org/article/over-the-counter-pills-left-out-of-fda-acetaminophen-limits
- U.S. Food and Drug Administration. Acetaminophen Overdose and Liver Injury — Background and Options for Reducing Injury. http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/DrugSafetyandRiskManagementAdvisoryCommittee/UCM164897.pdf
- U.S. Food and Drug Administration. FDA recommends health care professionals discontinue prescribing and dispensing prescription combination drug products with more than 325 mg of acetaminophen to protect consumers. http://www.fda.gov/Drugs/DrugSafety/ucm381644
- Shi CW, Bayard MA. Abuse of Over-the-Counter Medications Among Teenagers and Young Adults. Am Fam Physician. 2011; 84(7):745-750. http://www.aafp.org/afp/2011/1001/p745.html
- Ford JA. Misuse of Over-the-Counter Cough or Cold Medications Among Adolescents: Prevalence and Correlates in a National Sample. J Adol Hlth. 2009; 44(5): 505-507.
- National Institute on Drug Abuse. Drug Facts – Prescription and over-the-counter medications. November, 2015. https://www.drugabuse.gov/publications/drugfacts/prescription-over-counter-medications
- Cooper RJ. Over-the-counter medicine abuse – a review of the literature. J Subst Use. Apr 2013; 18(2): 82–107 doi: 10.3109/14659891.2011.615002 PMCID: PMC3603170.
- Benotsch EG, Koester S, Martin AM, et al. Intentional misuse of over-the-counter medications, mental health, and polysubstance use in young adults. J Community Hlth. 2014; 39(4): 688-695.
- Levine DA. 'Pharming': the abuse of prescription and over-the-counter drugs in teens. Curr Opin Pediatr. 2007; 19:270–274.
- Lessenger JE, Feinberg SD. Abuse of prescription and over-the-counter medications. J Am Board Fam Med. 2008 Jan-Feb;21(1):45-54. doi: 0.3122/jabfm.2008.01.070071
- Conca AJ, Worthen DR. Non prescription drug abuse. J Pharm Pract. 2012; 25(1): 13-21.
- Drug Enforcement Administration. CMEA (Combat Methamphetamine Act of 2005). http://www.deadiversion.usdoj.gov/meth/
- Wilson MD, Ferguson RW, Mazur ME, Litovitz TL Monitoring trends in dextromethorphan abuse using the National Poison Data System: 2000-2010. Clin Tox. 2011; 49(5): 409-415.
- Drug Enforcement Administration. Dextromethorphan. (2014). http://www.deadiversion.usdoj.gov/drug_chem_info/dextro_m.pdf
- Burns JM, Boyer EW. Antitussives and substance abuse. Subst Abuse Rehabil. 2013; 4: 75-82.
- Consumer Healthcare Products Association. Dextromethorphan: Preventing Teen Cough Medicine Abuse. http://www.chpa.org/dex.aspx
- United States Congress. H.R.3250 - DXM Abuse Prevention Act of 2015. https://www.congress.gov/bill/114th-congress/house-bill/3250/text
- Reeves RR, Ladner ME, Perry CL, et al. Abuse of Medications That Theoretically Are Without Abuse Potential. So Med J. 2015; 108: 151-157.
- Eggleston WE, Clark AH, Marraffa JM. Loperamide Abuse Associated With Cardiac Dysrhythmia and Death. Ann Emerg Med. 2016; DOI: http://dx.doi.org/10.1016/j.annemergmed.2016.03.047
- U.S. Food and Drug Administration. FDA Drug Safety Communication: FDA warns about serious heart problems with high doses of the antidiarrheal medicine loperamide (Imodium), including from abuse and misuse. http://www.fda.gov/Drugs/DrugSafety/ucm504617.htm
- Roerig JL, Steffen KJ, Mitchell JE, Zunker C. Laxative Abuse: Epidemiology, Diagnosis and Management. Drugs 2010; 70(12): 1487-1503.
- Pomeranz JL, Taylor LM, Austin SB. Over-the-Counter and Out-of-Control. Am J Pub Hlth. 2013; 103(2): 220-225.
- U.S. Food and Drug Administration. Deeming Tobacco Products To Be Subject to the Federal Food, Drug, and Cosmetic Act, as Amended by the Family Smoking Prevention and Tobacco Control Act; Restrictions on the Sale and Distribution of Tobacco Products and Required Warning Statements for Tobacco Products. Federal Register May 10, 2016; 81(90): 28974-29106. https://www.gpo.gov/fdsys/pkg/FR-2016-05-10/pdf/2016-10685.pdf
- U.S. Food and Drug Administration. Tobacco Control Act. http://www.fda.gov/TobaccoProducts/Labeling/RulesRegulationsGuidance/ucm246129.htm
- Cressey D. E-cigarettes: The lingering questions. Nature 2014; 513 (7516): 24-26. http://www.nature.com/news/e-cigarettes-the-lingering-questions-1.15762
- Sukkar E. Should pharmacies sell electronic cigarettes? Pharm J Oct. 15, 2014 http://www.pharmaceutical-journal.com/news-and-analysis/event/should-pharmacies-sell-electronic-cigarettes/20066760.article
- U.S. Food and Drug Administration. Over-The-Counter Drug Monograph System-Past, Present, and Future; Public Hearing. http://www.fda.gov/downloads/Drugs/NewsEvents/UCM396836.pdf
- Zettler P. FDA reconsidering how it regulates (most) OTC drugs. https://law.stanford.edu/2014/02/25/lawandbiosciences-2014-02-25-fda-reconsidering-how-it-regulates-most-otc-drugs/
- Cohen MR. 10 Over-the-Counter drugs abused by teens. Posted January 14, 2013. http://www.philly.com/philly/blogs/healthcare/10-over-the-counter-medicines-abused-by-teens.html
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