INTRODUCTION
In the USA, drugs are divided by law into two classes: those restricted to sale by prescription only and those for which directions for safe use by the public can be written. The latter category constitutes the nonprescription or over-the-counter (OTC) drugs. In 2004, the American public spent more than $15 billion on over 100,000 OTC products to medicate themselves for ailments ranging from acne to warts. These products contain approximately 1000 active ingredients in various forms and combinations.
It is apparent that many OTC drugs are no more than "me too" products advertised to the public in ways that suggest significant differences between them. For example, there are over 100 different systemic analgesic products, almost all of which contain aspirin, acetaminophen, nonsteroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen, or a combination of these agents as primary ingredients. They are made different from one another by the addition of questionable ingredients such as caffeine or antihistamines; by brand names chosen to suggest a specific use or strength ("women's," "migraine," "arthritis," "maximum"); or by special dosage formulations (enteric-coated tablets, geltabs, liquids, sustained-release products, powders, seltzers). There is a price attached to all of these features, and in most cases a less expensive generic product can be equally effective. It is probably safe to assume that the public is generally overwhelmed and confused by the wide array of products presented and will probably use those that are most heavily advertised.
Over the past 30 years, the Food and Drug Administration (FDA) has been engaged in a methodical review of OTC ingredients for both safety and efficacy. There have been two major outcomes of this review: (1) Ingredients designated as ineffective or unsafe for their claimed therapeutic use are being eliminated from OTC product formulations (eg, antimuscarinic agents have been eliminated from OTC sleep aids, attapulgite and polycarbophil can no longer be marketed as OTC antidiarrheal products); and (2) agents previously available by prescription only have been made available for OTC use because they were judged by the review panel to be generally safe and effective for consumer use without medical supervision (Table 64-1). Since the appointment of the Nonprescription Drugs Advisory Committee in 1993, the rate of switches from prescription to OTC status has accelerated. Indeed, more than 700 OTC products contain ingredients and dosages that were available only by prescription less than 30 years ago. Some agents such as docosanol and the nicotine polacrilex lozenge have bypassed the prescription route altogether and have been released directly to the OTC market. Other OTC ingredients previously available in low doses only are now available in higher-strength formulations. Examples of other prescription drugs currently under consideration for OTC reclassification are orlistat for weight loss, and second-generation nonsedating antihistamines (cetirizine, fexofenadine) for relief of allergy and cold symptoms. The prescription to OTC reclassification process is very rigorous, and many agents have not been approved for OTC use. For example, the cholesterol-lowering agents cholestyramine, lovastatin, and pravastatin were denied OTC status on the basis that these agents could not be used safely and effectively in an OTC setting. The advisory committee believed that diagnosis and ongoing management by a health care provider was necessary for the management of hyperlipidemia, a chronic, asymptomatic condition with potentially life-threatening consequences. In a similar recommendation, oral acyclovir for OTC use in the treatment of recurrent genital herpes was not approved because of concerns about misdiagnosis and inappropriate use leading to increased viral resistance.
There are three reasons why it is essential for clinicians to be familiar with the OTC class of products. First, many OTC medications are effective in treating common ailments, and it is important to be able to help the patient select a safe, effective product. Because managed-care practices encourage clinicians to limit the cost of drugs they prescribe, many will begin to recommend effective OTC treatments to their patients, since these drugs are rarely paid for by the insurance plan (Table 64-2). Second, many of the active ingredients contained in OTC drugs may worsen existing medical conditions or interact with prescription medications. (See Appendix II, Drug Interactions.) Finally, the misuse or abuse of OTC products may actually produce significant medical complications. Phenylpropanolamine, for example, a sympathomimetic previously found in many cold, allergy, and weight control products, was withdrawn from the United States market by the FDA several years ago based on reports that the drug increased the risk of hemorrhagic stroke. Pseudoephedrine, a decongestant contained in numerous OTC cold preparations has been used in the illicit manufacture of methamphetamine. A general awareness of these products and their formulations will enable clinicians to more fully appreciate the potential for OTC drug-related problems in their patients.
Table 64-2 lists examples of OTC products that may be used effectively to treat common medical problems. The selection of one ingredient over another may be important in patients with certain medical conditions or in patients taking other medications. These are discussed in detail in other chapters. The recommendations listed in Table 64-2 are based on the efficacy of the ingredients and on the principles set forth in the following paragraphs.
(1) Select the product that is simplest in formulation with regard to ingredients and dosage form. In general, single-ingredient products are preferred. Although some combination products contain effective doses of all ingredients, others contain therapeutic doses of some ingredients and subtherapeutic doses of others. Furthermore, there may be differing durations of action among the ingredients, and there is always a possibility that the clinician or patient is unaware of the presence of certain active ingredients in the product. Acetaminophen, for example, is in many cough and cold preparations; a patient unaware of this may take separate doses of analgesic in addition to that contained in the cold preparation, potentially leading to toxicity.
(2) Select a product that contains a therapeutically effective dose.
(3) Carefully read the product labeling to determine which ingredients are appropriate based on the patient's symptoms and underlying health conditions and whatever is known about the medications the patient is already taking.
(4) Recommend a generic product if one is available.
(5) Be wary of "gimmicks" or advertising claims of specific superiority over similar products.
(6) For children, the dose, dosage form, and palatability of the product are prime considerations.
Certain ingredients in OTC products should be avoided or used with caution in selected patients because they may exacerbate existing medical problems or interact with other medications the patient is taking. Many of the more potent OTC ingredients are hidden in products where their presence would not ordinarily be expected (Table 64-3). Although OTC medications have standardized label formatting and content requirements that specify the indications for use, dosage, warnings, and active and inactive ingredients contained in the product, many consumers do not carefully read or comprehend this information. Lack of awareness of the ingredients in OTC products and the belief by many physicians that OTC products are ineffective and harmless may cause diagnostic confusion and perhaps interfere with therapy. For example, innumerable OTC products, including analgesics and allergy, cough, and cold preparations, contain sympathomimetics. These agents should be avoided or used cautiously by type 1 diabetics and patients with hypertension, angina, or hyperthyroidism. Aspirin should not be used in children and adolescents for viral infections (with or without fever) because of an increased risk of Reye's syndrome. Aspirin and other NSAIDs should be avoided by individuals with active peptic ulcer disease, certain platelet disorders, and patients taking oral anticoagulants. Cimetidine, an H2-receptor antagonist, is a well-known inhibitor of hepatic drug metabolism and can increase the blood levels and toxicity of drugs such as phenytoin, theophylline, and warfarin.
Overuse or misuse of OTC products may induce significant medical problems. A prime example is rebound congestion from the regular use of decongestant nasal sprays for more than 3 days. The improper and long-term use of some antacids (eg, aluminum hydroxide) may cause constipation and even impaction in elderly people, as well as hypophosphatemia. Laxative abuse can result in abdominal cramping and fluid and electrolyte disturbances. Insomnia, nervousness, and restlessness can result from the use of sympathomimetics or caffeine hidden in many OTC products (Table 64-3). The long-term use of some analgesics containing large amounts of caffeine may produce rebound headaches, and long-term use of analgesics has been associated with interstitial nephritis. OTC products containing aspirin, other salicylates, acetaminophen, ibuprofen, naproxen, or ketoprofen may increase the risk of hepatotoxicity and gastrointestinal hemorrhage in individuals who consume three or more alcoholic drinks daily. Recent evidence suggests the long-term use of NSAIDs may increase the risk of heart attack or stroke. Furthermore, acute ingestion of large amounts of acetaminophen by adults or children can cause serious, and often fatal, hepatotoxicity. Antihistamines may cause sedation or drowsiness, especially when taken concurrently with sedative-hypnotics, tranquilizers, alcohol, or other central nervous system depressants. Finally, antihistamines, local anesthetics, antimicrobial agents, counterirritants, p-aminobenzoic acid (PABA) and preservatives contained in a myriad of OTC topical and vaginal products may induce allergic reactions.
There are three major drug information sources for OTC products. Handbook of Nonprescription Drugs is the most comprehensive resource for OTC medications; it evaluates ingredients contained in major OTC drug classes and lists the ingredients included in many OTC products. Nonprescription Drug Therapy is an annually updated reference that provides detailed OTC product information and patient counseling instructions. Physicians' Desk Reference for Nonprescription Drugs, Dietary Supplements and Herbs, a compendium of manufacturers' information regarding OTC products, is published annually but is somewhat incomplete with regard to the number of products included. Any health care provider who seeks more specific information regarding OTC products may find useful the references listed below.
REFERENCES
Brass EP: Changing the status of drugs from prescription to over-the-counter availability. N Engl J Med 2001;345:810.
Consumer Healthcare Products Association Web Page: http://www.chpa-info.org/
Francis SA, Barnett N, Denham M: Switching of prescription drugs to over-the-counter status: Is it a good thing for the elderly? Drugs Aging 2005;22:361.
Handbook of Nonprescription Drugs, 15th ed. American Pharmaceutical Association, 2006.
Nonprescription Drug Therapy: Guiding Patient Self-Care, 4th ed. Facts and Comparisons, 2005.
Physicians' Desk Reference for Nonprescription Drugs, Dietary Supplements and Herbs, 27th ed. Thomson Healthcare, 2006.
US Food and Drug Administration: Center for Drug Evaluation and Research. Over-the-Counter (OTC) Drugs Web Page: http://www.fda.gov/cder/offices/otc/default.htm