Increasing patient involvement in the diagnosis and treatment of common ailments has led to a greater interest in self-care and an increase in the use of nonprescription drug products. Nonprescription medications now account for about 60 percent of all medications used in the United States¹ and may be used to treat or cure about 400 ailments.² Thirty percent of new over-the-counter (OTC) drugs marketed between 1975 and 1994 were products that had been changed from prescription to OTC status.³ This article reviews the process by which drug products are approved for OTC use and changed from prescription to OTC status, lists the criteria that must be met before such a change may be approved, describes the potential impact of reclassified products on the U.S. health care system, discusses patient counseling about OTC products, and outlines the relevant drug category, active ingredients, indications for and usual dosages of products that have recently changed from prescription to OTC status.

FDA Approval Process

The Food, Drug, and Cosmetic Act of 1938 was the first piece of legislation to require that drugs be cleared by the U.S. Food and Drug Administration before being marketing for human use. This act required that all new drugs be proved safe for human use before marketing, prohibited the sale of dangerous, contaminated or misbranded products, and mandated labeling specifications. A new drug application (NDA) has been required for all new drug entities that have been introduced since the enactment of the Food, Drug, and Cosmetic Act. After an NDA is approved by the FDA, the drug product may be marketed only by the sponsor of the NDA. Additional manufacturers who wish to market similar products must seek approval to do so through submission of a separate NDA. In some cases, such as with generic medications, an abbreviated NDA may be submitted. NDAs are updated periodically to include postmarketing information and minor label changes.

In 1951, the Durham-Humphrey amendments to the Food, Drug, and Cosmetic Act established the distinction between prescription and OTC drugs. For drugs that could not be labeled with sufficient instructions to allow safe, unsupervised use by consumers, these amendments allowed labeling directed to physicians and pharmacists instead of to consumers. Drugs with physician- and pharmacist-directed labeling were then available by prescription only.

In 1962, the Kefauver-Harris amendments to the Food, Drug, and Cosmetic Act were passed, requiring that drug products be proved not only safe but also effective for their intended uses. Enactment of these amendments compelled the FDA to determine the effectiveness of more than 4,000 newer drug products, including more than 500 OTC products, that had been marketed before the enactment of the amendments. The OTC Drug Review was begun in 1972 as an FDA-initiated scientific review of OTC product ingredients in use at that time to ensure that appropriate safety, effectiveness and labeling standards are met. This review process consists of three phases: an advisory panel review, creation of a tentative monograph and publication of a final monograph.

During the first phase, a panel composed of scientists appointed by the FDA categorized each active product ingredient as belonging to Category I (generally recognized as safe and effective for the claimed therapeutic indication), Category II (not generally recognized as safe and effective or having unacceptable indications) or Category III (insufficient data available to permit final classification). The panel also recommended any labeling changes it deemed necessary, such as those involving dosage instructions or warnings about side effects.

After completion of the advisory panel review the FDA evaluates the findings of the panel, taking into account public commentary and newly available data when appropriate. Initial conclusions regarding the ingredients of the drug are published as a proposed monograph. The agency responds to each comment submitted about the proposed monograph, and a tentative final monograph is produced. The final monograph is published only after consideration of further comments and review of any additional data. In cases in which data are insufficient to formulate a monograph, negative monograph regulations are established. Thus, negative monograph regulations describe only ingredients that cannot lawfully be marketed for human use or those with labeling that contains unacceptable claims. Such ingredients are called “nonmonograph ingredients.”

As a result of the initial OTC drug review findings, approximately 33 percent of available OTC ingredients were determined to be safe and effective for their intended uses. About 33 percent were found to be ineffective, a small number were considered to be unsafe and the remainder required submission of additional data before safety and effectiveness could be established.

Reclassification Process

More than 40 primary product ingredients have been reclassified from prescription to OTC status as a result of the OTC Drug Review. In addition, there are three ways to make such a change outside of the drug review process.⁴ (1) If new clinical research provides information that allows a drug to be approved for an OTC indication or at OTC dosage levels, a new NDA may be filed by the manufacturer. (2) The FDA itself is allowed to file a petition for reclassification if it is determined that prescription status is not required for safe use of the drug. (3) A supplement to the original NDA may be filed if favorable postmarketing safety experience for a product provides evidence that the drug product may be safely used without supervision by a physician. Although these procedures have been criticized as overly time-consuming,⁵ they are structured to ensure that products that are reclassified to OTC status are safe and effective when used by the average consumer. The FDA's Nonprescription Drugs Advisory Committee provides direction to manufacturers who wish to send products through the reclassification process.

Reclassification Criteria

Before the FDA considers a prescription drug product for reclassification to OTC status, the drug must meet certain criteria. First, the indication or indications for which the product is to be used on an OTC basis should be similar to its prescription indication or indications and must permit easy diagnosis and monitoring by the patient. Second, the drug should have favorable adverse-event and drug-interaction profiles, relatively low toxicity and a low potential for abuse. This information is derived from clinical trial results and postmarketing safety surveillance data, and it is submitted to the FDA by the manufacturer of the product. Finally, the drug should not have properties that make it impractical for OTC use, such as special monitoring requirements or a narrow therapeutic index.⁶

Impact of Reclassified Products

Changing drugs from prescription to OTC status permits patients to conveniently and effectively self-treat a number of minor ailments. Consumers view reclassified products as strong, economic therapies.² Nine of the top-10 selling OTC products in 1993 were products that had been reclassified from prescription to OTC status, and it has been predicted that reclassified products will cause the $11 billion in OTC sales that occurred in 1993 to double by the year 2010.⁷ According to one argument, by allowing patients to self-treat minor illnesses, physicians are allowed more time to care for patients with more serious health problems.⁸ However, only 40 percent of physicians responding to a 1995 survey approved of reclassification of products from prescription to OTC status.⁸

Changing a product's status from prescription to OTC often allows the manufacturer to market the product for several more years without generic competition.⁹ Sales volume also increases when a product is reclassified to OTC status.⁷ Increased sales volume allows the manufacturer to decrease the retail cost of the product while maintaining profitability.⁷

Out-of-pocket costs for patients may increase somewhat with product reclassification because few third-party health insurance payers provide reimbursement for OTC products. Overall health care costs, however, may actually decrease because of the reduction in drug costs and elimination of office visits and pharmacy dispensing fees.¹⁰ Reclassifying cough and cold products to OTC status, for example, has resulted in an annual consumer health care savings of approximately $1 billion.²

Table 1 lists recently reclassified products and summarizes information regarding active ingredients, indications, costs and dosages for each product listed. Product labeling should be consulted for complete information on the use of these products.

Patient Counseling

Although manufacturers are required to provide appropriate OTC labeling for products classified as OTC medications, patients who are inexperienced in the interpretation of medication labels may have difficulty reading and understanding label instructions.¹¹ This difficulty could result in misuse of the product, leading to adverse events or drug interactions with prescription medications or other OTC medications.¹² Another concern with reclassified products is that their use may delay effective treatment of more serious medical disorders because symptoms are relieved by an OTC medication. To help prevent these problems, health care professionals should be prepared to effectively counsel patients regarding appropriate use of OTC medications.

Up to 60 percent of patients consult a health care professional when selecting an OTC product,⁸ so health care professionals have an excellent opportunity to prevent common problems associated with the use of reclassified drugs and other OTC products. Patients should be provided with verbal information about choosing an appropriate product, correct dosing, common side effects and drug interactions with other medications. While not possible in every situation, an effort should be made to verify that the patient understands the information provided. Asking questions such as, “Just to be sure that I did not forget to tell you anything important, will you tell me how you are going to use this medicine?” after counseling can help the physician assess a patient's understanding and recall of information.¹³ Written information can be provided as well but may be less effective without verbal instructions.