The "Prescription-to-OTC Switch" Movement
Its Effects on Antifungal Vaginitis Preparations
Martin S. Lipsky, MD;
Theresa Waters, PhD
Arch Fam Med. 1999;8:297-300.
More than 600 over-the-counter (OTC) products have ingredients or dosages that were previously available by prescription only. The criteria for switching drugs include a low potential for misuse or abuse, safety and efficacy, and the ability for effective use by the average person. In addition, the conditions the drugs treat should be benign and self-limited. In 1990, the first topical imidazole for candidal vaginitis was approved by the Food and Drug Administration for over-the-counter use. Suggested benefits of this switch were increased patient autonomy and reduced costs. Risks include potential for misdiagnoses, resulting in inappropriate use, unnecessary use, or delay in treatment, which could lead to increased cost and morbidity. Despite the wide use of these products, there is little evidence examining the outcome of the switch. Limited available data suggest that the switch of the antifungal preparations reduces costs with little objective evidence of harm resulting from the switch.
The "prescription-to-OTC switch" movement is a recent trend in which drugs that were previously available only by prescription become available as over-the-counter (OTC) products. More than 600 OTC drugs now use ingredients and dosages that 20 years ago were available only by prescription.1 The retail market value of these switched products totals about $8.8 billion and will most likely continue to increase in the future.2 Despite the substantial effects of OTC medications on medical care, the trend toward switching prescription medications to OTC status has not been extensively examined. We briefly discuss the OTC switch and examine the value and possible adverse effects of an OTC switch for one class of medications, the vaginal antifungal preparations.
THE OTC SWITCH MOVEMENT
Before 1938, all drugs except habit-forming or narcotic medications were available without prescription.3-4 In 1938, Congress passed the Food, Drug and Cosmetic Act, which required that all drug products on the market be safe and carry labels with detailed instructions for their proper use. The statute, however, exempted manufacturers from providing adequate labeling for drugs that carried a "caution" label. The caution label warned consumers that the medication should be used only as prescribed by a physician. The decision whether a drug should be available only by prescription, however, rested primarily with manufacturers. The Food, Drug and Cosmetic Act caused confusion for pharmacists because it did not provide clear standards for which drugs should be available for use by customers without prescriptions.
In 1951, the Durham-Humphrey Amendment5 set forth the statutory basis for distinguishing between prescription and OTC medications. The amendment specified that 3 classes of drugs be available by prescription6-7: habit-forming drugs, drugs that were unsafe for use except under expert supervision because of toxicity or other possible harmful effects, and drugs limited to prescription under a manufacturer's new drug application.
During the 1960s, the thalidomide controversy renewed government interest in the issue of drug regulation. In 1962, the Kefauver-Harris Amendment8 was passed, which required that drugs, including OTC medications, should be safe and effective for their labeled indications. Although full review of products for safety and efficacy was mandated by this amendment, this process did not begin in full force until 1972, when the Food and Drug Administration (FDA) convened expert panels to review medications.6 As a result of these massive reviews, many OTC products were withdrawn from the market or reformulated because there was insufficient evidence of their effectiveness. In addition, as part of this process, some medications were switched from prescription to OTC status.
In 1975, the FDA formalized the process of switching prescription drugs to OTC status by establishing 3 methods9: through an individually initiated petition, as a supplement to a new drug application submitted by the manufacturer, and through the OTC review process. Although the switching of some cold, cough, and allergy product to OTC status was initiated by the panel review process of the 1970s, most changes today are initiated by the manufacturer.
Although no formal guidelines exist for switching products from prescription to OTC status, the FDA uses several criteria for evaluating this change. First, switched drugs must be safe and effective without the supervision of a licensed practitioner. In addition, these drugs must have a low potential for misuse and abuse. The conditions these drugs treat should be common, benign, and self-diagnosable by the average person. Finally, the labeling instructions for OTC preparations must be understandable to the average person who will use the product.10
THE VAGINAL ANTIFUNGAL PREPARATIONS
Candidal vaginitis is one of the most common vaginal infections. Although exact figures are unavailable, about 3 of 4 women will have at least 1 incidence of infection in their lifetime, and about half of these women will have at least 1 recurrence.11-12 In 1990, the FDA approved the labeling of clotrimazole, an imidazole, as the first available OTC drug to treat vaginal candidal infections. Other antifungal medications, such as miconazole nitrate and butoconazole nitrate, have since been switched to OTC availability. Since these products have gone OTC, their use has increased rapidly. Sales have gone from prescription sales of 13.7 million units per year to more than 25 million units of combined prescription and OTC sales per year.13 Sales of the OTC antifungal products rose to more than $150 million in 1996.13
Clearly, the sales data suggest that there are powerful economic incentives for manufacturers to consider switching antifungal agents to OTC status. According to one industry survey,14 14 of the 23 drugs switched between 1975 and 1994 are now first or second in sales in their markets. For example, Monistat 7 [miconazole] became the top-selling vaginal antifungal agent within 3 months of going to OTC status in 1991. Monistat 7 was also nearing the end of its patent protection at the time of its switch. Drugs that are successfully switched from prescription to OTC status may be eligible for a 3-year extension on their patent life,14 thus providing another incentive for manufacturers to make this switch. In addition to protecting a drug from competition for another 3 years, a patent extension allows the company additional time to establish the OTC brand name in consumers' minds.
If the FDA criteria for an OTC switch are examined, the antifungal agents clearly meet the criteria for safety and efficacy. The topical antifungal drugs have a proven cure rate for vaginal candidal infections of 85% to 90%.15 These agents are also safe, with the most common adverse effects being local reactions such as stinging, burning, irritation, and pruritus.15 These local reactions occur in about 7% of women and are often caused by the vehicle, rather than a true drug effect. Serious adverse effects are extremely rare.
The most controversial aspect of the switch of fungal preparations to OTC status is the question whether the average person can self-diagnose yeast vaginitis. Symptoms related to candidal vaginitis include vaginal discharge, itching, soreness, discomfort, and dyspareunia. These symptoms are nonspecific, however, and could be caused by other pathogens or result from noninfectious conditions such as allergic or chemical reactions. Studies4, 12, 16-17 suggest that signs and symptoms have limited predictive value for physicians evaluating women with vaginal discharge. Although the criteria for the average person to self-diagnose do not require that no one make a mistake, many physicians are understandably concerned that patients may incorrectly diagnose their vaginal symptoms and inappropriately treat themselves for a yeast infection.18 Inappropriate diagnosis could lead to either the unnecessary use of antifungal agents or a delay in the treatment of a more serious condition.
Despite the apparent challenge of diagnosing candidal vaginitis, women generally feel confident about their ability to identify when they have a yeast infection.19 One explanation for this high level of confidence may be that the labeling instructions for the antifungal preparations state that only women who have been previously diagnosed by a health professional as having a yeast infectionand, thus, who can presumably recognize the symptomsshould use the product. The evidence20 to suggest that women can successfully recognize symptoms of vaginal candidiasis when they have been previously diagnosed and treated by a physician is limited. Despite clear labeling instructions, however, many women use the antifungal preparations without having been previously professionally treated for yeast vaginitis.19 These first-time users are less likely to correctly identify the cause of their vaginal discharge. Labeling instructions for the OTC preparations also advise women to seek professional advice for symptoms that persist despite treatment. Although not studied, perhaps this warning acts as a safety net that allows women to avoid serious consequences from misdiagnosis.
ADVANTAGES AND DISADVANTAGES OF SWITCHING ANTIFUNGAL AGENTS TO OTC STATUS
The primary advantages of switching the antifungal preparations to OTC status come from 2 health care trends. The first is a growing desire for patient autonomy. For many years, patients seemed content to consult physicians regarding their health and to comply with their recommendations. This model is becoming less popular and is being replaced by consumerism. Consumers of health care today are thought to be more informed, better educated, and consequently more able to make decisions about their health care. Health care professionals often encourage patients to take control of their health through lifestyle changes and becoming more knowledgeable about their medical problems. The movement to switch drugs from prescription to OTC status is consistent with the increasingly popular model of patients' central role in health care and affirms patients' control over their health and health care.21 Most American consumers generally embrace the concept of the increased availability of OTC medications, particularly to treat less severe medical conditions. About 60% of Americans attempt to treat their ailments without professional consultation and most often with an OTC medication.22 Women also appreciate the convenience and health empowerment that the OTC availability of vaginal antifungal agents provides. Some patients may prefer physicians who encourage and support responsible self-medication, which offers them more independent sources of information.23
The second major advantage is that health care experts view prescription-to-OTC switches as one means of reducing health care costs.24 The availability of OTC preparations may save millions of dollars by reducing the number of physician visits and the associated cost of a physician visit in travel and time lost from work. For example, it is estimated25 that Americans saved more than $1 billion in health care costs in the first 3 years after topical hydrocortisone acetate was switched to nonprescription status. One study26 that examined the effects of OTC availability of vaginal antifungal preparations on prescription patterns and physician services in a health maintenance organization (HMO) found that the switch reduced physician consultation and prescription costs to the HMO. Both the number of physician visits for vaginitis and the number of prescriptions for candidal vaginitis decreased considerably. Although there were substantial savings to the HMO for medications, some of the prescription savings were not true savings but represent the shifting of cost to patients because OTC medications were not covered by the health care plan.26 Cost shifting, however, was not a factor in the reduced number of physician visits and appears to represent a true reduction in health care costs. In addition, medication costs sometimes increase when the drug first goes OTC. In the long term, however, drugs that are switched to OTC status tend to go down in price when the patent runs out and competition becomes a factor.
Although a woman's opportunity to self-diagnose and treat vaginitis with OTC preparations appears to have considerable advantages, there are several possible disadvantages. These include the potential for misdiagnosis, an unnecessary use of the products in the absence of a yeast infection, a lack of a strong surveillance process for monitoring OTC products, and the risk that indiscriminate use may diminish these products' effectiveness. The most hazardous disadvantage of the OTC antifungal preparations is that if the medications are used for the wrong indication, delays in appropriate diagnosis and treatment may lead to increased cost and morbidity. Because the ability to diagnose vaginal infections by symptoms alone may be problematic, women with vaginal symptoms may use nonprescription remedies in a manner that will not benefit their condition. For example, the number of units of the antifungal preparations sold has increased dramatically since OTC availability, but there is no evidence of a concomitant increase in the incidence of yeast vaginitis. This suggests that some women use these products inappropriately. For those women who treat themselves unnecessarily, the primary risks are local irritation and the expense of ineffectual treatment. Potential adverse consequences for misdiagnosis seem greatereg, a woman who thinks her vaginal discharge is the result of a yeast infection could actually have a bacterial sexually transmitted disease, such as gonorrhea.
Despite this serious doubt about women's ability to self-diagnose vaginal candidiasis,12 there is little objective evidence that adverse consequences from self-treatment are a major issue. A survey19 of college students reported a high resolution of symptoms and level of satisfaction with the OTC antifungal preparations without any serious adverse effects. Although college students may represent a select, highly educated group, a study26 looking at an HMO population did not find any evidence of adverse effects from the switch of antifungal preparations from prescription to OTC. Perhaps a woman's ability to recognize serious symptoms or the labeling instructions to seek professional care if symptoms persist are sufficient to avoid serious problems. Still, postmarketing surveillance to examine the cost of unnecessary treatment and the actual risk of serious adverse effects seems appropriate. Yet, despite the perceived need to review products for OTC marketing, no formal surveillance system beyond the Adverse Drug Reaction System is in place once a drug becomes available OTC. Just as newly released prescription drugs need evaluation when used in typical clinical settings, it seems reasonable to monitor prescription products that are switched to OTC. It is possible that the real-world experience with a drug that has undergone this switch might be different from the product's profile as a prescription drug.
A final disadvantage of the switch of prescription drugs to OTC status is related to a shift toward more nonCandida albicans yeast infections causing vaginitis.27 In addition to the poor performance of imidazoles for treating nonC albicans yeast infections, the indiscriminate use of the OTC preparations may contribute to resistance and the change in the pattern of fungal infections.
The prescription-to-OTC switch movement results from the complex interaction of market forces. Both the growing desire of consumers to have greater control over their health care and economic factors have played important roles in this trend. The switch of drugs from prescription to OTC status presents opportunities to reduce health care costs and for the pharmaceutical industry to increase sales. The limited available information suggests that the switch of antifungal vaginal preparations from prescription to OTC status reduces health care costs and empowers consumers. Despite physicians' concern, there has been little objective evidence of serious harm resulting from this switch, and overall, it appears that the OTC availability of antifungal preparations may be beneficial. However, in view of studies that indicate that women may have difficulty self-diagnosing vaginal conditions, further studies and continued surveillance seem appropriate. In planning these studies, it will be important to balance the potential risks against the possible benefits while incorporating the perspective of consumers.
Reprints: Martin S. Lipsky, MD, Department of Family Medicine, Northwestern University Medical School, 303 E Chicago Ave, Morton 1-658, Chicago, IL 60611.
Accepted for publication October 15, 1998.
From the Department of Family Medicine, Northwestern University Medical School, Chicago, Ill (Dr Lipsky), and the Institute for Health Services Research and Policy Studies, Northwestern University, Evanston, Ill (Dr Waters).
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Changing the Status of Drugs from Prescription to Over-the-Counter Availability