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New OTC Drugs and Devices 2001: A Selective Review Gail D. Newton, Andrea J. Benninghoff, W. Steven Pray, and Nicholas G. Popovich

Objectives: To create a heightened awareness of two important issues that arose over the past year with respect to over-the-counter (OTC) drugs the possible switching of nonsedating second-generation antihistamines to OTC status and the continuing need for pharmacists to learn about dietary supplements and herbal products—and to educate pharmacists about newly introduced nonprescription products, devices, and diagnostic products. Data Sources: Recently published clinical and pharmaceutical industry literature. Data Synthesis: In a historical precedent, a third party insurer rather than a pharmaceutical company is attempting to force the switching of several prescription nonsedating antihistamines to OTC status. In addition, several developments related to the manufacture and use of dietary supplements have created concern for consumers and the pharmacists who advise them. It is critical for pharmacists to become knowledgeable about dietary supplements so they can appropriately counsel patients on the benefits and risks associated with supplement selection and use. In addition, numerous nonprescription products, including home diagnostic products and accessories, will continue to become available on the U.S. market. It is important that pharmacists become as knowledgeable as possible about these and be capable of educating the consuming public about their appropriate use. Conclusion: Patients will continue to place an increasing emphasis on self-care. To assist them, pharmacists must remain up-to-date on trends and have a balanced understanding of new nonprescription products and dietary supplements. The new nonprescription medications and diagnostic products discussed in this review article represent valuable additions to the growing array of self-care products. J Am Pharm Assoc. 2002;42:267–77.

As have previous installments of this series of annual reviews, the first section of this article highlights important and timely issues regarding over-the-counter (OTC) products pharmacists must be prepared to discuss with patients. This year, we focus on specific developments in 2001 with regard, first, to the prescription-to-nonprescription switch of nonsedating antihistamines and, second, to dietary supplements. Both of these product categories are used widely by patients who are self-treating, and, in the case of dietary supplements, in particular, both need to be carefully considered when used concurrently with other drug therapies. The Received December 10, 2001, and in revised form January 25, 2002. Accepted for publication January 25, 2002. Gail D. Newton, PhD, is associate professor of pharmacy practice; Andrea J. Benninghoff is a doctor of pharmacy student, School of Pharmacy and Pharmacal Sciences, Purdue University, West Lafayette, Ind. W. Steven Pray, PhD, is professor of nonprescription products and devices, School of Pharmacy, Southwestern Oklahoma State University, Weatherford, Okla. Nicholas G. Popovich, PhD, is professor and head, pharmacy administration, College of Pharmacy, University of Illinois–Chicago. Correspondence: Nicholas G. Popovich, PhD, Department of Pharmacy Administration, College of Pharmacy, University of Illinois–Chicago, Suite 161 (M/C 874), 833 South Wood Street, Chicago, Ill 60612-7230. Fax: 312-996-0868. E-mail: [email protected].

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second section of the article describes the OTC medications, diagnostic products, and accessories introduced during the past year that we believe will generate the most questions from, or pose the most potential problems for, patients.

Rx-to-OTC Switch of Common Allergy Drugs The movement to switch prescription nonsedating second-generation antihistamines (i.e., Claritin [loratadine—Schering], Allegra [fexofenadine—Aventis], and Zyrtec [cetirizine—Pfizer]) to nonprescription status gained momentum this past year, although not from the usual source. It was not the manufacturers of the products but Blue Cross of California that petitioned the Food and Drug Administration (FDA) to switch these drugs to nonprescription status. Between 1993 and 1998, health care systems experienced a 600% increase in antihistamine use, and this growth was secondary to the wide acceptance of these newer agents, which were being prescribed more frequently than any of the first-generation antihistamines. Anticipating that the costs of these prescription medications would continue to rise, Blue Cross took the unprecedented action of attempting to control costs by shifting

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them to the consumer (i.e., an estimated $18 million savings to the insurance company). The petitioner for the switch argued that current increases in prescription drug costs are becoming unaffordable and unsustainable. Pointing out that 40 million Americans lack insurance coverage and 25 million senior citizens have no prescription drug coverage, the petitioner maintained that keeping these drugs prescription has no protective benefit for the general public and imposes a burden on the health care system. Furthermore, the petitioner’s opinion was that because consumers can readily recognize most allergy conditions and safely and successfully selftreat them, there was little rationale for keeping these drugs prescription. The drugs’ manufacturers disagreed. Supported by the American Academy of Asthma, Allergy, and Immunology, they argued that switching these nonsedating antihistamines to OTC status would directly undermine the physician-managed approach to patient care for allergies. The manufacturers pointed out that allergies are chronic and complex and require long-term management, not episodic treatment of symptoms. Furthermore, they argued, the fact that comorbid conditions (e.g., asthma, sinusitis, otitis media, urticaria) can affect up to 40% of allergy patients is another reason that these patients should be under the care of their physician. In their counterargument, the manufacturers also reasoned that the second-generation antihistamines tend to be used in these complex patients and are not effective for colds due to their lack of anticholinergic activity. Lastly, the manufacturers held that a reasonable assessment of likely OTC pricing would lead to the conclusion that millions of patients—in particular, lowincome and Medicaid patients—will be unable to afford these drugs even as OTC products and that the petition was a veiled cost-shifting maneuver. The manufacturers also contended that the second-generation antihistamines have not been on the market long enough to reveal whether they can be used safely by consumers without physician supervision and that effective postmarketing surveillance would not be possible unless they remained prescription drugs. They cited the experience with terfenadine (Seldane—Dow), a drug that had been on the market for more than 10 years when postmarketing surveillance demonstrated that numerous patients suffered serious cardiac abnormalities after using terfenadine in combination with drugs that inhibited its metabolism. If the products were switched to OTC status, the three manufacturers would quite likely have to reduce their prices to remain competitive (current costs range between $60 and $90 for a 1month supply). The petitioners, however, were assuming that the switched antihistamines would be sold OTC at the same dosage as the prescription products. By comparison, when the H2 antagonists were switched to OTC status, there was a 66% drop in price, as these products were marketed OTC at one-half of the prescription dosage. What is interesting about this process is that switch petitions are typically brought by drug manufacturers. This is only the sec-

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ond time in the past 18 years that FDA has received a switch petition without the support of the drug’s manufacturer. The first was the ill-fated Alupent (metaproterenol—Boehringer Ingelheim) switch, which was quickly reversed after the product became available OTC. On May 11, 2001, responding to the petition, the FDA Nonprescription Drugs Advisory Panel recommended to the agency that second-generation antihistamines be switched to OTC status.1 However, several panel members urged that the drugs’ labeling incorporate strong warnings (e.g., “Not for use in renal/ hepatic/pregnancy/children under 6 years of age without first consulting a physician”) and precautionary language (e.g., concerning use in patients with asthma, seizure disorders, cardiac disorders, bleeding disorders). Currently, the manufacturers and FDA are carefully considering their next response as all involved parties continue to evaluate additional research and comments of the panel members with respect to nonsedating second-generation antihistamines.

Dietary Supplements and Herbal Products Since 1994 dietary supplement sales have grown by nearly 80%, from $8.8 billion to an estimated $15.7 billion in 2000.2 Sales of specific herbal remedies, such as echineacea, ginseng, Ginkgo biloba, and St. John’s wort, have exceeded $200 million per product per year, and these products are routinely used by millions of Americans.3,4 Indirectly constituting a third class of drugs, herbal products and dietary supplements are of great interest and importance to pharmacists. Because of legislative action in 1994 under the Dietary Supplement Health and Education Act (DSHEA), the FDA regulations covering dietary supplements are different from those covering “conventional” foods and drug products. Under DSHEA, the manufacturer of a dietary supplement is responsible for ensuring that it is safe before it is marketed. FDA is responsible for taking action against any unsafe dietary supplement product after it reaches the market. Generally, supplement manufacturers do not have to register their products with FDA nor get FDA approval before producing and selling them. Manufacturers must make sure, however, that the information on their products’ labels is truthful and not misleading. Also, the Federal Trade Commission (FTC), not FDA, regulates dietary supplement advertising. FDA carries out postmarketing surveillance, which includes monitoring safety (e.g., voluntary dietary supplement adverse event reporting) and product information (e.g., labeling, claims, package inserts, accompanying information). In November 2001, for example, FDA alerted consumers and health care professionals about LipoKinetix, a weight loss product marketed by Syntrax Innovations. The product, which contains the ingredients norephedrine (syn. phenylpropanolamine or PPA), caffeine, yohimbine, diiodothyronine,

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and sodium usniate, was implicated in at least six cases of serious liver injuries (e.g., acute hepatitis, liver failure) involving patients 20 to 32 years of age. These injuries occurred between 2 weeks and 3 months after patients used LipoKinetix. No apparent cause of the liver injury was identified in these reports other than the use of LipoKinetix. In a similar postmarketing surveillance action, on December 19, 2001, FDA began investigating the dietary supplement kava kava (also known as kava or Piper methysticum), which is used for a variety of conditions, including relief of stress, anxiety, tension, insomnia, and postmenopausal syndrome. Kava use has been associated with liver toxicity in Germany and Switzerland.5 One of these patients required a liver transplant. While FDA did not remove kava-containing products from the market as its sister regulatory agency in Switzerland did, FDA has encouraged health care professionals to report any cases of hepatic toxicity that they believe would be related to the ingestion of kava-containing dietary supplements.5 Pharmacists must develop a fuller understanding of the uses and potential hazards of herbal products and dietary supplements for several reasons. First, it has been estimated that more than one-half of Americans are taking at least one dietary supplement.6 Thus, as demonstrated by the LipoKinetix situation, there is a consistent risk of adverse effects and/or drug interactions with other medications.7,8 One can only imagine the implication of a consumer using LipoKinetix for weight reduction while using acetaminophen for occasional pain relief. Because fewer than 1% of all adverse events associated with dietary supplements are reported to FDA, pharmacists do not have a total picture of the adverse effect profile of dietary supplements.9 Second, pharmacists are responsible for educating the consuming public about the dangers these products can pose. Often, because herbal products and dietary supplements are perceived as “natural,” older patients, in particular, do not inform their physicians about using them.2 Many do not believe this information is important for the physician to have, or they may passively wait for the physician to ask them specific questions.2 Others fear the physician’s disapproval and/or lack of understanding.2 What is obvious, then, is that there is a need to educate consumers that dietary supplements behave as “traditional” drugs and can exacerbate an existing medical condition and/or have serious drug interactions. Indeed, various reports from poison control centers and practicing physicians describe examples of patients being harmed by taking these supplements.10,11 Third, individuals may be treating themselves for a life-threatening condition (e.g., heart failure) when an existing prescription medication (e.g., enalapril) has been shown to decrease morbidity and mortality to a greater extent than herbal products used for the condition. Indeed, there is much misinformation on the Internet, for example, extolling the benefits of miracle cures. Even though dietary supplement labels can contain health-related claims only when there is a documented link between the product and a specific health condition, consumers may be overwhelmed and

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impressed by fancy Web sites and often do not know how to evaluate the information. Many are not equipped to critically examine claims that are exorbitant and not truthful. Fourth, consumers mistakenly believe that these products are manufactured using Good Manufacturing Practices (GMPs) that ensure quality control. Research has demonstrated that the dosage and ingredients indicated on the label are not always present in the product itself, which might even be contaminated.12 In an effort to provide manufacturing standards for these products, the United States Pharmacopeial Convention began to incorporate monographs for the more prominent herbal drugs in the last published edition of the United States Pharmacopeia 24/National Formulary 19 (USP 24/NF 19), and this has continued with the release of its newest edition in January 2002, the USP 25/NF 20. It is important to understand that inclusion does not guarantee a drug is effective. It merely provides standards for packaging and storage, labeling, botanic characteristics (e.g., physical appearance of the herbal), level of acceptable contaminants, and any additional requirements. In an attempt to continue to keep dietary supplements out of the direct supervision and control of FDA, in the past year, the dietary supplement industry initiated two efforts to address the problem of quality control. One effort is directed at the root of the quality control problem—the lack of standards—and the other at the consumer’s perception of product quality. With respect to the issue of quality control, NSF International, a nonprofit group that develops standards, certifies products, and provides education on public health issues, released a draft standard for dietary supplements.6 This standard, drafted with input from various stakeholders (e.g., American Pharmaceutical Association, Council for Responsible Nutrition), provides methodology and evaluation criteria that are designed to ensure that dietary supplements contain the ingredients listed on the product labels. This standard also specifies certain levels of specific contaminants that pose health risks when exceeded. Ultimately, when FDA publishes its final GMPs with respect to these products, the final rule will be incorporated into the NSF International standard. NSF International publishes listings of tested and certified products on its Web site (www.nsf.org). Certification ensures that a product contains the dietary ingredient(s) listed on the product label in the quantities specified and does not contain unacceptable quantities of contaminants. In a recent survey, consumers supported FDA review of drug safety before marketing, increasing governmental authority to remove unsafe products from the market, and providing more oversight of advertising claims about the health benefits of dietary supplements.2 Pharmacists must also be aware that in the near future the dietary supplement industry will be making a concerted effort to improve consumers’ perceptions of the production and safety of these products.6 The anticipated industry campaign will supposedly address how these products are regulated and reassure consumers that the federal government monitors the safety of these products and the accuracy of their claims and labeling. Consumers can expect to hear the following messages from this campaign:

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Manufacturing and safety regulations are in place for dietary supplements and are as stringent as those required for commonly used foods. New supplement ingredients can only be marketed after advanced FDA notification and demonstration of supporting safety data. Detailed nutrition information must be provided on the label of dietary supplements. Health-related claims are only allowed when there is a documented link between a dietary supplement and a specific health condition (e.g., psyllium helps prevent coronary artery disease, soy protein lowers the risk of heart disease). FTC regulates industry product claims in advertising. Hopefully, the standard issued by NSF International will help the industry improve the quality control of its products. Realistically, however, some companies will not comply with these standards, and the unfortunate possibility will likely remain that someone may be seriously injured or die from using a supplement. Thus, pharmacists must continue to play a major role in guiding consumers toward the safe and appropriate use of these products. They must also be vigilant for adverse drug effects and/or drug interactions associated with herbal products and dietary supplements and report them to FDA (www.cfsan.fda.gov/~dms/supplmnt.html) This vigilance is particularly important in light of the survey results of Blendon et al.,2 which demonstrate that many consumers felt so strongly about their own experience with the dietary supplement that they would continue to use the product even though it was shown to be ineffective in scientifically conducted clinical trials.

New OTC Drugs and Devices—2001 The following new product reviews were developed in the spirit of professional obligation. The authors are hopeful that the information will assist pharmacists in their interactions and consultations with patients. For each product covered, the Discussion subsection provides background and context, while the Patient Information/Instructions subsection highlights information pharmacists should share with patients in the course of counseling.

Dermatologic Disorders Topical W ound C are First Aid Advanced Care Quick Stop (Johnson & Johnson) Active Ingredient: Calcium alginate Indication: Bandaging wounds and stopping bleeding Availability: Boxes containing six sterile 3-inch square gauze pads

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Discussion: Once thought to be a sign of proper healing, a scab (consisting of necrotic cells, fibrin, blood products, exposed cells, and tissues such as collagen and elastin) is the body’s attempt to cover an air-exposed and dried wound with a temporary barrier. The scabbing process actually hinders wound healing because migrating epidermal cells must begin at the lower surface of the scab and slowly heal upward as the scab loosens. For this reason, wounds are best kept covered with a dressing that allows them to retain moisture. Such coverings keep all surfaces active in healing and prevent or minimize scabbing and scarring. First Aid Advanced Care Quick Stop is an innovative new wound dressing. In addition to providing an occlusive covering, it utilizes a technology that interweaves calcium alginate with the fibers. When the natural fibers come into contact with blood, a protective gel is formed that stops bleeding twice as rapidly as do regular gauze pads. The gel cushion restores the injured area to an optimal moisture level. Patient Information/Instructions: Clean the wound gently with a mild soap and water; pat dry. Place the woven lower side of the Quick Stop gauze pad on the wound, applying gentle, steady pressure for 1 minute. Do not move or lift the pad until bleeding has stopped. A gel will be visible as wound fluids are absorbed. The gel should not be removed or washed off. Once bleeding has stopped, remove and discard the first pad. Apply an antibiotic ointment to the wound to help prevent infection. If necessary, apply another Quick Stop pad to the wound; it can be worn for several days. Secure all four sides of the pad with a hypoallergenic latexfree tape, such as Hurt Free tape.

Gastrointestinal Disorders Antacid C hew ing G um Surpass Chewing Gum (Wm. Wrigley Jr.) Active Ingredient: Calcium carbonate 300 mg (regular strength), 450 mg (extra strength) Indication: Relief of heartburn Availability: Regular strength packages of 10, 30, or 60 pieces in wintergreen or fruit flavor, extra strength packages of 10, 20, or 45 pieces in wintergreen or fruit flavor Discussion: In any given 2-week period, approximately 25% of American adults suffer from at least one episode of dyspepsia.13 The conditions underlying this complaint range from mild heartburn to serious gastrointestinal ulcers. Despite the availability of H2 blockers and proton pump inhibitors, the demand for OTC antacids remains strong. One reason for this demand is that antacids provide symptomatic relief of dyspepsia much more quickly than do other available self-care agents. Antacids work by neutralizing stomach acid and increasing

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stomach pH. Antacid products contain salts of calcium, magnesium, or aluminum, alone or in combination. These products are available in a wide variety of dosage forms, including oral tablets, liquids (i.e., gels, suspensions, solutions), chewable tablets, and lozenges. All of these products are safe and effective for the relief of heartburn symptoms and can be used in conjunction with other agents for enhanced relief. However, individual patient responses and preferences vary widely. Potential disadvantages of liquid formulations include the chalky taste and inconvenient dosage form. Chewable tablets also have a chalky taste and may not be very palatable. Surpass gum is more palatable and more convenient. It is advantageous because chewing stimulates saliva production, which in itself is a natural defense against indigestion. Combined with the quick release of calcium carbonate from the gum, Surpass offers dual relief of heartburn symptoms. Further, in clinical trials, this relief was sustained for more than an hour after subjects stopped chewing.14 Surpass is sugar-free and does not stick to most dental work. Patient Information/Instructions: Because antacids may interact with certain prescription drugs, ask a physician or pharmacist before using this product if you are presently taking prescription medications. Stop using the product and consult a physician if symptoms worsen or persist for more than 2 weeks. Keep the gum out of reach of children. Chew one or two pieces as symptoms occur. Repeat hourly if symptoms return or as directed by a physician. Do not use more than 26 pieces in 24 hours; do not use this maximum dosage for more than 2 weeks.

Laxative Citrucel Caplets (GlaxoSmithKline) Active Ingredient: Methylcellulose 500 mg Indication: Constipation Availability: Boxes containing 100 caplets Discussion: Intestinal regularity is an elusive goal for many Americans. The numerous reasons for this include insufficient fluid intake, lack of exercise, travel, and a low-fiber diet. Patients often resort to harsh stimulant laxatives (e.g., bisacodyl, oral sodium phosphate/biphosphate, magnesium hydroxide, castor oil, sennosides) that force a drastic evacuation of solid, semisolid, or liquid stool. These products can deplete body fluids, leading to electrolyte imbalance, and their consistent use can lead to laxative dependence. Proper diet and bowel hygiene are the preferred first steps in treating constipation. Should these steps fail, the optimal laxative products for constipation are the fiber replacement products known as bulk laxatives. These act solely by replacing the fiber that may be lacking in the patient’s diet and do not cause a drastic catharsis. Taken as a daily supplement, bulking agents also prevent constipation.

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However, some patients prefer not to take liquid bulk laxatives, which may be inconvenient to use when one is away from home. Others find that certain bulk laxatives can cause intestinal gas. Citrucel Caplets, a new methylcellulose product, may benefit these patients. Methylcellulose is not fermented by intestinal bacteria. Therefore, it does not increase the intraluminal gas volume, which would cause flatulence. Patients taking Citrucel Caplets may expect a bowel movement to occur within 12 to 72 hours. Patient Information/Instructions: The product is not recommended for children under the age of 6 years. Children aged 6 to 12 years may take one caplet up to six times daily. Those over age 12 may take two caplets up to six times daily. The product should not be taken by those who have difficulty swallowing. If using a laxative to treat constipation, do not take the product for longer than 1 week unless directed to do so by a physician. Take each dose with 8 ounces of liquid. Failure to do so can cause choking because Citrucel can swell and block the throat/esophagus. If experiencing chest pain, vomiting, difficulty in swallowing, or difficulty in breathing after ingestion, discontinue the medication and seek immediate medical attention. If noticing a sudden change in bowel habits that persists for 2 weeks, consult a physician. Do not use any laxative when abdominal pain, nausea, or vomiting are present because these symptoms may indicate appendicitis. In the event of rectal bleeding or failure to have a bowel movement, consult a physician.

Home Medical Equipment Early Result Pregnancy Test First Response Early Result Pregnancy Test (ArmKel) Indication: Pregnancy detection Availability: Box of one or two pregnancy tests Discussion: During early pregnancy, the hormone human chorionic gonadotropin (hCG) is produced by the developing placenta and is detectable in the mother’s urine 1 to 2 weeks after conception. The presence of this hormone in urine is the definitive evidence in any pregnancy test. Since their introduction onto the market in the late 1970s, many at-home pregnancy tests have been available. All of these tests employ monoclonal or polyclonal antibodies in an enzyme immunoassay to detect hCG in urine. Most at-home pregnancy tests require a woman to wait until she misses her period before performing the test.

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In contrast, the First Response Early Result Pregnancy Test allows the user to determine whether she is pregnant prior to the expected start of the menstrual cycle. Patented technologic advancements in enzyme immunoassay allow First Response to detect lower levels of hCG than other products. As a result, it is the only at-home test that can be used 3 days before an expected period, which is 4 days earlier than any other at-home test. In clinical trials, First Response detected hCG in 52% of women 3 days before their expected period, in 69% of women 2 days before their expected period, and in 86% of women 1 day before their expected period.15 Other test kits are designed for use on the first day after a missed period and are 99% accurate. However, testing earlier can ease the stress of waiting to find out whether one is pregnant. When the early result is positive, women who have high-risk pregnancies can obtain appropriate prenatal care earlier. Patient Information/Instructions: This product is for in vitro diagnostic use and should not be taken internally. Read all package instructions before performing the test. Do not use after the expiration date stamped on the side of the carton. Store the product in a dry place below 86 F. Do not freeze. Keep the test out of reach of children. Remove the test stick from the foil wrapper and take off the overcap. Holding the test stick by the thumb grip with the absorbent tip pointing downward and the result window facing away from the body, place the absorbent tip in the urine stream for 5 seconds only. Alternatively, collect urine in a clean, dry cup and immerse the entire absorbent tip in the urine for 5 seconds. With the absorbent tip still pointing downward, replace the overcap and lay the stick on a flat surface with the result window facing up. The results may be read after 3 minutes. Two pink lines in the results window indicate that you are pregnant and should consult a physician. One pink line in the results window indicates that you are not pregnant. If your period does not start within 7 days after performing your first test, perform a second test. If the second test is negative and your period has still not started, consult a physician.

Oral Disorders Cold Sore Patch TheraPatch Cold Sore (LecTec) Active Ingredients: Camphor 0.5%, lidocaine 4.0% Indication: Temporary relief of pain and itch associated with cold sores Availability: Boxes of 21 patches Discussion: Approximately 60% of Americans have experi-

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enced at least one outbreak of herpes labialis. Fever blisters, or cold sores, are the most visible symptom of this condition. These viral lesions commonly occur on the edge of the lips or in or around the nose. The lesions are caused by the herpes simplex virus type 1 and can be spread to other individuals through skinto-skin contact. Once the virus enters the body, it is present for life and can go through periods of dormancy and reactivation. Approximately 25% of American cold sore sufferers experience recurrent outbreaks each year. Common reactivation triggers include emotional stress, sunlight, tanning booths, windburn, and fatigue.16 A typical outbreak of herpes labialis usually lasts between 7 and 10 days and proceeds through at least four stages. During the first stage, before the lesion develops, the skin tingles and itches. A small patch of skin rises to form a blister during the second stage. During the third stage, the blister bursts to form a weeping sore. During this stage, the skin can crack and cause pain when one is eating, drinking, or speaking. A scab forms and the lesion heals during the fourth stage. Prescription and nonprescription antivirals are available to speed the healing of cold sores, but these products do not alleviate pain and itching and may, in fact, cause more irritation.17 Safe and effective nonprescription products for the relief of pain and itching associated with cold sores contain external analgesic/anesthetic and/or skin protectants. Most of the available products come in ointment, gel, or liquid dosage forms. TheraPatch Cold Sore is unique in that the dosage form used to deliver the active anesthetic ingredients to the painful area is a topical patch. The patch is less messy and may provide relief longer than other dosage forms. Patient Information/Instructions: This product is for topical use only and should not be taken internally. TheraPatch may be used in adults and children who are 5 years of age and older. For best results, use the patch at the first sign of tingling, itching, or burning. This product is indicated only for the relief of pain and itching due to lesions in their early stages of development; do not use it on extensive lesions or on late-stage lesions that are open, oozing, or crusting. Clean and dry the affected area. Open one pouch and remove the enclosed card. Peel the adhesive patch from the card and apply the product to the affected area(s) not more than three to four times daily. More than one patch may be used at once if needed to completely cover the lesion. Thoroughly wet the patch for easy removal.

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Pain Relief Hangover Relief Alka-Seltzer Morning Relief (Bayer) Active Ingredients: Aspirin 500 mg, caffeine 65 mg Indication: Temporary relief of minor aches and pains, headache, fatigue, and drowsiness associated with morning hangover Availability: Boxes of 12 or 24 effervescent tablets Discussion: Costs associated with absences and reduced job performance related to hangover are estimated at $148 billion per year in the United States.18 While this condition is self-limiting, its symptoms (e.g., headache, tremulousness, nausea, diarrhea, fatigue) may persist for several days.19 Ingredients that may be helpful in alleviating hangover include analgesics, antacids, and caffeine. Alka-Seltzer Morning Relief is the first combination product created specifically for hangover relief that has received widespread publicity. Patient Information/Instructions: Alka-Seltzer Morning Relief temporarily relieves the minor aches, pains, fatigue, and drowsiness associated with hangover. This product is for occasional use only and does not substitute for sleep and rehydration. The product should not be used by children under the age of 12 or by patients who are on a sodium-restricted diet and/or who have ever had an allergic reaction to an analgesic or antipyretic drug. Pregnant or breast-feeding women should consult a health care professional before using this product. Use of aspirin during the last 3 months of pregnancy can cause problems for the fetus and complications during delivery. Patients with asthma, peptic ulcers, recurrent stomach problems (e.g., heartburn, upset stomach, pain), or bleeding problems should consult a physician before using Alka-Seltzer Morning Relief. While using the product, limit intake of caffeine-containing beverages and foods and limit the use of medications for nervousness, irritability, sleeplessness, and tachycardia. Patients who are taking anticoagulants or medications for gout, arthritis, or diabetes should consult a physician or pharmacist before using Alka-Seltzer Morning Relief. Patients who consume three or more alcoholic beverages per day should consult a physician before using any aspirin-containing product. Stop using this product and consult a physician if an allergic reaction occurs, the ears ring or hearing is affected, the pain worsens or lasts longer than 10 days, or new symptoms arise (e.g., erythema, inflammation).

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Prevention of Hygiene-Related Oral Disorders O ral Dental C are GUM Protect Toothbrush With Antibacterial Bristle Protection (Butler) Active Ingredient: Chlorhexidine coating on the bristles of the brush Indication: Oral cleansing Availability: Package containing one brush (medium or soft bristles) and two replacement heads; children’s brush with smaller heads also available Discussion: Toothbrushing removes bacterial plaque before plaque organisms undergo internal calcification to become calculus. However, to be effective, the standard toothbrush must be used properly. Many common habits undermine this proper use: The toothbrush may become contaminated if it is rewetted with each use; it is invariably kept inside the bathroom, a site saturated with moisture, yeasts, molds, and bacteria; and with each brushing, residual food particles become interspersed with the bristles, facilitating organism growth. The toothbrush should be changed monthly to help reduce the incidence of mouth and throat infections.7 The GUM Protect Toothbrush with Antibacterial Bristle Protection makes use of chlorhexidine-infused bristles. According to the manufacturer, chlorhexidine delivers an antibacterial effect for 30 days. Each package contains two replacement heads so that a new head can be attached every 30 days; thus, one package provides for 90 days of use. The toothbrush also features an interdental bristle trim that cleans between the teeth and a raised center bristle design that cleans below the gingival line. Patient Information/Instructions: Replace the head of the toothbrush every 30 days. A replacement reminder schedule is printed on the back of the package. Rinse the brush after each use. Reach Whitening Floss and Tape (Johnson & Johnson) Active Ingredient: Silica Indication: Tooth whitening Availability: Container with 27 yards of floss/tape Discussion: Visible staining of the teeth is a cosmetic disfigurement that can cause patients to become self-conscious and hesitant to smile. White paint, bleaching systems containing unacceptable amounts of hydrogen peroxide, and harsh abrasives that cause microetching of the dental enamel have been marketed as dental stain removers. However, numerous safe and effective toothpastes containing gentle abrasives are available that whiten

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the teeth without removing enamel. Crest Whitestrips, discussed in last year’s review of new OTC products,20 make use of a safe but effective gel strip that contains an acceptable level of hydrogen peroxide. To date, however, no product has been able to reach between the teeth (interdental spaces), which are usually inaccessible to tooth brushing. Cleaning the interdental spaces can be critical to oral cosmetic care since the heaviest stain deposits usually form between the teeth. If an interdental stain remains, it may be visible as an unusually dark area. Reach Whitening Floss and Tape is the first product developed specifically to remove stains between the teeth. The floss/tape is impregnated with silica, a safe antistain ingredient that is clinically proven to whiten teeth. Patient Information/Instructions: Wind 18 inches of floss around the middle fingers, leaving a working distance of about 4 inches of floss between the fingers. Grasp each end of the floss firmly between the thumb and index finger. Gently move the floss back and forth in the first interdental space to ease it down between the first set of teeth, making sure it does not snap down onto the gum with force. Move the floss up and down along the edge of the tooth. Make sure it moves gently below the gumline. Move to the opposing side of that interdental space and repeat the cleaning motions. Move to the next interdental space and clean as above. Repeat until all interdental spaces have been cleaned. Clean the distal surfaces of the back molars. When the floss begins to fray, use a new piece.

used in “superbonding” adhesives is now available. Covering the interior of the canker sore lesion with Orabase Sooth-N-Seal relieves pain by instantly sealing off the sore’s nerve endings. According to the manufacturer, its fast-setting adhesive interacts with the oral tissues to form a barrier that remains effective for up to 6 hours. Patient Information/Instructions: Patients who are allergic to cyanoacrylates should not use Soothe-N-Seal. Saturate the pointed end of one swab in the adhesive liquid. Because the product is a fast-setting adhesive, avoid touching any surface with the swab to prevent unintended bonding. Pull the lip or cheek away from the mouth sore. Turn the swab so that its rounded end (which has no glue on it) is facing the canker sore. Dry the canker sore by dabbing the lesion with the rounded end. Dab the pointed end of the swab (saturated with adhesive) on the canker sore for no more than 1 second. Dab one additional time if needed. Do not release the lip or cheek for at least 5 seconds. Lightly touch the canker sore to make sure a textured film covers it. Discard the swab. Reapply as needed every 6 hours. If the condition worsens or does not improve after 10 to 14 days, consult a physician.

Respiratory Disorders Single-Agent Cough Therapy

O ral Discom fort Relief Orabase Soothe-N-Seal (Colgate) Active Ingredient: 2-octyl-cyanoacrylate Indication: Canker sore pain relief and healing Availability: Container with 1 mL bottle of 2-octyl cyanoacrylate and 10 applicators Discussion: Recurrent aphthous stomatitis (canker sore) affects as many as 55% of people in the United States at some time in their lives.21 The lesions can be recognized by their round shape, shallow-cratered appearance, encircling red halo, and white-yellow pseudomembranous covering. They usually appear on intraoral tissue such as the inside linings of the cheek, lips, and tongue. The tissue breakdown characteristic of aphthous stomatitis apparently cannot occur when tissues overlie alveolar bone, such as the hard palate and gingiva. Canker sores heal after 7 to 14 days and do not cause scarring. To date, nonprescription therapies have been limited, consisting of local anesthetics, cleaning agents, and gingival protectants. However, a new product using the same ingredient

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DexAlone (DexGen) Active Ingredient: Dextromethorphan hydrobromide 30 mg Indication: Temporary relief of cough due to throat or bronchial irritations related to the common cold or exposure to inhaled irritants Availability: Packages of 10, 30, or 100 (for hospitals and clinics) liquid gelcaps Discussion: Coughing is often related to an underlying minor condition, such as the common cold, and is commonly accompanied by other symptoms (e.g., congestion, runny nose, headache). However, because symptoms of the common cold often change as the viral infection runs its course, a combination product that may be appropriate at one stage of a cold when multiple symptoms are present could place the patient at unnecessary risk for adverse effects when only one symptom is bothersome. Furthermore, combination products can cause more serious problems in specific patients. For example, patients who suffer from hypertension and/or diabetes should

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not use products containing decongestants because these can exacerbate the disease process. Similarly, these patients should also avoid products containing sugar, sodium, and/or alcohol. In many instances, using single-entity products allows patients to avoid adverse drug effects and prevents the exacerbation of certain disease states. DexAlone is a single-entity antitussive product that contains dextromethorphan. In addition to the benefits just cited, DexAlone gelcaps are much easier to carry on one’s person than liquid formulations. They are also less messy and more palatable. DexAlone is dosed every 6 to 8 hours, whereas many combination products must be taken every 4 hours. Patient Information/Instructions: DexAlone should be used only by adults and children 12 years of age and older. Do not use this product for persistent or chronic cough such as occurs with smoking, asthma, or emphysema. A persistent cough may be a sign of a serious condition. If a cough persists for more than 1 week, tends to recur, or is accompanied by fever, rash, or persistent headache, consult a physician. Do not use DexAlone if cough is accompanied by excessive phlegm unless directed by a physician. Pregnant or breast-feeding patients should seek the advice of a physician before using this product. Do not use DexAlone if you are currently taking certain drugs for depression, psychiatric/emotional conditions, or Parkinson’s disease. Do not use the product if you are currently taking or for 2 weeks after stopping a monoamine oxidase inhibitor (MAOI). If you are uncertain whether your prescription medication contains an MAOI, consult a pharmacist before taking this product. Take one gelcap every 6 to 8 hours; do not take more than four gelcaps (i.e., 120 mg) in 24 hours unless directed by a physician.

Cough Relief Patch Triaminic Vapor Patch (Novartis Consumer Health) Active Ingredients: Camphor 4.7%, menthol 2.6% Indication: Temporary relief of cough due to a cold, cough due to minor throat and bronchial irritation, cough that disrupts sleep Availability: Packages of six patches with cherry or menthol scent Discussion: Menthol and camphor have been used topically for many years to relieve symptoms of the common cold. When inhaled, the vapors of these volatile oils produce a local anesthetic effect in the upper respiratory tract that relieves cough. The advantage of topical antitussives

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over oral dosage forms is the absence of systemic adverse effects. As a result, topical dosage forms can be used with other cough and cold preparations without increasing the risk of systemic adverse effects. Topical dosage forms are useful for patients (especially children) who dislike the taste of liquid antitussives or who have trouble swallowing solid dosage forms. Menthol and camphor are available in combination as topical ointments and steam inhalants. However, these dosage forms have drawbacks. Ointment dosage forms, for example, are often greasy, messy, and difficult to remove from the skin. They can stain clothing and bed linens and damage fabrics. Steam inhalants can be inconvenient because they necessitate the use of a vaporizer or some other source of steaming water (e.g., a wash basin) to volatilize the active ingredients. In contrast, the Triaminic Vapor Patch is easy to apply, easy to remove, mess free, and does not require the use of additional equipment. Furthermore, the product is long-acting and suppresses cough for up to 8 hours. One minor problem that may occur is skin irritation. Patient Information/Instructions: This product is for external use only. Consult a physician before using the product in children under 2 years of age. Do not use Triaminic Vapor Patch near an open flame. Do not warm the product in hot water or in a microwave oven. Consult a physician if cough is accompanied by excessive phlegm or for persistent or chronic cough such as occurs with asthma. Stop using this product and contact a physician if cough lasts for more than 7 days, recurs, or is accompanied by fever, rash, or persistent headache. Consult a physician in the event of excessive skin irritation at the application site. The risk of skin irritation can be decreased by removing patches as directed and by rotating application sites. The vapor patch can be used with other cough suppressant products. Do not place the patch in the mouth, nostrils, on open wounds, damaged skin, or near the eyes. If a Triaminic Vapor Patch is swallowed, call poison control immediately and seek medical attention. For children 2 to under 12 years of age, apply one patch to the chest or throat. Wear clothing loosely on the throat and chest to help the vapors reach the nose and mouth. More than one patch may be used at the same time for added relief. Patches should be changed up to three times daily or as directed by a physician.

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Reproductive and Genital Disorders U rinary Tract Infection Test First Response Uriscreen Urinary Tract Infection Test (ArmKel) Indication: For home screening of urinary tract infections (UTIs) Availability: Box of two tests Discussion: UTIs lead to approximately 7 million physician visits by patients annually.22 Men and women may develop UTIs, but women do so more frequently before age 50 because they have shorter urethras than men. After age 50, however, men are more likely to develop UTIs due to age-related changes in the prostate. UTIs occur following the entry of bacteria into the bladder and upper parts of the urinary tract. The higher the bacteria ascends into the urinary tract, the greater the risk of kidney involvement. Thus, early detection of a UTI could minimize this risk. Home UTI tests are indicated for the early detection of infections in patients with recurring UTIs or with risk factors associated with UTIs (e.g., pregnancy, diabetes, urinary stones or other obstructions). Patients may also use these tests after completing a course of treatment with an antibiotic to determine whether the UTI has been cured. The First Response Uriscreen Urinary Tract Infection Test is the newest home UTI test. It detects catalase, an enzyme produced by white blood cells and most bacteria. Thus, unlike older tests, this product can detect infections secondary to Gram-positive microorganisms as well as Gram-negative bacteria. The test involves mixing a urine sample with test reagents, then adding an activator to the mixture. The presence of foam means a UTI may be present; absence of foam indicates no infection was detected. It is the same easy-to-read foam method test used in many physician offices. Patient Information/Instructions: This test is for in vitro diagnostic use. It is not to be taken internally. The test should be used by adults only. Keep it out of reach of children. Read all package instructions before performing the test. The kit consists of two collection cups, two droppers, two results tubes, and a vial containing enough activator for two tests. Collect a urine sample in one of the collection cups. Set up one test stand and place a results tube in the stand. Use one dropper to fill the results tube to the line indicated on the test stand. Using the dropper, slowly mix the urine sample with the tube contents. Add four drops from the activator vial to the results tube. Read the result after 2 minutes. White foam on top of blue liquid indicates that bacteria and/or

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leukocytes are present in the urine. In this case, contact your physician as soon as possible for treatment. A blue liquid without white foam constitutes a negative test result. However, contact your physician immediately if you have any signs or symptoms of a UTI (e.g., urinary urgency, urinary discomfort, fever), even if the test result is negative. Store the product at room temperature between 59 F and 68 F. Do not freeze. Avoid exposure to moisture. The ingredients in this kit may stain or irritate the skin. Avoid contact with skin, eyes, or clothing. In case of contact with the body, wash the affected part immediately with water. Do not use the test after the expiration date stamped on the carton. Do not open the kit until you are ready to use it. Dispose of the tube and vial in the regular trash after use.

Conclusion We anticipate that the trend toward patient self-care will continue. To give patients comprehensive and balanced information, pharmacists must “seize the moment” and make the commitment to remain up-to-date on trends and new products. The new nonprescription medications and the diagnostic products cited in this review represent valuable additions to the increasing array of selfcare products. The authors declare no conflicts of interest or financial interests in any product or service mentioned in the manuscript, including grants, employment, gifts, stock holdings, and honoraria.

References 1. Joint meeting of the Nonprescription Drugs Advisory Committee and the Pulmonary–Allergy Drugs Advisory Committee [transcript]. Bethesda, Md: Center for Drug Evaluation and Research, U.S. Department of Health and Human Services. May 11, 2001. 2. Blendon RJ, DesRoches CM, Benson JM, et al. Americans’ views on the use and regulation of dietary supplements. Arch Int Med. 2001;161:805–10. 3. Gugliotta G. Health concerns grow over herbal aids: as industry booms, analysis suggests rising toll in illness and death. Washington Post. March 19, 2000:A1. 4. Americans take health care into own hands: CHPA survey reveals consumers are comfortrable with self-care. CHPA Executive Newsletter. March 30, 2001:1–2. 5. Letter to health care professionals about FDA seeking information on liver injury and kava products. Bethesda, Md: Office of Nutritional Products, Labeling, and Dietary Supplements, Center for Food Safety and Applied Nutrition, U.S. Food and Drug Administration. December 19, 2001. Available at: www.cfsan.fda.gov/~dms/ds-ltr27.html. Accessed January 31, 2002. 6. Kingston RL. Industry issues draft standard launches PR campaign. APhA. DrugInfoLine. 2001;2(8):8. 7. Fugh-Berman A. Herb–drug interactions. Lancet. 2000(9198);355:134–8. 8. Gregory PJ. Drug interactions with St. John’s wort. The Pharmacist’s Letter. March 23, 2000:1 4. 9. Hume AL, Strong KM. Herbal products. In: Popovich NG, Tietze KJ, eds; Allen LV, Berardi RR, DeSimone EM II, et al., eds-in-chief. Handbook of Nonprescription Drugs. 13th ed. Washington, DC: American Pharmaceutical Association. In press. 10. Angell M, Kassirer J. Alternative medicine: the risks of untested and unregulated medicine. N Eng J Med. 1998;339:839–41.

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New OTC Drugs and Devices 2001 11. Jonas WB. Alternative medicine: learning from the past, examining the present, advancing to the future. JAMA. 1998;280:1616–7. 12. Gurley BJ, Gardiner SF, Hubbard MA. Content versus label claims in ephedra-containing dietary supplements. Am J Health Syst Pharm. 2000;57:963–9. 13. Gonzalez ER, Grillo JA. Over-the-counter histamine2-blocker therapy. Ann Pharmacother. 1994;28:392–5. 14. Information for healthcare professionals. Surpass Antacid Gum Web site. Available at: www.surpassgum.com/info/index.htm Accessed December 5, 2001. 15. Early detection/pregnancy testing. Pregnancy. Pharmacists Professional Resource Center. First Response Web site. Available at: www. 1stresponse.com/ce/index.asp. Accessed December 4, 2001. 16. Pray WS. Oral problems. Nonprescription Product Therapeutics. 1st ed. Baltimore, Md: Lippincott Williams and Wilkins; 1999:70.

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17. Anti-infectives, topical: antiviral agents. Drug Facts and Comparisons. St. Louis, Mo: Facts and Comparisons; 2002: 1627–8. 18. Wiese JG, Shilpak MG, Browner WS. The alcohol hangover. Ann Intern Med. 2000;132:897–902. 19. Pray WS. Gastric distress. In: Nonprescription Product Therapeutics. 1st ed. Baltimore, Md: Lippincott Williams & Wilkins; 1999:74–95. 20. Newton GD, Pray WS, Popovich NG. New OTC drugs and devices 2000: a selective review. J Am Pharm Assoc. 2001;41:273–82. 21. Pray WS. Plaque-induced diseases: caries and gingivitis. In: Nonprescription Product Therapeutics. 1st ed. Baltimore, Md: Lippincott Williams & Wilkins; 1999:33–52. 22. Bacheller CD, Bernstein J. Urinary tract infections. Med Clin North Am. 1997;81:719–730.

T H R O U GH T H E A GES

Merrell Digitalis Bag William Withering is credited with describing the action and dosage of digitalis in 1785 in his Account of the Foxglove. Almost another hundred years passed before Johann Ernst Oswald Schmiedeberg reported on the isolation of digitoxin. Digitalis was one of the major staples of materia medica in the first half of the 1900s and had a number of official preparations in the United States Pharmacopeia (USP), including fluid extract, infusion, and tincture (USP IX). A number of preparations were available commercially, but the United States Dispensatory of the period (20th edition) warned that the action of the whole leaf was different from that of any single constituent. It was important that the whole leaf be used exclusively; no more than 2% of stems, flowers, or other extraneous matter was allowed. For the compounding pharmacist of the day, the recipe for a USP standard infusion of digitalis specified that bruised digitalis leaves should be macerated in boiling water for an hour before cinnamon water was added. Merrell offered a bag containing standardized leaf that could be added to boiling water and, when well cooled, be bottled as 8 ounces of USP standard digitalis infusion. There was no need to worry about adulteration, weighing, or waste. The appeal to the pharmacist was clear. Dennis B. Worthen, PhD, Lloyd Scholar, Lloyd Library and Museum, Cincinnati, Ohio. Photo courtesy of the Lloyd Library and Museum.

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