Drug labeling refers to all of the printed information that accompanies a drug, including the label, the wrapping and the package insert. Drug labeling isregulated by the Food and Drug Administration's Division of Drug Marketing,Advertising, and Communications. These regulations apply to prescription drugs, over-the-counter (nonprescription) drugs, and dietary supplements.
The Food and Drug Administration (FDA) requires that drug labeling be balanced and not misleading. The label must be scientifically accurate and provide clear instruction to health care practitioners for prescription drugs and to consumers for over-the-counter drugs and supplements. Labeling regulations require that the statement of ingredients must include all ingredients, in the order in which they are used in the drug. These ingredients must also be identified by their established name.
In evaluating prescription drug labels, the FDA looks at the overall usefulness of the information that accompanies the drug. The name of the medicine along with any critical warnings must be given top billing. The label must describe the uses of the medicine along with the conditions under which the medicine should not be used. The consumer must be given directions for the contraindications; for example, "Talk to your health care professional before takingthis medication if any of these apply to you."
Under FDA regulations, the label must describe foods, drugs and activities that the patient should avoid while taking the medication, along with any related precautions. The drug manufacturer must spell out the symptoms of any adverse reactions to the drug. The FDA requires the manufacturer to collect thisinformation. If the patient faces any risk of drug tolerance or dependency while taking the drug, the label must contain a warning.
The label must include instructions for correctly using the medicine, including the dosage and what to do if the patient misses a dose. This description should cover any special instructions such as taking the medicine with food orwater. In addition, the label should spell out storage instructions and general instructions, such as discussing questions with a health professional, because the label is not intended to be all-inclusive. The label should warn ofthe danger of giving the drug to someone other than the patient.
Although the FDA is generally regarded as operating the world's most stringent agency for drug safety, occasionally problems will arise after the FDA approves a drug. Sometimes these problems can be addressed by tightening up the warnings on the drug label, and the drug can stay on the market. For example,six deaths and several serious but nonfatal infections were reported in patients taking the drug Enbrel for rheumatoid arthritis. The original drug labelsaid Enbrel should not be given to patients suffering from sepsis, a blood infection. After the adverse reaction reports of death and illness, the drug label warning was expanded to say that Enbrel should not be given to patients with any active infection. The drug manufacturer and the FDA worked together to develop the revised label. Adverse reactions should be reported to the FDAthrough MedWatch at 1-800-FDA-1088. Usually the patient's physician will handle the reporting.
The FDA has developed a special kind of labeling for a handful of drugs thathave the potential to cause significant health problems. The rules took effect June 1, 1999, for Medication Guides, usually called MedGuides. The FDA predicts that pharmacies will issue MedGuides for only five or 10 drugs per year.In these special cases, the FDA has determined that more detailed labeling could help prevent serious adverse effects. In addition, the FDA requires MedGuides when the patient needs more information on the drug's serious risk-to-benefit ratio, or when the patient needs emphasis on a strict set of instructions to take the drug safely. The FDA approves the text and estimates that thepharmacy's cost for each MedGuide will be five seconds of time and 9 cents for the cost of the leaflet. The goal is to limit the MedGuide to one or two pages, with foreign language versions available but not required. The MedGuideis given with each new prescription and each refill of the targeted drugs.
In 1996,long before the 1999 MedGuide regulation, pharmacy groups tried to develop a voluntary plan for alerting patients to special drug precautions. However, the FDA decided to enact its own MedGuide regulation so there would beuniform guidelines with the force of law. Many pharmacies distribute their own drug leaflets for all kinds of prescriptions, but these publications are not regulated by the FDA and do not necessarily offer complete information.
The 1990s saw other new developments in drug information, including the marketing of prescription drugs directly to consumers (DTC). Statistics gathered by the National Women's Health Network show that the pharmaceutical industry spent $900 million on DTC advertising in 1998, making it the 13th largest advertiser in the United States. In the same year, consumers spent $81 billion onprescription drugs. The FDA's rules for drug advertising are similar to itsrules for drug labeling. However, watchdog groups observe that DTC advertisements sometimes follow the letter of the law by including all of the precautions from the package insert, while using imagery of contented, happy patientsplayed by models to imply that taking the drug is a completely positive experience.
The FDA has been working to make drug labels better and to promote safer andmore effective use of drugs, particularly with regard to prescription drugs used in children. In 1994, a final rule was established to revise requirementson the pediatric use subsection of professional labeling requirements for prescription drugs. The rule allows more complete information about the use ofdrugs in children to be included. More than 70% of prescription drugs listedin the Physician's Desk Reference have no dosing information for treating children, and the lack of information is an obstacle to pediatricians. The American Academy of Pediatrics published an article speculating that pharmaceutical companies focus their research on adults because people spend a proportionately short period of their life as children. Thus, there is little economic incentive for pediatric pharmaceutical research. There are also ethicalconsiderations in enrolling children in clinical trials, since they are tooyoung to give informed consent. However, economic and ethical considerationsdo not detract from the pediatrician's dilemma of not knowing whether a drugis safe for a child and not knowing the correct dosage. Frequently, drugs arenot even available in units appropriate for children. Only five of the 80 drugs used most frequently in the United States have been approved for children. To address these concerns, in 1999 the FDA formed a pediatric committee ofits Center for Drug Evaluation and Research.
The lack of pediatric labeling has forced some doctors into off-label use ofprescription drugs. That is, a doctor will use a drug to treat a patient, even when the FDA-approved label does not list the use of the drug for the doctor's intended purpose. The American Academy of Pediatrics (AAP) concluded thatoff-label use of drugs in children can be appropriate if the doctor bases the prescription on thorough study of the medical literature, previous experience, or expert opinion. The AAP points out that the package insert, with its cautionary note that it does not contain all-inclusive information, is not intended as a substitute for the physician's sound medical judgement. Under limited circumstances, off-label prescribing may be used for a variety of patients, including adults. When an adult uses a drug on an off-label basis, it is frequently a matter of the drug producing an effect that has not been fully proven in the pharmaceutical research. However, it is the physician's responsibility to fully inform the patient of potential risks. It is in the pharmaceutical company's interest to collect information on how its drug is being usedand if there is sufficient scientific evidence, the FDA may then allow a claim that was previously off-label to appear on a product's label. In 1998, theFDA lost a landmark case that revolved around the distribution of informationabout the unapproved uses of a prescription drug. A federal judge ruled thatthe FDA's attempt to limit the publication of true information about the drug amounted to a trampling of the drug company's First Amendment rights. Advocates have observed a philosophical and political change in the relationship between the FDA and the pharmaceutical industry in the late 1990s. The trend is for the federal courts to see the patient as being able to make up his or her own mind, without quite as much protection being provided by the FDA.
On March 27, 1999, the FDA published a final rule to require a new label format on nearly all over-the-counter (OTC) drug labels. The new format makes themain messages of the labeling more prominent, includes easier-to-read type,presents information in a standard order, and includes other requirements tomake it easier to read labels. The new labels were required starting April 16, 1999, and affect 100,000 nonprescription products. The revised regulationsfor OTC drugs were modeled on the regulations for food labels, with an emphasis on consistency across the board. In many cases, the old labels carried a lot of information, but it was hard to find and interpret. A study reported inFDA Consumer showed that 70 percent of caregivers had trouble deciphering OTC instructions in order to give the correct medicine dose to a child.The FDA estimates the drug companies' cost of changing to the new OTC labeling at $58 million, but companies are permitted to use up stock with the old labels. Since OTC drug labels are routinely redesigned ever few years for marketing purposes, the FDA does not anticipate any undue burden on the drug industry. The trend has been to move products from prescription to OTC whenever possible; from 1979 to 1999, more than 600 drugs have been opened up to over-the-counter availability. These 1999 drugs contain ingredients and doses that were available only by prescription in 1979. Americans use about 5 billion over-the-counter drugs every year.
Dietary supplements also fell under the March 1999 FDA rule. The definition of dietary supplements has expanded to include herbs, botanicals and other plant-based products, amino acids and enzymes, as well as constituents and extracts of these substances. Dietary supplements also include sports supplementsfor athletes and products for weight reduction.
Each product must contain a label with "Supplement Facts" in bold letters onthe front panel. This is the manufacturer's opportunity to identify the product. Below "Supplement Facts," the panel must state the serving size. This isdetermined by the manufacturer with no input from the FDA. The product must list its proportion to the patient's full dietary intake or "Daily Value" (DV). This can be difficult to calculate based on variations in what people eat.For example, a person who drinks milk every day or eats other calcium-rich foods would not need as much calcium by tablet as someone who does not. The DVis based on a diet of 2,000 to 2,500 calories.
Dietary supplements are required to list the components of the product and the percentage of the DV. However, DVs have not been established for many dietary supplements, and this must be stated. If a nutrient claims to be "high potency," it must supply 100% of the DV with the exception of high potency multivitamins, which are required to supply two-thirds of the DV. Each supplementmust list the product ingredients on the label, along with the amount and DV.Other ingredients must be listed, along with a list of what the product doesnot contain. This is vital for consumers with allergies and sensitivities. Manufacturers must list cautionary warnings, typically for children and pregnant women. Any health claims on the labels are regulated and are vague, such as "provides nutritional support." Dietary supplement labels may offer claimsabout the structure and function of the product, but the must include the disclaimer, "This statement has not been evaluated by the Food and Drug Administration. This produce is not intended to diagnose, treatment, cure, or preventany disease." The label must list information on contacting the manufacturer. Reports of adverse reactions to dietary supplements may be made by a healthprofessional or by consumers at 1-800-FDA-1088 or www.fda.gov/medwatch/report/hcp.htm. False advertising claims may be reported to 1-877-FTC-HELP (toll free) or www.ftc.gov.