specific medicines (as of July 2003) (Kennedy et al., 2004; FDA and Office of Women’s Health, 2006).

Negotiations about the wording of a drug label also come late in the process, when all the information about the drug has been pulled together. The label specifies conditions of safe use of the drug (CDER et al., 1998). It is the official description of a drug product and includes the drug’s indication; who should take it; adverse effects; special instructions for use of the drug in pregnant women, children, and other populations; and safety information for the patient. Although FDA can refuse to approve a drug if the sponsor fails to agree to what the regulators want in the label, the final label is typically a result of negotiations between regulators and sponsor.

In the case of serious safety concerns, FDA may direct the sponsor to highlight a safety warning in the label by putting a black box around it. These may be added to marketed drugs when new data become available. A recent example are antidepressant medications, which now require a black box warning describing the risk and emphasizing the need for close monitoring of suicidality of patients (FDA News, 2004).

Although the product labeling is intended to guide prescribers in use of a drug, studies show that prescribers often fail to follow the label (Public Health Newswire, 2006). For example, cisapride was contraindicated in patients at increased risk for cardiac arrhythmias, but 20 percent of its use was in such patients (Ray and Stein, 2006). The label for troglitazone specified that liver-function tests were required, but often they were not performed (Ray and Stein, 2006).

Some approved drugs (such as cisapride) have a narrow therapeutic index; that is, the toxic dose is close to the effective dose so that there is a small margin of error for triggering safety problems. Such drugs make it incumbent on the sponsor and FDA to develop careful risk management strategies and incumbent on practitioners to be cognizant of proper use. The Institute of Medicine report Preventing Medication Errors discusses matters related to patient comprehension of and adherence to medication labeling (IOM, 2007). In an effort to improve awareness of labeling directions, FDA in January 2006 announced a revision of the label format (FDA News, 2006a) (see Appendix A for more detail).

FDA requires sponsors to provide patient medication guides (known as MedGuides) for drugs with “special risk management information” (FDA and CDER, 2006a). There are 42 medications marketed by brand name and 38 by active ingredient that have MedGuides that must accompany them when they are dispensed (Wolfe and Public Citizen’s Health Research Group, 2005; CDER, 2006) (see Chapter 6 for additional discussion).

FDA has imposed restrictions on the distribution of some new drugs (such as drugs containing isotretinoin) which are discussed in Chapter 4. But there appears to be a lack of clarity about the scope of FDA’s authority



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