Until the late 1960s, the FDA had not devoted much attention to the issue of manufacturers providing prescription drug labeling directed to the patient. The FDA's inattention to this issue changed dramatically in 1970 when it issued a regulation requiring that information for the patient, PPIs, accompany oral contraceptive drugs explaining the drugs' uses, risks, and precautions (21 C.F.R. § 310.501). The FDA initiated this action because of the widespread popularity of oral contraceptives and the relative lack of awareness by women of the drugs' potential serious adverse effects, especially thrombophlebitis and pulmonary embolism. If this information is not contained on or in the product package, it must be provided as leaflets with the product. Furthermore, the manufacturer must instruct the pharmacist to distribute a leaflet with each prescription.

On the heels of this regulation, the FDA enacted regulations in 1977 requiring PPIs for estrogen-containing drugs (21 C.F.R. § 310.515), such as conjugated estrogens and diethylstilbestrol (DES) not intended for oral contraceptive use, and progestational drugs (21 C.F.R. § 310.516). The PPI requirement for progestational drugs was repealed in 1999; however, if a progestational drug is intended for use as an oral contraceptive, the oral contraceptive PPI is required. (Note: The FDA issued a draft guidance for noncontraceptive estrogen drug products in November of 2005 (https://www.govinfo.gov/app/details/FR-2005-11-16/05-22754). The authority of the FDA to promulgate these regulations was upheld in the case of Pharmaceutical Manufacturers Association v. Food and Drug Administration (discussed in detail in the case studies section of this chapter).

Manufacturers must include a PPI for each package that it intends will be distributed to the patient, and in turn, pharmacists must include a PPI with each container dispensed regardless of whether it is initially dispensed or a refill. Failure to do so is misbranding. PPI regulations apply not only to community pharmacies but also in a modified form to institutions. An institution may provide the PPI to the inpatient the same as to an ambulatory patient, or it may provide the PPI before the administration of the first dose and then once every 30 days thereafter. In Schlieter v. Carlos, Nos. 87-0955 SC, 11592 SC (D.N.M. Aug. 1989), an inpatient contended that the hospital was negligent in not providing her with a PPI when she was given estrogen (Premarin). The defendant hospital argued that it had a right to rely on the treating physician to provide the PPI if the physician so wished. The court disagreed, establishing that an institution cannot delegate its responsibility for providing a PPI to the prescribing physician. The court concluded that the intent of the regulation is that patients, not physicians, must be given the information.

Firmly believing in the importance of written drug information for patients, in 1980, the FDA enacted regulations requiring PPIs for all prescription drugs (45 Fed. Reg. 60754, Sept. 12, 1980). The proposal received strong opposition, however, from physician and pharmacy organizations on the grounds that the program would be unduly expensive and burdensome for providers and would not achieve the patient outcomes desired. Many of these organizations then proposed alternative means of providing information to the patient, causing the FDA to agree that private sector initiatives were preferable to a government-mandated program and to revoke the regulations (47 Fed. Reg. 39147, Sept. 7, 1982).