A package insert (formally prescribing information in the United States; in Europe, Patient information leaflet for human medicines or Package Leaflet for veterinary medicines) is a document provided along with a prescription or over-the-counter medication to provide additional information about that drug.
In the United States, the Food and Drug Administration (FDA) determines the requirements for patient package inserts. Other national or international organizations that regulate medical information include the European Medicines Agency (EMA), and the Japanese Ministry of Health, Labour, and Welfare (MHLW). Other country-specific agencies, especially in the case of EU (European Union) countries and candidates, plus countries of South America and many in Asia and the Far East, rely heavily on the work of these three primary regulators. Unless otherwise stated, all information in this article refers to patient package inserts in the United States.
In the United States, the FDA will occasionally issue revisions to previously approved package inserts, in much the same way as an auto manufacturer will issue recalls upon discovering a problem with a certain car. The list of 1997 drug labelling changes can be found on the FDA's website, here.
The first patient package insert required by the FDA was in 1968, mandating that isoproterenol inhalation medication must contain a short warning that excessive use could cause breathing difficulties. The second patient package insert required by the FDA was in 1970, mandating that combined oral contraceptive pills must contain information for the patient about specific risks and benefits.)
Sections of a package insert
Package inserts follow a standard format for every medication and include the same types of information. Different manufacturers may have different titles for their sections, however, to make them easier for the average person to read and comprehend—for example, instead of "Contraindications" the section may be headed, "Who should not take this medication?"
The first thing listed is usually the brand name and generic name of the product. The other sections are as follows:
- Clinical pharmacology - tells how the medicine works in the body, how it is absorbed and eliminated, and what its effects are likely to be at various concentrations. May also contain results of various clinical trials (studies) and/or explanations of the medication's effect on various populations (e.g. children, women, etc.).
- Indications and usage - uses (indications) for which the drug has been FDA-approved (e.g. migraines, seizures, high blood pressure). Physicians legally can and often do prescribe medicines for purposes not listed in this section (so-called "off-label uses").
- Contraindications - lists situations in which the medication should not be used, for example in patients with other medical conditions such as kidney problems or allergies
- Warnings - covers possible serious side effects that may occur
- Precautions - explains how to use the medication safely including physical impairments and drug interactions; for example "Do not drink alcohol while taking this medication" or "Do not take this medication if you are currently taking MAOI inhibitors"
- Adverse reactions - lists all side effects observed in all studies of the drug (as opposed to just the dangerous side effects which are separately listed in "Warnings" section)
- Drug abuse and dependence - provides information regarding whether prolonged use of the medication can cause physical dependence (only included if applicable)
- Overdosage - gives the results of an overdose and provides recommended action in such cases
- Dosage and administration - gives recommended dosage(s); may list more than one for different conditions or different patients (e.g., lower dosages for children)
- How supplied - explains in detail the physical characteristics of the medication including color, shape, markings, etc., and storage information (e.g., "Do not store above 95°")
January 2006 revisions
The patient package insert issue was revisited in 1980 and in 1995 without conclusive action being taken. Finally, in January 2006, the FDA released a major revision to the patient package insert guidelines, the first in 25 years. The new requirements include a section called Highlights which summarizes the most important information about benefits and risks; a Table of Contents for easy reference; the date of initial product approval; and a toll-free number and Internet address to encourage more widespread reporting of information regarding suspected adverse events.
Other uses and initiatives
In addition to the obvious use of inclusion with medications, package inserts have been used or provided in other forms. In the United States, the package inserts for thousands of prescription medicines are available at the DailyMed website, provided by the National Library of Medicine: http://dailymed.nlm.nih.gov South Africa has taken the initiative of making all package inserts available electronically via the internet, listed by trade name, generic name, and classification, and Canada is working on a similar capability. The UK-based electronic Medicines Compendium provides freely-available online access to both Patient Information Leaflets (intended for consumers) and Summary of Product Characteristics (aimed at healthcare professionals) for products available in the UK.
Patient information is, understandably, usually generated initially in the native language of the country where the product is being developed. This leads to inconsistency in format, terminology, tone, and content. PILLS (Patient Information Language Localisation System) is a one-year effort by the European Commission to produce a prototype tool which will support the creation of various kinds of medical documentation simultaneously in multiple languages, by storing the information in a database and allowing a variety of forms and languages of output.
- 33 Fed. Reg. 8812 (1968) (codified at 21 C.F.R. §201.305)
- 33 Fed. Reg. 9001 (1970) (codified at 21 C.F.R. §310.510)
- Schumann, Bret M. "FDA Regulation of Patient Package Inserts." (rtf format)
- FDA Announces New Prescription Drug Information Format (Jan 2006)
- "Labeling Requirements for Prescription Drugs and/or Insulin". Code of Federal Regulations Title 21, 201.57. United States Food and Drug Administration. 2010-04-01. Retrieved 2011-04-01.
- Requirements on Content and Format of Labeling for Human Prescription Drug and Biological Products (pdf) - Part 1 - Part 2 - Part 3
- Powerpoint presentation on new format requirements
- Sample package insert (for Elmiron)
- Sample package insert (for human rabies vaccine)
- South African Electronic Package Inserts
- Publishing Requirements in the Pharmaceutical Industry - good overview of pharmaceutical publishing worldwide, includes an explanation of the PILLS initiative