Package insert
Encyclopedia
A package insert or prescribing information (in Europe, Patient information leaflet
for human medicines or Package Leaflet for veterinary medicines) is a document provided along with a prescription medication to provide additional information about that drug
.
(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.)
The first thing listed is usually the brand name and generic name of the product. The other sections are as follows:
, better known as the PDR. 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.
Patient information leaflet
Patient information leaflets are leaflets containing specific information about medical conditions, doses, side effects that packed with medicines to give the user information about the product. PIL is the European version of the Package insert. The PIL is written by the manufacturing...
for human medicines or Package Leaflet for veterinary medicines) is a document provided along with a prescription medication to provide additional information about that drug
Drug
A drug, broadly speaking, is any substance that, when absorbed into the body of a living organism, alters normal bodily function. There is no single, precise definition, as there are different meanings in drug control law, government regulations, medicine, and colloquial usage.In pharmacology, a...
.
Responsible agencies
In the United States, the Food and Drug AdministrationFood and Drug Administration
The Food and Drug Administration is an agency of the United States Department of Health and Human Services, one of the United States federal executive departments...
(FDA) determines the requirements for patient package inserts. Other national or international organizations that regulate medical information include the European Medicines Agency
European Medicines Agency
The European Medicines Agency is a European agency for the evaluation of medicinal products. From 1995 to 2004, the European Medicines Agency was known as European Agency for the Evaluation of Medicinal Products.Roughly parallel to the U.S...
(EMA), and the Japanese Ministry of Health, Labour, and Welfare
Ministry of Health, Labour and Welfare (Japan)
The ' is a cabinet level ministry of the Japanese government. It is commonly known as Kōrō-shō in Japan. This ministry provides regulations on maximum residue limits for agricultural chemicals in foods, basic food and drug regulations, standards for foods, food additives, etc.It was formed with...
(MHLW). Other country-specific agencies, especially in the case of EU (European Union
European Union
The European Union is an economic and political union of 27 independent member states which are located primarily in Europe. The EU traces its origins from the European Coal and Steel Community and the European Economic Community , formed by six countries in 1958...
) 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
Product recall
A product recall is a request to return to the maker a batch or an entire production run of a product, usually due to the discovery of safety issues. The recall is an effort to limit liability for corporate negligence and to improve or avoid damage to publicity...
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
Isoproterenol
Isoprenaline or isoproterenol is a medication used for the treatment of bradycardia , heart block, and rarely for asthma...
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 pharmacologyClinical pharmacologyClinical pharmacology is the science of drugs and their clinical use. It is underpinned by the basic science of pharmacology, with added focus on the application of pharmacological principles and methods in the real world...
- 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 trialClinical trialClinical trials are a set of procedures in medical research and drug development that are conducted to allow safety and efficacy data to be collected for health interventions...
s (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 useOff-label useOff-label use is the practice of prescribing pharmaceuticals for an unapproved indication or in an unapproved age group, unapproved dose or unapproved form of administration...
s"). - 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 effectsAdverse drug reactionAn adverse drug reaction is an expression that describes harm associated with the use of given medications at a normal dosage. ADRs may occur following a single dose or prolonged administration of a drug or result from the combination of two or more drugs...
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 inhibitorsMonoamine oxidase inhibitorMonoamine oxidase inhibitors are a class of antidepressant drugs prescribed for the treatment of depression. They are particularly effective in treating atypical depression....
" - 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 dependencePhysical dependencePhysical dependence refers to a state resulting from chronic use of a drug that has produced tolerance and where negative physical symptoms of withdrawal result from abrupt discontinuation or dosage reduction...
(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.http://leda.law.harvard.edu/leda/data/85/bschuman.rtf Finally, in January 2006, the FDA released a major revision to the patient package insert guidelines, the first in 25 years.http://www.fda.gov/bbs/topics/NEWS/2005/NEW01272.html 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 compiled into a reference book called the Physicians' Desk ReferencePhysicians' Desk Reference
The Physicians' Desk Reference is a commercially published compilation of manufacturers' prescribing information on prescription drugs, updated annually...
, better known as the PDR. South Africa has taken the initiative of making all package inserts available electronically via the internet, listed by trade name, generic name
International Nonproprietary Name
An International Nonproprietary Name is the official nonproprietary or generic name given to a pharmaceutical substance, as designated by the World Health Organization...
, 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
Summary of Product Characteristics
The Summary of Product Characteristics is a specific document required within the European Commission before any medicinal product is authorized for marketing. This summary is the definitive description of the product both in terms of its properties, chemical, pharmacological and pharmaceutical...
(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
European Commission
The European Commission is the executive body of the European Union. The body is responsible for proposing legislation, implementing decisions, upholding the Union's treaties and the general day-to-day running of the Union....
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.
External links
- 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