The importance of the USAN
A generic, or nonproprietary, name given to a drug, pharmaceutical substance, or biologic product may be used by all who wish to refer to this substance. This differentiates it from the trade (brand) name, which is owned by the firm that markets a specific product.
In the United States (US), the generic name is officially called the United States Adopted Name (USAN) and serves as an important and unique designation for the active ingredient. It appears with the company's trade name on drug labels, advertisements, and other information and is also requested on FDA applications and in drug substance chemical descriptions. Because most journals request that authors use the generic name in clinical trial reports, it is used in publishing scientific data about investigational and established therapies. The USAN is also much shorter, easier to remember and pronounceable than the systematic chemical name.
The "one substance, one name" philosophy behind generic naming helps clearly identify the active substance across different brand or trade names, formulations, or in combination products.
Brand Names and Generic Names for Active Ingredients
Brand: Colemin, Lipex, Zocor, Vytorin
Brand: Gleevec, Glivec
Generic: imatinib mesylate
Unlike generic names, brand names vary from company to company and from country to country. In rare instances, a brand name may be used for two different active ingredients in different countries. More commonly, a company uses different brand names in different countries for the same drug, or two countries may market the same substance under different brand names. Finally, as part of "brand extension" business strategies, companies use the same brand name to refer to two different active ingredients.
The FDA reviews trade names separately. The USAN Program is not involved in brand/trade name development.
The USAN Council has been coining names since the early 1960s. The Code of Federal Regulations states that the USAN is an established name for a drug. The USAN Program assigns names through the USAN Council (USANC), a group of five volunteers nominated to the USANC based on their extensive and relevant knowledge and experience. Three USANC members represent the three organizations that jointly sponsor the Program: The American Medical Association (AMA), United States Pharmacopeia (USP) and the American Pharmacists Association (APhA). A liaison from the FDA and a member-at-large complete the USANC.
The AMA houses the offices of the USAN Program Secretariat and plays an important role in the day-to-day administration of the Program.
The Scope of USAN
USAN will be provided for the following:
-small molecule drugs
-biotechnology drugs including monoclonal antibodies, therapeutic vaccines, proteins and peptides, DNA, RNA, nucleoside and nucleotide therapies
-other biological substances deemed appropriate to be assigned a USAN by the USANC
-contact lens materials
-active ingredients in sunscreens
-veterinary products intended to control diseases in animals
-the base, salt, solvate, ester or other chemical derivative of a substance that has received a USAN
USAN will not be provided for the following:
-mixtures that do not have an IND number or do not require approval for human use by the FDA
-drug delivery mechanisms
-product formulations* (emulsions, suspensions, etc.)
-combination drug products
*An exception to the above will only be authorized by the USANC if there is a clear and well-documented need such that assignment of a name promotes safety and advances the USANC's nomenclature principles.
The number of names coined each year varies, but in recent years the USAN Program has been coining over 100 new names annually.
The process of assigning a USAN, referred to as a "negotiation," begins when a pharmaceutical firm or its representative files an application to name the substance. It ends with the statement of adoption, a document that formally assigns a USAN to a specific substance.
Before a statement of adoption is issued, the sponsoring firm, the USAN Council and the International Nonproprietary Names Expert Group (INN) must agree on a single name for the substance.
The USANC considers several criteria in evaluating potential names:
- Whether the names reflect the drug action and fit the naming scheme
- How well a name translates into languages other than English
- How easy a name is to pronounce and remember
The USAN is assigned while a drug is undergoing clinical trials. Companies may apply during Phase 1 studies, but many wait until Phase II studies begin. Most want the USAN before Phase III large-scale studies are complete, so that it will be available for publications and, when needed, to develop packaging, labeling and promotional materials.
Because many more drugs enter clinical trials than are approved for market, many USAN are assigned to substances that are never sold in the US, but could be available in countries other than the US. Thus, review by INN ensures that there will be a single name accepted by all countries worldwide.
Several decades ago when the USAN Program first began coining names (and even before its inception), condensing the systematic chemical name of a substance was a common way to coin drug names. This is no longer the case.
Now, most new names consist of three parts: a prefix, an infix and a stem.
Prefix: Means nothing; differentiates drug from others in class
Infix: Used occasionally; further subclassifies
Stem: Indicates place in nomenclature scheme; novel stems suggest novel drug action; drugs with the same stem are related
Stems are usually at the end of a name, with a few exceptions (e.g., cef-), and indicate the drug's place within the nomenclature scheme. Consequently, a new suffix often but not always suggests a new mechanism of action. Drugs with the same ending (stem) belong to the same pharmacologic family. Infixes, appearing in the middle of the word, are sometimes used to further classify the drug. Prefixes mean nothing. The sole purpose is to differentiate a drug from other members of the class.
As an example, consider sildenafil (Viagra™), vardenafil (Levitra™), and tadalafil (Cialis™). The -afil stem is formally defined as for PDE5 (phosphodiesterase 5) inhibitors. The -den- infix indicates that sildenafil and vardenafil have similar chemical structures. The prefixes are sil-, var- and tadal-.
In addition to this system, the USAN Program developed nomenclature schemes for some biologic products, which are expected to account for a much larger portion of pharmaceutical sales in the future. For example, monoclonal antibodies get names that incorporate the fantasy prefix, infixes to indicate the species from which the antibody was derived (important for predicting immune system response to the antibody) and the intended target, and a -mab suffix.
Brand names, generic names and what the name means
Lipitor™ (atorvastatin calcium)
meaning: enzyme inhibitors
stem subgroup: -vastatin
meaning: inhibitors of HMG-CoA, an enzyme involved in synthesizing cholesterol
Nexium™ (esomeprazole magnesium)
meaning: esomeprazole is a stereoisomer of omeprazole
meaning: agents to treat ulcer and/or heartburn that are chemically related to benzimidazole
meaning: antiallergics and antiasthmatics that are leukotriene receptor antagonists
Plavix™ (clopidogrel sulfate)
meaning: platelet aggregation inhibitors
Effexor XR™ (venlafaxine hydrochloride)
meaning: antianxiety, antidepressant inhibitor of norepinephrine and dopamine reuptake
Cymbalta™ (duloxetine hydrochloride)
meaning: antidepressants with a chemical structure related to fluoxetine
meaning: angiotensin II receptor antagonists
Meaning: antibiotics that are chemical derivatives of quinolone
meaning: antiviral compounds
stem subgroup: -cyclovir
meaning: chemical structure is related to acyclovir
meaning: monoclonal antibodies
stem subgroup: -zumab
infix: -ci- for circulatory system targets (e.g. inhibiting angiogenesis)
meaning: monoclonal antibodies
stem subgroup: -ximab
infix: -li- for immune system targets
Sources for prescribing/sales information are Fierce Pharma, Blue Cross/Blue Shield of Illinois and Pharmacy Times.
There are few prefixes and infixes with specific, defined meanings, some of which have been used to coin names for top-selling drugs. Ar-, es-, lev- and dex- are used to name stereoisomers of drugs that have already received a USAN. For example, esomeprazole is a stereoisomer of omeprazole. Peg- means that a biologic substance, such as peptide, is pegylated. -Io- has been used as an infix to suggest a high iodine content (amiodarone). When -fos- appears anywhere in a drug name, the element phophorous is present, often as a phosphate ester.
Drugs with two-word names are often salts, adducts with coprecipitated acid or solvent molecules, esters or prodrugs. The pharmacologically active portion is generally listed first in a two-word name. The second word designates the pharmacologically inactive portion of the substance, or the part of the ester or prodrug that is cleaved in vivo to generate the pharmacologically active species.
The USANC classifies drugs using the knowledge available when names are coined. Similarly, stems are defined according to the available knowledge at the time. If new indications are found for a stem class or drug, the name of the drug or the definition of the stem does not usually change. This means, for example, that the -prazole stem used to name lansoprazole (Prevacid™) was formally defined as for "antiulcer agents," although these drugs are now more often used to manage GERD. Lansoprazole has indications for both heartburn and GERD.
More knowledge may become available after a drug is named or a stem is coined, and nomenclature is an evolving art and science. Consequently, drugs have been named by different means over the last several decades. Early on, many drug names were coined by condensing the systematic chemical name. Later, the system was changed to the current prefix-infix-stem system, to reduce confusion of drug names and to make the drug name more directly refer to the class or function. The USAN Program expects that nomenclature practices will continue to evolve as new substances are developed and marketed by the pharmaceutical industry.