AMA Manual of Style - Stacy L. Christiansen, Cheryl Iverson 2020

Drugs
Nomenclature

Physicians and other health care professionals, patients, researchers, manufacturers, and the public may refer to drugs by several names, including the nonproprietary name (often referred to as the generic name) and at least 1 proprietary (brand) or trademark name selected by the manufacturer of the drug. Other drug identifiers include chemical names, trivial (unofficial) names, and code designations.¹ However, only 1 drug name, the nonproprietary name, is coined to ensure consistent usage and no duplication with other drugs. Once a drug has been assigned a nonproprietary name, the nonproprietary name should always be used to refer to the drug (see 14.4.2, Nonproprietary Names).

The nonproprietary name is established through nomenclature agencies, such as the United States Adopted Names (USAN) Council (https://www.ama-assn.org/about-us/usan-council), which work with the World Health Organization (WHO) to establish a single nonproprietary name. According to the WHO, “the existence of an international nomenclature for pharmaceutical substances, in the form of INN [international nonproprietary name], is important for the clear identification, safe prescription and dispensing of medicines to patients, and for communication and exchange of information among health professionals and scientists worldwide.”² The nonproprietary names of drugs that are to be marketed within the US must be approved by the USAN Council. The nomenclature rules provided in 14.4.13, Nomenclature for Biological Products, are established by the USAN Council.

The pharmaceutical naming system of the WHO has been in operation since 1953. When a drug is being considered for possible approval, the sponsoring manufacturer must file an INN application with the WHO Essential Drugs and Medicines team of Quality Safety and Medicines Policy or with one of the drug nomenclature councils, such as USAN or Japanese Adopted Names (JAN). The European Union does not have a separate council but requires that the INN be used for drugs marketed within the European Union. These organizations work in conjunction with the WHO to approve a nonproprietary name identical to the INN.³ Manufacturers in countries without a nomenclature agency can request an INN from the WHO directly or apply in a country that has a nomenclature agency.¹

14.4.1 The Drug Development and Approval Process.

This brief summary of the drug development process is provided to help define the origins of different names used to identify drugs.

Drugs intended for clinical use undergo several phases of development before they can be considered for human use. Animal studies are performed initially to assess pharmacologic and toxicologic effects. While clinical studies are being conducted, animal studies may continue to assess effects on reproduction, teratogenicity, and carcinogenicity.^4(pp7-11)

To perform clinical studies in the US, the developer or manufacturer must obtain an investigational new drug (IND) approval from the US Food and Drug Administration (FDA).^4(pp7-11) Once an IND application has been filed, the company must apply to the USAN Council for a nonproprietary name. Until a nonproprietary name has been approved, the developers of a drug may refer to it by the code name. The code designation is usually alphanumeric, with letters to refer to the institution or manufacturer that assigns the code designation for the drug and numbers to refer to the chemical compound.^1(pp17-18)

Drug developers should adhere to the Declaration of Helsinki⁵ and obtain institutional review board approval and patient informed consent to perform drug studies in humans. Phase 1 studies generally are conducted in 20 to 100 healthy volunteers to assess safety, biological effects, metabolism, kinetics, and drug interactions.^4(pp8-9),6 Phase 2 studies usually are conducted in up to several hundred people who have the disease or condition to establish the therapeutic efficacy of a drug for its proposed indication and to study dose range, kinetics, and metabolism.^4(pp8-9),6 Phase 3 studies typically are randomized clinical trials that assess a drug's safety and efficacy in a large sample of patients (generally 2000-3000).^4(pp8-9) The patients selected have the condition(s) for which the drug is thought to be effective and for which the manufacturer wishes to obtain approval. The 3 phases of clinical testing take 2 to 10 years (average, 5.6 years).^4(pp8-9) Phase 4 occurs once the drug or device has been approved by the FDA, during the postmarketing safety monitoring period.⁶

In the US, a drug cannot be marketed or prescribed (other than for specific exceptions) until it has been approved by the FDA. The FDA approves labeling for the drug for specific indications for which the FDA determines that sufficient evidence of effectiveness has been provided. Approved labeling defines the indications for which the drug can be marketed. The FDA does not approve indications for which a drug may be prescribed because a company may not study all possible conditions for which a drug may be effective. In what is known as off-label prescribing, physicians may prescribe a marketed drug for indications for which it does not have FDA approval for labeling or marketing. The approved labeling is included in prescribing information, marketing materials, and the National Library of Medicine’s DailyMed.⁷

Because the number of patients tested before a drug is approved is insufficient to identify rare adverse events, some countries require physicians to report adverse events experienced by patients, and some manufacturers may be required to systematically monitor drug adverse events after approval in a process known as postmarketing surveillance. Physicians and other health care professionals in the US should report adverse drug events to the voluntary reporting system MedWatch (https://www.fda.gov/safety/medwatch) or to the pharmaceutical manufacturer, which is obligated to file reports with the FDA. The United Kingdom, Canada, New Zealand, Denmark, and Sweden have legally mandated adverse event reporting systems.⁴ The Instructions for Authors for the JAMA Network journals advise as follows: “Authors submitting manuscripts or letters to the editor regarding adverse drug or medical device reactions, reportable diseases, etc, should also report this information to the relevant government agency.”⁸ In addition, the WHO maintains the WHO Collaborating Centre for International Drug Monitoring in Uppsala, Sweden. There are 123 official member countries and 28 associate member countries.⁹ In 2015, this group launched Vigimed, a “web-based forum for those working at national centres in the WHO Programme to enable them to have easy access to safety concerns in other countries, to check regulatory status, and to expedite the sharing of drug information.”⁹

14.4.2 Nonproprietary Names.

The nonproprietary name (eg, INN or USAN) identifies a specific pharmaceutical substance or active pharmaceutical ingredient. The nonproprietary name is in the public domain and can be used without restriction. It is sometimes referred to colloquially as the generic name.³ However, the terms generic and nonproprietary are not synonymous. Generic drugs are nontrademarked formulations of a drug that can be manufactured once a drug is no longer under patent restrictions. Generic drugs should be referred to by their nonproprietary name, just as proprietary drugs are.

The nonproprietary name reflects the chemistry, pharmacologic action, and therapeutic use through its stem. Herbal supplements (see 14.4.15, Herbal and Dietary Supplements), homeopathic products, mixtures, drugs in common use for decades (eg, morphine, codeine), and those with trivial chemical names (eg, acetic acid) do not receive nonproprietary names. The INN Expert Group, with representatives from national nomenclature committees worldwide (including the USAN Council), agree to a name that is then published as a proposed INN. During a 4-month comment period, any person can comment on or object to the proposed INN. If no objection is raised, the drug name is published as a recommended INN. New INNs are published in WHO Drug Information in English, French, and Spanish (http://www.who.int/druginformation). A cumulative INN list is published, which also includes INNs in Russian. More than 10 000 INNs have been designated as of 2014; 150 to 200 are added each year.²

14.4.2.1 Stems.

In addition to having a distinct sound and spelling to avoid confusion with other names, both the INN and USAN include a “stem” that designates the drug as a member of a family of related drugs, indicating that the drug has similar pharmacologic properties.²

The stem is usually a suffix common to a particular drug class that is incorporated into new drug names to indicate a chemical and/or pharmacologic relationship to older drugs.¹⁰ For example:

H₂-receptor antagonists: cimetidine, ranitidine, lupitidine (-tidine is the stem)

Tyrosine kinase inhibitors: canertinib, imatinib, mubritinib (-tinib is the stem)

β-Blockers: propranolol, timolol, atenolol (-olol is the stem)

Combined α- and β-blockers: labetalol, medroxalol (-alol is the stem)

For some classes of drugs, the position of the stem varies within the drug name. For the group of antiviral drugs (not necessarily having common pharmacologic properties), the stem may be vir-, -vir-, or -vir:

ganciclovir, enviradene, viroxime, alvircept, delavirdine

Approved stems are provided on the USAN website¹⁰ and in the USP Dictionary.^{1(pp1959-1969)}

The goal of the WHO INN system is to have a single INN for each drug used throughout the world. However, if the substance was in existence before the coordination of nomenclature by WHO, nonproprietary names may differ among countries. For example, acetaminophen is the USAN for the same drug that has the BAN and INN name paracetamol.^1(pp37) The USAN albuterol has a JAN of salbutamol (not to be confused with salmeterol, a longer-acting β-adrenergic agonist).^1(p56) For these few drugs for which nonproprietary names differ by country, the nonproprietary name used depends on the primary audience, although the European Union has required that nonproprietary names that differ from the INN will be phased out over time. In cases in which international recognition is essential (eg, adverse drug reactions), both names should be given at first mention.

Acetaminophen (paracetamol) was recommended in the practice guidelines.

The existence of more than 1 nonproprietary name is also important when performing searches on drugs in journals or databases; all nonproprietary names for a particular drug should be used for a complete search. The USP Dictionary¹ lists the INN and nonproprietary names by nomenclature agency, if they differ.

14.4.2.2 Orphan Drugs.

Drugs that may be used to treat relatively rare diseases but that otherwise are believed to have limited marketability are termed orphan drugs.¹¹ When a drug is designated an orphan drug by the FDA, the name it receives is not necessarily the name it will receive if it is approved or licensed for marketing.^1(p15) A list of orphan drugs is available at https://rarediseases.info.nih.gov/diseases/fda-orphan-drugs

14.4.2.3 Changes in Nonproprietary Names.

Nonproprietary names may be changed if they are deemed to be confusing or could result in medication errors or if they are proven to infringe on trademark. For example, the antineoplastic compound mithramycin became plicamycin to avoid confusing mithramycin with the similar-sounding antineoplastic mitomycin and its proprietary name Mutamycin. The nomenclature committees have procedures for applying to change the nonproprietary name.

14.4.3 Proprietary Names.

The manufacturer's name for a drug (or other product) is called a proprietary name or brand name.^1(p17) Proprietary names use initial capitals, with a few exceptions (eg, pHisoHex). In scientific publications, the trademark symbol (™) or the registered trademark symbol (®) is not recommended because capitalization indicates the proprietary nature of the name (see 5.6.15, Trademark). The International Trademark Association has information about specific trademarks and may be reached at https://www.inta.org or International Trademark Association, 655 Third Ave, 10th Floor, New York, NY 10017 or International Trademark Association Europe, 14B rue de la Science, 1040 Brussels, Belgium (see 5.6.15, Trademarks).

Proprietary names for drugs often differ among countries (eg, nifedipine initially was marketed as Procardia in the US and Adalat in Europe). Most US proprietary names are listed in the USP Dictionary¹ and are cross-referenced to their USAN name. Unlike the nonproprietary name, the proprietary name does not undergo a coordinated international effort to provide consistent naming. One example is albuterol, a β₂-adrenergic receptor agonist used for the relief of bronchospasm. It has been marketed by GlaxoSmithKline as Ventolin, Ventoline, Ventilan, Aerolin, or Ventorin, depending on the market; by Cipla as Asthalin and Asthavent; by Schering as Proventil; by Teva as Proair and Novo-Salbutamol HFA (Canada), Salamol, or Airomir; by Beximco (Bangladesh) as AZMZAOL; by Ad-din Pharma as Ventosol; and by Alphapharm as Asmol. Even when the same brand name does not refer to different drugs in different countries, a drug is often marketed under different brand names in different countries. Therefore, because the medical literature is read internationally and confusion about the intended drug could lead to patient harm, the nonproprietary name should always be used and the proprietary name should almost never be used in the medical literature.

The exceptions to this rule are reports of adverse events that might be unique to a specific product formulation or comparison of a generic formulation of a drug with the drug that was first approved. When both the nonproprietary and proprietary names are used in text, the nonproprietary name should appear first, with the proprietary name capitalized and in parentheses. Use of the proprietary name should be limited in these cases to only essential mention. Because proprietary drugs and manufacturers are listed in the USP Dictionary of USAN and International Drug Names¹ and other sources, the manufacturer does not need to be listed after the proprietary name.

The lot of penicillin G potassium (Pentids) was inspected and found to meet the industry production standards.

Proprietary names may be used in questionnaires when the individuals responding may be unfamiliar with the nonproprietary name or when the specific proprietary product is important; in these cases, the exact wording of the question should be maintained, but the nonproprietary name should still be provided.

Parents were asked, “Have you ever given your child Tylenol [acetaminophen, paracetamol] or products containing Tylenol?”

Herbal supplements and “natural” products generally do not have nonproprietary names. Whenever possible, the nonproprietary name (as listed in the USP Dictionary, for example) should be used. For some proprietary formulations that comprise a blend of ingredients, however, the proprietary name may be the only way to refer to the formulation (see 14.4.15, Herbal and Dietary Supplements).

The authors used mass spectrometry to analyze samples from a bottle of Niagra Actra-R_x and a bottle of Actra-R_x (Body Basics) for the presence of sildenafil.

14.4.4 Chemical Names.

The chemical name describes a drug in terms of its chemical structure.^1(pp15-16) Chemical names are provided in the American Chemical Society’s Chemical Abstracts (https://www.cas.org/) and can be listed in 1 of 2 ways; the first reflects the way in which Chemical Abstracts indexes inverted chemical names:

hydrazinecarboxyimidamide, 2-[-(2,6-dichlorophenoxy)ethyl]-, sulfate, (2:1)

The second is the uninverted form:

2-[-(2,6-dichlorophenoxy)ethyl] hydrazinecarboxyimidamide sulfate, (2:1)

Both forms follow the recommendations of the International Union of Pure and Applied Chemistry and the International Union of Biochemistry and Molecular Biology. Each chemical is also designated a registry number with the Chemical Abstract Society (https://www.cas.org). This number is included in the USP Dictionary¹ listing for the drug. Chemical names and registry numbers are rarely used in medical publications, and nonproprietary names are preferred.^1(pp15-16)

14.4.5 Code Designations.

A code designation is a temporary designation assigned to a product by the institution or manufacturer and may be used to refer to a drug under development before a nonproprietary name has been assigned. Codes may be numeric, alphabetic, or alphanumeric; letters in alphanumeric codes designate the institution or manufacturer assigning the code designation of the drug and are followed by numbers to designate the chemical compound.^1(pp17-18)

Once a nonproprietary name has been assigned, code designations become obsolete and are rarely used in medical publications. If both the code and the nonproprietary name are provided, such as in discussion of the history of a drug, the nonproprietary name should be used preferentially and the code name may be added in parentheses.

A new drug for the treatment of heart failure, consisting of sacubitiril and valsartan (Entresto; formerly known as LCZ696), was approved by the FDA in 2015.

Edoxaban (formerly known as DU-176) was approved by the FDA in early 2015.

Zidovudine (BW A509U) first became known as azidothymidine (commonly known as AZT) during testing and eventually was marketed as Retrovir.

14.4.6 Trivial Names.

Drugs occasionally become known by an unofficial trivial name, a term that does not give any indication as to the class of drug or chemical structure (eg, aspirin, caffeine, epinephrine). The trivial name should be used in biomedical publications only to reproduce the exact language used as part of a study (eg, in a questionnaire), for historical reasons, or rarely when readers may be unfamiliar with the nonproprietary name. When reproducing the exact language used in a study, the nonpropietary name should be provided in brackets after the term used in the study.

The participants were asked, “Have you ever taken AZT [zidovudine]?” Participants who said they had taken zidovudine were classified as having had prior exposure to antiretroviral agents.

When names other than the nonproprietary name are used for historical reasons or because readers are unfamiliar with the nonproprietary name, the nonproprietary name should be used preferentially and the alternative name provided in parentheses.

Semustine (NSC-95441) has been referred to in the scientific literature by its trivial name, methyl-CCNU, a contraction of its chemical name, 1-(2-chloroethyl)-3-(4-methylcyclohexyl)-1-nitrosourea.

14.4.7 Drugs With Inactive Components.

Many drugs contain a pharmacologically inactive component (eg, a base, salt, or ester) that is not responsible for the drug's mechanism of action but lends stability or other properties to the drug. Drugs with both an active and inactive component generally require a 2-part name that provides the active and inactive portion of the drug. Inorganic salts and simple organic acids are named in the order cation-anion (eg, sodium chloride, magnesium citrate). For more complex organic compounds, the active component is named first (eg, oxacillin sodium).^1(p904)

Pharmacologically inactive components are generally salts, esters, and complexes. Sodium, potassium, chloride, hydrochloride, sulfate, mesylate, and fumarate are common components of salts.

acyclovir sodium

midazolam hydrochloride

benztropine mesylate

morphine sulfate

Quaternary ammonium salts usually are designated by a 2-part name and have the suffix -ium on the first word of the name.

alcuronium chloride

aclidinium bromide

Salts and esters are frequently designated by 2 words, with the second word ending in -ate. Three-word names are used for compounds that are both salts and esters.

clomegestone acetate [ester]

hydrocortisone valerate [ester]

testosterone cypionate [ester]

methylprednisolone sodium phosphate [salt and ester]

roxatidine acetate hydrochloride [ester and salt]

Complexes of 2 or more components may include a term ending in -ex to indicate a complex.

bisacodyl tannex

nicotine polacrilex

codeine polystirex

Chemical names are often too complex for general use. In such cases, shorter nonproprietary names may be created. For example, for the drug erythromycin acistrate, acistrate refers to the 2′-acetate (ester) and octadecanoate (salt). For the drug erythromycin estolate, estolate refers to the double salt propanoate and dodecyl sulfate.^1(p480)

In the past, some INNs included inactive components as part of their name (eg, levothyroxine sodium). The WHO modified this policy so that the INN refers to only the active component of the drug (oxacillin, ibufenac). The name that includes the salt (oxacillin sodium, ibufenac sodium) is referred to as the modified INN (INNM). However, for drugs originally named for the full entity, such as levothyroxine sodium, the shorter (active entity only) name, for example, levothyroxine, is considered the INNM.² Through the USAN Program, names are provided for both forms of the drug substance: the parent species (active moiety) and the salt form. This is done because the drug may be formulated and dosages calculated in either form or both forms in the future.

When a drug is referred to as a general category, the nonproprietary name for the drug can be used without providing the inactive moiety.

The β-blockers most selective for β₁ activity are bisoprolol and metoprolol; acebutolol, carvedilol, and nebivolol are somewhat selective. All lose their selectivity when given at higher doses.

However, if a specific drug is discussed for a specific use, particularly when more than 1 formulation is available, the inactive moiety should be included with the drug name.

The patient was given erythromycin ethylsuccinate, 400 mg by mouth every 6 hours.

The inactive component should not be used when referring to an organism’s sensitivity to an antibiotic or to allergic reactions to drugs.

The strain of Streptococcus pneumoniae isolated by the laboratory was highly resistant to penicillin.

The patient's plasma lithium level at 8 AM was 2.0 mEq/L.

The woman developed urticaria after taking erythromycin.

14.4.8 Stereoisomers.

Some molecules may occur with identical atoms in the same sequence but with different spatial arrangements. These are referred to as stereoisomers. A stereoisomer that is nonsuperimposable on its mirror image is chiral, and an atom with 4 different substituents is a chiral center; the 2 mirror images are enantiomers.¹² An equal mixture of the 2 enantiomers is racemic. Generally, only 1 enantiomer is biologically active, as in the case of ibuprofen. In some cases, one enantiomer may be biologically beneficial, whereas the other enantiomer is harmful. For example, one enantiomer of thalidomide is a beneficial drug, whereas the other enantiomer causes birth defects when taken by pregnant women. The enantiomers may be designated by their optical activity, typically by using a polarimeter. The enantiomer that rotates plane-polarized light to the left is levorotatory (from Latin laevus, meaning left).¹² This is shown in the name with the prefix (−), for example, (−)-thalidomide, which has replaced the now-obsolete designation l-. The enantiomer that rotates plane-polarized light to the right is dextrorotatory (from Latin dexter, meaning right), shown in the name with the prefix (+), for example, (+)-thalidomide, replacing the now-obsolete designation d-. A racemic mixture has the prefix (±), which replaces the now-obsolete designation dl-, for example, (±)-thalidomide.

Molecules may also be designated by their spatial configuration. The enantiomers can be labeled with the prefix D- or L-, depending on the arrangement of the substituents of the chiral center in relation to those of glyceraldehyde; this system is typically used to label biomolecules, such as amino acids and carbohydrates. Conversely, the enantiomers may be labeled with the prefixes (R)- or (S)-, which refer to the priority given to the orientation of groups of atoms that surround the chiral center according to the Cahn-Ingold-Prelog priority rules, with (R)- if the rank by atomic number is clockwise and (S)- if it is counterclockwise; these designations are especially useful for describing compounds with multiple asymmetric centers. Note that the (+)/(−), D-/L-, and (R)-/(S)- naming systems are unrelated (eg, an L-labeled compound can be dextrorotatory).¹²

(S)-(−)-verapamil

(R)-(+)-secobarbital

D-lactic acid

For racemic mixtures, rac- or race- is added to the name of the compound (eg, racepinephrine). For the levorotatory form, the (S)- enantiomer may use the lev- or levo- prefix (eg, levamisole, levdobutamine), whereas the (R)- enantiomer may use the ar- prefix. For the dextrorotatory form, the (S)- enantiomer may use the es- prefix (eg, escitalopram), whereas the (R)- isomer uses the dex- or dextro- prefix (eg, dexibuprofin, dextroamphetamine, dexamisole).¹²

14.4.9 Combination Products.

For combination products (mixtures), the names of the active ingredients should be provided. The proprietary name of the combination may be given in parentheses if necessary to clarify the product to which the article refers.

pseudoephedrine hydrochloride and triprolidine hydrochloride (Actifed)

povidone and hydroxyethylcellulose (Adsorbotear)

If the list of active ingredients is too long to use when referring to the combination product, the active ingredients should be listed at first mention and an abbreviation or the proprietary name used thereafter.

The patient reported having taken several doses of Vanex-HD, a liquid suspension of hydrocodone bitartrate, 10 mg, phenylephrine hydrochloride, 30 mg, and chlorpheniramine maleate, 12 mg, per 30 mL, the previous day.

The patient had been given an artificial tear product that contained hydroxyethylcellulose, 0.42%, and povidone, 1.67% (Adsorbotear).

Only the active ingredients must be listed. However, in some circumstances it may be necessary to include all ingredients, including preservatives, if sensitivity to an ingredient may be important.

The patient reported red, itchy eyes after using an artificial tear product that contained hydroxyethylcellulose and povidone with edetate disodium and thimerosal as preservatives (Adsorbotear).

The USP may provide a pharmacy equivalent name (PEN)^1(pp14-15) to refer to a combination product, such as co-triamterzide for the combination of triamterene and hydrochlorothiazide. However, PEN terms are not official USP titles and should be used only if they are familiar and clear to readers. Because co-triamterzide is unlikely to be familiar to most readers, the following approach can be used:

Participants were given a capsule that contained a combination of 25 mg of hydrochlorothiazide and 50 mg of triamterene each day at 8 AM. Those not able to tolerate hydrochlorothiazide-triamterene were given 50 mg of metoprolol at 8 AM.

Trimethoprim-sulfamethoxazole (80 mg of trimethoprim and 400 mg of sulfamethoxazole) administered once daily effectively prevented reinfection in 93% of patients.

14.4.10 Drug Preparation Names That Include a Percentage.

Some drug names, such as those used in topical preparations, include the percentage of active drug contained in the preparation. In these cases, the percentage should be listed after the drug name.

The patient was treated with adapalene, 1%.

Metronidazole lotion, 0.75%, was applied twice a day.

14.4.11 Multiple-Drug Regimens.

Regimens that include multiple drugs may be referred to by an abbreviation after the nonproprietary names of the drugs have been provided at first mention (see 14.4.12, Drug Abbreviations, and 13.11, Clinical, Technical, and Other Common Terms). Drug regimens used in oncology frequently are referred to by abbreviations of combinations of antineoplastic agents, but often the abbreviations are not derived from the nonproprietary names. For example, the letter O in MOPP is derived from Oncovin, the proprietary name for vincristine sulfate, and the A in ABVD is derived from Adriamycin, the proprietary name for doxorubicin hydrochloride. Proprietary names may be provided in parentheses after the nonproprietary names to clarify the origin of the abbreviation.

The MOPP (methotrexate, vincristine sulfate [Oncovin], prednisone, and procarbazine hydrochloride) regimen has been replaced by ABVD (doxorubicin hydrochloride [Adriamycin], bleomycin sulfate, vinblastine sulfate, and dacarbazine) for the treatment of Hodgkin disease.

14.4.12 Drug Abbreviations.

Some drugs have commonly used abbreviations, such as INH for isoniazid and TMP for trimethoprim. However, abbreviations may be used inconsistently, be confused with other terms, or be unfamiliar to some readers. Because of the potential for harm from erroneous interpretation of abbreviated drug names, abbreviations should not be used except in rare instances (eg, trimethoprim-sulfamethoxazole may not fit in a table heading and may need to be abbreviated, eg, TMP-SMX; in that case the expansion should be provided in a table footnote).

14.4.13 Nomenclature for Biological Products.

Several categories of drugs are identical to or derived from biological products. Some hormones given as drugs, for example, require special mention because the drug name differs from the name used for the endogenous substance. Other categories of biologicals are derived from specific guidelines developed by the USAN Council, outlined below.

Using the appropriate name can help clarify that the substance referred to is a drug, although for less familiar drug names it may be necessary to include the endogenous hormone name in parentheses to clarify the action of the drug for readers. (For more information on appropriate abbreviations for hormones, see 13.11, Clinical, Technical, and Other Common Terms). The following information is based on the USP Dictionary.¹

14.4.13.1 Hypothalamic Hormones.

The suffix -relin denotes prehormones or hormone-release stimulating peptides, and the suffix -relix denotes hormone-release inhibiting peptides (Table 14.4-1). For example,

After venipuncture, protirelin (synthetic thyrotropin-releasing hormone) was injected.

Table 14.4-1. Nomenclature for Hypothalamic Hormones

14.4.13.2 Growth Hormone.

The som- prefix is used for growth hormone derivatives (Table 14.4-2).

Table 14.4-2. Growth Hormone Nomenclature

14.4.13.3 Thyroid Hormones.

Abbreviations for thyroxine and triiodothyronine are provided in parentheses and may be used after the name is expanded at first mention (Table 14.4-3).

Table 14.4-3. Thyroid Hormone Nomenclature

14.4.13.4 Insulin.

Insulin terms can be a source of clinically important confusion, particularly with regard to insulin concentrations and types. Insulin concentrations are as follows (not necessary to expand at first mention):

U100 contains 100 U of insulin per milliliter (the most commonly used concentration).

U40 contains 40 U of insulin per milliliter.

U500 contains 500 U of insulin per milliliter.

Insulin types include those that may be administered intravenously, subcutaneously, or intramuscularly (injections) and those that may be administered only subcutaneously or intramuscularly (suspensions). Another form of insulin may be inhaled.

Insulin is prepared with the use of recombinant DNA technology (referred to as human insulin because the source is human DNA) or as a synthetic modification of porcine insulin. Proprietary names are provided below because they are often used to refer to the potentially confusing various types of insulin preparations. For clarity and conciseness, use of proprietary terms in addition to the nonproprietary terms may be necessary in some cases. The following lists are not comprehensive but are intended to provide examples of the nonproprietary names that should be used and their corresponding proprietary names.

14.4.13.4.1 Injections.

Preferred terms and proprietary names for common injections are given in Table 14.4-4.

Table 14.4-4. Injection Nomenclature

14.4.13.4.2 Suspensions.

Insulin is available in single suspensions and combinations of injections and suspensions. Preferred terms and proprietary names for common suspensions and combinations of injections and suspensions are given in Table 14.4-5.

Table 14.4-5. Nomenclature for Suspensions and Combinations of Suspensions and Injections

^a NPH is the single exception to expressing drugs as abbreviations and can be used in its abbreviated form.

14.4.13.5 Interferons.

Interferon is defined as “proteins formed by the interaction of animal cells with viruses, capable of conferring resistance to virus infection in animal cells”^1(p597) (see 14.8, Immunology).

The 3 main types used for therapy are as follows:

interferon alfa (formerly leukocyte or lymphoblastoid interferon)

interferon beta (formerly fibroblast interferon)

interferon gamma (formerly immune interferon)

Subcategories are designated by a numeral and a lowercase letter. The lowercase letter after the number differentiates one manufacturer’s interferon from another’s. Examples of pure interferons are as follows:

interferon alfa-2a

interferon alfa-2b

interferon beta-1a

interferon beta-1b

interferon gamma-la

For naturally occurring mixtures of interferons, a lowercase n precedes the numeral:

interferon alfa-n1

interferon alfa-n3

See 14.8.4.6, Interferons, for abbreviations for these interferons.

14.4.13.6 Interleukins.

There are 12 interleukin derivatives (Table 14.4-6). All except interleukin 3 end in -kin (eg, aldesleukin). Interleukin 3 is designated by the -plestim stem (eg, daniplestim) and is a pleiotropic colony-stimulating factor (see 14.4.13.7, Colony-Stimulating Factors).

Table 14.4-6. Interleukin Derivatives

See 14.8.4.5, Interleukins, for abbreviations of these interleukins.

14.4.13.7 Colony-Stimulating Factors.

Therapeutic recombinant colony-stimulating factors are named according to the following guidelines^{1(pp1955-1973)} (see 14.8, Immunology).

The suffix -grastim is used for granulocyte colony-stimulating factors (G-CSFs):

lenograstim

filgrastim

The suffix -gramostim is used for granulocyte-macrophage colony-stimulating factors (GM-CSFs):

molgramostim

regramostim

sargramostim

The suffix -mostim is used for macrophage colony-stimulating factors (M-CSF):

mirimostim

The suffix -plestim is used for interleukin 3 (IL-3) factors, which are classified as pleiotropic colony-stimulating factors:

muplestim

daniplestim

The suffix -distim is used for conjugates of 2 different types of colony-stimulating factors:

milodistim

The suffix -cestim is used for stem cell-stimulating factors:

ancestim

14.4.13.8 Erythropoietins.

The word epoetin is used to describe erythropoietin preparations that have an amino acid sequence that is identical to that of the endogenous cytokine. The words alfa, beta, and gamma are added to designate preparations with different composition and carbohydrate moieties.^1(p1706)

epoetin alfa

epoetin beta

epoetin gamma

14.4.13.9 Monoclonal Antibodies.

Therapeutic monoclonal antibodies and fragments are designated by the suffix -mab. Monoclonal antibodies are derived from animals and humans, and the nomenclature is based on the source of the antibody (mouse, rat, hamster, primate, or human) and the disease target or antibody subclass. Some examples of monoclonal antibodies are abciximab, adalimumab, daclixumab, infliximab, ipilimumab, and satumomab pendetide.¹

The following letters are used to identify the source of the monoclonal antibody:

These identifiers precede the -mab suffix stem, for example:

The general disease state subclass is also incorporated into the name by use of a code syllable.

Key elements are combined in the following sequence: the letters that represent the target disease state, the source of the product, and the monoclonal root -mab used as a suffix (eg, biciromab, satumomab) (Table 14.4-7). When a target or disease stem is combined with the source stem for chimeric monoclonal antibody, the last consonant of the target or disease syllable is dropped to facilitate pronunciation.

Table 14.4-7. Monoclonal Antibody Nomenclature

14.4.13.10 Radiolabeled or Conjugated Products.

Some products are radiolabeled or conjugated to other chemicals, such as toxins. Such conjugates are identified by a separate, second word or other acceptable chemical designation. For monoclonal antibodies conjugated to a toxin, the "-tox" stem indicates the toxin (eg, zolimomab aritox, in which the designation aritox was selected to identify ricin A-chain). For radiolabeled products, the isotope, element symbol, and isotope number precede the monoclonal antibody¹ (see 14.9.2, Radiopharmaceuticals).

technetium Tc 99m biciromab

indium In 111 altumomab pentetate

A separate term is also used to designate a linker or chelator that conjugates the monoclonal antibody to a toxin or isotope or for pegylated (having polyethylene glycol, or PEG, attached) monoclonal antibodies.^1(p1707)

telimomab aritox

indium In 111 satumomab pendetide

enlimomab pegol

14.4.14 Vitamins and Related Compounds.

The familiar letter names of most vitamins generally refer to the substances as found in food and in vivo. With the exception of vitamins A, E, and B complex, the nonproprietary names for vitamins given therapeutically differ from their in vivo names. (To enhance clarity for readers, the equivalent vitamin name may also be provided.) Various types of carotenoids (alpha and beta carotene and beta cryptoxanthin) may be converted to vitamin A within the body, so the specific agent that is administered should be provided. The native form of vitamin A is most often supplied as retinol acetate. Other forms of vitamin A may be administered topically (eg, retinoic acid). Vitamin E refers to a group of tocopherol compounds, and the specific chemical names should be provided (eg, alpha tocopherol, gamma tocopherol, delta tocopherol, or mixed tocopherols). The specific stereoisomers and whether the product is natural or synthetic should be provided where relevant (eg, DL-alpha tocopherol acetate). For vitamin B complex, the specific components included in the B complex should be provided. Table 14.4-8 provides examples of USAN drug names equivalent to their vitamin names.¹

Table 14.4-8. USAN Drug Names and Equivalent Vitamin Names

14.4.15 Herbal and Dietary Supplements.

Herbal and dietary supplements do not receive nonproprietary names, and they are not regulated as drugs in many countries, including the US (as mandated by the Dietary Supplement Health and Education Act, passed in 1994¹³).

The US Congress has defined a dietary supplement as

a product taken by mouth that contains a “dietary ingredient” intended to supplement the diet. The “dietary ingredients” in these products may include: vitamins, minerals, herbs or other botanicals, amino acids, and substances such as enzymes, organ tissues, glandulars, and metabolites. Dietary supplements can also be extracts or concentrates, and may be found in many forms such as tablets, capsules, softgels, gelcaps, liquids, or powders. They can also be in other forms, such as a bar, but if they are, information on their label must not represent the product as a conventional food or a sole item of a meal or diet. Whatever their form may be, [Dietary Supplement Health and Education Act] places dietary supplements in a special category under the general umbrella of “foods,” not drugs, and requires that every supplement be labeled a dietary supplement.^13,14

Components of dietary supplements may be pharmacologically active, so accurate and specific nomenclature is essential. As noted above, dietary supplements are often mixtures of several ingredients, and quantities of each may be proprietary. Such a mixture makes standard nomenclature policy difficult to establish. Whenever possible, a nonproprietary name should be used to refer to a dietary supplement. However, if the dietary supplement is a mixture of many components, either an abbreviation derived from the components or the proprietary name must be used (see 14.4.9, Combination Products).

Metabolife 356 (Metabolife International Inc) was a dietary supplement that contained 19 labeled ingredients, including ephedra and caffeine (hereinafter abbreviated as DSEC), and is no longer manufactured.

The USP Dictionary,¹ Physicians’ Desk Reference for Nonprescription Drugs and Dietary Supplements,¹⁵ Physicians’ Desk Reference for Herbal Medicines,¹⁶ The Complete German Commission E Monographs: Therapeutic Guide to Herbal Medicine,¹⁷ and The ABC Guide to Herbs¹⁸ are useful resources for naming herbals and dietary supplements. If these resources are not productive, the web can be helpful in identifying substances as well, although of course the accuracy of the source should be considered.

Herbal medicines generally can be named according to their botanical genus and species, although the lack of regulation in some countries makes consistent nomenclature a challenge. A review of regulation of herbal medicines worldwide has been completed by WHO.^19,20,21 Monitoring of herbal medicines remains challenging.²² In countries in which botanicals are not regulated, the specific herbal and manufacturer, wherever relevant, should be included because different manufacturing techniques result in different biological activity. According to WHO,

[I]t is not unusual for a common name to be used for two or more different species. Unless the names of herbal plants follow an international system of plant nomenclature, the potential for confusion when exchanging information is enormous. The information attached to a name is thus crucial. As an example, because common names are often used, heliotrope (Heliotropium europaeum)—containing potent hepatotoxins—is often confused with garden heliotrope (Valeriana officinalis), which is used as a sedative and muscle relaxant. Identification of the herbal preparation by the Latin binomial system, in addition to the common name, is therefore essential.²¹

Thus, whenever possible, herbals derived from a specific plant should be named according to the botanical name (eg, Ginkgo biloba, Echinacea purpurea) to ensure that the correct entity is identified. When the plant is referred to, the genus and species may be abbreviated after being spelled out at first mention.

The main pharmacologic substances with immunostimulant activity in experimental and clinical studies are purified polysaccharides that can be extracted only in small quantity from pressed Echinacea purpurea.

Given our laboratory findings, the symptoms we have described may be attributed to an overdose of Illicium verum, contamination with Illicium anisatum, or a combination of both.

Kava is derived from the dried root of the pepper plant Piper methysticum. Kava has gained widespread popularity as an anxiolytic and sedative.

Extracts from St John’s wort, also known by its Latin botanical name, Hypericum perforatum, have been studied extensively for the treatment of depression in adults, with mixed results.

One day before taking Ginkgo biloba or placebo and again at the end of the 6-week double-blind period (while still taking G biloba and within 3 days of the end of the study), participants underwent neuropsychological evaluation, including tests of learning, memory, attention and concentration, and expressive language.

In some cases, the vernacular name is not the genus or species and should be provided as well to ensure that the reader understands which plant is intended.

Hypericum perforatum (St John’s wort) is a popular herbal product used to treat depression, but it has been implicated in drug interactions.

When referring to a specific product or formulation, as in a study, the specific proprietary name and manufacturer should be listed because formulations vary by manufacturing technique.

Participants were randomly assigned to 1 of 2 conditions: Ginkgo biloba (Ginkoba) or placebo control (1:1 ratio).

A marketed enteric-coated preparation (Tegra) that contains 5 mg of steam-distilled garlic (Allium sativum) oil bound to a matrix of beta cyclodextrin and matching placebos, whose coating tasted like garlic, was used.

Guggulipid, which is an extract from the plant Commiphora mukul (guggul), contains numerous other substances besides the small amounts of guggulsterones purported to be the active ingredients.

Principal Author: Cheryl Iverson, MA

Acknowledgment

Thanks to Stephanie C. Shubat, MS, USAN Program, American Medical Association, Chicago, Illinois; Anne Rentoumis Cappola, MD, ScD, JAMA, and Smilow Center for Translational Research, Philadelphia, Pennsylvania; and Karen Leslie Boyd, formerly with JAMA Network, for reviewing and providing comments.

References

1.USP Dictionary of USAN and International Drug Names. 53rd ed. US Pharmacopoeia; 2017.

2.Guidance on INN. World Health Organization. 1997. Accessed July 23, 2019. https://www.who.int/medicines/services/inn/innguidance/en/

3.Lists of recommended and proposed INNs. World Health Organization. Last updated 2018. Accessed July 23, 2019. https://www.who.int/medicines/publications/druginformation/innlists/en/

4.Rivera SM, Gilman AG. Drug intervention and the pharmaceutical industry. In: Brunton LL, ed; Chabner BA, Knollmann BC, assoc eds. Goodman & Gilman's The Pharmacological Basis of Therapeutics. 12th ed. McGraw-Hill Book Co; 2011:3-16.

5.World Medical Association. Declaration of Helsinki: ethical principles for medical research involving human subjects. JAMA. 2013;310(20):2191-2194. doi:10.1001/JAMA.2013.281053

6.US Food and Drug Administration. The drug development process. Last updated January 4, 2018. Accessed July 23, 2019. https://www.fda.gov/patients/learn-about-drug-and-device-approvals/drug-development-process

7.National Library of Medicine. DailyMed. Posted December 19, 2017. Accessed May 30, 2018. https://dailymed.nlm.nih.gov/dailymed/index.cfm

8.JAMA Instructions for Authors. Last updated July 15, 2019. Accessed July 23, 2019. http://jama.jamanetwork.com/journals/jama/pages/instructions-for-authors

9.Introduction to the WHO Programme for International Drug Monitoring. World Health Organization. Last updated 2016. Accessed May 30, 2018. http://www.who.int/medicines/areas/quality_safety/safety_efficacy/en/

10.Approved stems. USAN. Updated July 2018. Accessed March 1, 2019. https://www.ama-assn.org/about/united-states-adopted-names/united-states-adopted-names-approved-stems

11.Orphan Drug Act, Pub L No. 97-414. 1983. Accessed July 23, 2019. https://www.fda.gov/media/99546/download

12.Voet D, Voet JG, Pratt CW. Fundamentals of Biochemistry. 4th ed. John Wiley & Sons Inc; 2012:86-88.

13.National Institutes of Health, Office of Dietary Supplements. Dietary Supplement Health and Education Act of 1994. US Food and Drug Administration, Accessed July 23, 2019. https://os.od.nih.gov/About/DSHEA_Wording.aspx

14.US Food and Drug Administration. Dietary supplements. Updated July 22, 2019. Accessed July 23, 2019. https://www.fda.gov/food/dietary-supplements/

15.PDR for Nonprescription Drugs and Dietary Supplements. 34th ed. PDR Network; 2013.

16.PDR for Herbal Medicines. 4th ed. Thomson Healthcare; 2007.

17.American Botanical Council; Blumenthal M, Busse WR, Klein S, et al, eds. The Complete German Commission E Monographs: Therapeutic Guide to Herbal Medicines. Lippincott Williams & Wilkins; 1998.

18.Blumenthal M, ed. The ABC Guide to Herbs. American Botanical Council; 2003.

19.World Health Organization. Regulatory situation of herbal medicines: a worldwide review. Accessed July 23, 2019. https://apps.who.int/iris/handle/10665/6380

20.WHO Traditional Medicine Strategy 2002-2005. Accessed July 31, 2019. http://www.wpro.who.int/health_technology/book_who_traditional_medicine_strategy_2002_2005.pdf

21.Farah MH. Consumer protection and herbal remedies. WHO Drug Inf. 1998;12(3):141-142. Accessed August 5, 2019. https://apps.who.int/medicinedocs/index/assoc/s14169e/s14169e.pdf

22.Ekor M. The growing use of herbal medicines: issues relating to adverse reactions and challenges in monitoring safety. Front Pharmacol. 2014;4:177. doi:10.3389/fphar.2013.00177

Additional Readings and General References

PDR (Presaribers Digital Reference). Accessed July 23, 2019. https://www.pdr.net

WHO Drug Information. Updated February 2019. Accessed March 20, 2019. https://www.who.int/medicines/publications/druginformation/en/