Understanding Drug and Dosage

Thomas Reinders, Pharm.D. Emeritus Professor VCU School of Pharmacy Disclosure

Thomas Reinders declares no conflicts of interest, real or apparent, and no financial interests in any company, product, or service mentioned in this presentation, including grants, employment, gifts, stock holdings and honoraria. Objectives

▪ Identify the official organizations responsible for naming U.S. drugs and dosage forms. ▪ List common rules and limitations for assigning names to drugs and dosage forms.

▪ Describe how to decipher drug action based on generic drug names. Objectives

▪ List resources for information about drug and dosage form names.

▪ Identify recommendations for minimizing and reporting medication errors associated with drug names and dosage form nomenclature. Self-assessment

Which of the following organizations have legal authority in naming drugs and/or dosage forms? a. United States Pharmacopeia b. Drug Safety Institute c. Food and Drug Administration d. a and c e. All of the above Self-assessment

Match the following drug names with the appropriate pharmacological action based on a USAN stem.

__ 1. Gloximonam a. Angiotensin II receptor antagonist

__2. Losartan b. Antihyperglycemic

__3. Oteracil c. Monobactam antibiotic

__4. Gliflumide d. Uracil type antineoplastic Self-assessment Pharmacists can minimize medication errors associated with drug names by which of the following? a. Being aware of look-alike, sound-alike names b. Reporting medication errors to the FDA c. Being aware of enhanced lettering for drug names d. a and b e. All of the above What’s in a Name?

“That which we call a rose but any other name would smell as sweet.”

William Shakespeare’s Romeo and Juliet Drug Naming Perception

https://www.youtube.com/watch?v=DS-w2dzGsOk Drug Naming Process

Long and Arduous Path Organizations Responsible for Drug Nomenclature

USAN • United States Adopted Names Council

USP • United States Pharmacopeia

• United States Food and Drug FDA Administration

• International Nonproprietary Names INN Programme (World Health Organization) Standards Setting Harmonization

United States Adopted Names (USAN)

International Unites States Nonproprietary Pharmacopeia Name (INN) (USP) & Other Pharmacopeias Drug & Dosage Form Names Type Responsibility Nonproprietary (Generic) USAN / INN

Note: A generic name is the nonproprietary name used for an identical FDA approved proprietary product Proprietary (Trade/Brand) FDA

Chemical IUPAC / CAS

NPC Code FDA

UNII Code FDA / USP

Pronunciation USP / USAN

Dosage Forms USP United States Adopted Names Council

• Created in 1964, succeeding the AMA-USP Nomenclature Committee

• Co-sponsored by the American Medical Association, United States Pharmacopeia & American Pharmacists Association

• Major role in naming drugs, especially during their development USAN

To serve the health professions in the U.S. by P selecting simple, informative and unique nonproprietary names for drugs by establishing U logical nomenclature classifications based on pharmacological and/or chemical relationships. R Name is requested by sponsor when a drug P enters the clinical investigation stage. O Name is chosen with the expectation that it will S be suitable for prescription and dispensing purposes and for the designation as the title of E a monograph should the article be recognized by the USP USAN

What is Named Example Small molecule drugs Pitolisant (Treatment of narcolepsy) (Not yet marketed in USA) Biotechnology drugs Durvalumab (Imfinzi, AstraZeneca) Gene therapies Voretigene neparvovec (Luxturna, Spark Therapeutics) Contact lens materials Samfilcon B (Ultra, Bausch+Lomb) Cell Therapies Tisagenlecleucel (Kymriah, Novartis) Sunscreen active ingredients Bemotrizinol (Excalol S, Ashland) Veterinary products Tulathromycin (Draxxin, Pfizer) Selected mixtures & extracts Cannabidiol (Epidiolex, GW Pharmaceuticals) Guidelines for Coining USAN Names

• The name for the active moiety of a drug should be a single word, preferably of no more than 4 syllables. General • A common, simple word element (a "stem") should (e.g.) be incorporated in names of all members of a group of related drugs when pertinent, common characteristics can be identified (e.g., similarity of pharmacological action).

Specific • Cellular & Noncellular Therapies (e.g.) • Monoclonal Antibodies

https://www.ama-assn.org/about/apply-usan Coining a USAN Name - 21 Available Letters A B C D E F G H I J K L M N O P Q R S T U V W X Y Z USAN Stems (~ 300)

Stem Definition Example -dipine Phenylpryidine vasodilators (nifedipine type) Felodipine -erg Ergot alkaloid derivatives Pergolide -nermin Growth factors - tumor necrosis Sonermin -gli Antihyperglycemics Gliflumide -imex Immunostimulants Forfenimex -monam Monobactam antibiotics Gloximonam -olol Beta-blockers (propranolol type) Atenolol -racil Uracil type antineoplastics Oteracil -sartan Angiotensin II receptor antagonists Losartan -sporin Immunosuppressants (cyclosporine type) Geclesporin -tibant Antiasthmatics (bradykinin antagonists) Icatibant -xaban Anticoagulant (Factor Xa inhibitor) Tamixaban

https://druginfo.nlm.nih.gov/drugportal USAN Stems (~ 300)

https://druginfo.nlm.nih.gov/drugportal Stems – Recent Approvals Coining a USAN Name

Prefix Infix Stem Name

Beva ci zumab Bevacizumab Coining a USAN Name

Name Infix Stem Stem Meaning Subgroup

Levofloxacin -oxacin Antibiotics that are chemical (Levaquin) derivatives of quinolone

Atorvastatin -stat Enzyme inhibitors calcium (Lipitor) Rosuvastatin -stat -stat Enzyme inhibitor (Crestor) -vastatin Inhibitors of HMG-CoA

Bevacizumab -mab Monoclonal antibodies (Avastin) -zumab Humanized -ci- For circulatory targets USAN Naming Process

USAN and firm Application filed Statement of review the INN ($15,000 fee) adoption decision

Initial review International Publication of by staff review by INN name

Firm reviews USAN USAN Committee Committee balloting decision USAN Council Considerations

Conflict with other drug names

Inappropriate prefix (e.g., reference to company name, anatomy, implication of benefit)

Appropriate stem

Use of restricted letters (H, J, K. W, Y)

Pronunciation difficulty USAN Balloting Process ▪ F2F meetings are held in January and July ▪ Electronic balloting occurs throughout the year ▪ Approximately 150 names approved annually ▪ Five Voting Members Drug Name Pronunciation USAN Council Pronunciation Guide

General Principles ▪ Retain and build on established precedents. ▪ Keep the USAN stem intact if phonetically reasonable. ▪ Put the primary accent on the USAN stem, if reasonable. ▪ Insert a secondary accent to differentiate among the names with the same USAN stem. ▪ Be consistent with first syllables. ▪ Refer to common dictionaries for common first syllable usage and consider the influence of the pronunciations of popular trade names. Drug Name Pronunciation

Nonproprietary Pronunciation Name

Erenumab E ren’ ue mab

Vancomycin Van” koe mye’ sin Hydrochloride Hye” droe klor’ ide Plazomicin Pla” zoe mye’ sin

Lofexidine Loe fex’ o deen Hydrochloride Hye” droe klor’ ide Cannabidiol Kan” a bi dye’ol

Epoetin alfa E poe’ e tin al’fa USP Dictionary

▪ USAN staff propose pronunciation

▪ USP Pronunciation Expert Panel reporting to the USP Expert Committee on Nomenclature and Labeling ▪ Balloting process ▪ Consensus and approval ▪ Publication in USAN Dictionary USP Dictionary United States Pharmacopeia

▪ Non-profit scientific organization

▪ Founded in 1820

▪ Develops public compendial quality standards for medicines and other articles USP Nomenclature and Federal Law

▪ Food, Drug, and Cosmetic Act If USP has an applicable monograph, drug will be deemed misbranded unless its label bears the “official title” recognized in the USP-NF. FDCA 502(e)(3)

▪ Code of Federal Regulations FDCA & PHS Act drugs recognized in USP are deemed adulterated if they fail to meet USP standards for identity, strength, quality or purity. FDCA 501(b); 21 CFR 299.5 USP Nomenclature and Labeling Expert Committee Members

USP Official USP Staff FDA Total Members Liaisons Pharmacist 6 1 4 11

Nurse 1 1 2

Veterinarian 1 1 2

Physician 1 1

Scientist 4 1 5

Industry 4 4

Total 17 3 5 25 USP Nomenclature Rules

General Chapter <1121> Nomenclature

General Chapter <1151> Pharmaceutical Dosage Forms

Nomenclature Guidelines www.usp.org USP

What is Named Example Drug Products (USP Finafloxacin Otic Suspension Monograph) Drug Substances Finafloxacin (via USAN) Compounded Folic Acid Compounded Oral Preparations Solution Dietary Tangerine Peel Dry Extract Supplements

Excipients Amino Methyl Propanol

Biologics Epoetin Nomenclature Approvals During 2010-2015 Cycle

Type Amount Named

Drug Products 425 Drug Substances 139 Compounded 42 Preparations Dietary Supplements 62 Excipients 19

Biologics 7 Total 694 USP Monograph Title Format

[DRUG] [ROUTE OF ADMINISTRATION] [DOSAGE FORM]

Route of Administration Dosage Form Injection Release Pattern Topical Capsule Inhalation Cream Extended Emulsion Delayed Foam Powder Naming Novel Dosage Forms Foams (propellant vs. manual plunger)

Delayed Release Orally Disintegrating Tablet 38 Naming Novel Dosage Forms Monograph Naming Policy Example

▪ The strength of the product or preparation is expressed in terms of the active moiety except when clinically significant (Official May 1, 2013)

BEFORE AFTER

▪ Policy should be implemented early in drug development to avoid strength mismatch U.S. Food & Drug Administration

• U.S. drugs are regulated by the FDA pursuant to the Federal Food, Drug and Cosmetic Act

• Reviews and approves proprietary names

• Guidance document for the industry in submitting names for evaluation Assessment of Proposed Trade Names

Prescreen IND, NDA, ANDA and BLA applications (e.g., similarity in pronunciation or spelling to other names, absence of USAN stem)

Consider Misleading Nature or Error Potential (e.g., inclusion of dosage form, use of sponsor name, other promotional implications)

Misbranding Review (e.g., suggestion that a drug is safer or more effective or some unique composition when it isn’t supported by evidence)

Look-alike Sound-alike Safety Review (POCA) POCA Analysis

▪ Phonetic and Orthographic Computer Analysis (POCA) initiated by FDA in 2009

▪ Scoring system for look-alike and sound-alike names

▪ Similarity scores ▪ ≥ 70 % High ▪ ≥ 50% to ≤ 69% Moderate Federal Register / Vol. 74, No. 30 ▪ ≤ 49% Low Branding Consultants Recently Approved Trade Names

Proprietary Name Trade Name Sponsor

Erenumab-aooe Aimovig™ Amgen

Vancomycin Hydrochloride for Firvanq™ CutisPharma Oral Solution

Plazomicin Aemdri™ Achaogen

Lofexidine Lucemyra™ US WorldMeds

Cannabidiol Epidiolex™ Greenwich Biosciences

Epoetin alfa-epbx Retacrit™ Hospira International Nonproprietary Names Programme (INN)

▪ INN established in 1953 to name pharmaceutical substances or active pharmaceutical ingredients

▪ Drug name is generally recognized globally but has no role in U.S. federal law

▪ Works collaboratively with USAN General Principles for Coining Names

▪ Distinctive in sound and spelling ▪ Not inconveniently long ▪ Name for a substance belonging to a group of pharmacologically related substances should, where appropriate, show this relationship ▪ Not liable to cause confusion with other names in common use ▪ Worldwide acceptability Items Not Considered by INN

Mixtures

Herbal substances

Long history of medical use (e.g., morphine)

Trivial chemical names (e.g., acetic acid) INN Naming Process

• Application Filed ($12,000 fee) I

• INN Experts Consultation II

• Implementation of Meeting Decisions III

• Proposed INN List (pINN) Published IV

• Recommended INN List (rINN) Published V USAN / INN Negotiation Process Nomenclature Challenges

Names assigned to 21/26 available letters chemical entities that for coining names are not always marketed

Harmonization issues nationally and Industry’s marketing globally (i.e., names, strategies dosage forms, error reporting) Nomenclature Challenges Naming Biosimilars

INN FDA USAN USP

Working Toward Alignment Pharmacist Recommendations

Report Industry Medication Errors

Health ISMP FDA Professional

Consumer Pharmacist Recommendations

Report Medication Errors

https://www.fda.gov/Safety/MedWatch/default.htm

ISMP FDA

https://www.ismp.org/report-medication-error Pharmacist Recommendations

Examples of Actions from Reported Medication Errors

•Amrinone (INN) changed to Inamrinone by USAN to avoid confusion with Amiodarone

•Brintellix (Vortioxetine) changed to Trinetellix by FDA to avoid confusion with Brilinta (Vicagrelor)

•Kapidex (Dexlansoprazole) changed to Dexilant by FDA to avoid confusion with Casodex (Bicalutamide) and Kadian (Morphine) Pharmacist Recommendations

Be Aware of Enhanced “Tall Man” Lettering for Selected Drugs Pharmacist Recommendations Be Aware of Look-alike Sound-alike Names (e.g., FDA’s list of drug names with enhanced lettering)

Drug Name with Confused with Enhanced Lettering buPROPion BusPIRone chlorproMAZINE chlorproPAMide cycloSERINE cycloSPORINE DAUNOrubicin DOXOrubicin DOBUTamine DOPamine glipiZIDE glyBURIDE vinCRIStine vinBLAStine

https://www.fda.gov/Drugs/DrugSafety/MedicationErrors/ucm164587.htm Pharmacist Recommendations

Multiple infixes with -mab

More than 500 -mab drugs

Risk of error potential Pharmacist Recommendations Read the Label USAN, USP & INN follow rules and guidelines in naming drugs and dosage forms

USAN stems are useful in determining the pharmacological action of a drug

USP Dictionary is a useful tool for pronouncing drug names

Health professionals need to be aware of look-alike and sound-alike drug names

Medication error reports due to confusing drug nomenclature can have an impact Self-assessment

Which of the following organizations have legal authority in naming generic (nonproprietary) drugs? a. United States Pharmacopeia b. Drug Safety Institute c. Food and Drug Administration d. a and c e. All of the above Self-assessment

Match the following USAN names with the appropriate pharmacological action based on a USAN stem.

__ 1. Gloximonam a. Angiotensin II receptor antagonist

__2. Losartan b. Antihyperglycemic

__3. Oteracil c. Monobactam antibiotic

__4. Gliflumide d. Uracil type antineoplastic Self-assessment

Match the following drug names with the appropriate pharmacological action. c 1. Gloximonam a. Angiotensin II receptor antagonist a 2. Losartan b. Antihyperglycemic d 3. Oteracil c. Monobactam antibiotic b 4. Gliflumide d. Uracil type antineoplastic Self-assessment Pharmacists can minimize medication errors associated with drug names by which of the following? a. Being aware of look-alike, sound-alike names b. Reporting medication errors to the FDA c. Being aware of enhanced lettering for drug names d. a and b e. All of the above Self-assessment Pharmacists can minimize medication errors associated with drug names by which of the following? a. Being aware of look-alike, sound-alike names b. Reporting medication errors to the FDA c. Being aware of enhanced lettering for drug names d. a and b e. All of the above Questions / Comments