An Overview to RxNorm

      I. Introduction and Overview

What is RxNorm?

RxNorm, a standardized nomenclature for clinical drugs and drug delivery devices, is produced by the National Library of Medicine (NLM). In this context, a clinical drug is a pharmaceutical product given to (or taken by) a patient with a therapeutic or diagnostic intent. A drug delivery device is a pack that contains multiple clinical drugs or clinical drugs designed to be administered in a specified sequence. In RxNorm, the name of a clinical drug combines its ingredients, strengths, and/or form.

While ingredient and strength have straightforward meanings, clarification of what is meant by form may be needed. In RxNorm, the form is the physical form in which the drug is administered or is specified to be administered in a prescription or order. The RxNorm clinical drug name does not refer to the size of the package, the form in which the product was manufactured, its form when it arrived at the dispensary or the intended route.

RxNorm’s standard names for clinical drugs and drug delivery devices are connected to the varying names of drugs present in many different controlled vocabularies within the Unified Medical Language System (UMLS) Metathesaurus, including those in commercially available drug information sources. These connections are intended to facilitate interoperability among the computerized systems that record or process data dealing with clinical drugs.

Purpose of RxNorm

Because every drug information system that is commercially available today follows somewhat different naming conventions, a standardized nomenclature is needed for the smooth exchange of information, not only between organizations, but even within the same organization. For example, a hospital may use one system for ordering and another for inventory management. Still another system might be used to record dose adjustments or to check drug interactions. Several cooperating hospitals might have different systems, and find their data incomparable.

A standardized nomenclature that relates itself to terms from other sources can serve as a means for determining when names from different source vocabularies are synonymous (at an appropriate level of abstraction). The goal of RxNorm is to allow various systems using different drug nomenclatures to share data efficiently at the appropriate level of abstraction.

Objective of this Document

This document is intended to give new users a general idea of the purpose and structure of RxNorm. The RxNorm Release Documentation (http://www.nlm.nih.gov/research/umls/rxnorm/docs/index.html) contains a more detailed discussion of the technical aspects of RxNorm.

A Simple Idea Implemented Rigorously

RxNorm is organized around normalized names for clinical drugs and drug delivery devices. These names contain information on ingredients, strengths, and dose forms. In the case of the drug delivery devices, the quantity is also listed. For example:

Within RxNorm, generic and branded normalized forms are related to each other and to the names of their individual components by a well-defined set of named relationships. Thus, Acetaminophen 500 MG Oral Tablet is related to Acetaminophen 500 MG Oral Tablet [Tylenol], and both have relationships to Acetaminophen, Acetaminophen 500 MG, and Oral Tablet. Within the UMLS Metathesaurus, Acetaminophen 500 MG Oral Tablet and Acetaminophen 500 MG Oral Tablet [Tylenol] will each be linked to different names that are used for these entities in other vocabularies.

The Scope of RxNorm

RxNorm contains the names of prescription and many nonprescription formulations that exist in the United States, including the devices that administer the medications.

RxNorm is intended to cover all prescription medications approved for human use in the United States. Prescription medications from other countries may be included as opportunities allow, a principal consideration being that there be an authoritative source of information about these drugs. Over-the-counter (OTC) medications will be added and covered, as well, when reliable information about the medications can be found. Medications, whether prescription or OTC, with more than four ingredients are not fully represented at the present time.

Additions to the vocabulary will be made as new products are put on the market. Radiopharmaceuticals, because of the decay in strength over time and the requirement that they be ordered and prepared especially for a given time of administration, are listed only as ingredients. Contrast media such as barium compounds are also not represented.

      II. RxNorm in Detail: Structure and Operation

How RxNorm is Structured

An RxNorm clinical drug name reflects the active ingredients, strengths, and dose form comprising that drug. When any of these elements vary, a new RxNorm drug name is created as a separate concept (explained below). Thus, an RxNorm name should exist for every strength and dose of every available combination of clinically significant ingredients.

Nonnumeric named elements of the RxNorm clinical drug name are also individual RxNorm terms related by formal criteria to the clinical drug name.

Connections, in the form of predefined relationships, exist among the components of RxNorm and, additionally, between RxNorm data and data derived from other vocabularies also contained in the UMLS Metathesaurus.

RxNorm data is distributed in Metathesaurus Relational (MR) or Rich Release Format (RRF) tables. The tables that will be of particular relevance in the following discussion are the following:

• RXNCONSO, Concept and Source Information
• RXNREL, Relationships
• RXNSAT, Attributes
• RXNSTY, Semantic Type

For detailed information about the fields, their formatting, and possible values or to learn about other UMLS tables, see the links in the following section.

Details of UMLS and RxNorm Structure

• Complete information on the structure of the UMLS system, its data elements, and its tables can be found in the UMLS Documentation, available online at
• http://www.nlm.nih.gov/research/umls/umlsdoc.html
• In part because of their different schedules of updates, RxNorm file structure differs in some ways from that of the UMLS. Details on the relation between RxNorm and UMLS files may be found at
• http://www.nlm.nih.gov/research/umls/rxnorm/docs/index.html
• The RxNorm Navigator (RxNav) is an interactive graph built on the model of the figure in the section on RxNorm Relationships below. It allows you to query the RxNorm database by any of its components. RxNav can be found at:
• http://mor.nlm.nih.gov/download/rxnav

The Elements of a Normalized Form

RxNorm follows a standard format in the naming of clinical drugs. Drugs named in disparate ways in various other vocabularies are linked to a normalized name prepared according to RxNorm’s naming conventions.

The normalized form of the name of a clinical drug may be thought of as being composed of a number of elements, each a concept in its own right. Each element of the normalized form can be identified by the value of the TTY [Term Type] field of RXNCONSO. The possible values are as follows:

A term type not listed here is OCD (obsolete clinical drug). It is discussed below in the section on Obsolete Records.

One final element found in some normal forms is the Quantity Factor. The Quantity Factor is not a separate term type. (See description in technical documentation)

A Concept Orientation: RxNorm’s Links to Other Vocabularies

Like the UMLS Metathesaurus as a whole, RxNorm is organized by concept. A concept is a collection of names identical in meaning at a specified level of abstraction. It serves as a means whereby strings of characters from disparate sources may be taken to name things that are the same.

For example, Accuneb, 0.042% inhalation solution and Albuterol 0.417 MG/ML Inhalant Solution [Accuneb] names the same concept. In RxNorm, where a normalized form exists, it is designated as the preferred form of the name (by means of its association with the TS [Term Status] field in RXNCONSO). The concept is assigned an RxNorm concept unique identifier (RXCUI) of 575803. This RXCUI always designates the same concept, no matter the form of the name and no matter in what table it is found. Drugs whose names map to the same RXCUI are taken to be the same drug—identical as to ingredients, strengths, and dose forms. Conversely, drugs that differ in any of these particulars are conceptually distinct and will have different RXCUIs.

Acetaminophen 500 MG Oral Tablet and Acetaminophen 500 MG Oral Tablet [Tylenol], on the other hand, name two different concepts, with RXCUIs 198440 and 209459, respectively. The first of these bears the relationship “has_tradename” to the second and the second bears the reciprocal relationship “tradename_of” to the first.

Similarly, two drugs, identical in their generic components, may still refer to different concepts if they differ in brand name. For instance,

RxNorm Relationships

Relationships between concepts in RxNorm are reciprocal. Each direction of the relationship is represented as a separate row in RXNREL. A clinical drug consists of components, and the components constitute the clinical drug. That is to say, a concept with a TTY field value of SCD bears the relationship “consists_of” to certain other concepts with a TTY value of SCDC, and each of these, in turn, bears the relationship “constitutes” to the first concept. This is shown graphically in the two figures below.

For an interactive version of the diagram below, go to
http://mor.nlm.nih.gov/download/rxnav/.

RxNorm Concepts and Relationships Diagrams: RXCUI is the concept unique identifier. TTY is the term type. See the section of this document entitled “The Elements of a Normalized Form” above for an explanation of the TTY values.

Relationships at the level of Clinical Drug through the components of each drug to the ingredients

Relationships at the level of Drug Delivery Device to Clinical Drug

RxNorm contains the following relationships:

• constitutes / consists_of
  • These relationships obtain between an SCD and an SCDC and between an SBD and an SBDC or SCDC.
• contains / contained_in
  • These relationships hold between concepts naming clinical drugs and those naming the devices that dispense them (the latter being those concepts that have an STY [Semantic Type] field value of “Drug Delivery Device” in the table RXNSTY).
• dose_form_of / has_dose_form
  • These relationships obtain between a DF and an SCD, SCDF, SBD, or SBDF.
• form_of / has_form
  • These relationships hold between an IN and a PIN, if there is one, and may designate different salts of the same active ingredient.
• includes/included_in
  • These relationships hold between a base atom and a duplicate atom.
• ingredient_of / has_ingredient
  • These relationships obtain between an IN and an SCDC or SCDF and between a BN and an SBDC, SBD, or SBDF.
• isa / inverse_isa
  • These relationships hold between an SCD and an SCDF and between an SBD and an SBDF.
• precise_ingredient_of / has_precise_ingredient
  • These relationships obtain between an SCDC and a PIN to designate the relationship of the clinical drug to a (usually) nonclinically significant variant of the active ingredient.
• tradename_of / has_tradename
  • These relationships hold between a BN and an IN, between an SBDC and an SCDC, between an SBD and an SCD, or between an SBDF and an SCDF.

Rules and Conventions Used to Generate RxNorm Data

The ingredients named in the SCD, SBD, etc., are the active ingredients. Thus, in the example shown in the figure above, Cetirizine is used as the ingredient name. Though Cetirizine and Cetirizine Dihydrochloride are separate concepts, the normalized form of the drug name does not include the precise ingredient name since, in this case, the difference is without clinical significance.

Similarly, RxNorm makes no distinction between amoxicillin trihydrate, amoxicillin monosodium salt, or amoxicillin potassium salt, because the differences among them are not clinically significant. When there are significant differences among components, as is the case with Penicillin G, Benzathine and Penicillin G, Procaine, the entire compound name (the PIN) is always included as the ingredient.

For example, Bactrim and Bactrim DS both contain sulfamethoxazole and trimethoprim (and in the same proportions relative to one another), the DS indicating only that one product is twice as strong as the other. Records for both products link to the same BN.

However, in the case of Claritin (loratadine) and Claritin D (loratadine with pseudoephedrine), the “D” indicates an additional ingredient. RxNorm, therefore, contains distinct BNs for both Claritin and Claritin D.

If a drug contains one or more components and the proportions are different, this is also reflected in the BN. For example, Advair contains fluticasone and salmeterol. While the amount of salmeterol is constant, the dose of fluticasone can vary. So we end up with several BNs for Advair, including Advair Diskus 500/50 and Advair Diskus 100/50.

Ascorbic Acid 100 MG / Calcium Carbonate 625 MG / Ferrous Fumarate 122 MG / Folic Acid 1 MG Oral Tablet

In this example, the SCD bears the relationship “consists_of” to each of the several ingredient-strength pairs (essentially SCDCs) separated by slashes.

Strengths are expressed to three significant digits. Thus, nearly equal strengths, which may be expressed differently in different drug vocabularies, are treated as being equivalent. That is, when drug names derived from different source vocabularies would be taken to express the same concept (i.e., to name the same substance), except for a discrepancy in the strengths, and if the strengths given, upon conversion to common units, are identical to three significant digits, RxNorm treats the names as equivalent and assigns the same RXCUI to each string.

In most cases, the active ingredient will be the IN. Some drugs, however, will contain a mixture of salts, each of which has a significant and different clinical action. For example, Adderall contains two ingredients, amphetamine and dextroamphetamine. There are six variants of these two ingredients. Four of these variants are clinically active. The RxNorm SCD names each of these salts, with its individual strength, separately and in alphabetical order.

Amphetamine Aspartate 1.25 MG / Amphetamine Sulfate 1.25 MG / Dextroamphetamine Saccharate 1.25 MG / Dextroamphetamine Sulfate 1.25 MG Extended Release Capsule

In the case of small inorganic molecules, the strength will be expressed in terms of the salt given. For example, an oral tablet that contains 1250 MG of Calcium Carbonate and 500 MG of Calcium will appear as:

As time permits, there will be a SY added to the SCDs that shows both strengths:

The following units of measurement are used in RxNorm:

• MEQ
  • Milliequivalent.
• MG
  • Milligram.
• ML
  • Milliliter.
• UNT
  • Unit.
• %
  • Used only with gases, otherwise percentages are converted into ratios.

The following unit appears only in ratios:

• ACTUAT
  • Actuation. Refers to a measured dose per activation of a dispensing devise; e.g., in an inhaler, the strength of the clinical drug is given by how much is dispensed with each actuation.

The following ratios of units have been used in RxNorm:

• MEQ/MG
• MEQ/ML
• MG/ACTUAT
• MG/MG
• MG/ML
• ML/ML
• PNU/ML
• UNT/MG
• UNT/ML

• Standard conversion factors are used between metric units.
• One liquid ounce is taken to be equivalent to 30 milliliters or 240 ml per 8 ounces.
• A grain is 65 milligrams.

If a variable amount of diluent can be used, the minimum amount is used in RxNorm to calculate the concentration that determines the strength. For example, in the case of a drug that can be dissolved in 3 to 5 ml of diluent, RxNorm would use 3 ml. For drugs with multiple dilution steps, only the initial dilution is used to calculate the strength. For example, a vial containing 50 mg of a drug to be dissolved in 2 ml of water, then added to an IV solution, is expressed as having strength of 25 mg/ml.

Dihydroxyaluminum Sodium Carbonate 334 MG [Rolaids] became
Calcium Carbonate 550 MG / Magnesium Hydroxide 110 MG [Rolaids Reformulated Aug 2006]

In such cases, synonyms (TTY=“SY”) will be created in RxNorm as more manageable forms of the name.

      Amiodarone hydrochloride 200 MG Oral Tablet

National Drug Code (NDC)

NDCs are listed as attributes asserted by the source vocabulary. Additionally, RxNorm will assert, as an RxNorm attribute, what is believed to be the correct association with NDC codes. When conflicts arise between sources, other means of obtaining information about the drug may be used in order to determine the correct NDC.

In some cases these conflicts arise due to different naming philosophies. While RxNorm considers 21 and 28 day packs of oral contraceptives to be different concepts, some sources group these together and assign multiple NDCs to the same string.

RxNorm is creating duplicates of such source asserted atoms in order to properly associate NDC codes with RxNorm forms. When an atom is duplicated, the original source atom is considered to be a 'Base' atom and it is not assigned an RxNorm form. The duplicate atom's string is created by appending '_#N' to the Base atom string where 'N' is a number from 1 to N number of duplicates for this base atom.

The duplicate atoms will carry the same source asserted relationships and attributes as the Base atom except for the NDC code attributes. The NDC code attributes of the base atom will be assigned to the duplicate atoms that represent the different meanings of the base atom. RxNorm forms will be created to reflect the true meaning of the NDC code(s) assigned to each duplicate. An NDC code from a base atom can only be assigned to one duplicate atom at a time, but a duplicate atom can carry more than one similar meaning NDC codes from the base atom. The duplicate atom's term type will be created by prepending 'MTH_RXN_' to the base atom's term type.

Example of base atoms and duplicate atoms with normal forms:

Codes and CUIs

The values of the Code field (in RXNCONSO, for example) are taken from various source vocabularies and are used, in those sources, to identify particular items in the vocabularies.

At one time, RxNorm concepts had a code (used for internal processing) that was different from the RXCUI. Now, all concepts with a Source Abbreviation (SAB) field equal to “RxNorm” have RXCUIs identical to their codes.

The following list indicates the fields in the source vocabularies from which the Code is drawn.

For two other sources, the field from which the Code is taken is determined by the term type used in the source record.

The last two MMSL term types are loaded into RxNorm as “NoCode”.

NLM is now associating U.S. Food and Drug Administration (FDA) generated unique ingredient identifiers (UNIIs) to RxNorm (SAB=RXNORM) atoms of term type IN. The association is made by an exact string match to the RxNorm ingredient string (case insensitive) from the official FDA substance list. These UNII codes are found in RXNSAT.RRF as values of the attribute ATN='UNII_CODE'. The UNII is a non-proprietary, free, unique, unambiguous, non semantic, alphanumeric identifier based on a substance’s molecular structure and/or descriptive information. For more information on the FDA UNII codes, please refer to this FDA web page.

Cardinality

When a BN has more than one IN, this is noted as an attribute of the BN, with the value “multi”, in table RXNSAT. To find those ingredients, the user should follow the relationship attribute RELA in the RXNREL table (see Appendix 1, showing the values that RELA can take in relation to the term type BN.

Updates

The full set of files is included in the UMLS Metathesaurus. But while the Metathesaurus, as a whole, is two to three times a year, RxNorm is available as a full update on a monthly basis. In addition, a weekly update containing data from Daily Med and newly approved drugs is available weekly. Between releases of the UMLS, RxNorm update files will be made available through the UMLS Knowledge Source Server. These files will be consistent with the latest extant release of the UMLS, but will contain additional naming information available since that release.

It is important to note that the RxNorm files available include names and data from other sources, even though those names are not part of RxNorm. The availability of those names in the RxNorm subset should not be considered as an indication that these can be used without proper consideration of their UMLS licensing restrictions. The restrictions still apply. However, it seems advisable to make those names and relationships available in the updates, in order to support the maintenance of a current drug vocabulary.

Because RxNorm is updated so much more frequently than the rest of the UMLS, RxNorm maintains separate concept unique identifiers. At the time of a resynchronized release, UMLS CUIs and RxNorm RXCUIs should have a one-to-one relationship.

Tracking changes between versions of the Metathesaurus can be accomplished through the MRCUI file and other Metathesaurus change files.

Obsolete Records

Obsolete records are marked in three ways, depending on the source of the record and its relationships with other records.

(1) When one of RxNorm’s source vocabularies drops a clinical drug name—that is, when the name had been used in a previous version of that source’s vocabulary but is not found in the most recent version—the old clinical drug records are given the term type OCD (for obsolete clinical drug) in RXNSTY. The record is updated with RxNorm as the source (SAB field), but retains the original SAB, VSAB, TTY, and Code as attributes in RXNSAT. Any existing relationships to RxNorm records will be maintained.

(2) When a clinical drug disappears from the U.S. market, the RxNorm SCD should correspond only to OCDs; i.e., it will reside in the same concept exclusively with other records whose TTY fields contain the value OCD. At that time, it is flagged with an “O” (for Obsolete) in the Suppress field in RXNCONSO.

(3) If, during a resynchronization with the UMLS (see Updates, above), it is found that there is more than one RxNorm record in the same concept, then one of the records is marked as the preferred one and the others are archived. The archive file is called RXNATOMARCHIVE.

Downloading RxNorm

RxNorm files are available through the NLM download server:

and may be downloaded as zipped text files. Because of the difference in update frequency between RxNorm and the rest of the UMLS, the zip files will be the more current.

      III. RxNorm in Use

The following sample questions and algorithmic solutions illustrate the retrieval of RxNorm information using UMLS data tables.

In what follows, field labels are given in capital letters on the left side of the equals sign; field values are given within quotation marks; and field descriptive names, when provided for clarity, are given in square brackets.

Taking amoxicillin as exemplar throughout, we can first find all RxNorm concepts related to amoxicillin. In general, other algorithms than the ones shown here may also be available to achieve the same results.

3. Let {Ω} stand for the set containing all the RXCUIs retrieved in steps 1 and 2.

Q. What trade names is amoxicillin sold under?

Q. What strengths of amoxicillin are available?

Q. What dose forms of amoxicillin are available?

Q. What is the National Drug Data File (NDDF) code for amoxicillin?

Q. Given the NDDF code, how can I find the code for SNOMED, Version 3.5?

Use in Electronic Prescribing and Computerized Order Entry

The representation of the relationships between names of drugs from various drug information sources, their ingredients, strengths, and dose forms should provide a necessary structure for support of electronic prescription writing and physician order entry. However, in some instances, this set of relationships may not be sufficient to convey all of the desired attributes of an order. Some inactive ingredients may still be of interest; e.g., lactose, dextrose, alcohol, flavorings, or dyes. Where packaging of products may be of particular interest (e.g., dose packs), the link between the drug delivery device and the RxNorm form will present the necessary information. In other cases (e.g., vial size or the making up of intravenous solutions), the person preparing the solution will be obligated to review the material at hand, and choose appropriately.

Radiopharmaceuticals create a special case. Since they must be specially ordered to have the appropriate radioactivity at a given time, they will not be represented except as a range of approximate activities.