Tidy Utilities for RxNorm and NDC Resolution • rxref

rxref is an R package for working with medication identifiers from the National Library of Medicine’s RxNorm and RxClass APIs. It provides tidy, vectorized helpers for resolving medication names to RxCUIs, expanding ingredients to product concepts, mapping between RxCUIs and NDCs, retrieving clinical product attributes, and querying selected drug class relationships.

The package was designed for pharmacoepidemiologic and health services research workflows where medication exposure definitions often need to move between ingredient names, RxNorm concepts, National Drug Codes (NDCs), routes, dose forms, and therapeutic classes.

rxref was originally built to support the UF CVmedLab, where we often need reproducible, transparent medication definitions for prescriptions, pharmacy dispensings, and claims-based drug exposure measures.

What rxref can do

Common workflows include:

resolve free-text medication names to RxNorm ingredient concepts with find_ingredients() and resolve();
expand ingredient RxCUIs to product RxCUIs with products_for_ingredients();
include active-only or active plus historical RxNorm concepts using concept_status;
map between RxCUIs and NDCs with map_to(), map_rxcui_to_ndc(), and map_ndc_to_rxcui();
retrieve product metadata with get_properties() and get_clinical_attributes();
filter products by route with filter_products_by_route();
query selected RxClass relationships with helpers such as get_atc(), get_epc(), and get_medrt();
use predefined RxNorm term type sets with product_ttys() and tty_catalogue().

Installation

You can install the released version of rxref from CRAN:

install.packages("rxref")

You can install the development version of rxref from GitHub with:

# install.packages("pak")
pak::pak("ssmithm/rxref")

Basic Workflow: ingredients to products

This is a basic example for querying product RxCUIs associated with the ingredient lisinopril (a blood pressure-lowering drug):

library(rxref)
library(dplyr)
#> 
#> Attaching package: 'dplyr'
#> The following objects are masked from 'package:stats':
#> 
#>     filter, lag
#> The following objects are masked from 'package:base':
#> 
#>     intersect, setdiff, setequal, union

lisinopril_ing <- find_ingredients("lisinopril")

lisinopril_products <- products_for_ingredients(
  lisinopril_ing$rxcui,
  ttys = product_ttys("default"),
  include_combos = TRUE
)

# Resulting table 
lisinopril_products |> 
  dplyr::mutate(name = paste0("`", name, "`")) |> 
  knitr::kable()

ingredient_rxcui	product_rxcui	name	tty	n_ingredients
29046	104375	`lisinopril 2.5 MG Oral Tablet [Zestril]`	SBD	1
29046	104376	`lisinopril 5 MG Oral Tablet [Zestril]`	SBD	1
29046	104377	`lisinopril 10 MG Oral Tablet [Zestril]`	SBD	1
29046	104378	`lisinopril 20 MG Oral Tablet [Zestril]`	SBD	1
29046	1806890	`lisinopril 1 MG/ML Oral Solution [Qbrelis]`	SBD	1
29046	206765	`lisinopril 10 MG Oral Tablet [Prinivil]`	SBD	1
29046	206766	`lisinopril 20 MG Oral Tablet [Prinivil]`	SBD	1
29046	206771	`lisinopril 40 MG Oral Tablet [Zestril]`	SBD	1
29046	213482	`lisinopril 30 MG Oral Tablet [Zestril]`	SBD	1
29046	823971	`hydrochlorothiazide 25 MG / lisinopril 20 MG Oral Tablet [Zestoretic]`	SBD	2
29046	823982	`hydrochlorothiazide 12.5 MG / lisinopril 20 MG Oral Tablet [Zestoretic]`	SBD	2
29046	823986	`hydrochlorothiazide 12.5 MG / lisinopril 10 MG Oral Tablet [Zestoretic]`	SBD	2
29046	1806884	`lisinopril 1 MG/ML Oral Solution`	SCD	1
29046	197884	`lisinopril 40 MG Oral Tablet`	SCD	1
29046	197885	`hydrochlorothiazide 12.5 MG / lisinopril 10 MG Oral Tablet`	SCD	2
29046	197886	`hydrochlorothiazide 12.5 MG / lisinopril 20 MG Oral Tablet`	SCD	2
29046	197887	`hydrochlorothiazide 25 MG / lisinopril 20 MG Oral Tablet`	SCD	2
29046	205326	`lisinopril 30 MG Oral Tablet`	SCD	1
29046	311353	`lisinopril 2.5 MG Oral Tablet`	SCD	1
29046	311354	`lisinopril 5 MG Oral Tablet`	SCD	1
29046	314076	`lisinopril 10 MG Oral Tablet`	SCD	1
29046	314077	`lisinopril 20 MG Oral Tablet`	SCD	1



# Count of TTYs in resulting table
lisinopril_products |> 
  count(tty, n_ingredients, sort=TRUE)
#> # A tibble: 4 × 3
#>   tty   n_ingredients     n
#>   <chr>         <int> <int>
#> 1 SBD               1     9
#> 2 SCD               1     7
#> 3 SBD               2     3
#> 4 SCD               2     3

Active and historical RxNorm concepts

By default, products_for_ingredients() searches active RxNorm concepts:

products_for_ingredients(
  "29046",
  ttys = product_ttys("extended_product"),
  concept_status = "active"
) |> knitr::kable()

ingredient_rxcui	product_rxcui	name	tty	n_ingredients
29046	1806883	lisinopril Oral Solution	SCDF	1
29046	372613	hydrochlorothiazide / lisinopril Oral Tablet	SCDF	2
29046	372614	lisinopril Oral Tablet	SCDF	1
29046	1162124	hydrochlorothiazide / lisinopril Oral Product	SCDG	2
29046	1162125	hydrochlorothiazide / lisinopril Pill	SCDG	2
29046	1164689	lisinopril Oral Product	SCDG	1
29046	1164690	lisinopril Pill	SCDG	1
29046	1806882	lisinopril Oral Liquid Product	SCDG	1
29046	104375	lisinopril 2.5 MG Oral Tablet [Zestril]	SBD	1
29046	104376	lisinopril 5 MG Oral Tablet [Zestril]	SBD	1
29046	104377	lisinopril 10 MG Oral Tablet [Zestril]	SBD	1
29046	104378	lisinopril 20 MG Oral Tablet [Zestril]	SBD	1
29046	1806890	lisinopril 1 MG/ML Oral Solution [Qbrelis]	SBD	1
29046	206765	lisinopril 10 MG Oral Tablet [Prinivil]	SBD	1
29046	206766	lisinopril 20 MG Oral Tablet [Prinivil]	SBD	1
29046	206771	lisinopril 40 MG Oral Tablet [Zestril]	SBD	1
29046	213482	lisinopril 30 MG Oral Tablet [Zestril]	SBD	1
29046	823971	hydrochlorothiazide 25 MG / lisinopril 20 MG Oral Tablet [Zestoretic]	SBD	2
29046	823982	hydrochlorothiazide 12.5 MG / lisinopril 20 MG Oral Tablet [Zestoretic]	SBD	2
29046	823986	hydrochlorothiazide 12.5 MG / lisinopril 10 MG Oral Tablet [Zestoretic]	SBD	2
29046	1806887	lisinopril Oral Solution [Qbrelis]	SBDF	1
29046	368248	lisinopril Oral Tablet [Zestril]	SBDF	1
29046	368865	lisinopril Oral Tablet [Prinivil]	SBDF	1
29046	823970	hydrochlorothiazide / lisinopril Oral Tablet [Zestoretic]	SBDF	2
29046	1178275	Prinivil Oral Product	SBDG	1
29046	1178276	Prinivil Pill	SBDG	1
29046	1187277	Zestoretic Oral Product	SBDG	2
29046	1187278	Zestoretic Pill	SBDG	2
29046	1187283	Zestril Oral Product	SBDG	1
29046	1187284	Zestril Pill	SBDG	1
29046	1806888	Qbrelis Oral Liquid Product	SBDG	1
29046	1806889	Qbrelis Oral Product	SBDG	1
29046	1806884	lisinopril 1 MG/ML Oral Solution	SCD	1
29046	197884	lisinopril 40 MG Oral Tablet	SCD	1
29046	197885	hydrochlorothiazide 12.5 MG / lisinopril 10 MG Oral Tablet	SCD	2
29046	197886	hydrochlorothiazide 12.5 MG / lisinopril 20 MG Oral Tablet	SCD	2
29046	197887	hydrochlorothiazide 25 MG / lisinopril 20 MG Oral Tablet	SCD	2
29046	205326	lisinopril 30 MG Oral Tablet	SCD	1
29046	311353	lisinopril 2.5 MG Oral Tablet	SCD	1
29046	311354	lisinopril 5 MG Oral Tablet	SCD	1
29046	314076	lisinopril 10 MG Oral Tablet	SCD	1
29046	314077	lisinopril 20 MG Oral Tablet	SCD	1

For older prescribing (or dispensing) data, users may need products that are no longer active in the current RxNorm release. Set concept_status = "active_and_historical" to include active concepts plus selected historical statuses:

products_for_ingredients(
  "1369",
  ttys = "SCD",
  include_combos = FALSE,
  concept_status = "active_and_historical"
) |> knitr::kable()

ingredient_rxcui	product_rxcui	name	tty	n_ingredients	concept_status	active_start_date	active_end_date	release_start_date	release_end_date
1369	197394	bendroflumethiazide 5 MG Oral Tablet	SCD	1	Active	NA	NA	NA	NA
1369	308614	bendroflumethiazide 2.5 MG Oral Tablet	SCD	1	Active	NA	NA	NA	NA
1369	197393	bendroflumethiazide 10 MG Oral Tablet	SCD	1	Obsolete	042005	062014	042005
1369	308617	bendroflumethiazide 5 MG Extended Release Oral Tablet	SCD	1	Obsolete	042005	092010	042005
1369	429502	bendroflumethiazide 1.25 MG Oral Tablet	SCD	1	Obsolete	042005	072005	042005

Historical searches return additional status and date fields, including concept_status, active_start_date, active_end_date, release_start_date, and release_end_date.

Note: Historical searches are slower than active-only searches because they require broader RxNorm status lookups. rxref caches repeated API calls where possible, but active-only queries should be preferred when historical concepts are not needed.

Clinical product attributes and route filtering

get_clinical_attributes() retrieves product-level attributes such as ingredients, dose form, dose form group, route, strength, and ingredient count.

attrs <- get_clinical_attributes(lisinopril_products$product_rxcui)

attrs |>
  select(rxcui, related_rxcui, name, strength, dose_form, route, tty)
#> # A tibble: 22 × 7
#>    rxcui   related_rxcui name                     strength dose_form route tty  
#>    <chr>   <chr>         <chr>                    <chr>    <chr>     <chr> <chr>
#>  1 104375  104375        lisinopril 2.5 MG Oral … 2.5 MG   Oral Tab… ORAL  SBD  
#>  2 104376  104376        lisinopril 5 MG Oral Ta… 5 MG     Oral Tab… ORAL  SBD  
#>  3 104377  104377        lisinopril 10 MG Oral T… 10 MG    Oral Tab… ORAL  SBD  
#>  4 104378  104378        lisinopril 20 MG Oral T… 20 MG    Oral Tab… ORAL  SBD  
#>  5 1806890 1806890       lisinopril 1 MG/ML Oral… 1 MG/ML  Oral Sol… ORAL  SBD  
#>  6 206765  206765        lisinopril 10 MG Oral T… 10 MG    Oral Tab… ORAL  SBD  
#>  7 206766  206766        lisinopril 20 MG Oral T… 20 MG    Oral Tab… ORAL  SBD  
#>  8 206771  206771        lisinopril 40 MG Oral T… 40 MG    Oral Tab… ORAL  SBD  
#>  9 213482  213482        lisinopril 30 MG Oral T… 30 MG    Oral Tab… ORAL  SBD  
#> 10 823971  823971        hydrochlorothiazide 25 … 25 MG /… Oral Tab… ORAL  SBD  
#> # ℹ 12 more rows

Products can also be filtered by route:

oral_lisinopril <- filter_products_by_route(
  lisinopril_products,
  route = "ORAL"
)

oral_lisinopril 
#> # A tibble: 22 × 8
#>    ingredient_rxcui product_rxcui name       tty   n_ingredients route dose_form
#>    <chr>            <chr>         <chr>      <chr>         <int> <chr> <chr>    
#>  1 29046            104375        lisinopri… SBD               1 ORAL  Oral Tab…
#>  2 29046            104376        lisinopri… SBD               1 ORAL  Oral Tab…
#>  3 29046            104377        lisinopri… SBD               1 ORAL  Oral Tab…
#>  4 29046            104378        lisinopri… SBD               1 ORAL  Oral Tab…
#>  5 29046            1806890       lisinopri… SBD               1 ORAL  Oral Sol…
#>  6 29046            206765        lisinopri… SBD               1 ORAL  Oral Tab…
#>  7 29046            206766        lisinopri… SBD               1 ORAL  Oral Tab…
#>  8 29046            206771        lisinopri… SBD               1 ORAL  Oral Tab…
#>  9 29046            213482        lisinopri… SBD               1 ORAL  Oral Tab…
#> 10 29046            823971        hydrochlo… SBD               2 ORAL  Oral Tab…
#> # ℹ 12 more rows
#> # ℹ 1 more variable: dose_form_group <chr>

Mapping between RxCUIs and NDCs

RxCUIs can be mapped to NDCs (and vice-versa):

ndcs <- map_rxcui_to_ndc("314077")

ndcs
#> # A tibble: 249 × 3
#>    rxcui  ndc11       ndc_status
#>    <chr>  <chr>       <chr>     
#>  1 314077 00143971301 ACTIVE    
#>  2 314077 00143971310 ACTIVE    
#>  3 314077 00185062001 ACTIVE    
#>  4 314077 00185062010 ACTIVE    
#>  5 314077 00378207501 ACTIVE    
#>  6 314077 00378207510 ACTIVE    
#>  7 314077 00591040801 ACTIVE    
#>  8 314077 00591040810 ACTIVE    
#>  9 314077 00615825505 ACTIVE    
#> 10 314077 00615825530 ACTIVE    
#> # ℹ 239 more rows

The direction-agnostic map_to() function can be used when you want to map between identifier types with one interface:

map_to("314077", to = "ndc") 
#> # A tibble: 249 × 3
#>    rxcui  ndc11       ndc_status
#>    <chr>  <chr>       <chr>     
#>  1 314077 00143971301 ACTIVE    
#>  2 314077 00143971310 ACTIVE    
#>  3 314077 00185062001 ACTIVE    
#>  4 314077 00185062010 ACTIVE    
#>  5 314077 00378207501 ACTIVE    
#>  6 314077 00378207510 ACTIVE    
#>  7 314077 00591040801 ACTIVE    
#>  8 314077 00591040810 ACTIVE    
#>  9 314077 00615825505 ACTIVE    
#> 10 314077 00615825530 ACTIVE    
#> # ℹ 239 more rows

Drug class relationships

rxref includes selected helpers for querying RxClass relationships, including ATC, EPC, and MED-RT classes.

get_atc("29046")
#> # A tibble: 1 × 10
#>   input rxcui drug_name  drug_tty class_id class_name class_type class_url rela 
#>   <chr> <chr> <chr>      <chr>    <chr>    <chr>      <chr>      <chr>     <chr>
#> 1 29046 29046 lisinopril IN       C09AA    ACE inhib… ATC1-4     <NA>      ""   
#> # ℹ 1 more variable: rela_source <chr>
get_epc("29046")
#> # A tibble: 2 × 10
#>   input rxcui  drug_name drug_tty class_id class_name class_type class_url rela 
#>   <chr> <chr>  <chr>     <chr>    <chr>    <chr>      <chr>      <chr>     <chr>
#> 1 29046 15460… lisinopr… PIN      N000017… Angiotens… EPC        <NA>      has_…
#> 2 29046 15460… lisinopr… PIN      N000017… Angiotens… EPC        <NA>      has_…
#> # ℹ 1 more variable: rela_source <chr>
get_medrt("29046")
#> # A tibble: 43 × 10
#>    input rxcui drug_name drug_tty class_id class_name class_type class_url rela 
#>    <chr> <chr> <chr>     <chr>    <chr>    <chr>      <chr>      <chr>     <chr>
#>  1 29046 1546… lisinopr… PIN      D000799  Angioedema DISEASE    <NA>      ci_w…
#>  2 29046 1546… lisinopr… PIN      D003928  Diabetic … DISEASE    <NA>      may_…
#>  3 29046 1546… lisinopr… PIN      D003928  Diabetic … DISEASE    <NA>      may_…
#>  4 29046 1546… lisinopr… PIN      D004342  Drug Hype… DISEASE    <NA>      ci_w…
#>  5 29046 1546… lisinopr… PIN      D006333  Heart Fai… DISEASE    <NA>      may_…
#>  6 29046 1546… lisinopr… PIN      D006929  Hyperaldo… DISEASE    <NA>      ci_w…
#>  7 29046 1546… lisinopr… PIN      D006973  Hypertens… DISEASE    <NA>      may_…
#>  8 29046 1546… lisinopr… PIN      D007022  Hypotensi… DISEASE    <NA>      ci_w…
#>  9 29046 1546… lisinopr… PIN      D009203  Myocardia… DISEASE    <NA>      may_…
#> 10 29046 1546… lisinopr… PIN      D011247  Pregnancy  DISEASE    <NA>      ci_w…
#> # ℹ 33 more rows
#> # ℹ 1 more variable: rela_source <chr>

API use and caching

rxref queries public RxNorm and RxClass APIs. The package includes configurable rate-delay and caching behavior to reduce repeated API requests and to support longer medication-definition workflows. Note that RxNorm indicates a rate of no more than 20 API requests per second per IP.

rxref_conf()
#> $base_url
#> [1] "https://rxnav.nlm.nih.gov/REST"
#> 
#> $rate_delay
#> [1] 0.1
#> 
#> $cache
#> <cache_mem> <cachem>
#>   Methods:
#>     get(key, missing = missing_)
#>     set(key, value)
#>     exists(key)
#>     keys()
#>     remove(key)
#>     reset()
#>     prune()
#>     size()
#>     info()
rxref_conf(rate_delay = 0.1)
#> $base_url
#> [1] "https://rxnav.nlm.nih.gov/REST"
#> 
#> $rate_delay
#> [1] 0.1
#> 
#> $cache
#> <cache_mem> <cachem>
#>   Methods:
#>     get(key, missing = missing_)
#>     set(key, value)
#>     exists(key)
#>     keys()
#>     remove(key)
#>     reset()
#>     prune()
#>     size()
#>     info()

Notes

RxNorm concepts and NDC mappings can change over time. For reproducible research, consider recording the date of API access and retaining intermediate drug-definition outputs used in analyses.

rxref is intended to support research workflows and medication-definition development. Users should review outputs carefully before using them in any high-stakes regulatory, clinical, or production settings.

Funding

Development of rxref was supported in part by the U.S. National Heart, Lung and Blood Institute (NHLBI), grants K01HL138172 and R01HL171387. The content is solely the responsibility of the author and does not necessarily represent the official views of the National Institutes of Health.