TOOLS FOR ADVANCING PHARMACY PRACTICE
New drug information resources for pharmacists at the National Library of Medicine James E. Knoben and Steven J. Phillips
Abstract
Received on June 17, 2013, and in revised July 16, 2013. Accepted for publication July 16, 2013.
Objective: To provide an overview of selected drug information-related databases of the National Library of Medicine (NLM), with a focus on newer resources that support the professional information needs of pharmacists and other health care providers.
James E. Knoben, PharmD, MPH, is Drug Information Consultant, Specialized Information Services Division; and Steven J. Phillips, MD, is Director, Specialized Information Services Division, and Associate Director, National Library of Medicine, National Institutes of Health, Bethesda, MD.
Summary: NLM, which is the world’s largest medical library, provides an array of bibliographic, factual, and evidence-based drug, herbal remedy, and dietary supplement information resources. Five of the more recently introduced online resources include areas of particular importance to pharmacists, including a repository of current product labeling/package inserts, with automated search links to associated information resources; a portal to drug information that allows pharmacists to search multiple databases simultaneously and link to related medication and health care information resources; authoritative information on the effects of medications, herbal remedies, and dietary supplements in nursing infants and their mothers; comprehensive information, including a case registry, on the potential for liver toxicity due to drugs, herbal remedies, and dietary supplements; and a pill identification system with two intuitive search methodologies.
Correspondence: James E. Knoben, PharmD, MPH, National Library of Medicine, 6707 Democracy Blvd., Suite 510, Bethesda, MD 20892. Fax: 301-480-3537. E-mail: [email protected] Disclosure: The authors declare no conflicts of interest or financial interests in any product or service mentioned in this article, including grants, employment, gifts, stock holdings, or honoraria. Previous presentation: Keynote, Federal Pharmacy Forum, American Pharmacists Association Annual Meeting & Exposition, Los Angeles, March 1–4, 2013. Published online ahead of print at www. japha.org on December 20, 2013.
Conclusion: NLM provides several clinical–scientific drug information resources that are particularly useful in meeting the professional information needs of pharmacists. Keywords: Drug information, evidence based, hepatotoxicity, lactation, package inserts, search portal, structured product labeling. J Am Pharm Assoc. 2014;54:49–55. doi: 10.1331/JAPhA.2014.13123
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he National Library of Medicine (NLM), located on the campus of the National Institutes of Health in Bethesda, MD, is the world’s largest medical library, providing access to a vast collection of more than 19 million books, journals, manuscripts, and audiovisual items. In addition to on-site access to its collections, NLM provides information in an electronic format directly to end users, with the result that its online resources are searched billions of times each year by people around the globe. The library’s mission also includes the support and conduct of research, development, and training in biomedical informatics and health information technology, and it is a leading global resource for genomic information. Drug information was an important component of NLM’s strategic focus beginning in 1967, when Congress provided funds to form a drug literature program (DLP) at the library. Professional pharmacy associations partnered with the program, providing key contributions toward organizing and making drug information more readily available to practitioners. DLP funding was unsustainable, however, and the program was disbanded.1,2 Subsequently, drug information has been dispersed among a number of NLM health-related databases, and in more recent
At a Glance Synopsis: The National Library of Medicine (NLM) provides several clinical–scientific drug information resources that are particularly useful in meeting the professional information needs of pharmacists. Five of the more recently introduced online resources include areas of particular importance to pharmacists, including a repository of current product labeling/package inserts, with automated search links to associated information resources; a portal to drug information that allows pharmacists to search multiple databases simultaneously and link to related medication and health care information resources; authoritative information on the effects of medications, herbal remedies, and dietary supplements in nursing infants and their mothers; comprehensive information, including a case registry, on the potential for liver toxicity due to drugs, herbal remedies, and dietary supplements; and a pill identification system with two intuitive search methodologies. Analysis: The newer NLM resources described here are authoritative, available without charge, readily accessible, and complement other reliable NLM resources that pharmacists have used for years. NLM will continue to consider other potential drug-related databases that would be of benefit to health professionals.
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years, NLM has sought to provide an array of new drug/medication information–related resources for health care practitioners, patients/consumers, and researchers. This more recent effort acknowledges the importance of drugs as the most critical medical intervention in treating patients, the increased complexity of drug therapy, and the ubiquitous nature of drug information that is now readily accessible to patients and health care practitioners. NLM’s recent initiatives to provide more specialized drug information resources complement therapeutic information that is currently available in other health and medically related databases.
Objective Our goal is to describe NLM databases that support the drug information needs of pharmacists and other health care providers who practice in a range of professional settings, with an emphasis on those databases created in the previous several years. Guidance is provided on the drug information in the databases, as well as how to navigate these resources.
Data sources At least a dozen databases and data files containing drug information–related content are provided by NLM. These information resources and the type of data they provide are shown in Table 1. Although they vary by type of data/database, a common characteristic of these databases is that they all incorporate data selection, organization, and search capability. All of the resources in Table 1 are freely accessible though the NLM homepage (www. nlm.nih.gov; Figure 1), by clicking on “All NLM Databases & APIs” in the upper-left corner of the page display, under “Databases.” Users will be taken to an A-to-Z listing with links and to an alphabetic list of the database names with associated links.
Recently released databases Some of the aforementioned databases have been in existence for many years, including AIDSinfo, ClinicalTrials.gov, Hazardous Substances Data Bank, MedlinePlus, and PubMed/MEDLINE, and these are discussed in detail in a previous article, along with other NLM resources.2,3 For purposes of this review, five drug information databases are described that have been introduced in more recent years: ❚❚ DailyMed: repository of Food and Drug Administration (FDA) drug labeling ❚❚ Drug Information Portal: search gateway to drug information ❚❚ LactMed: drug effects on breast-feeding mothers and their infants ❚❚ LiverTox: drugs that induce liver injury ❚❚ Pillbox: pill identification system Journal of the American Pharmacists Association
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Table 1. Drug information content databases by type Database name AIDSinfo ClinicalTrials.gov DailyMed Dietary Supplement Label Database Drug Information Portal Hazardous Substances Data Bank LactMed LiverTox MedlinePlus Pillbox PubMed/MEDLINE RxNorm
Type Evidence based, factual Factual Factual (document repository) Factual (document repository) Search portal Factual Evidence based Evidence based Portal Factual (image repository) Bibliographic Nomenclature System
Each of the five databases provides drug-related information that is particularly useful to pharmacists and other health care practitioners in various practice environments. Taken together, these resources are sufficiently comprehensive that pharmacists can rely on them to provide an array of information to clinicians and patients about the proper use and safety of medications. DailyMed DailyMed is a document repository of FDA drug product labeling/package inserts and related information, sponsored as a health technology partnership of FDA, NLM, and the Veterans Health Administration. Before DailyMed, a long-standing need existed for ready access to current package inserts that were available principally as print media, either a folded paper insert with marketed products or in compendia such as the Physicians’ Desk Reference. The DailyMed initiative responded to the need for a systematic, online resource and coincided with FDA’s November 2, 2005, release of the Structured Product Labeling (SPL) regulations, which require manufacturers to provide package inserts with a standardized format and terminology, using extensible markup language (XML). XML encodes documents in a format that is human and machine readable, embedding computer tags to denote specific data sections that, in turn, enable electronic search capability. NLM receives daily SPL updates from FDA, so that the labels are posted in DailyMed within 1 day of FDA approval or submission to FDA (when no prior approval is needed). DailyMed now logs millions of accessions each month, attesting to its importance in the provision of health care. Labeling can be searched by drug name, FDA pharmacologic class, or National Drug Code. Once retrieved, the SPL sections of the package insert can be accessed by clicking on designated tabs at the top of the page (Figure 2), such as the drug’s description, clinical pharmacology, indications and usage, and contraindications. Other features include the capability for users to eJournal of the American Pharmacists Association
URL http://aidsinfo.nih.gov http://clinicaltrials.gov http://dailymed.nlm.nih.gov/dailymed/about.cfm http://dsld.nlm.nih.gov/dsld http://druginfo.nlm.nih.gov http://toxnet.nlm.nih.gov/cgi-bin/sis/htmlgen?HSDB http://toxnet.nlm.nih.gov/cgi-bin/sis/htmlgen?LACT www.livertox.nih.gov www.nlm.nih.gov/medlineplus http://pillbox.nlm.nih.gov www.ncbi.nlm.nih.gov/pubmed www.nlm.nih.gov/research/umls/rxnorm
mail label information to themselves or others, download labels, access SPL document archives, and receive update notices about new label postings. After a specific drug label is accessed, the sidebar provides other user options that relate to the specific drug. Users can (1) access the SPL history of the drug; (2) access a solid-dose image of the drug; (3) link directly to FDA’s MedWatch program to report an adverse event; (4) link directly to information about the drug in MedlinePlus; (5) link directly to a preprogrammed search for clinical trials about the drug; (6) link directly to a preprogrammed search of PubMed for all articles relating to the drug, or articles pertaining to adverse effects, therapeutic uses, or pharmacology of the drug; and (7) link directly to a preprogrammed search of the drug in LactMed. In summary, DailyMed provides a simple method for pharmacists and other health care providers in community and institutional settings to access current, official drug product labeling. Pharmacists also can use special features of DailyMed to easily and efficiently retrieve related drug-specific data and information. For example, linking directly from a DailyMed drug label display page to MedlinePlus (also available in Spanish) will retrieve information about the drug itself, as well as associated medical conditions and wellness issues that can enhance patient understanding and use of the medication. Drug Information Portal The Drug Information Portal (DIP) is a search gateway to Web-based drug information and resources in the public domain from NLM and other federal agencies. A portal generally is a search engine that provides multiple-resource searching for specific content and aggregation of the results. Thus, the DIP gives users an intuitive process for simultaneous retrieval of data about a specific drug or drug class from a broad range of relevant information sources (DIP homepage [Figure 3]). The information retrieved by the DIP includes drug j apha.org
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data from clinical trials through FDA approval and marketing. Primary resources (among others) that are searched by the portal include AIDSinfo, ChemIDplus, ClinicalTrials.gov, DailyMed, Dietary Supplement Label Database, DIP, Drugs@FDA, Hazardous Substances Data Bank, LactMed, LiverTox, MedlinePlus, Pillbox, PubMed/MEDLINE, and RxNorm. In addition, under the tab “Resources by Audience/ Class” accessible at the top of the homepage, the DIP provides “Drug Information for Health Professionals” that has direct links to other types of drug information available from federal agencies, such as clinical practice guidelines from the Agency for Healthcare Research and Quality, prescription drug plan finder from the Centers for Medicare & Medicaid Services, clinical trial results from the National Cancer Institute, and controlled substances schedules from the Drug Enforcement Administration. Further, again under the “Resources by Audience/Class” tab, users can access links to an array of other information about prescription and nonprescription drugs, dietary supplements, drugs of abuse, and investigational drugs. In summary, DIP is a very efficient system, providing pharmacists with a simplified “one-stop” process that involves a single search that will simultaneously retrieve specific drug information from a wide range of authoritative federal resources. Further, DIP provides pharmacists with a categorized listing of direct links to other types of useful professional information that can be used in their practice and in responding to inquiries from patients and health care providers.
Figure 1. NLM homepage
Figure 2. DailyMed Sample Label Page
Figure 3. Drug Information Portal homepage 52 JAPhA | 5 4 : 1 | JAN/F EB 2014
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LactMed LactMed is an evidence-based resource on drugs and chemicals to which breast-feeding mothers may be exposed and the effects of those agents on nursing infants and lactation. Breast-feeding and human milk are the reference normative standards for infant feeding and nutrition due to several factors: (1) human milk is the most complete form of infant nutrition, rich in nutrients and antibodies; (2) for premature babies, breast milk is easier to digest than formula; (3) breast milk helps protect infants against a number of diseases such as otitis media, atopic disease, and respiratory and gastrointestinal tract infections; and (4) human milk provides immunologic and other benefits that can last into childhood, adolescence, and adulthood. For those reasons, the American Academy of Pediatrics (AAP) recommends exclusive breast-feeding for 6 months, with continuation of breast-feeding for 1 year or longer, if feasible.4 Although drugs excreted in breast milk have potential risk with respect to nursing infants, mothers often discontinue breast-feeding unnecessarily when taking medications. This is largely because there is little reli able information about medication use during breastfeeding, and most available information, such as that Journal of the American Pharmacists Association
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found in package inserts, is often inaccurate. Absent adequate safety information about a drug, the decision for mothers and their physicians is whether to discontinue breast-feeding, breast-feed with uncertainty, or discontinue a medication. LactMed responds to this dilemma and an “urgent call” by the Centers for Disease Control and Prevention (CDC) for accurate, current, and accessible information on medication use during lactation.5 Since its release several years ago, LactMed has become one of the most accessed databases in NLM’s TOXNET suite of databases, and it has been endorsed by AAP as “the most comprehensive, up-to-date source of information regarding the safety of maternal medications when the mother is breastfeeding.”4,6 The LactMed homepage is shown in Figure 4. Currently, about 1,000 drug, herbal remedy, and dietary supplement records populate LactMed. Each drug record contains the following information: (1) identifier information, including generic name, drug class, Chemical Abstracts Service registry number, and structure; (2) summary of pertinent information regarding recommendations for use of the medication during lactation; (3) drug concentrations measured in the breast milk of lactating women; (4) drug concentrations measured in breast-fed infants; (5) adverse effects reported in breastfed infants; (6) possible effects of the drug on lactation; and (7) alternative medications with similar therapeutic effect that may be used during breast-feeding. A LactMed app for iPhone/iPod and Android devices also is available to users. In summary, LactMed provides pharmacists with an invaluable resource for determining medication safety during breast-feeding and proper counseling of mothers and physicians. Because of growing recognition of the importance of breast-feeding and acceptance of this database as the most authoritative resource on medication use by nursing mothers, LactMed will continue to increase its reach to an international audience.
Figure 4. LactMed homepage
Figure 5. LiverTox homepage
Figure 6. LiverTox sidebar Journal of the American Pharmacists Association
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LiverTox LiverTox is an evidence-based resource on drug induced liver injury (DILI) and clinical case registry. It provides an array of medical information in one site on the diagnosis, cause, frequency, patterns, and management of liver injury attributed to prescription and nonprescription medications, herbal remedies, and dietary supplements. This information resource serves as (1) a clinical resource for clinicians, specialists, and patients; (2) a research resource for specialists and investigators in liver diseases and toxicology; and (3) a teaching resource and virtual textbook. DILI is the cause of 5% of new-onset acute liver disease leading to hospitalization. It is the leading cause of acute liver failure in the United States and, absent transplantation, has a 30% fatality rate. DILI is the most common reason for failure of new drugs in clinical trials and, j apha.org
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of new information to LiverTox may generate sufficient scientific data and ultimately lead to a reduction in this serious medical condition.
Figure 7. Pillbox homepage until 2000, the leading cause of medication withdrawal from the market. The financial costs associated with liver transplantation and the development of new drugs is considerable. Liver transplantation surgery costs on average more than $500,000, plus about $20,000 per year for immunosuppressive drugs.7 The research and development costs for bringing a new drug to market are variably estimated to be hundreds of millions of dollars to more than $1 billion8 during a 10-year period. Thus, the early diagnosis and identification of drugs that have hepatotoxic potential would provide considerable financial benefits and, more importantly, less patient morbidity and mortality. LiverTox has four major components: (1) Clinical-Diagnostic Overview, (2) Drug Records, (3) Case Report Registry, and (4) Information Resources. As shown in Figures 5 (homepage) and 6 (sidebar), these four components correspond with the sections listed in the sidebar. Thus, the Clinical-Diagnostic Overview consists of write-ups on the clinical course and diagnosis of DILI, phenotype descriptions (including representative histology), causality assessment, severity grading, and discussion of the likelihood of drug association with DILI. Individual Drug/Drug Class Records are prepared on about 1,000 specific drugs, herbal remedies, and dietary supplements, with each record displayed in a standard format that includes an overview, case reports, histology, product information, and annotated references. The Case Registry allows users to submit clinical cases of DILI, and the registry software generates a determination of the causality of the liver injury and a case summary. LiverTox also provides links to relevant Information Resources, including research data from other programs. In summary, LiverTox is a comprehensive international database that provides a range of information that is useful to clinical practitioners, patients, and researchers, with the expectation that it will lead to greater understanding of the diagnosis, mechanisms involved, and treatment of DILI. The ongoing expansion and addition
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Pillbox Pillbox is a repository of images of pharmaceutical solid oral dosage forms with metadata used for an intuitive identification system. Pillbox combines high-resolution imaging with tablet/capsule physical appearance data that include color, imprint, scoring, shape, and size. This identification system, which is in the public domain, is of considerable use to health care providers and institutions, emergency personnel, poison control centers, and the public. Efforts also are in progress for the images to possibly become the FDA-structured product labeling standard for submission by pharmaceutical manufacturers. As shown in Figure 7, identifying an unknown tablet or capsule can be done in two related ways. The Quick Search primarily uses a method of providing a range of graphic choices (e.g., color choices) that might closely correspond with the subject tablet/capsule on which the user clicks, in order to progress through the physical appearance characteristics. An algorithmic feature progressively narrows the results field to arrive at a probable or definite identification of the dosage form. The Advanced Search uses a more detailed array of physical appearance characteristics in lists of text-based choices, plus fill-in boxes for the user. This method allows more defined criteria data input by the user. In summary, Pillbox is a very useful image repository that serves both as a reference standard and as a system for pharmacists (primarily) and other health care personnel and patients to accurately identify soliddosage-form medications.
Conclusion A number of drug information–related resources at NLM are very useful to pharmacists and other health care providers who practice in a variety of professional settings. Five of the more recently introduced online resources include areas of particular importance to pharmacists, including a repository of current product labeling/package inserts, with automated search links to associated information resources; a portal to drug information that allows pharmacists to search multiple databases simultaneously and link to related medication and health care information resources; authoritative information on the effects of medications, herbal remedies, and dietary supplements in nursing infants and their mothers; comprehensive information, including a case registry, on the potential for liver toxicity due to drugs, herbal remedies, and dietary supplements; and a pill identification system with two intuitive search methodologies. All of these resources are authoritative, avail-
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able without charge, and readily accessible. These newer information resources complement other reliable NLM resources, such as AIDSinfo, ClinicalTrials, MedlinePlus, and PubMed/MEDLINE, that pharmacists have used for years. NLM will continue to consider other potential drug-related databases that would be of benefit to health professionals. References 1. Miles WD. A History of the National Library of Medicine: the nation’s treasury of medical knowledge. Washington, DC: Government Printing Office; 1982. 2. Knoben JE, Phillips SJ, Szczur MR. The National Library of Medicine and drug information. Part 1: present resources. Drug Inf J. 2004;38:69–81.
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4. Section on Breastfeeding. Breastfeeding and the use of human milk. Pediatrics. 2012;129(3):e827–41. 5. Lagoy CT, Joshi N, Cragan JD, Rasmussen SA. Medication use during pregnancy and lactation: an urgent call for public health action. J Womens Health (Larchmt). 2005;14(2):104–9. 6. Sachs HC, Committee On Drugs. The transfer of drugs and therapeutics into human breast milk: an update on selected topics. Pediatrics. 2013;132(3):e796–809. 7. Bentley TS, Hanson SG. 2011 U.S. organ and tissue transplant cost estimates and discussion. http://us.milliman.com/insight/research/ health/2011-U_S_-organ-and-tissue-transplant-cost-estimates-anddiscussion. Accessed December 2, 2013. 8. Adams CP, Brantner VV. Spending on new drug development. Health Econ. 2010;19(2):130–41.
3. Knoben JE, Phillips SJ, Snyder JW, Szczur MR. The National Library of Medicine and drug information. Part 2: an evolving future. Drug Inf J. 2004;38:171–80.
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New drug information resources for pharmacists at the National Library of Medicine James E. Knoben and Steven J. Phillips
Abstract
Received on June 17, 2013, and in revised July 16, 2013. Accepted for publication July 16, 2013.
Objective: To provide an overview of selected drug information-related databases of the National Library of Medicine (NLM), with a focus on newer resources that support the professional information needs of pharmacists and other health care providers.
James E. Knoben, PharmD, MPH, is Drug Information Consultant, Specialized Information Services Division; and Steven J. Phillips, MD, is Director, Specialized Information Services Division, and Associate Director, National Library of Medicine, National Institutes of Health, Bethesda, MD.
Summary: NLM, which is the world’s largest medical library, provides an array of bibliographic, factual, and evidence-based drug, herbal remedy, and dietary supplement information resources. Five of the more recently introduced online resources include areas of particular importance to pharmacists, including a repository of current product labeling/package inserts, with automated search links to associated information resources; a portal to drug information that allows pharmacists to search multiple databases simultaneously and link to related medication and health care information resources; authoritative information on the effects of medications, herbal remedies, and dietary supplements in nursing infants and their mothers; comprehensive information, including a case registry, on the potential for liver toxicity due to drugs, herbal remedies, and dietary supplements; and a pill identification system with two intuitive search methodologies.
Correspondence: James E. Knoben, PharmD, MPH, National Library of Medicine, 6707 Democracy Blvd., Suite 510, Bethesda, MD 20892. Fax: 301-480-3537. E-mail: [email protected] Disclosure: The authors declare no conflicts of interest or financial interests in any product or service mentioned in this article, including grants, employment, gifts, stock holdings, or honoraria. Previous presentation: Keynote, Federal Pharmacy Forum, American Pharmacists Association Annual Meeting & Exposition, Los Angeles, March 1–4, 2013. Published online ahead of print at www. japha.org on December 20, 2013.
Conclusion: NLM provides several clinical–scientific drug information resources that are particularly useful in meeting the professional information needs of pharmacists. Keywords: Drug information, evidence based, hepatotoxicity, lactation, package inserts, search portal, structured product labeling. J Am Pharm Assoc. 2014;54:49–55. doi: 10.1331/JAPhA.2014.13123
Journal of the American Pharmacists Association
j apha.org
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he National Library of Medicine (NLM), located on the campus of the National Institutes of Health in Bethesda, MD, is the world’s largest medical library, providing access to a vast collection of more than 19 million books, journals, manuscripts, and audiovisual items. In addition to on-site access to its collections, NLM provides information in an electronic format directly to end users, with the result that its online resources are searched billions of times each year by people around the globe. The library’s mission also includes the support and conduct of research, development, and training in biomedical informatics and health information technology, and it is a leading global resource for genomic information. Drug information was an important component of NLM’s strategic focus beginning in 1967, when Congress provided funds to form a drug literature program (DLP) at the library. Professional pharmacy associations partnered with the program, providing key contributions toward organizing and making drug information more readily available to practitioners. DLP funding was unsustainable, however, and the program was disbanded.1,2 Subsequently, drug information has been dispersed among a number of NLM health-related databases, and in more recent
At a Glance Synopsis: The National Library of Medicine (NLM) provides several clinical–scientific drug information resources that are particularly useful in meeting the professional information needs of pharmacists. Five of the more recently introduced online resources include areas of particular importance to pharmacists, including a repository of current product labeling/package inserts, with automated search links to associated information resources; a portal to drug information that allows pharmacists to search multiple databases simultaneously and link to related medication and health care information resources; authoritative information on the effects of medications, herbal remedies, and dietary supplements in nursing infants and their mothers; comprehensive information, including a case registry, on the potential for liver toxicity due to drugs, herbal remedies, and dietary supplements; and a pill identification system with two intuitive search methodologies. Analysis: The newer NLM resources described here are authoritative, available without charge, readily accessible, and complement other reliable NLM resources that pharmacists have used for years. NLM will continue to consider other potential drug-related databases that would be of benefit to health professionals.
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years, NLM has sought to provide an array of new drug/medication information–related resources for health care practitioners, patients/consumers, and researchers. This more recent effort acknowledges the importance of drugs as the most critical medical intervention in treating patients, the increased complexity of drug therapy, and the ubiquitous nature of drug information that is now readily accessible to patients and health care practitioners. NLM’s recent initiatives to provide more specialized drug information resources complement therapeutic information that is currently available in other health and medically related databases.
Objective Our goal is to describe NLM databases that support the drug information needs of pharmacists and other health care providers who practice in a range of professional settings, with an emphasis on those databases created in the previous several years. Guidance is provided on the drug information in the databases, as well as how to navigate these resources.
Data sources At least a dozen databases and data files containing drug information–related content are provided by NLM. These information resources and the type of data they provide are shown in Table 1. Although they vary by type of data/database, a common characteristic of these databases is that they all incorporate data selection, organization, and search capability. All of the resources in Table 1 are freely accessible though the NLM homepage (www. nlm.nih.gov; Figure 1), by clicking on “All NLM Databases & APIs” in the upper-left corner of the page display, under “Databases.” Users will be taken to an A-to-Z listing with links and to an alphabetic list of the database names with associated links.
Recently released databases Some of the aforementioned databases have been in existence for many years, including AIDSinfo, ClinicalTrials.gov, Hazardous Substances Data Bank, MedlinePlus, and PubMed/MEDLINE, and these are discussed in detail in a previous article, along with other NLM resources.2,3 For purposes of this review, five drug information databases are described that have been introduced in more recent years: ❚❚ DailyMed: repository of Food and Drug Administration (FDA) drug labeling ❚❚ Drug Information Portal: search gateway to drug information ❚❚ LactMed: drug effects on breast-feeding mothers and their infants ❚❚ LiverTox: drugs that induce liver injury ❚❚ Pillbox: pill identification system Journal of the American Pharmacists Association
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Table 1. Drug information content databases by type Database name AIDSinfo ClinicalTrials.gov DailyMed Dietary Supplement Label Database Drug Information Portal Hazardous Substances Data Bank LactMed LiverTox MedlinePlus Pillbox PubMed/MEDLINE RxNorm
Type Evidence based, factual Factual Factual (document repository) Factual (document repository) Search portal Factual Evidence based Evidence based Portal Factual (image repository) Bibliographic Nomenclature System
Each of the five databases provides drug-related information that is particularly useful to pharmacists and other health care practitioners in various practice environments. Taken together, these resources are sufficiently comprehensive that pharmacists can rely on them to provide an array of information to clinicians and patients about the proper use and safety of medications. DailyMed DailyMed is a document repository of FDA drug product labeling/package inserts and related information, sponsored as a health technology partnership of FDA, NLM, and the Veterans Health Administration. Before DailyMed, a long-standing need existed for ready access to current package inserts that were available principally as print media, either a folded paper insert with marketed products or in compendia such as the Physicians’ Desk Reference. The DailyMed initiative responded to the need for a systematic, online resource and coincided with FDA’s November 2, 2005, release of the Structured Product Labeling (SPL) regulations, which require manufacturers to provide package inserts with a standardized format and terminology, using extensible markup language (XML). XML encodes documents in a format that is human and machine readable, embedding computer tags to denote specific data sections that, in turn, enable electronic search capability. NLM receives daily SPL updates from FDA, so that the labels are posted in DailyMed within 1 day of FDA approval or submission to FDA (when no prior approval is needed). DailyMed now logs millions of accessions each month, attesting to its importance in the provision of health care. Labeling can be searched by drug name, FDA pharmacologic class, or National Drug Code. Once retrieved, the SPL sections of the package insert can be accessed by clicking on designated tabs at the top of the page (Figure 2), such as the drug’s description, clinical pharmacology, indications and usage, and contraindications. Other features include the capability for users to eJournal of the American Pharmacists Association
URL http://aidsinfo.nih.gov http://clinicaltrials.gov http://dailymed.nlm.nih.gov/dailymed/about.cfm http://dsld.nlm.nih.gov/dsld http://druginfo.nlm.nih.gov http://toxnet.nlm.nih.gov/cgi-bin/sis/htmlgen?HSDB http://toxnet.nlm.nih.gov/cgi-bin/sis/htmlgen?LACT www.livertox.nih.gov www.nlm.nih.gov/medlineplus http://pillbox.nlm.nih.gov www.ncbi.nlm.nih.gov/pubmed www.nlm.nih.gov/research/umls/rxnorm
mail label information to themselves or others, download labels, access SPL document archives, and receive update notices about new label postings. After a specific drug label is accessed, the sidebar provides other user options that relate to the specific drug. Users can (1) access the SPL history of the drug; (2) access a solid-dose image of the drug; (3) link directly to FDA’s MedWatch program to report an adverse event; (4) link directly to information about the drug in MedlinePlus; (5) link directly to a preprogrammed search for clinical trials about the drug; (6) link directly to a preprogrammed search of PubMed for all articles relating to the drug, or articles pertaining to adverse effects, therapeutic uses, or pharmacology of the drug; and (7) link directly to a preprogrammed search of the drug in LactMed. In summary, DailyMed provides a simple method for pharmacists and other health care providers in community and institutional settings to access current, official drug product labeling. Pharmacists also can use special features of DailyMed to easily and efficiently retrieve related drug-specific data and information. For example, linking directly from a DailyMed drug label display page to MedlinePlus (also available in Spanish) will retrieve information about the drug itself, as well as associated medical conditions and wellness issues that can enhance patient understanding and use of the medication. Drug Information Portal The Drug Information Portal (DIP) is a search gateway to Web-based drug information and resources in the public domain from NLM and other federal agencies. A portal generally is a search engine that provides multiple-resource searching for specific content and aggregation of the results. Thus, the DIP gives users an intuitive process for simultaneous retrieval of data about a specific drug or drug class from a broad range of relevant information sources (DIP homepage [Figure 3]). The information retrieved by the DIP includes drug j apha.org
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data from clinical trials through FDA approval and marketing. Primary resources (among others) that are searched by the portal include AIDSinfo, ChemIDplus, ClinicalTrials.gov, DailyMed, Dietary Supplement Label Database, DIP, Drugs@FDA, Hazardous Substances Data Bank, LactMed, LiverTox, MedlinePlus, Pillbox, PubMed/MEDLINE, and RxNorm. In addition, under the tab “Resources by Audience/ Class” accessible at the top of the homepage, the DIP provides “Drug Information for Health Professionals” that has direct links to other types of drug information available from federal agencies, such as clinical practice guidelines from the Agency for Healthcare Research and Quality, prescription drug plan finder from the Centers for Medicare & Medicaid Services, clinical trial results from the National Cancer Institute, and controlled substances schedules from the Drug Enforcement Administration. Further, again under the “Resources by Audience/Class” tab, users can access links to an array of other information about prescription and nonprescription drugs, dietary supplements, drugs of abuse, and investigational drugs. In summary, DIP is a very efficient system, providing pharmacists with a simplified “one-stop” process that involves a single search that will simultaneously retrieve specific drug information from a wide range of authoritative federal resources. Further, DIP provides pharmacists with a categorized listing of direct links to other types of useful professional information that can be used in their practice and in responding to inquiries from patients and health care providers.
Figure 1. NLM homepage
Figure 2. DailyMed Sample Label Page
Figure 3. Drug Information Portal homepage 52 JAPhA | 5 4 : 1 | JAN/F EB 2014
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LactMed LactMed is an evidence-based resource on drugs and chemicals to which breast-feeding mothers may be exposed and the effects of those agents on nursing infants and lactation. Breast-feeding and human milk are the reference normative standards for infant feeding and nutrition due to several factors: (1) human milk is the most complete form of infant nutrition, rich in nutrients and antibodies; (2) for premature babies, breast milk is easier to digest than formula; (3) breast milk helps protect infants against a number of diseases such as otitis media, atopic disease, and respiratory and gastrointestinal tract infections; and (4) human milk provides immunologic and other benefits that can last into childhood, adolescence, and adulthood. For those reasons, the American Academy of Pediatrics (AAP) recommends exclusive breast-feeding for 6 months, with continuation of breast-feeding for 1 year or longer, if feasible.4 Although drugs excreted in breast milk have potential risk with respect to nursing infants, mothers often discontinue breast-feeding unnecessarily when taking medications. This is largely because there is little reli able information about medication use during breastfeeding, and most available information, such as that Journal of the American Pharmacists Association
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found in package inserts, is often inaccurate. Absent adequate safety information about a drug, the decision for mothers and their physicians is whether to discontinue breast-feeding, breast-feed with uncertainty, or discontinue a medication. LactMed responds to this dilemma and an “urgent call” by the Centers for Disease Control and Prevention (CDC) for accurate, current, and accessible information on medication use during lactation.5 Since its release several years ago, LactMed has become one of the most accessed databases in NLM’s TOXNET suite of databases, and it has been endorsed by AAP as “the most comprehensive, up-to-date source of information regarding the safety of maternal medications when the mother is breastfeeding.”4,6 The LactMed homepage is shown in Figure 4. Currently, about 1,000 drug, herbal remedy, and dietary supplement records populate LactMed. Each drug record contains the following information: (1) identifier information, including generic name, drug class, Chemical Abstracts Service registry number, and structure; (2) summary of pertinent information regarding recommendations for use of the medication during lactation; (3) drug concentrations measured in the breast milk of lactating women; (4) drug concentrations measured in breast-fed infants; (5) adverse effects reported in breastfed infants; (6) possible effects of the drug on lactation; and (7) alternative medications with similar therapeutic effect that may be used during breast-feeding. A LactMed app for iPhone/iPod and Android devices also is available to users. In summary, LactMed provides pharmacists with an invaluable resource for determining medication safety during breast-feeding and proper counseling of mothers and physicians. Because of growing recognition of the importance of breast-feeding and acceptance of this database as the most authoritative resource on medication use by nursing mothers, LactMed will continue to increase its reach to an international audience.
Figure 4. LactMed homepage
Figure 5. LiverTox homepage
Figure 6. LiverTox sidebar Journal of the American Pharmacists Association
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LiverTox LiverTox is an evidence-based resource on drug induced liver injury (DILI) and clinical case registry. It provides an array of medical information in one site on the diagnosis, cause, frequency, patterns, and management of liver injury attributed to prescription and nonprescription medications, herbal remedies, and dietary supplements. This information resource serves as (1) a clinical resource for clinicians, specialists, and patients; (2) a research resource for specialists and investigators in liver diseases and toxicology; and (3) a teaching resource and virtual textbook. DILI is the cause of 5% of new-onset acute liver disease leading to hospitalization. It is the leading cause of acute liver failure in the United States and, absent transplantation, has a 30% fatality rate. DILI is the most common reason for failure of new drugs in clinical trials and, j apha.org
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of new information to LiverTox may generate sufficient scientific data and ultimately lead to a reduction in this serious medical condition.
Figure 7. Pillbox homepage until 2000, the leading cause of medication withdrawal from the market. The financial costs associated with liver transplantation and the development of new drugs is considerable. Liver transplantation surgery costs on average more than $500,000, plus about $20,000 per year for immunosuppressive drugs.7 The research and development costs for bringing a new drug to market are variably estimated to be hundreds of millions of dollars to more than $1 billion8 during a 10-year period. Thus, the early diagnosis and identification of drugs that have hepatotoxic potential would provide considerable financial benefits and, more importantly, less patient morbidity and mortality. LiverTox has four major components: (1) Clinical-Diagnostic Overview, (2) Drug Records, (3) Case Report Registry, and (4) Information Resources. As shown in Figures 5 (homepage) and 6 (sidebar), these four components correspond with the sections listed in the sidebar. Thus, the Clinical-Diagnostic Overview consists of write-ups on the clinical course and diagnosis of DILI, phenotype descriptions (including representative histology), causality assessment, severity grading, and discussion of the likelihood of drug association with DILI. Individual Drug/Drug Class Records are prepared on about 1,000 specific drugs, herbal remedies, and dietary supplements, with each record displayed in a standard format that includes an overview, case reports, histology, product information, and annotated references. The Case Registry allows users to submit clinical cases of DILI, and the registry software generates a determination of the causality of the liver injury and a case summary. LiverTox also provides links to relevant Information Resources, including research data from other programs. In summary, LiverTox is a comprehensive international database that provides a range of information that is useful to clinical practitioners, patients, and researchers, with the expectation that it will lead to greater understanding of the diagnosis, mechanisms involved, and treatment of DILI. The ongoing expansion and addition
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Pillbox Pillbox is a repository of images of pharmaceutical solid oral dosage forms with metadata used for an intuitive identification system. Pillbox combines high-resolution imaging with tablet/capsule physical appearance data that include color, imprint, scoring, shape, and size. This identification system, which is in the public domain, is of considerable use to health care providers and institutions, emergency personnel, poison control centers, and the public. Efforts also are in progress for the images to possibly become the FDA-structured product labeling standard for submission by pharmaceutical manufacturers. As shown in Figure 7, identifying an unknown tablet or capsule can be done in two related ways. The Quick Search primarily uses a method of providing a range of graphic choices (e.g., color choices) that might closely correspond with the subject tablet/capsule on which the user clicks, in order to progress through the physical appearance characteristics. An algorithmic feature progressively narrows the results field to arrive at a probable or definite identification of the dosage form. The Advanced Search uses a more detailed array of physical appearance characteristics in lists of text-based choices, plus fill-in boxes for the user. This method allows more defined criteria data input by the user. In summary, Pillbox is a very useful image repository that serves both as a reference standard and as a system for pharmacists (primarily) and other health care personnel and patients to accurately identify soliddosage-form medications.
Conclusion A number of drug information–related resources at NLM are very useful to pharmacists and other health care providers who practice in a variety of professional settings. Five of the more recently introduced online resources include areas of particular importance to pharmacists, including a repository of current product labeling/package inserts, with automated search links to associated information resources; a portal to drug information that allows pharmacists to search multiple databases simultaneously and link to related medication and health care information resources; authoritative information on the effects of medications, herbal remedies, and dietary supplements in nursing infants and their mothers; comprehensive information, including a case registry, on the potential for liver toxicity due to drugs, herbal remedies, and dietary supplements; and a pill identification system with two intuitive search methodologies. All of these resources are authoritative, avail-
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able without charge, and readily accessible. These newer information resources complement other reliable NLM resources, such as AIDSinfo, ClinicalTrials, MedlinePlus, and PubMed/MEDLINE, that pharmacists have used for years. NLM will continue to consider other potential drug-related databases that would be of benefit to health professionals. References 1. Miles WD. A History of the National Library of Medicine: the nation’s treasury of medical knowledge. Washington, DC: Government Printing Office; 1982. 2. Knoben JE, Phillips SJ, Szczur MR. The National Library of Medicine and drug information. Part 1: present resources. Drug Inf J. 2004;38:69–81.
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4. Section on Breastfeeding. Breastfeeding and the use of human milk. Pediatrics. 2012;129(3):e827–41. 5. Lagoy CT, Joshi N, Cragan JD, Rasmussen SA. Medication use during pregnancy and lactation: an urgent call for public health action. J Womens Health (Larchmt). 2005;14(2):104–9. 6. Sachs HC, Committee On Drugs. The transfer of drugs and therapeutics into human breast milk: an update on selected topics. Pediatrics. 2013;132(3):e796–809. 7. Bentley TS, Hanson SG. 2011 U.S. organ and tissue transplant cost estimates and discussion. http://us.milliman.com/insight/research/ health/2011-U_S_-organ-and-tissue-transplant-cost-estimates-anddiscussion. Accessed December 2, 2013. 8. Adams CP, Brantner VV. Spending on new drug development. Health Econ. 2010;19(2):130–41.
3. Knoben JE, Phillips SJ, Snyder JW, Szczur MR. The National Library of Medicine and drug information. Part 2: an evolving future. Drug Inf J. 2004;38:171–80.
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