ashp guidelines on preventing medication errors with ......ashp reports 1648 am j health-syst...

ASHP REPORTS

1648 Am J Health-Syst Pharm—Vol 59 Sep 1, 2002

Antineoplastic agents

ASHP Guidelines on Preventing Medication Errorswith Antineoplastic Agents

DEVELOPED THROUGH THE ASHP COUNCIL ON PROFESSIONAL AFFAIRSAND APPROVED BY THE ASHP BOARD OF DIRECTORS ON APRIL 19, 2002

Am J Health-Syst Pharm. 2002; 59:1648-68

PurposeThe purpose of these guidelines is

to assist practitioners in improvingtheir antineoplastic medication-usesystem and error-prevention pro-grams. They supplement ASHP’sGuidelines on Preventing Medica-tion Errors in Hospitals and addresserror prevention within diversehealth care settings.1 Further, theseguidelines provide updated generalguidance to include a standard defi-nition of a “medication error” andapplicable aspects of recommenda-tions from the National CoordinatingCouncil on Medication Error Report-ing and Prevention (NCCMERP).

NCCMERP’s definition of a med-ication error is “any preventableevent that may cause or lead to inap-propriate medication use or patientharm while the medication is in thecontrol of the health care provider,patient, or consumer. Such events

David R. Kohler, Pharm.D.; Michael Montello, M.S.; Barry R. Gold-spiel, Pharm.D., FASHP, BCPS; Robert DeChristoforo, M.S.; CarlHuntley, M.B.A.; Joe High; Alfred Fallavollita Jr., M.S.; Aiman Shala-bi, Pharm.D., BCOP; Beverly Meadows, R.N., M.S., O.C.N.; Lau-rence Green, Pharm.D., FASHP; and Robert J. Ignoffo, Pharm.D.,FASHP; are acknowledged for drafting this document.

The following individuals are acknowledged for reviewing andsubmitting comments on interim drafts of these guidelines: CharlesL. Bennett, M.D., Ph.D.; Marty Polovich, M.N., R.N., AOCN; Bar-bara Siegler, R.N., MNED, CORLN; Betsy Althaus; Don Baker,Pharm.D., BCPS; Dennis Beaudoin, BCOP; Carol Balmer, Pharm.D.;Deborah Boyle, R.N., M.S.N., AOCN; Jule Bravyak, J.D.; Robert J.Cersosimo, Pharm.D., BCOP; Kathy M. Diener, Pharm.D., BCOP;Jean Ezell; Susan Goodwin, Pharm.D.; Kathleen M. Gura, Pharm.D.;Christopher A. Hatwig, M.S., FASHP; David W. Henry, M.S.,FASHP, BCOP; Donald A. Hutcherson; Dwight Kloth, Pharm.D.,FCCP; Jill Kolesar; Mary Macmillan, BCOP; Jeannine McCune; Ed-

ward F. McKenna, Pharm.D., BCPS, BCOP; Raymond J. Miller, M.S.,FASHP; Lynne Nakaskima, Pharm.D.; Jeanine Peters; John F. Pres-ley; Bonnie Senst, M.S.; Dominic A. Solimando Jr., M.A.; DawnMarie Stull, Pharm.D., BCOP; Peter V. Tortorice, Pharm.D., BCOP;James A. Trovato, Pharm.D., BCOP; Julie Uraibhandhu; AubreyWaddell, Pharm.D., BCOP; Keith Wagner; and Suzanne M. Walton,Pharm.D., BCPS, BCOP.

The bibliographic citation for this document is as follows: Ameri-can Society of Health-System Pharmacists. ASHP guidelines on pre-venting medication errors with antineoplastic agents. Am J Health-Syst Pharm. 2002; 59:1648–68.

Index terms: Administration; American Society of Health-SystemPharmacists; Antineoplastic agents; Errors, medication; Guidelines;Organizations; Pharmacy, institutional, hospital; Toxicity

Copyright © 2002, American Society of Health-System Pharma-cists, Inc. All rights reserved. 1079-2082/02/0901-1648$06.00.

may be related to professional prac-tice, health care products, proce-dures, and systems, including pre-scribing; order communication;product labeling, packaging, and no-menclature; compounding; dispens-ing; distribution; administration; ed-ucation; monitoring; and use.”2

Comprehensive recommenda-tions are provided in these guidelinesfor preventing errors with antineo-plastic agents in health care organiza-tions, with an emphasis on hospitalsand ambulatory care clinics that offerdirect pharmacy services. Neverthe-less, it is strongly recommended thatthe guidance also be adopted by oth-er settings, including physician of-fice practices and home care. Therecommendations cover knownprocedural, technical, and behavior-al elements that could systemati-cally reduce a health care organiza-tion’s vulnerabilities to errors.

However, strict adherence to goodpractice recommendations is not suf-ficient. Since the complexities of an-tineoplastic therapy afford unlimitedopportunities for system failures,continuous diligence to verify accu-racy is critical by all persons respon-sible for medication-use functions.

These guidelines focus on themedication-use responsibilitiesshared by and unique to specific pro-fessional health care disciplines, pro-gressing from general to specific ap-plications. The structure of theguidelines, by necessity, includes therepetition of some material, repeatedand enhanced in specific sectionsand recommendations for differenthealth care disciplines.

The guidelines contain the follow-ing major sections:

1. Recommendations for health careorganizations,


1649Am J Health-Syst Pharm—Vol 59 Sep 1, 2002

ASHP REPORTS

2. Recommendations for multidisci-plinary monitoring of medication useand verification,

3. Recommendations for prescribingsystems and prescribers,

4. Recommendations for medicationpreparation and dispensing systemsand roles for pharmacists,

5. Recommendations for medicationadministration systems and roles fornurses,

6. Recommendations for patients,7. Recommendations for manufacturers

and regulatory agencies, and8. Managing medication errors.

Because of the complexity of anddifferences in practice settings andorganizational arrangements, aspectsof these guidelines may be more ap-plicable to some practice settingsthan others. Pharmacists, physicians,nurses, and other health care provid-ers should use their professionaljudgment in assessing and adaptingthe guidance to their own setting.These guidelines address a specificaspect of the medication-use processand should be augmented as appro-priate by other ASHP practice state-ments and guidelines.

Background

The prevalence of medication er-rors associated with antineoplasticagents, as with other drug categories,is not precisely known, but it may besurmised that incorrect use of anti-neoplastic agents consistently pro-duces serious adverse effects in pa-tients. Antineoplastics are drugproducts that cause serious toxici-ties at FDA-approved dosages andwith FDA-approved administra-tion schedules. Extra precautionsare therefore necessary to preventantineoplastic-related medicationerrors. Advocates for safe medica-tion use and oncology pharmacyspecialists have recommended thathealth care organizations improvetheir medication-use systems specifi-cally to prevent medication errors withantineoplastics.3-6 Antineoplastic-

related medication-error preventionhas become a priority, especially inhospitals. However, many antineo-plastic therapies are also administeredoutside the inpatient setting. An in-creasing number of patients receivetreatment for cancer in ambulatorycare settings. Thus, error-preventionstrategies should be applicable to thediverse settings in which antineo-plastic agents are used.

Recommendations for health care

organizations

Optimal and comprehensive pa-tient care, especially for patients re-ceiving antineoplastic agents, re-quires the participation of multiplehealth care disciplines. Systems arenecessary to coordinate the functionsthroughout the medication-useprocess of prescribing, preparing,dispensing, and administering drugs,and to educate and counsel patients.

Health care organizations inwhich multiple disciplines are repre-sented should establish committeeswith representatives from each disci-pline to develop policies and proce-dures for the medication-use processand to oversee its operation. Theseshould include educational and com-petency requirements for personswith medication-use responsibilities,general system requirements thatminimize vulnerabilities to errors,and periodic auditing of physicians’,pharmacists’, and nurses’ proficiencywith the system. Further, near missesand errors should be analyzed, andproblems in the procedures thatplace patients and staff at risk shouldbe resolved.

Education, competency, and cre-dentialing. All practice settingsshould establish policies and proce-dures ensuring that health care pro-viders who prescribe, prepare, dis-pense, and administer antineoplasticmedications and monitor patientsreceiving those medications are com-petent to perform those functions.For pharmacists and nurses, specificeducation and experience or board

certification in a practice specialtymay be included in the credentialingprocess.

Employers should evaluate pro-spective employees’ training and pre-vious practice experiences for knowl-edge and mastery of the skills that areessential prerequisites for the newposition. Prerequisites for employ-ment should include discipline-appropriate training in how to safelyhandle antineoplastic drug products.Deficiencies in applicants’ trainingand experience must be identifiedand remedied before new employeesassume patient care responsibilities.Training for new and current em-ployees should emphasize collabora-tion among health care providers toensure optimal patient care and out-comes and worker safety.

All health care providers who pre-scribe, prepare, dispense, and ad-minister antineoplastic medicationsand monitor patients receiving thosemedications should be oriented intheir practice setting before com-mencing patient care responsibilities.Orientation should introduce to newemployees all of the departments, ser-vice providers, and functions that af-fect patient care. Each provider’s rolesand responsibilities should be identi-fied, and it should be clarified howhealth care providers from differentdisciplines are expected to interact.

Further, health care organizationsshould require that all personnelwho prescribe, prepare, dispense, ad-minister, and handle hazardousdrugs and materials that are contam-inated with hazardous drugs and thatall persons who may be exposed tohazardous-drug-contaminated ma-terials during their job performancecomplete job-appropriate trainingand evaluation. They should demon-strate competence, knowledge, andproficiency in techniques and proce-dures for safely handling (preventingexposure to oneself, other persons,and the environment, and managingaccidental exposure) hazardousdrugs. Those competencies should

ASHP REPORTS



be reassessed annually or more fre-quently if performance problemsoccur. It is the responsibility ofmedication-use system administra-tors and supervisory personnel toknow the current government re-strictions that limit or prohibit somehealth care providers from preparingand administering antineoplasticmedications.

Health care providers who partici-pate in an antineoplastic medication-use process and those who monitorpatients receiving antineoplasticsshould be knowledgeable and havecurrent information available abouteach of the following factors on theantineoplastic drug products used intheir practice setting:

1. Names of antineoplastic drug formu-lations,

2. Indications and whether those indi-cations comply with the FDA-approved labeling or are part of aninvestigational protocol,

3. Routes of administration,4. Administration schedules,5. Appropriate dosages and, when ap-

plicable, constraints for the maxi-mum dose of medication that canbe safely given during a singleadministration,

6. Appropriate handling conditions,7. Potential adverse effects, and8. Potential drug interactions.

Every practice setting where can-cer patients receive antineoplastictherapy should provide opportuni-ties for continuing professional andtechnical education related to anti-neoplastic drug use. A portion of theannual continuing-education pro-grams for health care providers spe-cializing in oncology should be relat-ed to antineoplastic agents and theiruses.

Providers who use drug-deliverydevices, such as i.v. pumps and infu-sion controllers, to administer anti-neoplastic medications should be re-quired to demonstrate competenciesrelated to the clinical application,

function (general use, operationallimits, alarms), and care of these de-vices; problems that may occur withthe devices; and troubleshooting.

Communication and access toinformation. Many errors occurringin the medication-use process arecaused or promulgated by inade-quate patient-specific information.Patients’ medical records shouldbe organized and made readily ac-cessible for use by all providerswho prescribe, dispense, and ad-minister antineoplastic medicationsto enable independent confirmationthat all prerequisite criteria havebeen met before commencing anti-neoplastic treatment. In some cases,individual disciplines may keep addi-tional patient records that supple-ment the patient’s primary medicalrecord. For example, it has historical-ly been the responsibility of pharma-cists and pharmacies to maintainpatient-specific medication profiles,records of medications that were pre-scribed and dispensed for eachpatient.

Providers who practice at siteswhere pharmacists do not participatein patient care also should docu-ment and maintain medicationprofiles for their patients. Medica-tion profiles for antineoplastic thera-pies should include at least the fol-lowing information:

1. Patient’s name and a unique identify-ing code or number,

2. A brief medical history that identifiesa patient’s cancer diagnosis,

3. Known drug-related adverse events,allergies, and medication-, nutrient-,and food-related sensitivities,

4. Vital statistics that may affect treat-ment intensity, particularly thoseneeded to calculate medication doses,including height, weight, body sur-face area (BSA), age, sex, and perti-nent laboratory values (e.g., serumcreatinine, creatinine clearance, livertransaminases),

5. Data about all medications used by apatient, including the date the medi-

cations were prescribed if it differsfrom the date they were prepared andadministered, the date the medica-tions were prepared and dispensed ifit differs from the date the medica-tions were administered, drug identi-ty, drug dosage, total drug dosageadministered per unit interval (e.g.,day, week, treatment cycle), adminis-tration route, administration sched-ule as a function of the treatment plan(e.g., every three hours; days 1, 8, and15), rate of administration (when rel-evant), prescribed duration of use(e.g., number of doses to administer;number of treatment hours, days, orweeks), and the product manufactur-er’s identity and product lot numbersand expiration dates for drugs dis-pensed from that facility,

6. Additional ingredients and dilutingagents and the amounts used inextemporaneously compoundedmedications,

7. Primary references that describe thetreatment regimen, and

8. An up-to-date treatment history, in-cluding the treatment cycle or coursenumber for each treatment repeti-tion, the dates on which a patient lastreceived treatment, how previoustreatment was tolerated, and the cu-mulative amount of drug previouslyadministered for medications with es-tablished absolute cumulative dosagelimits (e.g., anthracyclines, bleomycin)or constraints against repeated ad-ministration as a function of time.

Ambulatory care, home care, andmanaged care organizations are vul-nerable to the same communicationand interpretation errors that occur inhospitals. These settings and organ-izational arrangements, however, in-troduce additional opportunitiesfor errors of omission and duplica-tion when treatments and otherservices are provided at multiplelocations and by more than oneparticipating provider or group ofproviders. In hospitals and integrat-ed health systems, patient-specificmedical information has traditional-



ASHP REPORTS

ly been communicated through asingle comprehensive medicalrecord. In contrast, providers in pri-vate practice, home care, and man-aged care organizations generallycannot rely on the availability of acomprehensive medical record, be-cause medication prescribing, pre-paring, and administering may occurat geographically separate facilities.

Local policies should be devel-oped to ensure that orders for a pa-tient’s antineoplastic medications aretransmitted accurately and com-pletely, simultaneously protectingpatient confidentiality. Electronicmeans of communication are recom-mended to transmit up-to-date, ac-curate, and comprehensive patient-specific medical information amongproviders. Thus, data entered intothis electronic system by any oneprovider are immediately available toall. Until a single unifying networkbecomes available for all health careproviders, portable printed and elec-tronic records that ensure patientsafety and confidentiality must bedevised.

Schedule coordination. Since on-cology patients often receive carefrom more than one health care pro-vider, their primary provider shouldcoordinate patient care with otherproviders and facilities. Efficient or-ganizational systems should havesomeone to coordinate a patient’shealth care needs with the providers’schedules. Administrative coordina-tors are an interface between a pa-tient’s primary provider and otherproviders and services. They planand document scheduling for pa-tients’ treatments, laboratory tests,follow-up visits, consultations, sup-portive care, and assistance fromhome health care contractors, hos-pice facilities, and social services.

Standardize medication ordering.To the extent possible, medicationprescribing, preparation, dispensing,and administration should be stan-dardized. Patient care facilities shoulddevelop and use standardized pre-

printed medication-order forms orforms that are retrievable from acomputerized database for request-ing frequently used antineoplastictreatments and treatment-relatedservices. Well-designed standardizedmedication-order forms decreasepotential errors by organizing treat-ment information in a clear, consis-tent, and uniform format.

Standardized forms should be de-veloped collaboratively with all localhealth care providers who prescribe,prepare, and administer antineoplas-tic medications. Forms should bepreprinted with treatment-specificinformation, such as generic drugnames, specifications for drug dosageand dosage modifications as a func-tion of patient-specific variables, andadministration routes and schedules.They should also include space forprescribers to note laboratory test re-sults that affect dosages, administra-tion rates, and treatment duration.These forms may also permit pre-scribers to schedule laboratory testsand request other services for com-prehensive patient care.

Standardized medication-orderforms simplify and expedite orderingmedications by requiring prescribersto supply only patient-specific infor-mation, such as

1. Patient’s name and unique identify-ing code or number,

2. Date the order was generated,3. Time and date treatments are to be

administered,4. Patient-specific laboratory values

(e.g., height, body weight, BSA, perti-nent laboratory values) from whichdosages and administration rates arecalculated,

5. Planned medication dosages andadministration rates as a functionof patient-specific factors and thecalculated doses and rates to beadministered,

6. Patient’s allergies and medication andnutrient sensitivities,

7. Prescriber’s name and signature, and8. Prescriber’s telephone, pager, or fax

number (or another means to com-municate with the prescriber).

Preprinted forms should specify,by protocol number or publicationreference, the treatment that is to beadministered.3,7

For investigational antineoplastictreatments, standardized formsshould also include the study nameand protocol number. Color-codedforms, for example, may be used todesignate different types of treat-ment, such as commercially market-ed antineoplastic and investigationalmedications.

Standardized order forms elimi-nate many of the problems related tomisinterpreting medication ordersthat are commonly associated withnonstandardized orders; however,health care providers must be awarethat interpretation errors may stillresult from illegible handwriting.Multipurpose preprinted forms thatlist antineoplastic medications al-phabetically may also contribute toprescribing errors when two similardrug names appear in close proximi-ty. Since lined paper can obscure thedetails of a prescriber’s orders, pre-printed forms should be printed onunlined paper.

Self-replicating forms (e.g., car-bon copies, no-carbon-required pa-per) can produce copies that are dif-ficult to read. Providers who prepareand administer medications on thebasis of a copy of a prescriber’s ordershould be wary of ambiguous nota-tions, artifact markings, and omis-sions on the copy. Each facilityshould restrict antineoplastic order-ing (e.g., access to medication-orderforms) to providers with the appro-priate clinical privileges. Health careorganizations that depend on stan-dardized forms must also ensure thatonly the most current versions ofstandardized forms are available andthat obsolete forms are recalled anddestroyed.

Computerized prescriber orderentry. Computerized prescriber

ASHP REPORTS



order-entry (CPOE) systems providemany of the same safety and conve-nience features as preprinted orderforms with several important advan-tages, including an efficient meansfor simultaneously disseminating or-ders to various providers. CPOE sim-plifies prescribing and eliminates thepotential for introducing errors intoa medication-use system when inter-mediaries are required to accuratelyinterpret and transcribe orders into amanual database.

CPOE can also provide online in-formation about drug dosages andadministration schedules, both ofwhich can be updated from a centrallocation. Computer software can alsoprovide additional safety and conve-nience features, such as automatedscheduling of multiple-day treat-ments, repeated treatment cycles,and laboratory tests and automatedcalculation of mathematicallyderived patient-specific data (e.g.,BSA, lean body weight, drug dosag-es). In addition, software can de-crease the likelihood of errors byincorporating features that detectdrug dosages and administrationschedules greater than and less thanpredetermined limits and by alertingsystem users when potentially inter-acting medications are prescribed.8

Safeguards are also required forCPOE systems. Access privilegesshould be limited to authorizedhealth care providers. The systemshould electronically record whenusers enter, change, and discontinueorders. Providers should review andverify orders before treatment isstarted.

Oral orders for antineoplasticmedications. Except for discontinu-ing treatment, medication-use sys-tems should not permit health careproviders to transmit or accept or-ders to commence or modify antine-oplastic medication that are com-municated orally.3,4,9 Oral ordersfor medications, spoken face-to-face or by telephone, circumventan essential checkpoint in the

order-verification process, wheth-er they are communicated directlyto persons who prepare medicationsor received and reported by one ormore intermediaries.10

Stat orders for antineoplasticmedications. It is rarely necessary tobegin antineoplastic treatment asquickly as possible. In general, Statorders for antineoplastic medica-tions potentially compromise essen-tial order-verification safeguards andare almost never appropriate. Exceptfor urgently required treatments, an-tineoplastic medication preparationand administration should be sched-uled when staffing is adequate to en-sure that appropriate safety checksare performed and to implementtreatment. It is essential that patientcare is not compromised under anycircumstances. Persons who designmedication-use systems are chal-lenged to incorporate antineoplasticmedication-order-verification sys-tems that cannot be circumventedand do not introduce unnecessarydelays in processing the orders.

Standardize dosage calculation.Medication-use systems should es-tablish whether drug dosages shouldbe routinely calculated as a functionof actual or ideal (lean) body weightand develop standardized criteriathat direct dosage calculation as afunction of this weight. Treatmentplans and medication orders shouldindicate whether patients’ actual orideal body weight was used in calcu-lating drug dosages and identify theequation from which dosages werecalculated.

Methods should be standardizedfor calculating BSA and ideal bodyweight, rounding calculated results(e.g., drug dosages and administra-tion rates), and changing dosagesand administration rates in responseto changes in patients’ weight andstature. For dosage and administra-tion rates calculated from pharmaco-kinetic data, the mathematical equa-tions that describe how calculatedvalues were derived should appear in

the treatment plans and medicationorders.

Standardize medication orders.Standards should be established forthe content of an acceptable medica-tion order, requirements for patient-specific measurements, and data thatmust be included on medication-order forms.11,12 The following stan-dards are recommended:

1. All orders for patient care servicesshould be clearly dated;

2. When ordering antineoplastic medi-cations, the generic drug name shouldbe used; use generic drug names ap-proved by the United States AdoptedNames (USAN) program. Brandnames are not acceptable unless theyaid in identifying combination drugproducts or a particular drug formu-lation (e.g., to distinguish between li-posomal and nonliposomal productformulations);

3. Specify the dosage form;4. Orders for medications should in-

clude the patient-specific data fromwhich drug doses are calculated(height, weight, BSA, laboratory testresults). When drug dosages andschedules are modified for current oranticipated pathologies, treatmentplans and medication orders shouldexplicitly identify the factors on whichtreatment modifications are based;

5. Drug dosages and calculated dosesshould be expressed in metric no-tation whenever possible. Theword units should never be abbre-viated in medication orders wheredrug dosages and administrationrates are expressed in biological ac-tivity units (e.g., aldesleukin, aspara-ginase, bleomycin);

6. Medication orders should specifythe drug dosage, calculated dose,and append the total cycle or coursedosage;

7. Administration vehicle solutionsand volumes should be specified,unless standard solutions and vol-umes have been established;

8. Specify the administration route;9. Specify the administration rate;



ASHP REPORTS

10. Specify the administration scheduleand the duration of treatment.Treatment plans and medication or-ders should specify the interval be-tween repeated doses, the days onwhich each dose is to be given withina treatment cycle or course, and thetotal length of a treatment cycle orcourse;

11. Specify the dates and times whendrug administration is to com-mence, or identify the temporal se-quence in which each medication isto be administered. When 1200 iswritten as 12 a.m. or 12 p.m., it maybe incorrectly interpreted. Direc-tions indicating events for 1200should be written as 12:00 noon, or12:00 midnight, or expressed in the24-hour system.

A medication order that complieswith these recommendations wouldappear as follows for a patient with aBSA of 2 m2: Azorhubarb injection100 mg/m2/dose = 200 mg in 100 mL5% dextrose injection/dose, admin-ister by continuous intravenous infu-sion over 24 hours, every 48 hoursfor three doses days 1, 3, and 5. Startat 8:00 a.m. on April 1, 2001 (totaldose/cycle = 600 mg).

Although health care providershave traditionally used abbrevia-tions, acronyms, and nicknames todescribe antineoplastic medicationsand treatment regimens (e.g., ADR[doxorubicin], MTX [methotrexate],VBL [vinblastine], “platinum” [car-boplatin or cisplatin], ICE [ifosfa-mide, carboplatin, and etoposide],MOPP [mechlorethamine, vincris-tine, procarbazine, and prednisone],ProMACE [prednisone, methotrex-ate, doxorubicin, cyclophosphamide,and epipodophyllotoxicin], and Cy-TBI [cyclophosphamide and totalbody irradiation]), the practice is po-tentially dangerous and should beavoided. Abbreviations for drugnames, scheduling information, anddirections for medication use shouldbe prohibited in medication orders.Nonstandard abbreviations, Latin

abbreviations, and apothecaries’weights and measures should not beused in orders for antineoplasticmedications. Whenever possible,measurement units should be ex-pressed in metric notation.

Establish dosage limits and ac-ceptable routes of administration.Medication-use systems should in-clude utilization limits for antineo-plastic medications. Constraintsshould be developed to limit maxi-mum antineoplastic drug dosagesand administration routes andschedules. Multidisciplinary peer re-view should be completed before es-tablished drug administration limitsare exceeded.3,4 These constraintsshould include the maximumamount of an antineoplastic drugthat may be administered as a singledose, the maximum amount thatmay be administered during a de-fined time interval (including maxi-mum administration rates forparenterally administered medica-tions), and the routes by which eachdrug should be administered.

Constraints for dosage and ad-ministration rate may be defined bytreatment regimens and protocolsand may vary among protocols. Incontrast, the types of treatments ad-ministered in some practice settingsmay be consistently similar, permit-ting the establishment of absolutemaximum dose limits within thatpractice setting.

Limits should also be establishedfor the maximum amount of an anti-neoplastic drug that may be adminis-tered during one treatment course orcycle and, when appropriate, themaximum amount of drug that maybe administered to a single patientwithin his or her lifetime.3 In addi-tion, dosage limits should be estab-lished for antineoplastic medicationsused in specific combination regi-mens (defined for each drug) inwhich clinical toxicities may be exac-erbated by combining agents withoverlapping adverse-effect profiles.

Antineoplastic drug-use limits

should appear prominently in print-ed treatment descriptions (e.g., pro-tocol summaries, “care maps,” sche-matic treatment diagrams) and onprinted medication-order forms andcomputer-based medication-ordertemplates. Computer software thatalerts health care providers wheneveran order for antineoplastic medica-tions exceeds defined limits would beideal.13 For patients who receive anti-neoplastic medications for which cu-mulative dosage limits have been es-tablished, cumulative dosage datashould be constantly updated in theirpermanent medical records and inany supplementary records. Patients’cumulative dosage data should beaudited and independently con-firmed by health care providers whenverifying orders for antineoplasticmedications.3,14

In each health care organization,the medication-use system shouldinclude a multidisciplinary commit-tee that oversees matters related tomedication-use limits. The commit-tee should proactively develop andestablish policies and procedures forresolving disagreements related topatient treatment among providers;whether medications should be pre-pared, dispensed, and administeredif a discrepancy cannot be resolved;and how medication-use-related dis-putes are to be resolved. Committeemembership should comprise allproviders who have responsibilitiesin the medication-use process in theorganization.3

Investigational antineoplasticmedications. Cancer patients oftenreceive investigational (i.e., experi-mental) anticancer treatments at fa-cilities participating in clinical trials.Consideration must be given to en-sure that the same safety precautionsand checks that are used for FDA-approved antineoplastic therapiesapply similarly to prescribing, pre-paring, dispensing, and administer-ing investigational medications andmonitoring patients who receivethose therapies.

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Facility administrators should en-sure that adequate staff is maintainedto support an investigational drugprogram.10 Ideally, nurses and phar-macists should be involved early inthe process of developing clinicalprotocols involving the use of com-mercially marketed and investiga-tional antineoplastic medications.15

This helps to ensure that investiga-tional medications are prepared andadministered in accordance with lo-cal policies and procedures. Nursesand pharmacists should be votingmembers on regulatory and reviewcommittees that evaluate the scientif-ic and ethical treatment of patientsreceiving antineoplastic medicationsand monitor investigational thera-pies (e.g., institutional reviewboards).3

Because a protocol governs andsupplies the rules for drug use inclinical trials, an up-to-date copy ofthe study protocol should be avail-able for review at all sites where med-ications are prepared and adminis-tered. All staff should be informedthrough inservice education pro-grams before new protocols are im-plemented. Inservice programs andstudy-related information shouldbe provided by persons associatedwith the investigational study (e.g.,principal investigator, associate in-vestigators, protocol chairperson,study-coordinating personnel). If aninvestigational protocol is to be con-ducted at more than one site within ahealth care system, proceduresshould be developed to ensure thatup-to-date information is availableat all study sites where patients re-ceive protocol-directed care.

Procedures for supplying healthcare providers with informationabout patients’ dose assignments,drug dosage, and schedule modifica-tions should also be devised. A sepa-rate procedure should be establishedallowing independent dose-checkingactivity among all disciplines in-volved in the medication-use processfor investigational drugs.

Recommendations for

multidisciplinary monitoring of

medication use and verificationIndependent medication-order

verification is an essential safeguardthat ensures the accuracy and appro-priateness of medical treatment. It isimperative that health care providersresolve any questions related to med-ication orders before treatment com-mences. Providers should recognizethat medication-order verificationand other system safeguards ensurepatients’ safety.3,7,14

Lack of information about pa-tients and their medications has beendescribed as the most frequent causeof medication errors.9,16 In order toindependently verify prescribers’ or-ders for medications, all persons whoprepare and administer antineoplas-tic medications and those who moni-tor patients who have received anti-neoplastics should also have access tocomplete, up-to-date copies of treat-ment protocols and patient-specificdata.3,9,14 Drug information and ref-erence materials should be readilyavailable to all persons who providepatient care.

Each health care provider has a re-sponsibility to share informationwith other providers and consultantsto ensure patient safety and an opti-mal treatment outcome. Policies thatregulate treatment verification stan-dards should describe how prescrib-ers, medically responsible and seniorauthorizing physicians, pharmacistsand pharmacy technicians, personsresponsible for administering medi-cations, and other persons who areresponsible for transcribing andtransmitting medication ordersshould interact.

Providers who prescribe, prepare,dispense, and administer antineo-plastic medications should performas many independent manual checksas possible. Treatment-verificationsystems may incorporate computer-ized medication-order safety checksbut should also include as many in-dependent manual checks as possi-

ble.3,10 Ideally, computerized systemsare used to calculate and verify dos-ages and the rate and route of admin-istration for antineoplastic drug or-ders and to screen medication ordersfor compliance with dosage limits. Inaddition to facilitating chemotherapy-order processing, computer softwarecan also serve as a double check onprescribers’ orders. Systems requir-ing pharmacists to transcribe pre-scribers’ medication orders into acomputerized or manual drug-ordering system should have a sec-ond pharmacist recheck all order-processing documents and productlabeling before a drug product isdispensed.

Providing medications to patientsincludes four discreet steps: prescrib-ing, preparation, dispensing, and ad-ministration. The ideal verificationsystem has nine established check-points to ensure that an antineoplas-tic drug is accurately prescribed, pre-pared, dispensed, and administeredto the patient for whom it was in-tended (Figure 1). Different individ-uals should complete each check sothat no single person bears responsi-bility for checking his or her ownwork.

Prescribing antineoplastic medica-tions (checkpoint 1). Health care pro-viders who prescribe, prepare, andadminister antineoplastic drugsshould be familiar with the entiretreatment regimen. A prescribershould complete as many orders aspossible comprising a patient’s an-tineoplastic treatment regimen andinclude orders for preparative andsupportive care medications. Thispractice ensures that orders can bechecked for completeness and accu-racy and compliance with plannedtreatment.

When orders for antineoplasticdrugs must be countersigned by a sec-ond medically responsible individual,the person who countersigns themedication orders should criticallyevaluate each order for an antineo-plastic treatment. This is checkpoint 1.



ASHP REPORTS

The orders should be compared withpatient-specific data and verifiedagainst original reference sourcesthat describe the treatment regimen(e.g., a published article, validatedstandard reference text, investiga-tional protocol).

Preparing antineoplastic medica-tions (checkpoints 2–4). Checkpoint 2requires persons receiving a prescrib-er’s order for antineoplastic medica-tions to review the original writtenmedication orders and independent-ly verify them against published stan-dards (e.g., product package labeling,reports published in professionaljournals, treatment protocols, stan-dard reference textbooks).

Because erroneous informationsometimes appears in published in-formation, orders for noninvestiga-tional antineoplastic medicationsshould be verified against the prima-ry reference in which the specifictreatment was described (e.g., pub-lished reports, study protocols, meet-ing proceedings). If a primary refer-ence is not available, the treatmentregimen should be confirmed with aresource that previously had been

validated as accurately describing theplanned treatment (locally compiledhandbooks, guides, and compendia)or at least two alternative publica-tions, including reviews and refer-ence textbooks.3,12 Investigationaldrug doses and administrationschedules must be verified against astudy protocol that was approved byall relevant regulatory agencies andstudy sponsors (e.g., institutional re-view board, National Cancer Insti-tute, FDA).

Although preprinted order formspreclude the necessity of repeatedlyverifying drug names, dosages,routes, and schedules each time apreprinted form is used, all medica-tion orders should be evaluated forcompleteness, compliance with theplanned regimen, and, during re-peated courses, deviations from pre-vious treatments by following theserequirements:

1. Measurements from which a patient’smedication dosage and administra-tion rate are calculated should beconfirmed (e.g., height, weight, BSA);

2. The date a patient was last treated and

the next planned treatment dateshould be compared to ensure that anappropriate interval has elapsed sincetreatment was last administered;

3. Patient-specific data (e.g., height,weight, BSA) should be remeasuredand, when applicable, recalculated todetermine whether changes from pre-vious measurements indicate corre-sponding changes in dosage oradministration rates;

4. Appropriate laboratory test and phys-ical assessment values should be evalu-ated, and primary treatment referencesshould be consulted to determinewhether they are within acceptableranges or if treatment modificationsare indicated; and

5. A patient’s allergy, drug sensitivity,and adverse drug effect histories andhis or her current medication profileshould be evaluated for potentialdrug interactions with planned anti-neoplastic treatment.

Orders prescribed by physicians-in-training and nonphysician healthcare providers with prescribing privi-leges (e.g., nurse practitioners, physi-cians assistants) should be verifiedwith at least one medically responsi-ble person, other than the prescriber,who is knowledgeable about medicaloncology. Verification includes con-firming correct treatment beforecommencing the initial cycle, dosageand administration schedule modifi-cations, and deviations from plannedor expected treatment.

For patients who receive treat-ment in clinical studies in whichmore than one primary or ancillarytreatments are prescribed (e.g., dose-and duration-escalating studies),treatment assignment and dosageand administration schedule modifi-cations should be confirmed with atleast one person directly associatedwith the clinical trial, other than theprescriber (e.g., the principal investi-gator, an associate investigator, re-search nurses or pharmacists, a studycoordinator or chairperson). Con-sult with the prescriber when expect-

Figure 1. Medication-order verification system. These nine established checkpoints ensure

that an antineoplastic drug is accurately prescribed, prepared, dispensed, and administered

to the patient for whom it was intended.

Product Checked with Patient(Checkpoint 9)

Prescribing

Order Generated Order Authorization(If Required) (Checkpoint 1)

PreparingOrder Evaluated (Checkpoint 2)

Worksheet Setup (Checkpoint 4)

Product Evaluated (Checkpoint 3)

DispensingProduct Dispensed to Patient

Product Evaluatedwith Patient (Checkpoint 5)

Product Dispensed to Caregiver

Order Evaluated(Checkpoint 6)

Product Evaluated(Checkpoint 7)

Administering

Patient Examines Productand Labeled Instructions (Checkpoint 8)

ASHP REPORTS



ed treatment modifications were notordered or when nonstandard modi-fications were prescribed.

Instructions for diluents, drug ad-ministration sequence and duration,number of doses, and starting dateand time should be checked. Reviewand confirm that appropriate ancil-lary and supportive medications thatfacilitate antineoplastic drug deliveryand those required by protocol havebeen prescribed and are completeand accurate (e.g., premedications,hydration, cytoprotectant and“rescue” medications, antiemetics,hematopoietic growth factors). Dis-crepancies between prescribed medi-cations and planned treatmentshould be brought to the prescriber’sattention and resolved before medi-cation preparation proceeds.

At checkpoint 3, after treatmentorders have been verified, all workrelated to medication-order process-ing and preparation accuracy shouldbe routinely documented in a stan-dardized format. Drug preparationwork sheets (sometimes referred toas work cards or admixture or com-pounding logs, sheets, and cards)identify the drug products preparedfor each patient and the persons whoprepared and checked the medica-tions. Although layout and designmay vary among work sheets, anddata may be organized as a continu-ous log in which each drug productappears on separate consecutive linesor as a separate record for each pa-tient, all work sheets should detailthe techniques used in preparing thedrug products. They should alsoidentify special preparation and dis-pensing information, such as the in-dication of special product contain-ers, requirements for filtration, theneed for special diluents, intermedi-ate dilution steps, and how and whenadministration sets should be at-tached to the drug product contain-er. Order processing, drug prepara-tion, and processing records shouldbe confirmed by a second individual(preferably a pharmacist).3,4 The cal-

culations written on preparationwork sheets should be independentlyverified by a second health care pro-vider who did not prepare the worksheet. Independent verificationshould include checking the worksheet for completeness and accuracyof content, with particular attentiongiven to special preparation instruc-tions. A checklist identifying the nec-essary elements in a drug preparationwork sheet may be helpful for thisstep (Figure 2).3

At checkpoint 4, drug productsshould be checked, after preparation,against both the preparation worksheet and the original order by anindividual who was not involved inpreparing the work sheet. Checklistsmay also be helpful for this step.3

Dispensing antineoplastic medica-tions (checkpoint 5). Checkpoint 5 re-quires persons dispensing medica-tions to patients or caregivers foroutpatient use to verify a patient’sidentity when a medication is dis-pensed. Patients who self-administertheir medications or personal care-givers should visually examine themedication, confirm whether its ap-pearance meets their expectations,and compare its instructions with in-formation they received from theirhealth care providers (e.g., a chemo-therapy calendar).

Dispensing and administering anti-neoplastic medications (checkpoints 6–9). At checkpoint 6, before startingtreatment, each antineoplastic medi-cation should be checked against theprescriber’s orders by at least two in-dividuals who are trained and com-petent to administer antineoplasticmedications. All dosage- and admin-istration rate-related calculationsshould be independently confirmed.Health care providers should rou-tinely confirm that the medicationwill be administered to the intendedpatient by comparing a patient’sname and unique identifying code ornumber with medication labels (e.g.,alpha–numeric characters or barcodes) and that a drug product’s

identity, ancillary components (e.g.,additional medications, diluent, andvehicle solutions), route of adminis-tration, and schedule are correct.

At checkpoint 7, health care pro-viders should examine the medica-tion container and note whether thecontent’s general appearance is whatwas expected. Many chemotherapeu-tic parenteral products have distinctivecolors, and product coloration shouldbe confirmed before administration.

At checkpoint 8, patients whoself-administer their medications (orreceive it from personal caregivers)should carefully read the container’slabel to confirm the product’s identi-ty and review its instructions for useeach time they take a medication.

At checkpoint 9, patients shouldbe encouraged to ask questionsabout their treatment before its ad-ministration and compare its ap-pearance and medication label withinformation they received about thetreatment.

In ambulatory care practice, it iscommon for patients to receiveparenteral antineoplastic medica-tions in a setting where a physicianand a nurse complete all tasks relatedto prescribing, preparing, adminis-tering, and monitoring treatmentwithout a pharmacist’s participation.Under these circumstances, the twohealth care providers involvedshould check the other’s work. Bothproviders should be involved in theentire process. The person preparingantineoplastic medications shouldwork from written orders.

Recommendations for prescribing

systems and prescribers

Antineoplastic prescribing is com-plicated by numerous medical publi-cations that report indications, dos-ages, and administration schedulesinconsistent with FDA-approvedproduct labeling. Antineoplastictreatments are frequently based onpreliminary reports, meta-analyses,and promising, albeit anecdotal, in-formation. Prescribers must exercise



ASHP REPORTS

Checklist for Preparingand Labeling Antineoplastic Drugs

For each order you check, verify that each element is correctwith a check mark.Patient ________________________ Drug ____________Date _____________

Label check

Patient name is same as on front of work card __________

Drug name on label matches drug name written on back ofwork card ____________

Dose on label matches dose written on back of workcard_____________

Diluent on label matches diluent written on back of workcard _____________

Volume of diluent on label matches volume of diluent onback of work card _____________

Correct date to prepare _____________

Expiration date and time _____________

Correct time (expiration date not greater than administra-tion time) _____________

For each drug/additive

Correct drug used ________ Proper protocol supply ____

Drug concentration in each vial _____________

Additives, such as sodium bicarbonate solution, for which largestock bottles are used (which remain in hood) are visuallychecked, lot number is verified, and technician is asked toverify volume used _____________

Syringe plunger is pulled back to volume required fordose _____________

Drug lot number on each vial matches lot number written onwork card _____________

Calculations are checked _____________

Drug has not expired _____________

For each diluent

Correct diluent ______ Volume of diluent _____

Diluent has not expired _____________

Special instructions followed

Air purged from bag ____

Tubing affixed/primed to end of line ________

Diluent for reconstitution _______

Correct container _____ Proper overfill ___ Drug in overfill ___

Final miscellaneous steps

Chemotherapy work card checklist is in card pocket _____

Solution is inspected for impurities/floaters_____________

Label is initialed (on left-hand side of label just belowlast additive or drug) after being affixed to correctadmixture _____________

Total volume to be infused ______ Red chemo i.v. seal _____

“Caution chemo” label _____ Other auxiliary labeling ____

Zip-lock bag __________

Work card is initialed _____________

Pharmacist’s initials _______________ Date _____________

Supervisor’s initials _______________ Date _____________

Figure 2. Antineoplastic drug preparation checklists.

Checklist for Initial Setupof Antineoplastic Drug Work Card

This form should be completed by the pharmacist checking the workcard. Place check mark (or N/A) in each space after each check iscompleted. Your check marks and initials at the bottom of this worksheet are your personal assurance that you checked all these items foraccuracy in the setup and transcription of information onto the workcard. Each drug requires a separate checklist.

Patient _________________________ Drug _______________

Start date _____________

Administration time _____________

Stop date _____________

Duration _____________

Correct drug name _____________

Number of doses ______

Dose _____________

Drug concentration _____________

Drug volume _____________

Diluent _____________

Volume of diluent ______ Overfill _____ Drug in overfill ____

Expiration time _____________

Special delivery devices (tubing, cassette, container, etc.)

_____________

Correct route of administration __________________________

Correct mixing instructions (special directions, e.g., “DoNot Filter”) _____________

Auxiliary label information (e.g., “Do Not Refrigerate,” “UseIn-line Filter,” “For Intrathecal Use Only”) _____________

Correct total volume _____________

Pharmacist’s initials ________________ Date ______________

This record should remain with the work card for the duration of theorder and be saved for the supervisor for review after discontinuationof the order.

Supervisor’s initials _________________ Date ______________

ASHP REPORTS



great care in correctly interpretingthis information and clearly commu-nicating orders for antineoplasticmedications with other health careproviders.

System administrators shouldweigh the merits of requiring ordersfor all antineoplastic medicationsand other high-risk drugs prescribedby physicians-in-training to be coun-tersigned by a senior physician withexpertise in the specialty to safeguardagainst errors in interpretation andprescribing.

Health care providers with privi-leges of prescribing antineoplasticdrugs should complete an orienta-tion of local policies and proceduresrelated to prescribing antineoplasticsbefore they are permitted to orderthem for patient care.

Health care providers should lo-cally develop standardized dosageand administration schedule modifi-cations for each antineoplastic medi-cation. Treatment modificationsmay be appropriate for patients withthe following characteristics: (1) pre-existing pathologies and whosehealth may be compromised bytreatment with particular antineo-plastics (e.g., withholding or decreas-ing bleomycin dosages in patientswith preexisting pulmonary dysfunc-tion or cardiotoxic agents in patientswith congestive heart failure), (2) ahistory of severe, prolonged, or cu-mulative adverse effects after previ-ous antineoplastic treatments, (3)impaired physiological function thatpredisposes patients to altered phar-macodynamic responses (e.g., renalor hepatic impairment), and (4) lowor decreased performance status.

Health care providers should alsoestablish standardized guidelines forprescribing drugs that are routinelyadministered concomitantly with an-tineoplastic medications. Medication-use guidelines for supportive careand ancillary agents (e.g., antiemet-ics, hydration, chemoprotectants)should be made accessible to allhealth care providers who prescribe,

prepare, and administer antineoplas-tic drugs and for persons who per-form clinical monitoring.

When generating medication or-ders in a setting where preprinted or-dering forms, CPOE, and other elec-tronic and mechanical means (e.g., atypewriter) are not available, pre-scribers should legibly print thenames of medications, dosages,routes of administration, and ad-ministration schedules in plain blockletters and Arabic numerals. Unless itis considered inappropriate by theprescriber, handwritten medicationorders should include the indicationsfor which they are prescribed (e.g.,for sore mouth, for nausea, forchronic lymphocytic leukemia).

When antineoplastic treatment(ordering, preparing, and adminis-tering) is coordinated at a single lo-cation, it is the prescriber’s responsi-bility, or in the conduct of clinicaltrials, it is the principal investigator’sresponsibility, to provide informa-tion about the treatment (e.g., proto-cols, publication reprints) to thosewho prepare and administer medica-tions and monitor patient outcomes.It remains the prescriber’s responsi-bility to answer questions and pro-vide information to other health careproviders when treatment is imple-mented in a place that is geographi-cally separate from the prescriber’slocation. Prescribers, clinical investi-gators, and medically responsiblestaff are strongly urged to provide tohealthcare providers who prepareand administer antineoplastic medi-cations a complete printed (or elec-tronically reproduced) copy of thetreatment regimen.

General guidelines for prescrib-ing antineoplastic medications.3,5,7,17

The following are general guidelinesfor prescribing antineoplastic drugs:

1. Instructions for medication regimensshould be explicit, complete, clear,and easy to follow. Treatment regi-mens should be described accuratelyand consistently in all written and

published materials in which antine-oplastic medication use is described;

2. Medication-use systems should re-quire health care providers to usestandardized vocabulary and nomen-clature for describing treatment withantineoplastic medications;

3. Use uniform and consistent notationsto express quantifiable amounts (dos-age, concentration, volume, and time);

4. Never trail a whole number with adecimal point followed by a zero (e.g.,write “5 mg,” not “5.0 mg”);

5. When writing amounts less than one,the expression should be written witha leading zero, which precedes thedecimal point (e.g., “0.125 mg”);

6. In all treatment plans and medicationorders, identify the dosage, the calcu-lated dose, and, parenthetically, thetotal dosage (the amount of drug as afunction of body weight, BSA, or oth-er factors) that patients are to receiveduring a treatment cycle; and

7. When treatment day enumeration isarbitrary, day 1 typically describes theday treatment commences. In con-trast, hematopoietic progenitor-celltransplantation regimens often in-clude day 0, and significant treatment-related events both before and after aprogenitor-cell graft is administeredare distinguished by negative (mi-nus) and positive (plus) prefixes,respectively.

Specific recommendations forparenterally administered medica-tions.7 Health care providers shouldadhere to the following guidelines forparenteral antineoplastic drugs:

1. In treatment plans and orders, dosesshould be expressed as the totalamount of medication to be adminis-tered from a single container (i.e., thetotal amount of medication per sy-ringe, bag, or other container);

2. For medication admixtures that canbe prepared in more than one way,practitioners should institute a priori,standard, and consistent methods di-recting how each medication will beprepared and administered; and



ASHP REPORTS

3. For drug products with extendedstability and when a medication isadministered from a single con-tainer for more than 24 hours, aprescriber’s order for treatmentshould specify the amount of medi-cation to be administered duringeach 24-hour interval.7 A drug or-der for a patient with a BSA of 2 m2

should read: “Drug XYZ” (8 mg/m2/day × 3 days) 48 mg in 150 mL0.9% sodium chloride injectionby continuous intravenous infu-sion over 72 hours, days 1–3. Starton 04/01/2001 at 0800 (total dose/cycle = 48 mg).

Specific recommendations fororally administered medications.7

Health care providers should adhereto the following guidelines when oralmedications are the prescribed anti-neoplastic treatment:

1. In treatment plans and medicationorders, describe drug doses andschedules as the amount of medica-tion to be taken per dose, not as atotal daily dose that is to be taken individed doses;

2. In treatment plans, medication or-ders, and instructions to a patient,identify the number of doses to beadministered or taken;

3. When doses for a solid orally admin-istered dosage form are greater or lessthan available dose strengths, specifywhether and how doses are to berounded to the nearest capsule or tab-let strength (e.g., Should tablet for-mulations be broken to deliver acalculated dose? Should high and lowdoses be administered on alternatingdays to deliver an average dose?);

4. Whenever possible, include instruc-tions about how medications are tobe taken with respect to food inges-tion and whether particular types offood may affect medication activity;and

5. Explicitly identify essential ancillarymedications and supportive care thatshould accompany an antineoplastictreatment regimen.

Recommendations for medication

preparation and dispensing

systems and roles for pharmacistsFor each practice setting, persons

representing the various healthcare disciplines that prescribe, pre-pare, and administer antineoplas-tic medications should participatein planning and managing localmedication-use systems.

Standardize medication prepara-tion guidelines. Health care provid-ers should establish standardizedguidelines for reconstituting, dilut-ing, admixing, packaging, and label-ing commonly used antineoplasticsand other medications that are rou-tinely administered with antineo-plastics. Each practice facilityshould also establish a standard-ized method for labeling multidosevials and reconstituted drug prod-ucts. Standardized medication prep-aration guidelines should be promi-nently displayed (e.g., as a chart) foreasy accessibility in areas where or-ders are processed and medicationsprepared.

Policies and procedures should bedeveloped for situations in whichmedications are prepared at facilitiesthat are geographically removedfrom where treatment is adminis-tered. Procedural protocols shoulddescribe requirements for medica-tion packaging, storage conditionsduring transportation, duration oftransport, and handling after deliv-ery. Medication couriers should re-ceive training in organizational poli-cies for handling medications andshould immediately report whenconditions and handling practicesdeviate from procedural standards.In addition, handling proceduresshould ensure patient confidentialityand provide guidelines for emergen-cy situations, such as hazardous-drug spills.

Persons who prepare and dispenseantineoplastic medications shouldensure timely drug delivery to pa-tients and patient care areas after re-ceiving written orders. If dispensing

is delayed for any reason, health careproviders awaiting the medicationsshould be notified.3

Quality assurance. In collabora-tion with health care providers whoprescribe and administer medica-tions, pharmacists and persons whoprepare and dispense medicationsshould take the initiative in develop-ing and managing quality-assuranceprograms for their medication-usesystems. These programs should pre-eminently include surveillance andreporting systems that track poten-tial and actual medication errors andevaluate the proximal causes of er-rors among processes and systemsand preventive measures.3,18 Themajor advantage of multidisci-plinary participation is that eachdiscipline’s perspectives and meth-ods for conceptualizing systemflaws and solutions can be incorpo-rated in designing strategies for pre-venting medication errors. Confi-dential reporting is essential to thesuccess of a medication-error sur-veillance and reporting system. Onlyby understanding what causes andcontributes to errors can the numberof errors be reduced. In designing amedication-error surveillance andreporting system, strategic emphasisshould be placed on understandingwhy errors occur and not on blamingor censuring personnel.19

Orientation on medication-errorreduction. Pharmacy supervisorsand managers should develop an ori-entation program about medicationerrors commonly associated withantineoplastic drugs to train phar-macy personnel who prepare anddispense antineoplastic medications.Pharmacists should develop ongoinginterdisciplinary educational pro-grams that focus awareness on po-tential medication errors with anti-neoplastic medications, strategies forpreventing errors, and local and na-tional medication-error reportingand evaluation systems for allpractitioners who have direct patientcontact.

ASHP REPORTS



Pharmacists should engage thesupport of medical and nursing ad-ministrators and supervisors to en-courage their staff (particularly thosein professional training programs) tocomplete antineoplastic medication-error awareness programs.9 Educa-tional programs should be disciplinespecific. Program content should in-clude medication-error case scenariosand discussion about the effects thatmedication errors have on patients’quality of life and the health system.3,10

Standardize drug procurementand storage. Pharmacists who selectand procure drugs should strive tominimize or eliminate look-alikedrug product containers and limitthe availability of different vial sizesfor parenteral medications wheneverpossible.4 Frequent additions to thevariety of available drug productsand changes among alternative man-ufacturers’ drug products can con-tribute to medication-use errors andshould be avoided. When practicable,drug products with similar names andpackaging should not be stored next toeach other. Medication-use systemsthat involve a formulary should sepa-rate nonformulary products fromthose that are on the formulary.Health care providers should famil-iarize themselves with antineoplasticdrugs that are not on their formularybefore prescribing, preparing, andadministering them.

Standardize medication prepara-tion and dispensing. Antineoplasticmedications should be dispensedin ready-to-administer dosageforms whenever possible. Generally,antineoplastics for intermittentparenteral administration should beprepared so that each medicationcontainer has only one dose. The riskof incorrect medication use is in-creased when the amount of drugdispensed in a single container ex-ceeds the amount to be adminis-tered during a 24-hour period. It isessential that individuals and com-mittees responsible for developingand overseeing medication-use sys-

tems establish guidelines on whetherprescribers may order antineoplasticpreparations to be administeredfrom a single container for morethan 24 hours. In all practices whereparenteral drugs with extended sta-bility (more than 24 hours) are sanc-tioned, it is imperative that the dura-tion of their use is clearly labeled andthat health care providers are trainedto correctly prescribe, prepare, andadminister them.7

When preparing an antineoplasticadmixture, a quantity of medicationthat most closely approximates theprescribed dose should be segregatedfrom other drug supplies. For treat-ment regimens that include two ormore drugs, especially when medica-tions are to be administered by dif-ferent routes, the medicationsshould be physically segregatedduring preparation and when ad-ministered. Compounded medica-tions should be prepared one at atime, using standardized techniqueswhenever possible. When measuringdiluent solutions used to reconstitutemedications and drugs to be addedto a secondary container, a personother than the individual who mea-sured the volume should visuallyconfirm the measurement before thesolutions are transferred from themeasuring device to the secondarycontainer. This may be accomplishedby visual inspection or by weighingsyringes, other transfer devices, andintermediate product containers be-fore fluid transfer is completed. Al-ternatively, post hoc methods forchecking medication preparation in-clude “pulling back” syringe plung-ers and marking syringe barrels todemonstrate the volume of fluid thatwas injected into the secondary con-tainer. In any medication-checkingsystem, the person who confirms thetechnical accuracy of the person whoprepares the admixture should ex-amine all containers used duringpreparation.

Antineoplastic agents are admin-istered parenterally by many routes

other than the intravenous route(e.g., intrathecally, intrahepatically,intrapleurally, intraarterially). Inad-vertent administration by the wrongroute (e.g., giving vincristine intra-thecally) can result in serious or fatalconsequences. Medication-use sys-tems should include policies andprocedures that distinguish medica-tions administered by the intrave-nous route from those intended foradministration by other routes.

Standardize medication labeling.Strict procedures should be estab-lished for standardizing medicationlabeling. A uniform, systematic label-ing method should be used, especial-ly when multiple drugs are preparedfor a single patient. Medication labelsshould be mechanically printed (nothandwritten). Extemporaneouslycompounded antineoplastic medica-tions should be labeled immediatelyafter preparation. Oral medicationsshould also be sealed with childproofor poisoning-prevention closures.Auxiliary labels may facilitate distin-guishing among medications that areadministered by particular deliverymethods.

Labels for oral dosage forms, rectalsuppositories, and topically appliedunit-dose products should include allof the following information:

1. Patient’s name and unique identify-ing code or number and patient’s lo-cation within a treatment facility(when applicable),

2. Date (with or without specifyingtime) the medication was dispensed,

3. Generic drug name,4. Dosage form and strength,5. Amount of medication per dose

(when the container dispensed holdsmore than one dose),

6. Administration route,7. Detailed instructions to the patient for

self-administering the medication,8. Supplemental administration in-

structions, such as the starting andcompletion dates and times, numberof doses to administer, cautionary in-formation about when medications



ASHP REPORTS

are to be taken in relation to foodingestion and other medications, andinstructions and warnings regardingadministration route, storage condi-tions, and container closures, and

9. The number of drug product unitsdispensed within each container (thenumber of tablets, capsules, or suppos-itories, packaged in a single container).

Labels for injectable dosage formcontainers should include all of thefollowing information:

1. Patient’s name and unique identify-ing code or number and patient’s lo-cation within a treatment facility(when applicable);

2. Generic drug name;3. The amount of medication per con-

tainer and the amount of medicationper dose when a product containerholds more than one dose, as drugproduct containers may hold moremedication than is intended for asingle administration (e.g., multipledoses for intermittent administra-tion). Identify how much overfill isadded to a container when excessmedication and fluid volumes areadded to displace air from the tubinglumen (“dead space”) in administra-tion sets;

4. Route of administration; for exam-ple, medications prescribed for ad-ministration other than by theintravenous route—especially thosefor intrathecal administration—should bear ancillary labels that dis-tinctively identify the intendedadministration route;

5. The name and either the amount orconcentration of all drug additives ina drug product;

6. Diluent (vehicle fluid) name;7. The volume of fluid to be adminis-

tered. Volume to be administeredshould be specified, especially whenit differs from the total volume with-in a medication container (i.e., whenthe product contains an amount offluid in excess of the volume to bedelivered);

8. Administration rate and duration.

Ideally, both administration rate andduration should be specified. Be-cause administration rates can becalculated from the volume to be ad-ministered and duration of adminis-tration, duration is the essentialcomponent;

9. Supplemental administration in-structions, such as starting and com-pletion dates and times, prohibitionsabout when medications are not tobe administered in relation to othermedications, instructions and warn-ings regarding administration route,handling, and storage conditions(e.g., information about special re-quirements for administration sets in-cluding inline filtration, warnings toavoid intrathecal administration withvinca alkaloid drugs, and hazardous-drug warning labels);

10. When it is necessary to prepare morethan one medication intended forsequential administration, the con-tainer labels should be numbered.Indicate the sequence in which eachcontainer is to be used plus the totalnumber of containers (e.g., bag 1 of3, bottle 3 of 7);

11. Date (with or without specifyingtime) the medication was ordered orprepared. Investigational com-pounds, in particular, should be la-beled with the date and time theywere prepared;

12. Date (with or without specifyingtime) after which a medicationshould no longer be used (expirationinformation);

13. Cautionary warnings as required forhazardous-drug products;20

14. Storage specifications; and15. The name (with or without specify-

ing location or telephone number)of the institution, pharmacy, orpractice from which a medicationwas dispensed and the prescriber’sidentity.

Credentialing pharmacists forantineoplastic medication-use pro-grams. Pharmacy managers and su-pervisors should require pharmacistemployees to complete training and

demonstrate competencies related toantineoplastic medication use, evalu-ating medication orders, preparingantineoplastic medications, safe han-dling procedures, error surveillanceand reporting programs, and localpolicies as a prerequisite to phar-macist credentialing. Health careorganizations should periodicallyreassess pharmacist employees’competencies related to their re-sponsibilities, increasing the fre-quency of reassessment if perfor-mance problems occur.6

Roles for pharmacists. Amongprimary health care providers, phar-macists generally are best positionedto ensure that medications are usedrationally and safely and increaseothers’ awareness about medicationerrors and how to prevent them.Pharmacists should participate in allaspects of patient care related to anti-neoplastic treatment, including de-veloping rational policies for safe andappropriate medication use and oth-er services consistent with pharma-ceutical care.3,9 Pharmacists shouldparticipate with other primaryhealth care providers in multidisci-plinary groups that develop, im-plement, and periodically reevalu-ate practice-specific procedures andprocesses for verifying antineoplasticmedication orders, resolving proce-dural questions related to confirmingand processing medication orders,and evaluating and resolving dis-putes among health care providers.

Each organization should estab-lish a minimum acceptable level ofpharmacist participation in theerror-prevention elements of patientcare, such as proactively reviewingmedication orders, screening labora-tory results, providing drug informa-tion and patient counseling, and re-viewing drug storage conditions.3,21

The following areas are recom-mended for pharmacist participation:

1. Educate health care providers aboutmedication errors,

2. Independently verify medication dos-

ASHP REPORTS



ages, routes of administration, andschedules,

3. Participate in multidisciplinary ef-forts to establish drug-specific utiliza-tion constraints that limit maximumdoses, administration rates, and ad-ministration schedules for antineo-plastic medications,

4. Participate in multidisciplinary ef-forts to standardize the prescribingvocabulary,

5. Participate in multidisciplinary ef-forts to educate patients, their fami-lies, and personal caregivers,

6. Improve communication amonghealth care providers and amonghealth care providers, patients, andcaregivers, and

7. Work with drug manufacturers.

Drug information resources and ed-ucation for providers. Pharmacistsshould help ensure the availability ofup-to-date references on the appro-priate use of antineoplastic drugs forall health care providers involved inmedication use.3,10 Drug informa-tion resources should provide in-formation about drug products’FDA-approved labeling and inves-tigational uses. Information shouldbe developed or selected, includingdrug-specific precautionary warn-ings and information about adverseeffects, particularly dosage- andschedule-limiting effects; potentialinteractions with other drugs, diseasestates, and foods; administrationmethods, including drug admixturestability and compatibility data; usu-al adult and pediatric dosages; dosagerecommendations for single- andmultiple-treatment courses; treat-ment modifications for persons withconcurrent pathologies or end-organimpairment; and pharmacokinetical-ly based dosing and monitoringguidelines.

Pharmacists should develop andprovide discipline-specific educationalmaterials about antineoplastic medi-cation use to health care providerswho prescribe, prepare, and admin-ister antineoplastic medications.

The instructional tools developedfor each professional health carediscipline should complement thematerials developed for the otherdisciplines.3 Whenever new antineo-plastics, treatment regimens, andtreatment protocols are introducedinto their practice setting, pharma-cists should assume a continuous,proactive leadership role in develop-ing educational programs and mate-rials for health care providers, pa-tients, and caregivers.3,10

For patients whose care is trans-ferred from oncologists to nonspe-cialist practitioners, oncologypharmacy specialists should devel-op and provide drug monographs,medication-use summaries, and oth-er treatment-related materials de-scribing how antineoplastic medica-tions and treatment regimens are tobe accomplished.4,9 The need is es-pecially acute among organizationsand practitioners who provide lo-cal care for patients enrolled in clini-cal trials or receiving investigationalantineoplastic treatments.

Treatment protocols. Oncologypharmacy specialists should partici-pate in developing treatment proto-cols for standard treatments andclinical investigations. In practicesettings where antineoplastic agentsand treatment regimens are usedroutinely, pharmacists should ini-tiate the development of tools thatstandardize the way medications areordered, thereby facilitating accu-rate and appropriate prescribing,order interpretation and verifica-tion, and medication processingand dispensing.10,22 Pharmacistsshould lead initiatives to standardizedrug preparation procedures, in-cluding reconstitution, dilution,and drug admixture methods forcommonly used parenteral antineo-plastic medications.4

CPOE. When circumstances andresources permit, pharmacists shouldwork with information systems per-sonnel, computer programmers, andsoftware vendors to develop CPOE

systems. System requirements shouldinclude mechanisms for standardiz-ing medication orders, decreasingopportunities for error by mini-mizing data entry, and screeningorders for medication doses andadministration schedules that ex-ceed established limits. Pharmacistsshould advocate for and participate inestablishing maximum safe anti-neoplastic dosage and scheduling lim-its with physicians, nurses, and otherprimary health care providers.

Vocabulary and nomenclature.Pharmacists are uniquely qualified tolead multidisciplinary efforts towarddeveloping and implementing clear,detailed, standardized vocabularyand nomenclature for antineoplastictreatment regimens, medication or-ders, and administration instruc-tions. Pharmacists should participatein the early stages of protocol devel-opment for standard treatments andclinical investigations to ensure thatpharmacotherapeutic regimens areclearly described, easily understood,and incorporate standardized lan-guage, content, abbreviations, andunits of measure.3,7,9

Patient education and counseling.When meeting or interviewing pa-tients, their family members, or oth-er home-based caregivers (e.g., com-pleting medication-use and allergyhistories, screening blood pressure,performing ongoing treatment re-sponse assessment, dispensing medi-cations), pharmacists should providemedication education and counsel-ing. They should verify that patientsand their caregivers understand thefollowing:

1. The purpose of the medication and itsintended use,

2. The appropriate use and safe han-dling of medications and administra-tion devices,

3. Appropriate temperature and safestorage conditions,

4. Special precautions to prevent expo-sure to hazardous materials that maybe present in patients’ clothing, lin-



ASHP REPORTS

ens, body fluids, and excreta duringand after treatment,

5. The potential interactions with othermedications and foods,

6. Common and possible adverse effectsassociated with the medication,

7. Methods for preventing and manag-ing adverse effects, and

8. What to do if potentially serious ad-verse effects occur.3,13

Pharmacists should provide educa-tional materials to patients and suggestsupplemental and alternative informa-tion resources, such as the NationalCancer Institute information servic-es department (1-800-4-CANCERor 1-800-422-6237 and www.nci.nih.gov), the American Cancer Society, li-braries, and bookstores.3

Advocates for patients’ rights. Phar-macists should encourage patientsand their caregivers to participate intheir own care and advise patientshow to protect themselves frommedication errors. Pharmacistsshould advise patients that they areentitled to satisfactory answers fromtheir health care providers. Pharma-cists should encourage patients todouble-check the details of theirtreatment, including drug names anddosages, and to request dosage recal-culation if their biological measure-ments change. Pharmacists who par-ticipate in developing treatmentplans and protocols should ensurethat consent-for-treatment formstruly secure patients’ informed con-sent. Pharmacists should help to pre-pare treatment consent forms; pro-vide patients with an accurate anddetailed description of their treat-ment plan in clear, unambiguous,and easily understood language andanswers to their questions about thetreatment and alternative treatmentoptions; and assess patients’ under-standing of expected and possibleoutcomes. Pharmacists should alsodescribe their role as primary care pro-viders and the care they provide.3,4

Clinical intervention, analysis, andperformance improvement. In addi-

tion to dispensing medications,pharmacists in various settings canprovide a vital service toward im-proving the quality of patient care byimplementing a proactive clinical in-tervention program and document-ing health care providers’ deviationsfrom planned antineoplastic treat-ments. Longitudinal data collection,analysis, and reporting can revealsystem flaws that failed to prevent orfacilitated prescribing errors, suggesttargets for quality improvement, andvalidate pharmacists’ interventions.

Pharmacists should proactivelywork with other primary care pro-viders to establish medication-usereporting and surveillance programs.Committees established for this pur-pose should comprise representa-tives from medical, nursing, pharma-cy, and risk-management disciplines.Programs should continually evalu-ate local medication-use systems toidentify potential problems and solu-tions related to medication use andprevent medication errors.3,18 Suchprograms in institutions shouldseek endorsement from appropriatelocal multidisciplinary committees(e.g., pharmacy and therapeutics,medical executive, and clinical prac-tice committees).

Feedback for pharmaceuticalmanufacturers and regulators.Pharmacists should work withpharmaceutical manufacturers andFDA to eliminate ambiguous, con-fusing, and potentially misleadingdrug product and treatment infor-mation from published resources(e.g., product packaging, package in-serts, official compendia, and pro-motional information). Pharmacistsworking in the pharmaceutical man-ufacturing industry should proac-tively identify preventable causes ofproduct-user errors and adverse ef-fects associated with product label-ing, packaging, and promotion.23

Pharmacists’ voluntary participationin national reporting programs canincrease the awareness of medicationerrors and promote error prevention

throughout the nation’s health caresystem. These aggregate data promotechanges in product identity, packag-ing, labeling, commercial information,and marketing practices that are sub-ject to manufacturers’ control andgovernmental regulation.3,17

Recommendations for medication

administration systems and roles

for nurses

Nurses are often the last link inthe chain of health care providerswho provide treatment with antineo-plastic medications. To safeguard pa-tients from mistakes that have poten-tially lethal consequences, elaboratesystems have evolved that include

• Requirements for credentialing per-sons who administer antineoplasticmedications,

• Tools and methods to facilitate docu-mentation and identification of cor-rect medication use,

• Independent verification of medica-tion orders,

• Accurate documentation of medica-tion use and effects and patient care,

• Strict compliance with regulationsand practice standards, and

• Patient education regarding medica-tion safety.

Credentialing nurses for antine-oplastic medication-use programs.Nursing managers and supervisorsshould require nurse employees tocomplete training and demonstratenursing care-related competencies,such as administering antineoplasticmedications, caring for patients whohave received antineoplastic medica-tions, and knowing about local poli-cies. Specialty certification is encour-aged. Nurses may be required tocomplete additional training andcompetency assessments before theyare permitted to administer experi-mental medications. Training usual-ly combines didactic and supervisedpractical instruction. Didactic in-struction generally includes trainingabout specific antineoplastic agents,

ASHP REPORTS



appropriate dosages and dosageranges, adverse effects and clinicaltoxicities, administration techniques,and safe handling. Technical experi-ence in administering antineoplasticmedications commonly starts withrole-playing exercises and practicingtechnical skills on nonhuman mod-els and proceeds through clinical in-teractions under the supervision ofan experienced mentor. Perfor-mance evaluations test trainees forsatisfactory cognitive and motorcompetencies. Health care organi-zations should periodically (annu-ally or more frequently if perfor-mance problems occur) reassessnurses’ competencies related to theirresponsibilities.

Standardized tools for recordingmedication administration. Nurseswith a variety of experiences have de-vised and contributed to designingtools to facilitate the prevention ofdrug administration errors, such asstandardized work sheets used to cal-culate medication dosages and ad-ministration rates and checklists ofpertinent laboratory results andphysiological measurements. Treat-ment flow sheets provide easily inter-pretable information about when apatient’s previous treatments wereadministered, whether dosages andmedication delivery deviated fromplanned treatment, and the cumula-tive amount of medication adminis-tered. Thoughtfully designed treat-ment flow sheets may become part ofa patient’s permanent medical recordand can be an invaluable resource forpatient care.

Checking orders and equipmentfor administering antineoplasticmedications. Medication orders forantineoplastics are commonlychecked by two nurses working inde-pendently. As has been discussedpreviously, double checks by two li-censed health care providers help toensure that medications are pre-scribed and administered appropri-ately. In addition, nurses shouldevaluate and confirm the functional

integrity of vascular access devices(and devices for other administra-tion routes), medication pumps, andother devices that control medica-tion delivery. For adjustable and pro-grammable mechanical and electron-ic devices, mechanical adjustmentsor electronic programming for deliv-ering the correct dose at the appro-priate rate should be verified withanother health care provider who isknowledgeable about the delivery de-vice before it is used to administermedications. Another individualwho checks adjustments and pro-gramming should independently ex-amine the adjustments made to thedevice and review the programming.

Recording and tracking antineo-plastic use. After medications havebeen administered, it is a nurse’sresponsibility to manually or elec-tronically record the activity. Thedocumentation should include thepatient’s name, the names of allmedications administered, dosag-es, administration routes, rates ofadministration, the date and timeadministration began, the durationof administration or time that treat-ment was completed, and whetheradverse effects were observed or re-ported by the patient during or afteradministration. Communicationswith patients, other health care pro-viders, and personal caregiversshould be documented in an objec-tive, chronological narrative style, re-porting the dates and times theevents occurred, the names of in-volved persons, and how questionsand problems were resolved.

Nurses and other personnelshould immediately report to medi-cally responsible personnel and theirsupervisors any instance in whichmedications were used incorrectlyand the events attributable to the er-ror. In response to discovering amedication-use error, a provider’sprimary responsibility is to ensurethe patient’s safety. Subsequently, theerror and related circumstancesshould be recorded as is indicated by

specific policies and procedures.Medication-use error reports (alsocalled occurrence or incident re-ports) should be written in an objec-tive, chronological, narrative stylewithout editorial remarks and specu-lative comments. Comprehensive in-cident reports are useful in discover-ing and evaluating system flaws andmay provide the impetus for improv-ing medication-use systems.

To prevent medication errors,nurses and other personnel who ad-minister antineoplastic medicationsmust comply with policies and pro-cedures that define standards ofpractice. It is important, however, toperiodically reevaluate practice stan-dards in order to assess how well amedication-use system functions,make appropriate changes, and, ulti-mately, improve patient safety andthe quality of care.

Health care providers administer-ing antineoplastic medicationsshould not deviate from previouslystated guidelines for ordering, pre-paring, and administering antineo-plastic agents. Examples of inappro-priate practice include borrowingmedications from a patient’s drugsupply to give to another patient andpreparing agents without the properfacilities or staff. Medication admin-istration schedules should be fol-lowed as closely as possible; provid-ers and caregivers should strive tocomply with treatment plans. Drugadministration should be document-ed promptly after it is completed,and providers administering antine-oplastic medications should rigor-ously comply with local requirementsfor documenting treatment. To pre-vent the inadvertent duplication oftreatment, it is recommended that oneindividual assumes the primary re-sponsibility for each patient during awork period (shift or tour of duty).

Nurses and patient education.Nurses and other personnel who ad-minister antineoplastic medicationsshould encourage patients and theirpersonal caregivers to ask questions



ASHP REPORTS

about their treatment. Patient educa-tion guidelines may be included intreatment maps and clinical careplans.

Recommendations for patient

education

Well-informed patients (and theirauthorized caregivers) are the vitallast link in the safety chain to preventerrors related to antineoplastic medi-cations. Patients are entitled to knowall pertinent facts about the medica-tions they receive during theirtreatment. Health care providershave an obligation to encouragepatients to ask questions and toprovide answers. The followingsuggestions are offered to help pa-tients and their caregivers ensureoptimal outcomes from the cancertherapy medications.

Multifocal medication educa-tion. Patients need multifocal edu-cation about the purpose, adverseeffects, schedules, routes of admin-istration, and descriptions (e.g.,colors, shapes) for all the medica-tions they will receive during theirtreatment. This includes the primaryantineoplastic regimen and all ancil-lary and supportive medications,such as antiemetics and medicationsthat hasten bone marrow recovery.When patients are well informed andthe information they receive is rein-forced by nurses, pharmacists, andother caregivers, they are better pre-pared to detect a misinterpretedmedication order and assertivelyquestion conflicting information.24

Health care professionals should besensitive to the emotional aspects ofpatients with cancer when planningmedication education. Educationshould take place at a time when apatient is able to listen and under-stand. Medication education shouldnot be attempted when patients aresedated or confused as a result ofmedications or immediately after re-ceiving their cancer diagnosis.

Patients should participate intheir care by asking questions about

their cancer treatment and relatedmedications and by confirming theregimen with their nurse before re-ceiving treatment. Health care pro-viders should make educational ma-terials available in counseling andtreatment areas to encourage pa-tients to learn more about their can-cer therapies.

Health-system procedures edu-cation. Patients should understandthe health system’s plan for antineo-plastic medication-error prevention.They should become familiar withtheir providers’ routine proceduresfor checking medication orders sothat they can understand the safe-guards that have been establishedand why delays may occur beforetheir treatment can be started. Forexample, patients can remind theperson administering chemotherapyto compare medication labels with apatient’s identity and can verify theirheight and weight each time they aremeasured.

Patient participation in a medica-tion-use system. Patients (or their car-egivers) should be knowledgeableabout their medications and the waysin which the medications are to be ad-ministered according to their treat-ment plan. In some circumstances, pa-tients should be encouraged to takeresponsibility for some of their care tohelp improve their quality of life. Ex-amples include self-administeringmedications, maintaining the patencyof vascular access devices, givingthemselves a subcutaneous injection,and troubleshooting a problem withthe portable infusion pump. Patientsshould demonstrate their abilities toperform these functions if they are in-cluded in the therapy plan.

Patients should be given a detailedtreatment calendar that identifies allof the medication events that are ex-pected to occur throughout theirtreatment. Patients should be en-couraged to keep their calendar withthem to compare the expected treat-ment with what is being dispensedand administered.

Patients’ responsibilities. Pa-tients should be taught to detect andto seek help in managing adverse ef-fects that may occur during theircancer treatment. Patients shouldpromptly inform their health careproviders about adverse effects expe-rienced during a chemotherapy cyclebefore the next cycle commences. Pa-tients should keep a list of the medi-cations that they self-administered totreat these adverse effects.

It is important for health careproviders to be able to determine apotential for interactions betweena patient’s nonantineoplastic medi-cations and the chemotherapy theyare to receive. Therefore, patientsshould provide to their providers alist of all medications they are using,including over-the-counter prepara-tions, natural products and dietarysupplements, and other complemen-tary and alternative medicines.

Recommendations for

manufacturers and regulatory

agencies

Pharmaceutical manufacturershave a responsibility to exercise carein designing product packaging andlabeling and in promoting theirproducts, as these features may con-tribute to errors in prescription,product selection, preparation, andadministration. Companies thatmarket antineoplastic agents shoulddevelop and support educationalprograms that encourage safe and ac-curate prescribing, preparation, ad-ministration, and handling of theirproducts. The following guidelinesaddress some of the major areas.

Product naming, packaging, andlabeling. Companies should avoidtrademarking drug names that lookor sound similar to those of otherdrug products. Proprietary drugnames for new products and productformulations should be dissimilarfrom other generic and proprietarynames. Manufacturers should avoidappending letters and numbers todrug names as this practice can re-

ASHP REPORTS



sult in potential confusion withdosage strengths, medication quan-tities, and the amount of medica-tion to be administered.

Product packaging and labelingshould provide clear, easily distin-guished features to identify a drugand the amount of drug per dosageunit (e.g., tablet, capsule, wafer) andwithin a product container (e.g., vi-als, bags, bottles, prefilled syringes).It is particularly important that adrug product’s USAN-approved ge-neric name appear more prominent-ly than other information on theproduct label. Drug names should beprinted on both the front and back ofthe containers and packaging ofparenteral drugs; “TALL man” char-acters should be used to distinguishbetween similar drug names. Con-tainer labels for drugs that are in so-lution and for those that require re-constitution or dilution before theyare used should identify the total drugcontent in mass units (or biologicalactivity units) rather than concentra-tion.24 Product packaging and labelingthat include both mass and concentra-tion values should be designed to dis-play mass units more prominently.

Labels should be unique and welldesigned. Distinguishing colors andcontrasting hues facilitate identifyingand distinguishing drug productsand products in different strengthsand concentrations. Warnings andspecial or unique instructions shouldbe prominently displayed on productpackaging and labeling. Unique la-beling and packaging techniquesshould be used to prevent productmisidentification and to warn aboutdosing errors and unique character-istics that predispose medication us-ers to potentially serious or life-threatening toxicities. Examplesinclude the unique way that thePlatinol-AQ brand of cisplatin in-jection (Bristol-Myers Squibb,Princeton, NJ) is packaged to preventmisidentification with carboplatinand the cautionary statements on vi-als containing vincristine sulfate in-

jection that warn against using theentire contents of a vial for a singlepatient (on bulk packages) and thatintrathecal administration may befatal.

A statement that declares a drug’sapproved routes of administration isoptional and may or may not appearon product packaging. If the agent isapproved for administration by onlyone route, it must be clearly indicated.

Appropriate storage temperaturesor conditions should be clearly visi-ble on drug labeling and packaging.

Drug labeling and packaging mustidentify the manufacturer’s productlot or control number.

Drugs that must be reconstitutedand diluted before clinical use shouldinclude reconstitution instructionsthat identify appropriate diluentsand volumes.

A manufacturer’s drug productpreparation date (for experimentaldrugs) or an expiration date should beclearly visible on the product label.

Special instructions, such as“Shake Well,” “Do Not Shake,” “Al-bumin Required,” and instructionsfor dilution, should appear on prod-uct labeling. In cases where impor-tant information will not fit on aproduct label, a package insert maybe required as part of the labelingand packaging.

Product changes should be widelycommunicated to prescribers, phar-macists, nurses, and other health careproviders involved in drug prescrib-ing, preparation, and administration.

Package inserts and product in-formation that describe medical in-dications, medication doses, admin-istration schedules, and product useshould not include abbreviations.This is especially important for drugsused in complex treatment regimens.

Educational materials and pro-grams. Pharmaceutical manufactur-ers and drug product sponsorsshould be encouraged to provide ed-ucational materials and programsthat promote and encourage safe useof their drug products. Programs

should clearly explain the indicationsappearing on FDA-approved label-ing, dosages, methods for prepara-tion, and administration routesand schedules. Treatment descrip-tions should be standardized andconsistent with guidelines designedto prevent medication-use errors.7

Medication names and administra-tion information should not be ab-breviated in educational and promo-tional materials.

Regulatory oversight. Regulatoryagencies have a responsibility to re-view product packaging, labeling,and advertising to ensure that theircontent accurately reflects safety andefficacy data and conforms with lan-guage that has been approved by theFDA. A key component in those re-views should be that the productpackaging and labeling facilitate safeand appropriate use and prevent us-ers from making errors in selecting,preparing, and administering a drugproduct. Pharmacists should be con-sulted in screening proprietary drugnames, product packaging, and la-beling before drug products are ap-proved for commercial use.

Managing medication errors

Medication-use errors with anti-neoplastics are distinguished fromerrors with other types of drugs intwo important ways, both of whichrelate to antineoplastics’ inherenttoxicity. Individually and categori-cally, the therapeutic index for anti-neoplastic drugs is less than that forany other class of drugs. Adverse ef-fects are an expected pharmacody-namic consequence attendant withantineoplastic use, and clinical toxic-ities may occur and persist at sub-stantially lower dosages and sched-ules than are therapeutically used.The second characteristic distin-guishing between antineoplastics andother types of drugs is that with thelatter, subtherapeutic doses may notproduce adverse effects that delay re-treatment. In contrast, antineoplasticmedications given in error at sub-



ASHP REPORTS

therapeutic doses (or underdoses)may not provide a therapeutic bene-fit, but they may compromise pa-tients’ ultimate response to therapyby delaying effective treatment untiladverse effects are resolved. Under-doses may also cause or contribute tocumulative long-term patient harmas a result of adverse effects, delayedtreatment, or both. It should be not-ed that antineoplastic treatments arealmost always repeated, and the ef-fect of a medication-use error maynot be apparent until long after theerror occurred. Consequently, iftreatment plans and medication or-ders are not verified during eachtreatment cycle, errors may be com-pounded during repeated cycles andgo undetected throughout an entiretreatment course.

In addition to the actions alreadyset forth in the “ASHP Guidelines onPreventing Medication Errors inHospitals,”1 the following are recom-mended after detecting a medicationerror6:

1. Implement monitoring and interven-tions for controlling injurious effectsand ensuring patient safety;

2. Determine if an error could have pre-viously occurred during prior treat-ment in the same patient and in otherpatients. Medication preparationwork sheets or logs and drug admin-istration records should be evaluated.Unexpected toxicities and an appar-ent or unaccountable lack of thera-peutic and adverse effects should beinvestigated when it is suspected thata medication error occurred;

3. Seek the advice of health care profes-sionals from various disciplines. Theperspective of providers in other dis-ciplines may facilitate discoveringand understanding the circumstanc-es that allowed a medication error tooccur;

4. Determine whether an immediatetemporizing or “stopgap” change inpolicy or procedure is necessary toprevent recurrence of an error whilethe proximal cause is being analyzed;

5. Provide immediate professionalcounseling and support for employ-ees implicated in causing or contrib-uting to an error resulting in seriouspatient harm. Counseling and sup-port should be offered to all person-nel who learn that they have beeninvolved in a medication error with-out regard for how recently the erroroccurred;

6. Establish procedures to inform andfollow up with patients and their fam-ilies about a medication error;

7. Understand that reporting medica-tion errors and adverse drug reactionsis a responsibility that should beshared by all health care providers.However, health systems may desig-nate a person or committee specifi-cally responsible for reporting andinvestigating medication errors andadverse drug reactions. In investiga-tional drug studies, a study’s principalinvestigator must report serious ad-verse events to the trial’s sponsors(the drug manufacturer and the in-vestigational new drug applicationholder) and to the institutional re-view board that oversees study con-duct. Investigational drug sponsorsare required to report to the FDA se-rious adverse effects associated withinvestigational agents, even if they arecaused by a medication-use error;and

8. Encourage practitioners to reportmedication errors to a nationalmedication-error tracking program.This allows other providers to learnhow medication errors occur andhow they can be prevented. Reportingmechanisms for medication-use sys-tems should be standardized by poli-cy. Mechanisms must be developedfor ongoing, interdisciplinary analysisand use of information that is report-ed to medication-error databases.25

Categorizing medication errors.In practice settings where a variety ofdisciplines provide patient care, seri-ous potential and actual errorsshould be reported to an oversightcommittee composed of representa-

tives of all the disciplines that pro-vide care. By standardizing the waymedication errors are reported, com-parisons between reports and data-bases are facilitated, error trends aremore easily identified, and system-based solutions can be developed.26

Continuous oversight by a multidis-ciplinary quality-assurance commit-tee promotes continuity and permitsall primary patient care providers toevaluate system flaws and developand improve the quality of processesand systems that safeguard patientcare.18 Medication-use oversightcommittees are advised to reviewmedication-error reports from sys-tems other than their own and evalu-ate their local medication-use systemfor design characteristics that maypermit similar errors.9,15

“ASHP Guidelines on PreventingMedication Errors in Hospitals”1 rec-ommend adopting a system for cate-gorizing medication-error severitysuch as the one developed by Myersand Hartwig et al.25,26 Although thissystem is generally applicable to er-rors of occurrence with antineoplas-tic drugs, it categorizes errors by se-verity and prioritizes them withoutconsideration for the frequency atwhich repeated errors occur. Accord-ingly, errors with the highest severityranking receive the greatest effortstoward remediation. In contrast, po-tential errors are assigned a “zero”ranking, the lowest severity level, asthey do not reach patients. By rele-gating potential errors to the lowestpriority category, this outcomeseverity-based system risks trivializ-ing system-design flaws. Errors dis-covered before they reach patientscould cause devastating consequenc-es, yet serious nascent errors are of-ten transformed into potential errorsonly by serendipitous discovery.Therefore, potential errors should bedistinguished from errors of occur-rence and subcategorized based ontheir potential to cause harm.25,26

However, potential errors should notbe taken less seriously than errors of

ASHP REPORTS



occurrence. When serious potentialerrors are discovered, the systemsand processes that contributed to theerrors should be evaluated and theirproximal causes identified. The great-est efforts toward remediation of po-tential errors and errors of occurrenceshould be concentrated on eliminatingthe causes of errors that could haveand had, respectively, the greatest ad-verse effects on patients’ health.

NCCMERP’s definition for medi-cation errors includes any event thatmay cause or lead to inappropriatemedication use.2 The definition iscomplemented by the NCCMERPTaxonomy of Medication Errors, acomprehensive expandable toolintended for use in developing da-tabases and analyzing medication-error reports. The Taxonomy pro-vides standardized language andstructure for recording and track-ing medication-error-related data forerrors of occurrence and potentialerrors. NCCMERP permits interest-ed persons to adopt it as it is present-ed or adapt it for use in a particularpractice setting.

References

1. American Society of Hospital Pharma-cists. ASHP guidelines on preventingmedication errors in hospitals. Am J HospPharm. 1993; 50:305-14.

2. National Coordinating Council on Medi-cation Error Reporting and Prevention.About medication errors. www.nccmerp.

org (accessed 2001 Jun 4).3. Cohen MR, Anderson RW, Attilio RM et

al. Preventing medication errors in can-cer chemotherapy. Am J Health-SystPharm. 1996; 53:737-46.

4. Attilio RM. Caring enough to under-stand: the road to oncology medicationerror prevention. Hosp Pharm. 1996;31:17-26.

5. Beckwith MC, Tyler LS. Preventing med-ication errors with antineoplastic agents,part 1. Hosp Pharm. 2000; 35:511-23.

6. Beckwith MC, Tyler LS. Preventing med-ication errors with antineoplastic agents,part 2. Hosp Pharm. 2000; 35:732-47.

7. Kohler DR, Montello MJ, Green L et al.Standardizing the expression and no-menclature of cancer treatment regi-mens. Am J Health-Syst Pharm. 1998;55:137-44.

8. Berard CM, Mahoney CD, Welch DW etal. Computer software for pharmacy on-cology services. Am J Health-Syst Pharm.1996; 53:733,752-6.

9. Kloth DD. Assuring safe care for cancerpatients through an organized multidisci-plinary team effort. Hosp Pharm. 1997;32(suppl 1):S21-5.

10. Fischer DS, Alfano S, Knobf MT et al.Improving the cancer chemotherapy useprocess. J Clin Oncol. 1996; 14:3148-55.

11. Lajeunesse JD. Quality assurance meth-ods in chemotherapy production. HospPharm. 1997; 32(suppl 1):S8-13.

12. Attilio RM. Strategies for reducing che-motherapy-related medication errors:improving the chemotherapy prescrib-ing, dispensing, and administration proc-ess, and the patient’s role in ensuringsafety. Hosp Pharm. 1997; 32(suppl 1):S14-20.

13. Hutcherson DA, Gammon DC. Prevent-ing errors with antineoplastic agents: apharmacist’s approach. Hosp Pharm.1997; 32:194-202,209.

14. United Kingdom Joint Council for Clini-cal Oncology. Quality control in cancerchemotherapy. Managerial and proce-

dural aspects. Oxford, England: RoyalCollege of Physicians of London, 1994.

15. Cohen MR. Enhancing chemotherapysafety through medication system im-provements. Hosp Pharm. 1997; 32(suppl1):S1-7.

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