1. Preventing Medication Errors in Cancer Chemotherapy1

2. Learning Objectives
Recall errors associated with antineoplastic agents
Discuss the magnitude of errors involving cancer chemotherapy
Explain common causes of chemotherapy-related errors
Describe error reduction strategies
Describe the role of the multidisciplinary team in error prevention 2

3. Adverse Drug Events ADEs are injuries that result from drug use
May be preventable or nonpreventable
Potential ADEs result from medication errors with potential for harm but:
Are intercepted before reaching patient, or
Reach patient but do not cause harm .

4. Chemotherapy
Medications used alone or in combination to target cancer cells in the body
Goals of chemotherapy
Increase quality of life
Decrease tumor burden
Provide remission period
Provide a cure
Medications may be administered in any form: oral, IV, IM, subcutaneous, intrathecal, etc.

5. Chemotherapy
Chemotherapy is a biohazard to those preparing and administering the agents
May cause adverse effects to any individual who comes in contact with the agents
Special protocols required for preparation, administration, and disposal of chemotherapy
Medication errors may cause harm to patients or practitioners

6. Sample Chemotherapy Protocol
Placeholder for faculty to insert sample of a chemotherapy protocol used at a local institution
Use this protocol to demonstrate the complexity of the order form and the potential for the form to cause errors

7. Magnitude of Problem
Medication error rate: estimated that 500 deaths occur annually in the United States from chemotherapy medication errors
Approximately 3% of errors involving chemotherapy are reported
63% of oncology nurses reported occurrence of chemotherapy errors in their place of work
Northfelt DW, et al. Proc Am Soc Clin Oncol. 2003;22:542. Abstract 2181.
Schulmeister L. Oncol Nurs Forum. 1999;23:1033–42.

8. Error Bringing National Attention
Betsy Lehman (Boston Globe reporter)
Breast cancer patient
Ambiguous order: “4 g/m2 over four days”
Intended dose of cyclophosphamide
1 g/m2 daily for 4 days
Dose of cyclophosphamide administered
4 g/m2 daily for 4 days!
Result: fatal cardiac toxicity
Knox RA. Boston Globe. June 26, 1995. 8

9. Reasons for Increased Risk
Complex chemotherapeutic regimens
Multiple medications make up each regimen
Adriamycin plus cyclophosphamide, followed by taxol
Chemotherapeutic agents combined with supportive therapies
Antiemetics, colony-stimulating factors, etc.
Each regimen may require three to four “pre-medications” for prevention of nausea or other adverse effects
Some pre-medications may be administered by the patient at home

10. Reasons for Increased Risk
Complex dosing calculations
Dosing using body surface area (BSA)
1 g/m2 daily
Multiple-day regimens
1 g/m2 daily given on days 1,3,5
1 g/m2 daily given every 2 weeks for four cycles
Administration variability
Same drug administered IV push, intermittent IV infusion, multiple-day continuous infusion
Oral administration of IV or subcutaneous products

11. Reasons for Increased Risk
Nonstandard nomenclature
Use of abbreviations
AC = (A)driamycin and (C)yclophosphamide
CHOP =
(C)yclophosphamide
Adriamycin (H)ydroxydoxorubicin
Vincristine (O)ncovin
(P)rednisone
Nonstandard or investigational protocols
Dosing protocols may not be available in published textbooks for verification

12. Outline of Error-Prevention Measures
Educating Health Care Providers
Verifying the Dosage
Establishing Dosing Limits
Standardizing
Working With Pharmaceutical Manufacturers (Problems With Labeling)
Educating Patients
Improving Communication 12

13. Educating Health Care Providers
Intensive education specific to each provider’s core function should be mandatory
Prescribing, dispensing, preparing, administration, monitoring
Include examples of serious medication errors in competency training
If chemotherapy is allowed to be dispensed and administered on all shifts, then all providers, regardless of which shift they typically work, should be trained 13

14. Educating Health Care Providers
Recommended training schedule
Upon initial hire
Annually, as supported by The Joint Commission competency standards
When a new drug is added to the formulary
When an investigational protocol is initiated 14

15. Educating Health Care Providers
Incorporate various methods of education
Live lectures
Video simulations of compounding
Written programs
Newsletters
Witnessed simulations 15

16. Reference Materials Must be readily available where needed
Must be kept up to date
Reference materials should include:
Appropriate uses of medications
Precautions
Adverse effects
Dose-limiting and infusion-limiting effects
Solution preparation and infusion methods
Usual adult and pediatric doses
Doses for single and multiple courses of therapy 16

17. Reference Materials Institution-specific materials should include:
Investigational protocols
Process to keep references current
Outdated material must be removed
Site-specific policies and procedures for:
Prescribing
Dispensing
Administration/Disposal
Monitoring

18. Outline of Error-Prevention Measures
Educating Health Care Providers
Verifying the Dosage
Establishing Dosing Limits
Standardizing
Working With Pharmaceutical Manufacturers (Problems With Labeling)
Educating Patients
Improving Communication

19. Dosage Verification Process
Include several independent double checks
Two individuals checking the steps without bias from each other
Policy should define:
When and by whom double checks will be done
How double checks will be documented

20. Dosage Verification Process
Examples of when double checks might be performed:
After drug is ordered
Checked by second authorized prescriber
Checked by a pharmacist referring to treatment protocol and patient-specific data (e.g., current weight, serum creatinine, liver enzyme levels)
If treatment protocol is unavailable, check literature support for regimen or obtain documented support for regimen from prescriber
Calculations used for dose
Checked by two pharmacists
After medication is prepared
Final product checked by second pharmacist referring to original order and drug vials used during preparation
Just prior to administration
Label on dose checked by two nurses against original order

21. Dosage Verification Process
Focus on:
Calculations
Base on correct dose
Individual dose
Daily dose
Weekly dose
“Course” dose
“Cycle” dose
Base on correct body size measure
Body surface area
Total body weight
Ideal body weight

22. Dosage Verification Process
Focus on:
Protocol parameters
Have the correct lab values been checked?
Has the patient been properly hydrated?
Are the correct antineoplastic drugs ordered?
Have ancillary drugs been ordered?
Have drugs been ordered with the correct doses and frequencies?

23. Dosage Verification Process
Other specific issues to address
Where will the double checks be?
Who will do the double checking?
How will double checking be documented?
Which staff may administer chemo?
Which nursing units are equipped with staff and supplies necessary for administration?
Will administration be allowed only on day shift or within specified staffing ratios? 23

24. Outline of Error-Prevention Measures
Educating Health Care Providers
Verifying the Dosage
Establishing Dosing Limits
Standardizing
Working With Pharmaceutical Manufacturers (Problems With Labeling)
Educating Patients
Improving Communication

25. Establishing Dosing Limits
Define upper and lower dosing limits
Utilize published literature
Involve multidisciplinary sources
An upper limit for one regimen may not equal an upper limit for another regimen
Include these limits in computerized order entry programs or dosing software 25

26. Establishing Dosing Limits
Include dosing limits in preprinted order forms or protocols
Establish limits for infusion rate and duration
For situations in which prescribers want doses that exceed published guidelines:
Define review process to address doses that fall outside predetermined limits

27. Methotrexate and Lomustine
High risk of errors due to multiple dosing schedule possibilities
Both agents often self-administered at home
Methotrexate may be utilized orally for non-cancer indications
Typically dosed weekly
Lomustine should only be administered every 6 weeks 27

28. Methotrexate and Lomustine
Build alerts into electronic prescribing and pharmacy computer systems
Ask the indication for use
Provide clear written patient instructions in addition to label instructions
Lomustine
Include the words “SINGLE DOSE ONLY” on the label or medication administration record
Dispense quantity for only one dose
Counsel, counsel, counsel

29. Inadvertent Intrathecal Administration
Multiple reports of inadvertent intrathecal administration of vincristine
Often administered in regimens that include other drugs administered via intrathecal route
Often administered in unit-dose syringe because of small dose
Easily mistaken for an intrathecal dose

30. Inadvertent Intrathecal Administration
Prevention:
Restrict route of vincristine administration to IV only
Enlist additional warning labels and special packaging
Prepare vincristine for IV administration in a small-volume IV bag instead of a syringe
Use a forcing function in which intrathecal medication is not dispensed until empty vincristine bag returned to pharmacy
Dispense intrathecal medication just prior to use
Never deliver IV and intrathecal medications together
Establish list of drugs for intrathecal administration; ban all other drugs from lumbar puncture procedure rooms
Have at least two practitioners independently verify and document all intrathecal doses before administration
Adopt syringes for intrathecal or epidural use that are not interchangeable with syringes for IV use
Have accrediting and regulatory bodies provide oversight

31. Outline of Error-Prevention Measures
Educating Health Care Providers
Verifying the Dosage
Establishing Dosing Limits
Standardizing
Working With Pharmaceutical Manufacturers (Problems With Labeling)
Educating Patients
Improving Communication

32. Standardizing
Require orders to be written using only approved generic names
Do not allow abbreviations of drug names or protocols to be used
Doses should specify daily drug dose, followed by number of days to be administered
1 g/m2 IV daily for 4 days 32

33. Standardizing Use caution with decimal point placement
Wrong Right
.1 mg 0.1 mg
1.0 mg mg
Standardize method for calculating body surface area (BSA)
Include dose according to BSA and calculated dose in the order
1 g/m2 IV daily (1.63 g) 33

34. Standardizing Develop multidisciplinary procedures
Procedures should be site specific
Determine prescriptive authority
Attendings or oncology specialists only
Do residents have authority to prescribe chemo?
Use standardized order sheets
Decreases potential for handwriting errors
Careful attention should be paid to format of order sheets
Integrate precautions for look-alike, sound-alike therapies 34

35. Standardizing Date (D/M/Y) and time all orders
Record patient’s weight and BSA on order
No verbal orders
Use only generic names for drugs
No abbreviations for drugs or protocols
Prescribe using metric weight or units
Use decimals appropriately
Express dose in dosage unit/m2 or dosage unit/kg (i.e., mg/m2 or mg/kg)

36. Standardizing
Express daily dose times the number of days—not total course dose
Specify route and duration of infusion
Do not allow re-orders or resume orders
Perpetuates error from one cycle to another
A patient’s weight may change between cycles 36

37. Outline of Error-Prevention Measures
Educating Health Care Providers
Verifying the Dosage
Establishing Dosing Limits
Standardizing
Working With Pharmaceutical Manufacturers (Problems With Labeling)
Educating Patients
Improving Communication

38. Working With Pharmaceutical Manufacturers
Problems with labeling
– Look-alike, sound-alike (LASA) vials or packaging
– Confusing package insert wording
– Labeling ambiguity
– Confusing reconstitution instructions 38

39. Look-Alike, Sound-Alike Drug Names
Cisplatin
Cytoxan
Dactinomycin
Xeloda
Neupogen
Isotretinoin
Taxotere
Mitoxantrone
Folic acid
Carboplatin
Cytosar
Daptomycin
Xenical
Neumega
Tretinoin
Taxol
Mitomycin
Folinic acid 39

40. Look-Alike, Sound-Alike Drug Names
Prevention strategies
Use of TALL-man lettering
• Examples:
vinblastine vinBLAStine
vincristine vinCRIStine
Physically separate look-alike, sound-alike drugs when storing
Use generic names when discussing antineoplastic agents

41. Additional Information on Look-Alike and Sound-Alike Medications and Packaging Available in Slide Deck for Chapters 6 and 7

42. Confusing Package Insert Labeling
Confusing cyclophosphamide package insert
Cardiotoxicity observed with doses of 120–270 mg/kg administered over a few days
120–270 mg each day for several days?
120–270 mg in divided doses over several days?
Is 120–270 mg the recommended dose?

43. Labeling Ambiguity
Medication vials with volumes greater than 1 mL labeled with concentration only in mg/mL
Examples:
Camptosar (irinotecan) labeled 20 mg/mL (in 5 mL vial)
Entire contents of the vial (100 mg) mistaken as 20 mg
Vinorelbine labeled 10 mg/mL (in 5 mL vial)
Entire contents of the vial (50 mg) mistaken as 10 mg
Fix:
Label all vials with both:
Total amount of drug per total volume (e.g., 50 mg/5 mL)
Amount of drug per mL (e.g., 10 mg/mL)

44. Improved Labeling Name warnings Dose warnings
Label with total vial amount and
concentration per mL
Note: These improved
labeling strategies should also be used on the vial itself. 44

45. Confusing Reconstitution Instructions
Labeled concentrations: unclear if they refer to concentration before or after reconstitution
Taxotere (docetaxel) 20 mg
Packaged with two vials: concentrated drug vial + diluent vial
Concentrated drug vial labeled as “20 mg/0.5 mL”
Misread as concentration after dilution
Mylotarg (gemtuzumab ozogamicin)
Labeled as “each 20 mL vial contains 5 mg of Mylotarg”

46. Confusing Reconstitution Instructions
Medication packaged with incorrect volume of diluent
Neumega (oprelvekin)
Only 1 mL of diluent should be used but packaged with 5 mL of diluent

47. You Can Made a Difference
Be on the lookout for confusing or ambiguous labeling
Report problems
1-800-FAIL-SAFE 47

48. Outline of Error-Prevention Measures
Educating Health Care Providers
Verifying the Dosage
Establishing Dosing Limits
Standardizing
Working With Pharmaceutical Manufacturers (Problems With Labeling)
Educating Patients
Improving Communication 48

49. Educating Patients Counsel patients on chemotherapy agents
A medication error may be averted
Information for patients:
Generic and brand names of all agents
Indication
Usual and actual doses
Expected and possible adverse effects
Methods of preventing and treating adverse effects
Prescribers should discuss the therapy regimen with patients
The pharmacist then serves as a double check with the patient while counseling 49

50. Educating Patients
Include a family member or caregiver in the education process
Caregiver is a double check for the patient at home
Recommend that patients write down everything
Instructions from prescribers
Keep track of when “pre-meds” taken, supportive therapies, and chemotherapy
It is very easy to lose track of what is being taken and when
Record adverse effects and timing of these effects

51. Informed Consent to Participate in Clinical Research
Provide clear information to educate potential trial participants
Institutional review boards should review the entire informed consent process—not just the document
Provide sufficient time to decide about participation
Simplify consent form; use 3rd- to 6th-grade reading level
Include information concerning compensation of investigators
Consent process should be dynamic and ongoing
A variety of tools can be used to inform potential participants 51

52. Outline of Error-Prevention Measures
Educating Health Care Providers
Verifying the Dosage
Establishing Dosing Limits
Standardizing
Working With Pharmaceutical Manufacturers (Problems With Labeling)
Educating Patients
Improving Communication

53. Improving Communication
Listen carefully to:
Other practitioners
Patients and family members
Multidisciplinary communication improves outcomes
Evaluate any medication error made
Determine root cause
Outline future prevention strategies 53

54. Need for Pharmacist Involvement in Chemotherapy
Be involved at any site where antineoplastics are provided
Provide double checks
Participate in multidisciplinary decisions
Provide education to practitioners and patients 54

55. References
Knox RA. Response is slow to deadly mixups. Too little done to avert cancer drug errors. Boston Globe. June 26, 1995:29,33.
Northfelt DW, Allbritton DW, Parra LS, et al. Medication errors in cancer therapy: review and proposal for systematic study. Proc Am Soc Clin Oncol. 2003;22:542. Abstract 2181.
Schulmeister L. Chemotherapy medication errors: descriptions, severity, and contributing factors. Oncol Nurs Forum. 1999;23:1033–42.