Medication errors in Oncology - a literature review

1 Introduction

The focus on medication errors started in 1999 when the Institute of Medicine (IOM) in the United States released a report entitled “To err is human”. The report stated that 44 000 to 98 000 patients die in US hospitals annually due to medical errors. Medication errors alone accounted for over 7 000 deaths annually.
Not only are medication errors costly, but they also place an unnecessary burden on cancer patients’ quality of life and on the health system.
Antineoplastic agents are the second most common cause of fatal medication errors. Over the years the complexity and dosing of cancer treatment has increased.
Pharmacists are best positioned to ensure that medications are used rationally and safely and should participate in all aspects of patient care related to antineoplastic treatment.

2 Medication errors associated with chemotherapy

2.1 Definition

Chemotherapy can be defined as all antineoplastic agents used to treat cancer, given through oral, parenteral or other routes.

Any class of drugs can be susceptible to errors, but chemotherapy presents special dangers, because:

• these drugs have a narrow therapeutic index;
• these drugs are toxic even at therapeutic dosages;
• chemotherapy regimens are highly complex; and
• cancer patients are a vulnerable population with little tolerance.

Factors associated with medication errors in oncology include the following:

• Look alike / sound alike drug names
• Handwritten prescription drug orders
• Transcription errors due to unwise use of trailing zeros, or leading decimals, which have the potential to cause a ten-fold dosage error
• Total course dose for one cycle (q 21 days) given every day
• Fatal intrathecal administration of vinca alkaloids and anthracyclines

While over-dosage is likely to result in permanent damage to the patient, under-dosage may compromise the success of therapy.

2.2 Prescribing errors

Medication errors can occur in the prescribing, dispensing or administration of a drug irrespective of whether such errors lead to adverse consequences or not.

Prescribing is an early point at which medication errors can arise. A study conducted in a teaching hospital in France looking at medication errors that occurred during chemotherapy treatment, found that 91% of errors were represented by prescribing errors, but that most of these errors were intercepted before they could cause harm.

2.3 Types of errors during prescribing

Prescribing errors that can occur in oncology which are supported in literature include:

• under-dose;
• over-dose;
• wrong drug’
• wrong dose frequency’
• drug / dose omission; and
• pre-medication / supportive care medication omitted.

2.3.1 Under-dose

Under-dosing in chemotherapy is significant because the efficacy of cancer chemotherapy is generally established on the basis of randomized controlled clinical trials evaluating a particular drug or combination using a specific dose and schedule.

2.3.2 Over-dose

Ten-fold over-doses:
Reasons for the ten-fold dose errors can be:

• the failure to round drug doses to the nearest whole integer when the decimal point is not seen;
• the unwise use of a “trailing zero” or a “leading decimal” which resulted in transcribing errors, because of handwritten prescriptions instead of computerized orders.

The following typical cases were documented in the literature:

• Doxorubicin 415mg instead of 41.5mg
• Vinorelbine 3000mg instead of 30mg
• Etoposide 1830mg instead of 183mg

Due to the nature of the toxicity of cytotoxic drugs, these errors can be fatal if not intercepted in time.

Over-doses can also occur due to the following reasons:

• the variation of doses for different diseases. For example a ‘‘normal dose” of methotrexate can range from 10 to 20 000mg and the total doses for 5-fluorouracil in the regimens for colorectal cancer can vary widely.
• confusion with look- alike /sound - alike drug names with the following examples
• • the dose of paclitaxel was used for the dose of docetaxel which is much higher; 175mg/m2 instead of 75mg/m2;
  • the dose of carboplatin was used for the dose of cisplatin.
• multiday treatments, when the total dose for a cycle is given every day, such as:
• • the total dose for five days of cyclophosphamide was given every day for five days, with fatal results.

  2.3.3 Wrong drug

  The reason for this kind of errors may also be due to similar sounding names of drugs used in oncology as described above:

  • vincristine prescribed instead of vinblastine, but at a dose appropriate for vinblastine, which can be fatal; or
  • vinblastine instead of vincristine.

  Accidental intrathecal administration of the wrong drug (vincristine, daunorubicin and doxorubicin) can also happen and is almost always fatal.

  2.3.4 Wrong dose frequency,

  Chemotherapy drugs are prescribed according to standard protocols which can include complex dose frequencies, like single or multiday treatments once weekly or every three weeks.
  Errors in this category can easily occur when:

  • prescriptions are handwritten;
  • multiday treatments are prescribed.

  Dose frequency errors can lead to significant high cumulative doses with fatal consequences.
  The following example is well supported by available literature:

  • Daily dosing of oral methotrexate instead of weekly.

  2.3.5 Chemotherapy drug / dose omitted

  The omission of a drug has the same consequences as under-dosing which is described above.
  This type of error happens due to complex chemotherapy regimens or the lack of quality checks and the lack of verification.

  2.3.6 Pre/supportive care medication omitted

  It has been demonstrated that proper premedication and supportive care medication enables cancer patients to tolerate and benefit from standard chemotherapy regimens. Without premedication patients can suffer severe side effects due to the toxicity of the drugs.
  Anti-emetics in moderate to high emetogenic regimens, anti-histamines as well as supportive care medication after chemotherapy can reduce possible toxicities and prevent organ damage.
  Standard premedication with the administration of the following drugs is well supported by literature:

  • Docetaxel
  • Paclitaxel
  • Cisplatin
  • Cyclophosphamide.

  3 The role of the pharmacist in the prevention of medication errors

  The pharmacist is expected to play a critical role in preventing medication errors. The value of a pharmacist in prescription verification is both lifesaving and cost-saving.
  To be able to identify prescribing errors prior to dispensing in a specialised setting like oncology, pharmacists need to be well-trained with specialised skills, knowledge and experience of antineoplastic drug usage, as well as insight into treatment plans, appropriate dosages and premedication, upper dose limits, possible side effects and the clinical application of treatments.

  4 Published errors and outcomes in oncology

  Some of the selected published medication errors that appeared in the press within the past decade have been summarised by Kloth. This listing confirms the devastating consequences of antineoplastic drug errors.

  Drug	Error and outcome
  Carboplatin	Overdose administered to 2 children; possible deafness in 1 child
  Carboplatin and Cisplatin	Confusion of proper dose ranges; cisplatin administered at dose intensity appropriate for carboplatin; consistently fatal outcome
  Docetaxel and conventional paclitaxel	An incorrect dose of 260mg docetaxel was administered instead of 260mg paclitaxel ; patient died 5 days later,although the error may not have caused the death
  Idarubicin	An incorrect dose of 60mg idarubicin was administered daily for 4 days instead of a single dose over 4 days; patient death
  Methotrexate	Multiple cases of accidental daily administration of oral methotrexate when weekly dosing was intended; at least 25 fatalities and an equal number of incidents of serious patient harm
  Vincristine	Accidental intrathecal administration; multiple patient deaths over many years(universally fatal when this error occurs); patient harm
  Vincristine and vinblastine	Accidentally given at dose appropriate for vinblastine; patient death

  5 Recommendations

  The American Society of Hospital Pharmacists (ASHP) emphasizes the fact that antineoplastic treatments are almost always repeated (every 3 weeks or every 2 weeks) and the effect of an error may not be apparent until long after the error occurred. Therefore, treatment plans and medication orders need to be verified during each treatment cycle to prevent errors that may be compounded during repeated cycles and go undetected throughout an entire treatment course.

  Some of the recommendations for the safe use of antineoplastic agents are:

  • • appropriate training for all staff to demonstrate competence;
    • developing standardised pre-printed medication order forms (hard copy or electronic);
    • prohibiting verbal orders in oncology;
    • implementing prescribing guidelines and using full drug names not abbreviations;
    • establishing a routine procedure for double-checking filled prescriptions.

  6 Conclusion

  It has been recognised that antineoplastic medicine are high-risk medicines and errors among this class of drugs can be fatal. This confirms the valuable role that pharmacists have in ensuring the safety and quality of chemotherapy services.
  Pharmacists are best positioned to ensure that medications are used rationally and safely and should participate in all aspects of patient care related to antineoplastic treatment.

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