Errors due to Bleomycin Nomenclature
To the EDITOR: The consequences of errors involving anticancer drugs
can be devastating. Seale correctly states that protocols requiring
intrathecal methotrexate and intravenous vincristine to be administered on
the same day are contributing factors to the erroneous intrathecal
injection of vincristine.1 Such errors in administration arise from
inadequate time, training and supervision of medical staff.1 However,
errors can also occur due to poorly written or structured protocols. A
patient at a comprehensive cancer centre in the US died of a drug overdose
during treatment for metastatic breast cancer.2 An ambiguous order for
cyclophosphamide 4g/m2 over 4 days was misinterpreted by several health
professionals. What should have been ordered was a daily dose of 1g/m2 for
4 consecutive days. Instead, the patient received 4g/m2 per day for 4
days. The patient died. This error was due to the ambiguous way the
protocol was written. Such ambiguity is associated with the nomenclature
for bleomycin. Protocols in the literature quote bleomycin doses in
milligrams (mg), international units (IU) or United States Pharmacopoeia
units (USP units). This inconsistency in nomenclature appears to be
universal and can lead to incorrect interpretation of medical literature.
Better protocols and standardized nomenclature are important aspects in
preventing medical errors.
Historically, bleomycin dosage has been described in terms of
milligram-potency (mg-potency), where 1mg-potency corresponded to 1 unit.
In the original preparations, 1mg-potency was also equivalent to 1mg by
weight (mg-weight), but modifications and improvements in purification
meant that ampoules labelled as containing 15mg (ie.15 units) contained
less than 15mg-weight of bleomycin.3 This alteration, coupled with the
fact that differences also exist in the term units used in the US and
those used in Europe, Britain and Australia, can lead to confusion.
In 1995, the labelling of the bleomycin products in Australia changed
from USP units to IU in line with changes in the British Pharmacopoeia
(BP) and European Pharmacopoeia (Ph Eur). The 10mg vial, formerly labelled
as containing 15 USP units, is now labelled as containing 15,000 IU. This
has resulted in considerable confusion when older protocols are used or
when referring to literature from the US. Currently, the BP and Ph Eur
specify a potency of 1,500 IU per mg, while the USP specifies a potency of
1.5-2 USP units per mg.3-5 That is, 1.5-2 USP units is equivalent to
1,500 IU, and is equivalent to 1mg (by weight, not by potency). Protocols
that state bleomycin in mg or mg/m2, refer to mg-potency, not mg-weight.
Therefore, 1.5-2 USP units is equivalent to 1,500 IU, which is
approximately 1.5mg (by potency).
Considerable problems arise when consulting protocols where the
bleomycin nomenclature is stated as mg or mg/m2. We have anecdotal
evidence of patients prescribed bleomycin 30mg as part of the BEP
(bleomycin, etoposide, cisplatin) protocol, erroneously receiving 45,000
IU. In the original BEP protocol, the total dose of bleomycin is specified
as 30 units.6 This refers to 30mg-potency (not 30mg-weight), which is
equivalent to 30 USP units or 30,000 IU.
This highlights the essential need for bleomycin dosages to be
stated in terms of units (USP units in the US, or IU in Europe, Britain,
Australia), and NOT as mg or mg/m2. The risk of misinterpretation,
incorrect conversion and potential overdose of bleomycin is dangerous.
Variations in nomenclature will lead to incorrect interpretation of
medical literature and potential overdoses of bleomycin. Standardization
of bleomycin nomenclature is an important issue for all health care
professionals and is one method of minimizing errors with cytotoxic
Angela Stefanou BPharm
Senior Pharmacist, Drug Information Service
Cancer Institute, East Melbourne, 3002, Australia
Jim Siderov BPharm Grad Dip Hosp Pharm BCOP CHP
Senior Pharmacist, Research and Cancer Services
Austin & Repatriation Medical Centre, Heidelberg, 3084, Australia.
On behalf of the Society of Hospital Pharmacists of Australia Committee of
Specialty Practice in Oncology.
Address for correspondence:
Senior Pharmacist, Drug Information Service,
Peter MacCallum Cancer Institute,
St Andrew’s Place,
East Melbourne, 3002, Australia
1. Seale JRC. Erroneous intrathecal injection results from a problem
with protocols. BMJ 2001;322:548
2. Knox RA. Response is slow to deadly mix-ups. Too little done to avert
cancer drug errors. Boston Globe 1995; Jun 26; 29,33
3. Parfitt K, editor. Martindale The Complete Drug Reference. 32nd ed.
London: Pharmaceutical Press, 1999: 507-9
4. United States Pharmacopoeial Convention, Inc. The United States
Pharmacopoeia. 24th revision. And The national formulary, 19th ed., 1999.
Rockville: USPC Inc.; 1999 and supplements
5. British Pharmacopoeia Commission. British Pharmacopoeia. London: Her
Majesty’s Stationery Office; 1993, and addenda
6. Williams SD, Birch R, Einhorn LH, Irwin L, Greco FA, Loehrer PJ.
Treatment of disseminated germ-cell tumors with cisplatin, bleomycin, and
either vinblastine or etoposide. N Engl J Med 1987;316: 1435-40
Competing interests: No competing interests