Lowdown on lomustine: Wed hate
CeeNU make this mistake
From the July 15, 2004 issue
Problem: Last month we learned about three errors
with lomustine (CeeNU) that sounded hauntingly similar to
methotrexate errors we reported in our April 3, 2002 newsletter.
When used to treat rheumatoid arthritis and other non-oncologic
conditions, a single dose of oral methotrexate should be taken
just once or twice a week. A single dose of oral lomustine
(130 mg/m2), used to treat brain cancer and Hodgkins
disease, should only be taken once every 6 weeks. Similar
to methotrexate, lomustine has been repeatedly dispensed and
administered daily, often with tragic results.
Two of the lomustine errors are recent. In one case, a cancer
patients usual dose of lomustine 140 mg was due the
day after she had been admitted to the hospital for a laparoscopic
procedure. Her oncologist ordered a single dose of the drug,
but the hospital pharmacist mistakenly entered it as a daily
dose, which appeared on the nurses computer-generated
medication administration record. Five days after receiving
the drug daily, routine lab tests detected severe thrombocytopenia,
azotemia, and neutropenia. By then, the patient was febrile
with severe bruising and hematuria. The oncologist discovered
the error, and after a prolonged hospitalization, the patient
Another recent error happened in a community pharmacy, where
a patient presented with a prescription for a single 160 mg
dose of lomustine. The pharmacist decided to offer the patient
a full package containing 20 capsules (40 mg each), since
the drug was costly and he would likely have to discard the
remaining capsules. While the directions on the package correctly
stated to take just four capsules, the patient misunderstood
the instructions and took four capsules daily for 5 days.
The error was discovered when the patient attempted to refill
the prescription. The pharmacist contacted the oncologist,
and the patient was admitted to the hospital where he apparently
recovered, although the full effects of toxicity are still
Several years ago, a 24-year-old woman with brain cancer
died as a result of a lomustine overdose. A physician had
written a poorly legible prescription for lomustine 190 mg
every 6 weeks. The pharmacist misunderstood the directions
as daily for 6 weeks and dispensed a 6-week supply
of capsules with directions to take 190 mg daily. The patients
physician had not explained how to take the medication, so
the patient complied with the label directions and took 190
mg daily for 21 days. She was hospitalized with severe bone
marrow suppression and acute bleeding, and died a month later.
Safe Practice Recommendation: Bristol-Myers Squibb
has enhanced the labeling and the packaging of CeeNU. Single
Dose Only is now printed in red on the label, and Dispense
Single Dose Only is embossed on the cap of stock bottles.
However, its clear in the more recent cases that these
warnings were overlooked. A boxed warning in the package insert
also states that the drug should not be administered more
frequently than every 6 weeks; however, the warning could
be overlooked as it is embedded within information about the
potential risk for bone marrow depression. Thus, there are
several other safeguards that should be considered with this
Provide alerts. Program warning messages such as single
dose only into order entry systems. Also configure the
system to limit the quantity prescribed or dispensed to 300
mg or less for each prescription or order.
Use unit-of-use Dose Packs. Prepare patient prescriptions
or doses using unit-of-use Dose Packs available from the manufacturer.
Each 300 mg Dose Pack contains two 100 mg capsules, two 40
mg capsules, and two 10 mg capsules, with instructions for
the pharmacist to select the correct patient dose (within
10 mg), place the capsules in a single vial, and affix the
special patient label provided.
Enhance labels. When possible, present dosing frequency
directions on patient labels and nursing medication administration
records using bold font or all capital letters (e.g., CAUTION:
SINGLE DOSE ONLY). Use large print to assist elderly patients
with poor eyesight.
Provide patient counseling. Establish a system to
ensure that patients receive counseling when picking up new
prescriptions and refills (e.g., mark the bag with a red flag
to alert clerical staff that counseling is required, not optional).
Require the pharmacist to review the prescription label with
the patient or caregiver, and to request verbal confirmation
to ensure that the patient understands the dosing schedule.
Supply leaflets. Ensure that written drug information
leaflets are given to patients and that they contain clear
advice about the single dose only dosing schedule.
Require education. Provide pharmacists, technicians,
and nurses who handle oral (and parenteral) chemotherapy with
initial and ongoing education. Allow only certified oncology
nurses to administer chemotherapy (oral and parenteral).