|
Urgent Drug Safety Message
Medication errors with certain lipid-based
drug products
August 18, 1998
To: Directors of Nursing
Directors of Pharmacy
Risk Managers
We wish to call your attention to medication errors resulting
from confusion between certain lipid-based drug products and
their conventional counterparts. Serious medication errors,
including deaths, have occurred. Do not confuse lipid-based
products with conventional forms of the same drug!
Amphotericin B
Medication errors, including deaths, have resulted from confusion
between lipid-based forms of amphotericin (Abelcet®,
Amphotec®, Ambisome®) and conventional amphotericin
B desoxycholate (available generically and as Fungizone®).
Conventional amphotericin B desoxycholate doses should not
exceed 1.5 mg/kg/day. Doses of lipid-based products are higher
but vary from product to product. Please see TABLE I for a
comparison of the various agents.
Doxorubicin and daunorubicin Accidental administration of
the pegylated liposomal form of doxorubicin (Doxil®),
instead of the conventional form, doxorubicin hydrochloride,
has resulted in severe side effects and death. Doxil is indicated
for AIDS-related Kaposi's sarcoma. Doxorubicin hydrochloride
(Adriamycin®, Rubex®) is used in leukemias and lymphomas,
as well as breast, ovarian, and other forms of cancer. The
lipid-based formulation dosing guidelines differ significantly
from the non-lipid formulations because the plasma clearance
of the liposomal form is reduced compared to free doxorubicin.
The standard dose of the liposomal product is 20 mg/m2 given
at 21-day intervals, compared to doses of 50 to 75 mg/m2 every
21 days for conventional drug. A liposomal form of daunorubicin
(DaunoXome®, daunorubicin citrate liposomal) is also
available and has been confused with conventional daunorubicin
hydrochloride (Cerubidine®). Doses of liposomal daunorubicin
are typically 40 mg/m2 repeated every two weeks while doses
of conventional daunorubicin hydrochloride vary greatly and
may be administered more frequently. Please see TABLE II for
a comparison of the various agents.
The following measures should be considered in order to prevent
tragic errors with lipid-based formulations
- All staff involved in the medication use process must
be made aware of the differences between conventional and
lipid-based formulations of these drugs. In addition to
in-house newsletters or other communication mechanisms,
education about medication errors, including errors with
these products, should take place at the time of new employee
orientation and during continuing education programs. We
recommend that this letter be posted in prominent locations.
Staff education should also include long term care and home
care staff
- In the pharmacy, conventional and lipid-based products
should not be stored together. Consider the use of cautionary
labels or other mechanism to remind staff about the differences
between products.
- In order to preserve a redundant check system, these products
are best restricted to dispensing by a pharmacist after
required preparation and labeling is accomplished. Storage
in patient care areas and automated dispensing equipment
is discouraged.
- Encourage staff to refer to the lipid-based products by
their brand names. Get this information into the medical
staff newsletter or use other available methods to communicate
this to medical staff.
|
Table 1
Comparison of Amphotericin B products |
|
Lipid-based products: |
|
Brand Name |
Generic Name |
Usual Dose*
|
|
AbelcetÒ
(The Liposome Co.) |
amphotericin B lipid complex |
5 mg/kg daily administered as a single infusion at
a rate of 2.5 mg/kg/hr |
|
AmphotecÒ
(Sequus Pharmaceuticals) |
amphotericin B cholesteryl sulfate complex for injection |
3 to 4 mg/kg daily,
do not exceed 7.5 mg/kg daily. Infuse at rate of 1
mg/kg/hour |
|
AmBisomeÒ
(Fujisawa USA /NeXstar Pharmaceuticals) |
amphotericin B liposome for injection |
3 to 5 mg/kg daily administered over 1 to 2 hours |
|
Conventional product: |
|
FungizoneÒ (Apothecon),
AmphocinÒ (Pharmacia
and Upjohn) |
amphotericin B
desoxycholate |
1 mg test dose then 0.25 mg/kg daily increased as tolerated.
Must not exceed 1.5 mg/kg/day |
|
Table 2
COMPARISON OF DOXORUBICIN and daunorubicin
PRODUCTS |
|
Lipid-based product: |
|
Brand Name |
Generic Name |
Usual Dose*
|
|
DoxilÒ
(Sequus Pharmaceuticals) |
pegylated liposomal doxorubicin injection |
20 mg/m2 every three weeks
|
|
Conventional product: |
|
AdriamycinÒ (Pharmacia
and Upjohn), RubexÒ
(Bristol-Myers Oncology) |
doxorubicin HCl |
50 to 75 mg/m2 as single IV injection at
21 day intervals |
|
Lipid-based product: |
|
DaunoXomeÒ
(NeXstar) |
daunorubicin citrate liposomal |
40 mg/m2 every two weeks
|
|
Conventional product: |
|
CerubidineÒ
(Wyeth-Ayerst) |
daunorubicin HCl |
30 to 60 mg/m2/day for 3 to 5 days. Total
lifetime cumulative dose should not exceed 400 - 600
mg/m2 |
Important: see product labeling for complete
dose information, including required dose modifications, dose
limits, and appropriate therapeutic endpoints. Prepared by
the Institute for Safe Medication Practices, 200 Lakeside Drive, Suite 200, Horsham, PA 19044. Tel 215 947
7797. E-mail: ismpinfo@ismp.org
The Institute for Safe Medication Practices
(ISMP) is a nonprofit organization that provides independent
review of medication error reports submitted to the USP Medication
Errors Reporting Program which is operated in cooperation
with ISMP (call 1 800 23 ERROR to report medication errors
in confidence). ISMP works closely with practitioners, regulatory
agencies, healthcare institutions, professional organizations
and the pharmaceutical industry to provide education about
medication system errors and recommend preventive measures
when appropriate. ISMP is an FDA MEDWATCH partner
ISMP expresses its appreciation to The Liposome
Company for donating funds to help to defray expenses associated
with the mailing of this letter. The company did not institute
the letter nor did they have input into its content
Contact: Michael R. Cohen, RPh, MS, FASHP,
Institute for Safe Medication Practices, 215 947 7797 |
