POST-MARKETING
SAFETY REVIEW
Division of
Medication Errors and Technical Support Office of
Drug Safety (DMETS; HFD-420) |
||
DATE PREPARED:
8-13-2002 |
DUE DATE: 11-08-2002 |
ODS CONSULT #: 02-0048 |
TO: John Jenkins, MD
Director,
Office of New Drugs HFD-020 THROUGH: Kim Colangelo
Associate Director for Regulatory Affairs, Office of New
Drugs HFD-020 |
||
PRODUCT NAMES: See Table 1 (Page 2) |
SPONSORS: See Table 1 (Page 2) |
|
SAFETY EVALUATOR: Marci Lee, PharmD |
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BRIEF SUMMARY: The Division of Medication Errors and
Technical Support (DMETS) conducted a post-marketing review of medication
error reports submitted to the Agency through the MedWatch Adverse Event
Reporting Program and Drug Quality Reporting System (DQRS) with regard to the
labeling and packaging of various drug products packaged in low-density
polyethylene (LDPE) plastic vials. |
||
DMETS RECOMMENDATION: Due to the challenging nature of the
issues explored and described in this consultation, DMETS recommends a
collaborated effort from the Office of New Drugs, Office of New Drug
Chemistry, Office of Generic Drugs, DMETS, CBER and the pharmaceutical
industry to identify potential solutions to these problems. Most importantly, DMETS acknowledges that
practitioner/caregiver input is vital to the identification of
solutions that will not create new problems for those who administer
these medications. It may be
beneficial to discuss the issues surrounding safe use of drug products in
LDPE plastic vial containers in a public forum. |
||
_______________________________
________________________________ Carol
Holquist, RPh
Jerry Phillips, RPh Deputy Director
Associate Director Division of
Medication Errors and Technical Support Office of Drug Safety Office of Drug
Safety Center for Drug
Evaluation and Research Phone: (301) 827-3242 Fax: (301) 443-9664 Food and Drug Administration |
Table 1. NAMES OF PRODUCTS AND SPONSORS
NDA #
|
Division
|
Project Manager
|
Established Name
|
Proprietary Name
|
Dosage Strengths
|
Sponsor
|
19-773 19-269 19-243 73-533 75-358 75-050 72-652 75-063 74-543 75-343 75-394 74-880 75-664 75-129 |
HFD-570 HFD-615 |
Craig Ostroff H. Greenberg |
Albuterol |
Ventolin Proventil |
0.083%, 0.5% |
GlaxoSmithKline Schering Alpharma Bausch and Lomb Hi Tech Pharma Ivax Pharms Morton Grove Nephron Roxane |
20-949 |
HFD-570 |
Craig Ostroff |
Albuterol Sulfate |
AccuNeb |
0.021% 0.042% |
Dey |
20-950 |
HFD-570 |
Craig Ostroff |
Albuterol and
Ipratropium |
DuoNeb |
0.083%-0.017% |
Dey |
18-761 71-786 70-804 75-586 771-855 71-726 75-403 |
HFD-570 HFD-615 |
Sandy Barnes H.Greenberg |
Metaproterenol
Sulfate |
Alupent |
0.4%, 0.6% |
Boehringer
Ingelheim Dey Morton Grove Nephron Novex |
20-228 75-111 75-693 75-835 74-755 75-313 75-562 75-441 75-867 75-507 |
HFD-570 HFD-615 |
Ladan Jafari H.Greenberg |
Ipratropium Bromide |
Atrovent |
0.02% |
Boehringer
Ingelheim Alpharma Aslung Pharm Bausch and Lomb Dey Ivax Pharms Nephron Novex Roxane Warrick Pharms |
20-929 |
HFD-570 |
Colette Jackson |
Budesonide |
Pulmicort Respules |
0.25 mg/2 mL 0.5 mg/2 mL |
Astra Zeneca |
18-596 75-067 75-585 74-209 75-271 75-346 75-333 75-175 75-437 20-479 |
HFD-570 HFD-615 HFD-570 |
Colette Jackson H.Greenberg Colette Jackson |
Cromolyn Sodium |
Intal Gastrocrom |
10 mg/mL 100 mg/5 mL |
Aventis Pharms Alpharma Dey Ivax Pharms Morton Grove Novex Roxane Warrick Pharms Celltech Pharms |
87-389 86-711 88-226 87-324 86-899 |
HFD-615 |
Harvey Greenberg |
Isoetharine |
None None None Beta-2 None None |
0.1% 0.08% and 0.143% 1% 0.167% 0.2% 1% |
Dey Intl Medication Nephron Roxane Roxane Roxane |
20-837 |
HFD-570 |
Craig Ostroff |
Levalbuterol |
Xopenex |
0.021% base and
0.042% base |
Sepracor |
20-533 |
HFD-170 |
Kimberly Compton |
Ropivacaine |
Naropin |
2 mg/mL, 5 mg/mL, 7.5 mg/mL, 10 mg/mL |
AstraZeneca |
Pre-1938 |
HFD-615 |
Harvey Greenberg |
Sodium Chloride |
NONE |
|
Various |
50-753 |
HFD-520 |
Raquel Peat |
Tobramycin |
Tobi |
300 mg/5 mL |
Chiron |
06-488 |
HFD-170 |
Kimberly Compton |
Lidocaine HCl
Injection USP |
Xylocaine |
1%, 1.5 %, 2% |
AstraZeneca |
Pre-1938 |
HFD-560 |
David Hilfiker |
Racepinephrine |
Racepinephrine |
2.25% (0.5 mL unit of use
vial) |
Nephron (over-the-counter) |
17-651 |
HFD-180 |
Diane Moore |
Heparin |
NONE |
10 units/mL |
APP |
CBER |
HFM-570 |
NA |
Dornase alfa |
Pulmozyme |
1 mg/mL in 2.5 mL |
Genentech |
POST- MARKETING SAFETY REVIEW
Division of Medication Errors and
Technical Support
Office of Drug Safety
HFD-420; Parklawn Rm. 6-34
Center for Drug Evaluation and
Research
Date of Review: August 13, 2002
NAMES OF
DRUGS: See Table 1
NDA/ANDA HOLDER: See Table 1
I.
EXECUTIVE
SUMMARY
The Division of Medication Errors and Technical Support (DMETS) identified safety concerns involving several drug products, packaged in low-density polyethylene (LDPE) plastic vials following receipt of 87 cases of medication errors through the FDA Adverse Event Reporting System (AERS), as well as the Drug Quality Reporting System (DQRS). In some cases, the patient received the wrong medication or the wrong strength of the medication. The outcomes of these errors ranged from “no patient harm” to “difficulty breathing”. Since many of these medications are used to treat pulmonary conditions, there is potential for an error to result in life threatening respiratory complications. See Table 1 on page 2 for a complete list of the drug products identified in the medication error reports submitted to the AERS and DQRS reporting programs.
After careful analysis of the reports received, DMETS identified nomenclature, packaging or labeling issues that may be contributing to medication errors involving these products. This post-marketing safety consultation summarizes the error-prone characteristics of the various drug products that are packaged in LDPE plastic vials. In addition to medication error reports, DMETS also considered information provided by Nephron Pharmaceuticals, a letter from Senator Harkin, a Draft guidance for Industry document from FDA, a letter from the USP Safe Medication Use Expert Committee, and the medication safety literature.
Due to the challenging and complex nature of the issues explored and described in the review, DMETS recommends a collaborative effort from the Office of New Drugs, Office of New Drug Chemistry, Office of Generic Drugs, DMETS, CBER and the pharmaceutical industry to identify potential solutions to these problems. Most importantly, DMETS acknowledges that practitioner and caregiver input is vital to the identification of solutions that will not create new problems for those who administer these medications. It may be beneficial to discuss the issues surrounding safe use of drug products in LDPE plastic vial containers in a public forum. DMETS recommends that members of the groups listed above meet to identify ways to ensure that the outer (secondary) labeling and the primary container label are readable for all products packaged in LDPE vials.
II.
BACKGROUND
The Division of Medication Errors and Technical Support (DMETS) conducts monthly post-marketing meetings consisting of a panel of safety evaluators who review medication error reports submitted to MedWatch, the FDA Safety Information and Adverse Event Reporting Program. After review of these reports, DMETS conducted a search for additional reports in the Adverse Event Reporting System (AERS) database, as well as the Drug Quality Reporting System (DQRS) database. After careful analysis of the reports, DMETS identified safety concerns related to the labeling and packaging of various drug products in LDPE plastic vials. In addition to the analysis of the medication error reports, DMETS also considered information provided by Nephron Pharmaceuticals, a letter from Senator Harkin, a Draft guidance for Industry document from FDA, a letter from the USP Safe Medication Use Expert Committee, and the medication safety literature as outlined below.
A.
Information from Nephron Pharmaceuticals
Between
February 28, 2002 and October 2, 2002, Nephron Pharmaceuticals submitted data
to the United States Pharmacopeia (USP) in response to safety concerns with the
LDPE plastic vial containers. The
submissions were sent in response to several customer complaints about the
readability of the medication container label information. The products specifically addressed in the
submissions were IPRATROPIUM BROMIDE Inhalation Solution 0.02% and ALBUTEROL
SULFATE Inhalation Solution. In
response to the customer complaints, Nephron decided to manufacture individual
foil pouches for each plastic vial. In
March 2002, Nephron indicated that the individually packaged ALBUTEROL SULFATE
Inhalation Solution 0.083% (NDC 00487-9501-01) and IPRATROPIUM BROMIDE
Inhalation Solution 0.02%
(NDC
00487-9901-01) vials would be available later this year. Nephron states that the ALBUTEROL SULFATE
Inhalation Solution 0.5% was recently approved in an individually foil pouched
unit-of-use (0.5 mL) container. (See Figure 1)
Nephron also states that they have expanded this concept to provide
individually pouched vials for all of Nephron’s sterile unit- dose or
unit-of-use products.
Figure 1. Individual pouches proposed by Nephron
B. Congressional Inquiry
On
May 22, 2002, Dr. Lester Crawford received a letter from Senator Tom
Harkin. This letter was in regard to a
concern over the FDA policy on medication labeling. Specifically, the products of concern were IPRATROPIUM BROMIDE
0.02% and ALBUTEROL SULFATE 0.083%.
Both products are packaged by Automatic Liquid Packaging for Alpharma
Inc. One of the Senator’s constituents
wrote a letter to him with several questions to determine why the “different
colored labels” are no longer used on the plastic vials. In addition, the letter describes the
“raised letters” as “hard to read”. The
author also notes that customers in an older age segment will likely have
difficulty reading the plastic vials that have the raised letters instead of
the colored labels. Finally, there is a
request to “reconsider putting easily readable labels on these liquid packaging
medicines again.”
The
materials from Senator Harkin also include a letter from Alpharma Inc. This letter describes the reasons for the
design of this package. The letter
includes statements regarding the need for sterile products, foil wrappers to
protect the drug product from light and prevent medication errors, an embossed
product name, lot number and expiration date to make this information “always
present and legible”. “The raised
letters that are part of the vial can never become smeared or defaced through
normal handling or wetting.” In
addition, Alpharma states that these letters serve as a textured surface to
assist in gripping the vial when opening by twisting off the top.
C. Draft guidance document
On
July 26, 2002, a Federal Register
notice announced the availability of a draft guidance for industry entitled,
“Inhalation Drug Products Packaged in Semipermeable Container Closure
Systems.” http://www.fda.gov/cder/guidance/4168dft.pdf This draft guidance provides recommendations
on: (1) Appropriate protective secondary packaging, (2) embossing and/or
debossing of the primary container in lieu of paper labels, and (3) general
guidance on the number of unit-dose containers to be contained within each
protective secondary package. The
guidance identifies potential sources of chemical contamination for inhalation
drug products in LDPE plastic vials. The
FDA recommendation for labeling is to directly emboss the information on the
plastic vial to prevent contamination by components found in paper labels
(e.g., adhesives, varnish, ink). A
secondary package is also recommended to protect the drug product from
environmental contaminants. The
guidance states that the ideal approach for the secondary package is to
individually wrap each container.
D.
USP Safe Medication Use Expert Committee (SMU EC)
On October 28, 2002, Yana Ruth Mille,
Chief, FDA Compendial Operations Staff, received a letter from the USP Safe
Medication Use Expert Committee (SMU EC).
This letter was in regard to a continuing concern of the Committee and
also healthcare practitioners regarding the inability to identify drug products
in plastic ampuls that is secondary to inadequate labeling. The letter describes practitioner reports
submitted to the USP Medication Errors Reporting Program that identify embossed
imprinting as being difficult to read and sometimes illegible. The author states that the SMU EC
unanimously voted to encourage FDA to establish an alternate method of labeling
these plastic ampuls, so that these products are clearly identifiable. Since the use of plastic ampuls with difficult-to-read
or illegible labeling continues to be the subject of numerous medication
errors. The SMU EC recommends that the
FDA cease approving these products in these containers, until a suitable
resolution is identified.
E.
Product Information for drug products that are packaged in
LDPE vials (See Table 2.)
Table
2. PRODUCT INFORMATION TABLE
Product
Name |
Established
name Dosage
form (ORAL,
INHALATION OR INJECTION) Dosage
strengths |
Usual
dose |
Ventolin Proventil |
Albuterol
Sulfate Inhalation
Solution 0.083%, 0.5% |
ADULT: 2.5 mg 3 to 4 times daily by nebulization PEDS 2 to 12
years: 2.5 mg 3 to 4 times daily by
nebulization. Children less than 15
kg who require less than 2.5 mg/dose should use the 0.5% inhalation solution.
Deliver over 5 to 15 minutes. |
AccuNeb |
Albuterol
Sulfate Inhalation
Solution 0.021%,
0.042% |
PEDS 2 to 12
years: 1.25 mg or 0.63 mg
administered 3 or 4 times daily as needed by nebulization. Deliver over 5 to 15 minutes. |
DuoNeb |
Albuterol
Sulfate and Ipratropium Bromide Inhalation
Solution 0.083% -
0.017% |
One 3 mL
vial administered four times daily via nebulization with up to two additional
3 mL doses allowed per day. |
Alupent |
Metaproterenol
Sulfate Inhalation
Solution 0.4%, 0.6% |
Administer
the unit-dose vial by oral inhalation using an intermittent positive pressure
breathing (IPPB) device. ADULTS: 0.2 mL to 0.3 mL (or 5 to 15 inhalations
via a hand bulb nebulizer) PEDS 6 to 12
years: 0.1 mL to 0.2 mL |
Atrovent |
Ipratropium
Bromide Inhalation
Solution 0.02% |
500 mcg (1
unit dose vial) administered 3 to 4 times daily by oral nebulization, with
doses 6 to 8 hours apart. |
Pulmicort
Respules |
Budesonide Inhalation
Suspension 0.25 mg/2 mL 0.5 mg /2 mL |
PEDS 12
months to 8 years: 0.5 mg once or
twice daily OR 1 mg once daily. |
Intal ***************** Gastrocrom |
Cromolyn
Sodium Inhalation
Solution 10 mg/mL ************************************* Oral
Concentrate 5 mL/100 mg |
ADULTS AND
PEDS over 2 years: 20 mg inhaled 4
times daily at regular intervals.
Hand operated nebulizers are not suitable. [Gastrocrom
Dosing]************************************** ADULTS: 200 mg by mouth 4 times daily; Do NOT mix
with milk, juice or food. PEDS 0 to 2
years: 20 mg/kg/day PO divided QID PEDS 2 to 12
years: 100 mg PO QID; MAX DOSE is 40
mg/kg/day; PEDS over 12
years: 200 mg PO QID; Do NOT mix
with milk, juice of food. |
None |
Isoetharine Inhalation
Solution 0.1%, 0.08%,
0.143%, 1%, 0.167%, 0.2% |
Hand
bulb: 4 inhalations Oxygen
aerosolization: 0.5 mL IPPB: 0.5 mL |
Xopenex |
Levalbuterol
Inhalation
Solution 0.021%,
0.042% |
PEDS 6 to 11
years: 0.31 mg administered 3 times
daily by nebulization; do not exceed 0.63 mg 3 times daily. ADULTS and PEDS 12 years or older: 0.63 mg administered 3 times daily by
nebulization; Once foil
pouch is opened, use the vials within 2 weeks; Once the vial is removed from
the foil pouch and is not used immediately, protect from light and use within
one week. Discard if solution is not
colorless. |
Xylocaine |
Lidocaine
Hydrochloride Injection 1%, 1.5%, 2% |
Dose depends
on the indication for use. The
maximum recommended dose per 90 minute period of lidocaine for paracervical
block in obstetrical and nonobstetrical patients is 200 mg total. One half of the dose is usually
administered to each side. Inject
slowly 5 minutes between sides. |
Naropin |
Ropivacaine Solution
for Injection 2 mg/mL, 5
mg/mL, 7.5 mg/mL and 10 mg/mL |
Dose depends
on the indication for use. For
surgical anesthesia, the dose ranges from 5 mg – 300 mg. For labor pain management, the dose ranges
from 20 mg – 40 mg initially followed by 12-30 mg/h (continuous infusion or
incremental injections). For
postoperative pain management, the dose ranges from 12 – 28 mg/h as a continuous infusion. |
Tobi |
Tobramycin Inhalation
Solution 300 mg/5 mL |
ADULTS and
PEDS 6 years and older: 300 mg twice
daily in repeating cycles of 28 days ON and 28 days OFF. Doses should be 12 hours apart. Administer over 10 – 15 minutes |
Pulmozyme |
Dornase alfa Inhalation
Solution 1 mg/mL in
2.5 mL |
One 2.5 mg
single-use ampule inhaled once daily using a recommended nebulizer. Some patients benefit from twice daily
administration. Pulmozyme should not
be mixed with other drugs in the nebulizer.
|
None |
Heparin Solution
for Injection 10 units/mL
in 5 mL |
IV flush to
maintain patency of indwelling IV catheter in intermittent IV therapy or
blood sampling; not intended for therapeutic use. |
III.
ROOT CAUSE
ANALYSIS
This safety review focuses on the
medication error reports submitted to FDA with regard to drug products packaged
in LDPE plastic vials. DMETS will
identify ways in which the manufacturers can minimize the risk potential and
decrease the medication errors associated with these products.
Several issues have already been raised
by the draft guidance, the letter from Senator Harkin and his constituent, the
USP Safe Medication Use Expert Committee and the Nephron Pharmaceuticals
Corporation. Some of these issues
include the need for sterile drug containers, the risk for contamination of the
drug product and the need for protective secondary packaging. In addition, some users of these products
identified the readability of the embossed label on the LDPE plastic vial
container as difficult and problematic.
A.
Adverse Event Reporting System
DMETS searched
the FDA Adverse Event Reporting System (AERS) database for all post-marketing
safety reports of medication errors reported for “tobi”, “albuterol”, “naropin”, “pulmicort”, “duoneb”,
“ipratropium”, “xopenex”, “gastrocrom” “xylocaine”, “heparin” “pulmozyme”
“cromolyn”, “atrovent”, “intal”, “levalbuterol” using the Meddra Preferred
Term, MEDICATION ERROR. This search strategy retrieved 60 pertinent cases of
medication error. The error cases are
summarized in Appendix A.
Of the 60
medication errors reported on these drug products, a total of 13 (22%) actual errors were identified. The actual
errors included those in which the wrong medication or wrong dosage strength
was administered to the patient (46%) and
those that were detected prior to medication administration to the patient
(54%). A total of 47 (78%) potential medication errors were
reported citing concerns for difficult-to-read label information and look-alike
packaging for the drug products packaged in plastic vials.
B.
DQRS
In addition,
the Drug Quality Reporting System (DQRS) database was searched for similar
reports with “albuterol”, "alupent ", "atrovent", “duoneb ", "ipratropium ", "proventil ", "pulmicort", "sodium chloride
", "ventolin", and
“xopenex”. A total of twenty-seven
pertinent medication error reports were retrieved with this search and are
summarized in Appendix B.
Of the 27
medication error reports, all but one were potential
medication error reports citing concerns regarding the labeling and packaging
of the drug products.
C.
Safety Evaluator Risk Assessment
DMETS has identified several additional
concerns for inhalation and injectable solutions packaged in LDPE vials. These concerns are based upon careful
analysis of the medication error reports summarized in APPENDIX A (AERS
Reports) and APPENDIX B (DQRS Reports).
1. Difficult-to-Read
Labels and Look-alike Packaging among Inhalation Solution Products
Although the use of embossed label
information addresses the concern for drug product contamination by the
volatile components of the paper label, it also creates an opportunity for
medication errors. The fact that these vials are difficult to read is likely a
contributing factor in almost every medication error reported to FDA. This is a concern that has been voiced by
numerous practitioners, patients and caregivers.
See the excerpts below that describe
the readability of the embossed label information from some of the medication
error reports:
“…raised lettering in clear
plastic…very difficult to see clearly the name of the drug, the product
ingredients, the lot numbers, and the expiration date. While the foil pouch is clearly marked, we
have noted the practice of opening the pouch, taking the vials out and then
discarding the pouch. The result is
loose vials that are not clearly marked.”
“The raised lettering on the clear
plastic container…makes it difficult to read the name of the product and the
ingredients.”
“..both in clear containers with raised
lettering making it difficult to read the name of the drug.”
“…they have to be angled just right in
the light to read it.”
“Label on individual
vials is almost impossible to read in most light. This is an embossed label…”
“…the product identification can be
very difficult due to the low visual contrast between the label and container.”
“None of the information on the vial is
legible, imprinted clear on clear.”
The letter from the USP SMU EC states,
“This imprinting is perceived by healthcare practitioners reporting to the USP
Medication Errors Reporting Program as being difficult to read and sometimes
illegible.”
Photo submitted with ISR # 3895532-9
2. Difficult-to-Read Labels and Look-alike
Packaging for Oral and Injectable Products and Potential for Confusion with
Nebulizer Medications
A. In addition to
the multitude of inhalation solutions, there is an oral drug product that is
packaged in LDPE plastic vials.
Gastrocrom was identified as having packaging similar to Xopenex. In one medication error report of ACTUAL
confusion, an error occurred when someone was returning unused medications from
the patient care area to the pharmacy stock.
B. A new concern
identified is the potential for confusion between the inhalation drug product
with several injectable solutions now available in plastic ampules. Multiple medication error reports warned of
potential for confusion with injectable medications packaged in similar plastic
vial containers. The main concerns
expressed were the readability of the labels on the PolyAmp DuoFit containers
and the potential for confusion with inhalation solution products. Although the label information is not
embossed on the Naropin containers, it appears as black type on a clear label
affixed to the plastic ampul.
Additionally, the POLYAMP DUOFIT plastic ampules are made of polypropylene.
See the excerpts below from a
medication error reports that describe safety concerns for the PolyAmp
packaging:
“Astra Zeneca is ceasing to manufacture
their glass vials of Naropin
(Ropivacaine) and some Xylocaine
(mainly the MPF). They have created a
POLYAMP, a plastic ampule to which a syringe can be directly luer locked...In
addition, the smaller amps could possibly be mistaken for nebulizer meds
that come in similar containers (they look like the ‘pillows’).” [See page 10
for product photos.]
“We have noted an issue with the new
polyamp packaging by AstraZeneca for Xylocaine-MPF 2% and Naropin 10
mg/mL. Both containers are identical in
size, shape, clear color, and black writing once removed from their overwrap
packaging. Our LDRP noticed the
potential medication error on their epidural cart when the medications were
removed from their original packaging so that they would fit in the cart.”
Figure 2. Naropin and Xylocaine POLYAMP DUOFIT
C. In addition to Naropin and Xylocaine, there
is also a Heparin 10 units/mL (5 mL)
product available from American Pharmaceutical Partners, Inc. (APP), which is
packaged in a plastic vial container. See Figure 3.
See the excerpt below from a medication
error report that describes a safety concern for a heparin product packaged in
a plastic ampule:
“Are you aware that APP is marketing a heparin 10 units/mL (5 mL) plastic
container? One of their reps showing it
to me last week. I showed him all of
the respiratory medications and the poor labeling. He was also surprised. The clincher is that their heparin product
is almost identical to the tobramycin for inhalation product, Tobi.”
Figure 3.
Heparin 10 units/mL (5 mL)
3.
Routine Handling of the Inhalation Solutions
Another issue to consider is the
routine handling of the LDPE vials containing inhalation solutions. While Nephron addresses this issue in their
materials by stating, “We note that in prior complaints the end user bypassed
this important packaging step by allowing respiratory therapists to routinely
carry loose vials in their lab coats.
Under such conditions, the manufacturer is not responsible for product
contamination or misuse if the product was not retained in its intended
package.”
DMETS sees this as an opportunity for
the industry to respond to the needs of the users of their products. Perhaps a foil pouch containing 30 vials is
not the packaging configuration that best meets the needs of the practitioners
and caregivers that administer these medications. Nephron has also proposed the individual foil pouch for
individual vials of their medications.
The best way to determine if this is a viable solution to the problem is
to involve the practitioners and
caregivers and incorporate their input into the problem-solving
process. Additionally, the medication
error reports demonstrate that the labels on the foil pouches containing 30
vials are not enough to prevent errors.
As this is the current package configuration for most products and
errors are still occurring.
DMETS acknowledges that while the
proposal for an individually foil wrap plastic ampule is likely a step in the
right direction to improve the safe use of these drug products, this proposal
does not address the problem of what happens when the plastic ampules are
removed from the foil. Even if the
plastic ampules are individually foil-wrapped, there is still going to be the
problem of unused, loosely stored plastic ampules that are difficult to read
and error-prone.
See the excerpts below from some of the
medication error reports that describe safety concerns with the vials that are
no longer in the foil pouch:
“While the foil pouch is clearly
marked, we have noted the practice of opening the pouch, taking the vials out
and then discarding the pouch. The
result is loose vials that are not clearly marked.”
“The fact that the vials are packaged
in clearly marked foil packages does not compensate for the poorly marked vials
because the usual practice is take the vials from the packaging and throw away
the foil wrapper.”
“There is also a problem with the
product being light sensitive. It comes
in a foil pouch and then any product not used after two weeks is to be
discarded. Why is the product not in an
opaque container to begin with to eliminate the light sensitivity? The warning to discard discolored is not on
the individual container, and even if it were it couldn’t be read. The reporter considers this product to be
poorly designed, poorly labeled, and dangerous.”
“It is easy to administer one
strength for another when both strengths are kept in a respiratory therapists
pocket.”
“Our respiratory therapists often carry
individual unit dose containers in their pockets without the outside
packaging.”
4. Expiration Date Issue
Another aspect of the problem with
difficult to read container labels is that the expiration date is difficult to
see. This places a burden on
practitioners, who are trying to identify expired medications in their
inventory.
See the excerpt below from medication
error reports that describe the safety concerns with the readability of the
label information, especially the expiration date:
“The plastic vials are impressed on
one end with the lot number and expiration date on opposite sides. Due to the vial composition of clear
plastic, it is difficult to distinguish what the expiration date and lot number
are.”
“The result is difficulty in
confirming the name of the drug, the strength of the ingredients, and the
expiration dating.”
“…very difficult to see clearly the
name of the drug, the product ingredients, the lot numbers, and the expiration
date.“
DMETS
recommends that manufacturers consider alternative packaging configurations for
the drug products that are currently available in LDPE plastic vials. One recommendation might be to consider
something similar to the Timoptic OCUDOSE design below. (See Figure 4.) These container labels are similar to the paper labels used by
some manufacturers. They are easier to see than the embossed labels and can use
color to facilitate product differentiation.
Figure 4. Timoptic
OCUDOSE
DMETS acknowledges that there are
several factors that may contribute to the medication errors we see with the
drug products packaged in LDPE plastic vial containers. Some of these factors include practitioners
with poor eyesight, poor lighting conditions in the settings where these
medications are administered, storage issues, and so on. However, there is room for improvement in
the packaging of these products that would minimize the potential for error. By modifying the current practices of
packaging and labeling the LDPE vials, the industry will relieve the
practitioners and care-givers of the burden of relying only on their vigilance
to prevent medication errors with these drug products.
Although we have identified many
contributing factors to the errors described in the medication error reports
sent to FDA, many of the errors go undetected and unreported. This is especially true for the inhalation
solutions because it is common to administer more than one of these products to
a single patient. For example, if a
patient is to receive ipratropium and albuterol via nebulization, an error by
which the patient receives albuterol two times in error and no ipratropium
could go undetected because of the mechanism of action of these drugs. Even in this error scenario, the patient’s
breathing would improve and the treatment would be considered a success.
Several options for possible solutions
to the problems facing our health care community have been proposed by
different sources, such as the individual foil wrappers for each vial proposed
by Nephron. DMETS believes we should
consider changing the container material to something that is not permeable or
use the texture and shape of the plastic vials to differentiate them. Another
proposal submitted with a medication error report by a practitioner was to
assign a universal color plastic for each inhalation solution to ensure that
the vials do not look alike. Due to the
complexity of this issue, these and other potential solutions to this problem
need to be evaluated by OND, ONDC, OGD, CBER and the industry, while taking
into consideration the input from the practitioners and caregivers that use
these products.
IV.
RECOMMENDATIONS
A. The
recommendations should come from a collaborative effort of the Office of New
Drugs, Office of New Drug Chemistry, Office of Generic Drugs, DMETS, CBER and
the pharmaceutical industry.
B. Practitioner
and caregiver input is vital to the identification of solutions that will not
create new problems for those who administer these medications.
C. It may be
beneficial to discuss the issues surrounding safe use of drug products in LDPE
plastic vial containers in a public forum.
D. Ensure that
the outer (secondary) labeling and the primary container label are readable
for all products packaged in LDPE vials.
DMETS would appreciate feedback of the
final outcome of this consult (e.g., copy of revised labels/labeling). We are willing to meet with the Division for
further discussion as well. If you have any questions concerning this review,
please contact Sammie Beam at 301-827-3242.
_________________________________
Marci Lee,
PharmD
Safety
Evaluator
Division of
Medication Errors and Technical Support (DMETS)
Concur:
__________________________________________
Denise Toyer, PharmD Date
Team Leader
Division of Medication Errors and Technical Support
Office of Drug Safety
cc: ANDA See Table 1
HFD-615: Division Files/Harvey Greenberg,
Project Manager
HFD-611: Peter Rickman, Division Director
cc: NDA See Table 1
HFD-170: Division Files/Kimberly Compton,
Project Manager
HFD-570: Division Files/Craig Ostroff,
Project Manager
HFD-570: Division Files/Parinda Jani,
Project Manager
HFD-570: Division Files/Colette Jackson,
Project Manager
HFD-570: Division Files/Ladan Jafari,
Project Manager
HFD-570; Sandy Barnes, Chief Project
Manager
HFM-224: Ann Gaines, Safety Evaluator
HFD-170: Bob Rappaport, Acting Division Director
HFD-570: Badrul Chowdry, Division Director
HFD-570: Guirag Poochikian
HFM-570: Karen Weiss, Division Director,
DCTDA, CBER
HFD-330: Kathy Miracco, Office of
Compliance
HFD-006: Anne Henig, OEP, CDER
HFD-420: Denise Toyer, Team Leader, DMETS
HFD-420: Sammie Beam, Project Manager,
DMETS
HFD-420: Marci Lee, Safety Evaluator,
DMETS
HFD-420: Carol Holquist, Deputy Director,
DMETS
L:\ODS02\LEE\POSTMARKETING
CONSULTS\INHALATION SOLNS\DRAFTS\02-0048 LDPE PLASTIC VIAL CONTAINERS FIN.doc
APPENDIX
A
Post-Marketing
Reports involving low density polyethylene (LDPE) ampuls from the AERS database
ISR
NUMBER EVENT
DATE LOCATION ACTUAL
OR POTENTIAL OUTCOME |
Summary |
3855426 FEB
2002 Unknown
location Potential
error |
As you know,
several of the respiratory medications available have similar, if not
duplicative packaging. With the
addition of DuoNeb to this group,
we have yet another item to add to the category. I understand that the FDA has a lot to do with this by
disallowing inks directly on the packaging and other stability requirements. We currently do not add any ancillary
labeling – more steps in the process just adds more opportunities for
error. Fortunately for us, most of
these respiratory drugs (dispensed from Pharmacy) are given by the
therapists, who can be alerted with relative ease. |
3815572-5 SEPT
28, 2001 Potential
error |
The packaging
for the inhalation product, DuoNeb, is difficult to read and there exists the
risk of error in using the drug. DuoNeb consists of
3 mL inhalant solution (ipratropium and albuterol) packaged in a clear
plastic vial, with several vials in a foil pouch. The pouch is clearly labeled DuoNeb with the ingredients, lot
numbers, dating and other information.
The problem occurs when the clear vials are removed from the
packaging. The vials are clear
plastic, containing clear solution. In addition,
the labeling on the foil package shows the albuterol sulfate content to be
3.0 mg. The small print makes the
strength appear to be 30 mg. The
practice of adding trailing zeroes to the strength of drugs is commonly
implicated in medication errors. We
feel that this type of packaging and labeling may lead to medication errors
if the wrong vial is picked up. |
3786947-8 Report
date AUG
23, 2001 Unknown
location Potential
error |
The raised
lettering on the clear plastic container of DuoNeb makes it difficult to read the name of the product and the
ingredients. If you do not look
closely, you might not notice that DuoNeb contains Ipratropium Bromide and
Albuterol Sulfate. |
3794775-2 Report
date SEPT
7, 2001 Potential
error |
Potential
for error regarding the respiratory care unit dose medications Albuterol and Cromolyn (manufactured for Alpharma),
Pulmicort Respules (Astra), and Pulmozyme (Genentech). These products are packaged in clear
plastic single-use ampules whose labeling (on each ampule) is terrible. The letters are raised on the plastic
container, but not in a different color.
The letters are the same material as the plastic container. I have had many respiratory care
therapists complain of this, concerned that a wrong dose or wrong medication
will be administered to the patient.
What were they thinking? |
3786946-6 Report
date AUG
29, 2001 Unknown
location Potential
error |
The
packaging of Ipratropium Bromide
0.02% 0.5 mg/2.5 mL (Alpharma) and Albuterol 0.083% 2.5 mg/3 mL (Alpharma) is
similar. Also, both are in clear
containers with raised lettering making it difficult to read the name of the
drug. Suggestion: Attach a label to the container or add
some color. The pharmacy is
considering purchasing a different product at an additional cost because of
packaging concern. |
3869036-3 Report
date FEB
12, 2002 Potential
error |
The
packaging of some nebulizer solutions are very difficult to read. Xopenex
and generic Albuterol (Alpharma)
are in clear plastic ampules. The
companies label the products by using raised lettering in the plastic. Besides the fact that one product looks
like another, they have to be angled just right in the light to read it. |
3469147 Report
date MAR
5, 2000 Potential
error |
Similar
packaging of Roxane’s ipratropium
premix unit dose amps and Alpharma’s albuterol
premix unit dose amps |
3613218-2 and 3565542-X and DQRS
M-129611 Report
date SEPT
7, 2000 Actual
error Patient
survived |
My mom has
emphysema and has had severe difficulty breathing for 3-4 days. She hasn’t been able to sleep or eat as
her breathing was so difficult. I had
been in constant contact with her doctor and my mother had said she needed to
go to the hospital that her Nebulizer wasn’t even helping. The problem turned out to be a severe
mix-up with her nebulizer medications.
Medicare has supplied Albuterol and ipratropium solution by mail to my
mother for over a year. Recently
Medicare has changed the drug supplier from Dey to Zenith Goldline and has
changed the packaging of the vials.
What she has always used was a clearly marked vial of ipratropium with green and purple
label and a clear vial of Albuterol. With the new packaging – the
ipratropium also comes in a clear
vial. What has been happening is she
has been getting the clearly marked old ipratropium and another clear vial
but this vial was also ipratropium.
If I hadn’t caught this mistake I doubt my mother would be alive!!!!!
This is a very SERIOUS PROBLEM!! We are talking about elderly people and also
caregivers mixing these two meds and they should be advised of this change.
Also, the clear vials are VERY difficult to read!! These two meds come premixed
but we didn’t know that until I called the company that provides the
meds. Please help before someone dies
from this change in packaging. Please
help to see that these clear vials are better marked so they are easily
identified. Thank you. |
3778267-2 Report
date AUG
14, 2001 Potential
error |
The product
is DuoNeb, an inhalation solution
of ipratropium and albuterol sulfate.
The inhalation solution is packaged in “Sterile Unit Dose Vials” that
are plastic. The problem is that the
vials are clear plastic, the solution is clear, and the printing on the vials
is not printing, but raised lettering in clear plastic. The clear plastic makes the lettering
difficult to read. The result is
difficulty in confirming the name of the drug, the strength of the
ingredients, and the expiration dating.
The fact that the vials are packaged in clearly marked foil packages
does not compensate for the poorly marked vials because the usual practice is
take the vials from the packaging and throw away the foil wrapper. |
3771756-6 Report
date AUG
1, 2001 Potential
error |
I would like
to report that the labeling of Xopenex
(levalbuterol) inhalation solution unit dose vials made by Sepracor Inc,
Marlborough, MA 01752 USA provide an opportunity for medication errors due to
their appearance. Both strengths 1.25
mg in 3 mL and 0.63 mg in 3 mL are manufactured in the same color and size
container. Additionally, the
medication and dose information is very difficult to read since it is
embossed on a clear plastic. This is
provided for your review. Please consider requiring a labeling change.
Thanks. |
3456491-6 Report
date JAN
27, 2000 Potential
error |
A
respiratory therapist brought this concern to the attention of the
pharmacy. The inhalation solutions, Ipratropium Bromide 0.02% (Roxane), Cromolyn Sodium 20mg/2 mL (Arcola
Labs), and Xopenex 0.63 mg/3 mL
(Sepracor) unit-dose vials look almost identical to each other and the labels
on the vials are difficult to read. |
3569194-4 JUN
29, 2000 Unknown
location Actual
error Patient
survived. |
Healthcare
provider entered prescription for Intal
nebulization solution. It was filled
with Atrovent nebulization
solution and dispensed to the patient.
Filling pharmacist realized error later in day and called patient at
home. Prescription returned for
correction. Patient was 5 years old. |
3836346-5 Report
date NOV
28, 2001 Unknown
location Potential
error |
Three
different medications are supplied in very similar unit dose vials. This greatly increases the chance of
delivering the wrong medication to the patient, which could adversely effect
clinical course. They look almost
identical. Cromolyn, Ipratropium,
and Levalbuterol. (Alpharma,
Roxane, and Sepracor) |
3838040-3 Report
date DEC
10, 2001 Potential
error |
Alpharma Ipratropium Bromide inhalation
solution 0.02% unit dose vial is identical in shape and size to Sepracor Xopenex (levalbuterol HCl) inhalation
solution 1.25 mg/3 mL and 0.63 mg/3 mL.
There is no color difference and no paper label on the unit dose vials
potentially leading to drug administration errors. |
3825538-7 JAN
29, 2001 Unknown
location Actual
error Patient
survived |
Doctor
called in a prescription to the pharmacy and the intern tried to take it over
the phone, but did not understand the doctor. I took over and received the prescription. The intern was confused. The prescription was typed into the
computer as ipratropium instead of Intal (cromolyn), then the prescription
was filled, but was not properly checked before dispensing to the patient’s
parent. Both the ipratropium 0.02% (Alpharma) and cromolyn 20 mg/2 mL (Alpharma) nebulizer solution boxes looked
similar. Thus, it is
hypothesized that the medication was picked before the prescription was typed
in and it could have been typed based on the wrong medication selected. Patient was 2 years old. The doctor discovered the error after
calling the parent’s to follow up the day after the office visit. |
3825509-0 Report
date OCT
31, 2001 Potential
error |
The reporter
may have not had an incident but they see a potential for errors with the
product Xopenex (levalbuterol HCl)
by Sepracor. They produce two
strengths of the medication in unit dose packages. The unit packs look the same, the difference in dose is stamped
on the vial, but it is the same color as the rest of the package. You have to look very hard in good light
to note the difference. |
3786966-1 Report
date AUG
24, 2001 Potential
error |
This
potential error was reported to me by the respiratory staff. We recently switched companies that supply
respiratory product due to a contract change. The ipratropium
bromide inhalation solution 0.02% 2.5 mL unit dose vials distributed by
Alpharma (00472-0751-23) look identical to Xopenex inhalation solution unit dose vials (63402-0513-34). Both
vials are opaque with raised lettered no color writing. They are very hard to read even when there
was not a similar product. The
respiratory staff is afraid that they will accidentally be substituted. |
3803901-8 and 3692545-7 Report
date MAR
30, 2001 Potential
error |
Xopenex 1.25 mg/3
mL and 0.63 mg/3 mL. Difficult to
read imprint on unit dose packages – possibility of giving incorrect
dosage. Suggest color coding or
change labeling in both individual unit dose vials. |
3805475-4 Report
date SEPT
27, 2001 Potential
error |
I would like
to report another two look alike respiratory drugs to the ISMP. Ipratropium
Br 0.02% 2.5 mL inh soln and Levalbuterol HCl (Xopenex) 1.25 mg/3 mL inh soln.
Both drugs are packaged in similar clear, plastic containers. |
3728008-X Report
date MAY
22, 2001 Potential
error |
Xopenex is packed
in clear plastic tubes. The strength
is on one end but difficult to read.
It is easy to administer one strength for another when both strengths
are kept in a respiratory therapists pocket. |
3698827-7 MAR
12, 2001 Actual
error Did
not reach patient |
Prior to
administration of a dose of Xopenex,
a physician noticed that the respiratory therapist had mistakenly opened the
wrong strength of medication. By
inspecting the unit dose package, the physician prevented the error. The error almost occurred because the two
product strengths are virtually identical in appearance, the only significant
difference being “0.63” embossed on one vial and “1.25” embossed on the
other. Both packages are already
difficult to read, being clear plastic with raised lettering. The potential exists to give 50% or 200%
of the prescribed dose. Suggestion
to prevent similar errors: The
medication require different packaging and/or labeling. Printing the name and strength of the
medication in color would be most useful.
A consideration to prevent potential errors in the future is to remove
the medication from the hospital formulary, since safe and effective
alternatives exist. |
3689503-5 Report
date MAR
13, 2001 Potential
error |
The
respiratory therapist at our hospital sees a potential error caused by
packaging of the drug Xopenex
(lebalbuterol, Sepracor) in the 1.25 mg and 0.63 mg unit dose vial. While outer wrappers (box and inner foil
wrapper) of two strengths of the drug differ in appearance, the vials
themselves are distinguishable only upon very careful examination of the
labels. |
3683478 Report
date MAR
5, 2001 Potential
error |
The product
is packaged in a clear plastic container.
There is no label on the container; the product information is
imprinted on the plastic, which is difficult to read. Fortunately
this has not been either a potential or actual occurrence. However, I receive a number of phone
messages from respiratory therapists and pulmonologists on staff regarding
the labeling of the Xopenex
(levalbuterol) jets. Any efforts you
can utilize to encourage the manufacturer to change its labeling habits would
be most appreciated. |
3603388-4 MAY
11, 2000 Unknown
location Actual
error Patient
did not use. |
Patient
received 1.25 mg/3 mL instead of 0.63 mg/3 mL Xopenex. The error was
detected by the patient’s mother, who returned the medication before
administering a dose to her child. This product
is very new to market. There is an
error that when the labeling process, the NDC come out on label without name
of product. The pharmacist who fills
this RX did (not) know this medicine come out in two strengths, that she
didn’t check the NDC number is why the error occurs. |
3641106-4 Report
date JAN
3, 2001 Potential
error |
Possible
confusion with (Xopenex)
levalbuterol 1.25 mg/3 mL and 0.63 mg/ 3 mL once they are removed from
outside packaging. The vials
(plastic) are difficult to read and are the same size. Recommend vials of different colors. |
3613219-4 and
DQRS
M-128797 Report
date MAR
21, 2000 Potential
error |
Xopenex 0.63 mg/3
mL. All 3 package in same container
with no differing marks. Potential
error. Ingredients embossed on
container, but look very similar and difficult to read. |
3416728-6 Report
date DEC
8, 1999 Potential
error |
Packaging
for Xopenex is identical for 0.63
mg and 1.25 mg. The reporter is concerned
that the look alike packaging for the different strengths could lead to a
medication error. Both strengths are
in same size containers. The plastic
covering the product is embossed and difficult to read. |
3668821 Report
date FEB
14, 2001 Actual error No patient
harm |
Poor
labeling on ipratropium bromide inhalation solution 0.02% unit dose vials 2.5
mL almost caused a med error in our ER.
Once the outer foil packaging is removed it is very difficult to read
the clear, raised letter on each unit. The manufacturer is Roxane.
We will try to order another brand that has each unit more clearly
marked. |
3459383-1 JAN
28, 2000 Potential
error |
Packaging of
Ipratropium Bromide inhalation
solutions 0.02% (Roxane) does not have label affixed to it but is marked by
raised lettering on plastic. As a
result, it is difficult to read and may be mistaken for other inhalation
solutions. Other manufacturers of
inhalation solutions have colored labels that differentiate between different
solutions so as to prevent such errors. |
3869207-6 Report
date JAN
28, 2002 Potential
error |
We are
concerned about the new packaging for the unit dose inhalation
solutions. The specific brand we are
now stocking is Nephron Pharmaceuticals Corporation. The albuterol 0.083% solution and the ipratropium 0.02% solution both come in clear, unit dose
vials. The vials are the same shape,
with the ipratropium a little taller.
The ipratropium has an embossed “I” on the top and the albuterol an
embossed “A”. |
3837302-3 Report
date NOV
27, 2001 Potential
error |
Respiratory
therapist brought to our attention that the plastic ampules for Novaplus’ ipratropium and Alpharma’s albuterol look identical and have
extremely difficult to read labeling – leading to a large error potential. |
3782023-9 Report
date AUG
13, 2001 Potential
error |
The
packaging and labeling for Ipratropium
bromide (Alpharma) and albuterol
sulfate (Zenith Goldline) inhalation solutions are practically identical and hard to read. The drug names and dosing information are
extremely hard to read due to their almost transparent font. There is a high potential for confusion
among these two products. |
3667775 Report
date FEB
6, 2001 Potential
error |
It was
brought to my attention by the respiratory department at some hospitals that
the following inhalation products are packaged similarly and could contribute
to a medication error. Albuterol sulfate (Zenith), Ipratropium (Roxane). They are in ready to use vials and the
boxes are different but since most respiratory techs break open the foil
packs and carry the vials, there needs to be some distinguishing features to
the individual packaging (colored plastic in the vial or a label on the
outside of the vial similar to Dey’s albuterol inhalation solution.) |
3863171-1 Report
date JAN
22, 2002 Potential
error |
Xopenex Solution
Inhalation 0.63 mg/3 mL (Sepracor)- Label unreadable – Absolutely hard to
read ingredients. Cannot distinguish
which is which. Serious patient safety risk.
Resp Therapist complaining to us. |
3863170 Report
date JAN
22, 2002 Potential
error |
Ipratropium Bromide
Inhalation Solution 0.02% (2.5 mL) (Nephron)- Label unreadable – Absolutely
hard to read ingredients. Cannot
distinguish which is which. Serious patient safety risk. Resp Therapist complaining to us. |
3497904-3 Report
date MAY
8, 2000 Potential
error |
Ipratropium Bromide
0.02% (Roxane) 2.5 mL inhalation solution and Xopenex (levalbuterol HCl) 0.63 mg/3 mL inhalation solution. Both drugs
are in a clear plastic twist-off top unit-dose design with raised letters
very difficult to read. Respiratory
uses both drug and have already come close to a mixup. Both drugs
need an adhesive label on the unit of use containers to prevent mixup. |
3468841-5 Report
date FEB
22, 2000 Unknown
location Potential
error |
Pharmacist
called to report possible mixup between Atrovent
(Boehringer Ingelheim) and Xopenex
(Sepracor) clear plastic ampules. |
3456502-8 Report
date Feb
10, 2000 Potential
error |
I am a
registered respiratory therapist at a large hospital in New Jersey. We recently began using Xopenex (levalbuterol) in addition to
our regular regime of Albuterol
and ipratropium bromide
(Atrovent). The potential problem
lies with the packaging of Xopenex, which is almost identical to
Atrovent.*******Both are packaged in unit dose vials that are clear with
printing stamped on them, making them particularly difficult to
differentiate. Until we started using
Xopenex this was not a problem.
However, it will be very easy to mix them up and give patients the
wrong medication.***********The company representative from Sepracor
acknowledged this problem and stated that it is very difficult to change the
packaging because it was already approved by the FDA. Thank you for addressing this issue promptly
before any serious medication errors occur. |
3316590-6 Report
date JUL
11, 1999 Potential
error |
Xopenex
(levalbuterol) 0.63 mg/3 mL and Ipratropium
Bromide 0.5 mg/2.5
mL (Roxane). Look-alike products with hard-to-read labels. |
3668823-4 Report
date FEB
14, 2001 Potential
error |
Xopenex (levalbuterol)
0.63 mg 3 mL and Ipratropium
Bromide 0.02% 2.5 mL (Roxane). A reporter wrote to suggest that labeling
of respiratory inhalation treatment vials be considered as an issue by ISMP. Specifically, labeling of respiratory
medication pre-mix vials by imprinting the labeling info during the molding
process for the vial. Many people
find this very difficult to read, including myself. Many inhalation solutions come in pre-mixed vials which are
labeled only by the imprinting of product information on the exterior of the
vial. The attached photo file
demonstrates the anonymity of these vials.
The addition of a paper label or a color identifier would greatly aid
in the discrimination of one vial from another. On the left is levalbuterol, on the right is ipratropium. See Appendix C photo 1 for image |
3698831-9 Report
date MAR
29, 2001 Potential
error |
Xopenex
(levalbuterol) 0.63 mg/3 mL and Ipratropium
Bromide 0.02% (Roxane). Xopenex SVN
package is very hard to read clear plastic with raised lettering for the drug
name and strength. This product comes
in two strengths. Identical packaging
to Roxane product: Ipratropium SVN (Clear plastic with raised lettering). What a set up for a med error! |
3710666-7 Report
date APR
17, 2001 Potential
error |
The packaging
for Dornase Alfa (Pulmozyme) 2.5
mg/2.5 mL container by Genentech NDC 50242-0100-39 is very similar to Xopenex and Ipratropium (Roxane). All
are in clear plastic ampuls for nebulization. It is difficult to read the writing on the ampuls because it is
the same color as the plastic ampul. Recommendations: Could the manufacturer add colored ink or
a label to the products? We have made
the following changes in order to prevent an error from occurring. 1 Two info-grams sent to all pharmacy
location via the order entry computer pharmacy staff of the similar
appearance of these products (Xopenex, Ipratropium and Pulmozyme). 2 The hospital has ordered a new brand of
Ipratropium (DEY) 3 Central pharmacy
will dispense all Xopenex in a zip lock bag with a label indicating that it
contains levalbuterol. |
3710664-3 APR
9, 2001 Actual
error No
patient harm |
Xopenex
(levalbuterol) 1.25 mg/3 mL and Ipratropium
Bromide 0.5 mg/2.5
mL (Roxane). Xopenex was administered
to a patient by the respiratory therapist instead of Ipratropium. No harm reported. Containers are very similar. Both are clear plastic amps for
nebulization. It is difficult to read the writing on the amps because it is
the same color as the plastic amp. |
3762579-2 Report
date JUN
13, 2001 Potential
error |
Xopenex
(levalbuterol) 0.63 mg/3 mL, 1.25 mg/3 mL, and Ipratropium Bromide 0.5 mg/2.5 mL (Roxane). Levalbuterol (Xopenex) med nebs look
almost exactly like the ipratropium med nebs from Roxane. There is a serious potential for error
here! |
3779866-4 Report
date AUG
3, 2001 Potential
error |
Alpharma’s Albuterol Sulfate and Ipratropium, and Sepracor’s Xopenex
are packaged in identical plastic vials with raised letters. Only the product name is different. The Alpharma products have an “A” or “I”
on the appropriate tab on the vials but it is only on one side of the
tab. Add some sort of coloring to the
vials or use an actual label on the vials instead of the raised lettering. |
3484929-7 MAR
20, 2000 Unknown
location Actual
error Did
not reach patient |
Gastrocrom (cromolyn) 5 mL (Medeva) and Xopenex (levalbuterol) 3 mL
(Sepracor) have similar packaging and can easily be mixed up. There was an
error after someone was putting away “returned” medications. However the error was discovered before
the patient received the incorrect drug. |
3935798 APR
19, 2002 Potential
error |
Our
respiratory staff asked us to initiate a medication alert for some inhalation
products. The unit dose packaging for
the two strengths of Pulmicort
Respules (0.25 mg/2 mL and 0.5 mg /2 mL) unit dose packaging are very
similar. All are made of clear
plastic and have raised lettering.
None have any coloration for easy identification. Our respiratory therapists often carry
individual unit dose containers in their pockets without the outside
packaging. |
3631747-2 NOV
4, 2000 Unknown
location Actual
error Did
not reach patient |
Pulmicort respules
0.25 mg/2 mL and 0.5 mg/2 mL are very similar in packaging size and were
mixed up in pharmacy storage bins.
The incorrect strength was placed in a patient’s medication
drawer. Respiratory therapist caught
the mistake and the error did not reach the patient. Suggestions: If the company can’t mark the plastic
respule with a color or identifying mark, then the different strengths should
be separated when shipped in, placed in well-marked bins and have some sort
of identifying sticker placed on them when dispensed. Care should be taken when crediting and
returning the respule to storage bins. |
3650346 JAN
1, 2001 Actual
error Unknown
outcome |
Pulmicort
(Budesonide) 0.5 mg respules dispensed and administered instead of the 0.25
mg respules because of poor labeling; strength is a clear imprint on clear
plastic and is very small, making it very difficult to read. |
3698700-4 MAR
30, 2001 Potential
error |
Pulmicort Respules
are manufactured in two strengths.
Because the two product strengths are virtually identical in
appearance, the only significant difference being “0.25” embossed on one vial
and “0.5” embossed on the other. Both
packages are already difficult to read, being clear plastic with small raised
lettering. The potential exists to
give 50% or 200% of the prescribed dose.
Suggestions: The
medications require different packaging and/or labeling. Printing the name and strength of the medication
in color would be most useful. A
consideration to prevent potential errors in the future is to remove the
medication form the hospital formulary. |
3745136-3 JAN
17, 2001 Unknown
location Actual
error Patient
experience CNS and GI adverse effects |
A
three-year-old boy received Pulmicort
0.25 mg twice daily. After two
months, he received Pulmicort 0.5 mg twice a day for a period of three weeks,
in error. |
3824265 OCT
12, 2001 Actual
error Did
not reach patient |
Regular
pharmacy staffing chose wrong medication.
The prescription needed to be filled with Pulmicort 0.5 mg nebulizer solution (120 mL). In error, Pulmicort 0.25 mg (60 mL) was
prepared. The pharmacist detected the
error while counseling the patient. |
3978167-9 AUG
15, 2002 Unknown
location Potential
error |
Differentiation
between Pulmicort Respules 0.25
mg/2 mL and 0.5 mg/2 mL
is difficult to identify (hard to read strength imprinted on top). Dosing indicated on each individual ampule
is only on top piece with no color contrast. |
1944216 Report
date APR
4, 1997 Actual
error Patient
had trouble breathing |
NDA Field Alert report from DEY for Ipratropium Bromide Inhalation
Solution, 0.02%. An elderly patient
who mis-dosed herself due to a confusion with the packaging of the product.
******The patient reported she mistakenly treated herself with two doses of
Ipratropium Bromide Inhalation solution, 0.02%, instead of her prescribed
dosage of one unit-dose vial of ipratropium bromide combined in a nebulizer
with one unit-dose vial of Albuterol
Sulfate Inhalation Solution 0.083%, also manufactured by Dey
Laboratories. As a result of these
treatments, she did not receive the needed relief from the products, she had
trouble breathing, and she could not walk.
The patient reported that the graphics of the labeling are similar and
the shelf cartons are similar in size and color as well. |
3487461 APR
5, 2000 Unknown
location Potential/?Actual Unknown
if patient received wrong medication in error |
Respiratory
therapist (RT) was requesting missing dose of Tobi. When he came to get it he was unaware that Tobi and Pulmozyme
looked so similar. When he went back
to the unit, he found 3 amps (2 labeled and 1 unlabeled) There had been no
extra requests for Tobi so it is questionable if the patient got the
medication. Medications are too
similar in appearance. |
3973282-8 AUG
7, 2002 Unknown
location Potential
error |
Are you
aware that APP is marketing a heparin
10 units/mL (5 mL) plastic container?
One of their reps showing it to me last week. I showed him all of the respiratory meds
and the poor labeling. He was also surprised. The clincher is that their heparin product is almost identical
to the tobramycin for inhalation product, Tobi. |
3720124-1 Report
date APR
30, 2001 Potential
error |
Astra Zeneca
is ceasing to manufacture their glass vials of Naropin (ropivacaine) and some Xylocaines (mainly the MPF).
They have created a polyamp, a plastic ampule to which a syringe can
be directly luer locked.
Unfortunately, the amps look almost exactly alike, plastic with black
writing. Practitioner who have become
accustomed to the color coding of the different strengths of the lidocaines
will now have to read very carefully to make sure they not only have the
right drug but also the right strength.
In addition, the smaller amps could possibly be mistaken for nebulizer
meds that come in similar containers (i.e. they look like the “pillows”).
I have contacted Astra Zeneca and asked them to consider packaging
modifications that would be more helpful in distinguishing the two
products. I also asked them to
consider larger print for the warning “Not for inhalation” printed on the
amp. My requests are being forwarded
to their product quality division. |
3586159-7 Report
date AUG
8, 2000 Potential
error |
Label on
Astra Zeneca’s PolyAmp DuoFit package (for Naropin and Xylocaine)
is almost impossible to see. This may
also be prelude to similar injectable labeling by other manufacturers. FDA should immediately examine this
situation to prevent additional drug packaging that is similar. This will cause serious errors. |
3254863-6 Report
date APR
14, 1999 Potential
error |
The PolyAmp
DuoFit packaging of Naropin
(ropivacaine HCl) and Xylocaine
MPF (lidocaine HCl injection USP) is very similar to that of Ipratropium bromide inhalation
solution and could potentially be confused.
Suggestions: Change the
package, label well, distribute notices of potential for error. |
3951163-3 Report
date MAY
6, 2002 Potential
error |
We
have noted an issue with the new polyamp packaging by AstraZeneca for
Xylocaine-MPF 2% and Naropin 10 mg/mL.
Both containers are identical in size, shape, clear color, and black
writing once removed from their overwrap packaging. Our LDRP noticed the potential medication error on their
epidural cart when the medications were removed from their original packaging
so that they would fit in the cart. |
APPENDIX B
Albuterol inhalation |
M 133173 |
The packaging of
some nebulizer solution are very difficult to read. Xopenex and generic albuterol (Alpharma) are in clear
plastic ampules. The companies label
the product by using raised lettering in the plastic. Beside the fact that one product looks
like another, they have to be angled just right in the light to read it. |
|
||
|
M 128924 |
The packaging on
the above mentioned medications almost identical. The problem is compounded by the fact that the labeling is
embossed making it extremely difficult to read. If there was a way to color code the containers or if the
labels were printed so they could be easily read, it would correct the
problem. |
|
||
Alupent inhalation solution |
D 100206 |
The plastic vials
are impressed on one end with the lot number and expiration date on opposite
sides. Due to the vial composition of
clear plastic, it is difficult to distinguish what the expiration date and
lot number are. |
|
||
|
U 017643 |
The expiration date
is embossed on one side of a plastic tab that extends from the vials and the
lot number is embossed on the other side, making both illegible. The reporter feels that the manufacturer
should extend the tab so that the lot and expiration date are one above the
other on the same side of the tab |
|
||
Atrovent Inhalation solution |
D 115046 |
Embossed label is
difficult to read. Recommend affixing
label with darker lettering. |
|
||
|
116620 |
Label on individual
vials is almost impossible to read in most light. This is an embossed label on opaque plastic with clear liquid
inside. A paper label attached to the
vials would be much easier to read. |
|
||
|
M 116222 |
The reporter states
the product information is printed on a clear plastic container and it is
very difficult to read. Also, this
product looks very similar to another product (Ventolin nebules) with the exception of the “V” shaped twist
top. |
|
||
|
U 022262 |
Clear ampule for
inhalation labeled in clear raised lettering. Concerned may cause administration errors. Should be labeled in black or possibly
colored lettering. Very, very
difficult to read. |
|
||
Duoneb inhalation solution |
M 131971 |
The product is DuoNeb, an inhalation solution of ipratropium bromide and albuterol sulfate. The inhalation solution is packaged in
“Sterile unit dose vials” that are plastic.
The problem is that the vials are clear, the solution is clear, and
the printing on the vials is not printing, but raised lettering in clear
plastic. The clear plastic makes the
lettering difficult to read. The
result is difficulty in confirming the name of the drug, the strength of the
ingredients, and the expiration dating.
The fact that the vials are packaged in clearly marked foil packages
does not compensate for the poorly marked vials because the usual practice is
to take the vials from the packaging and throw away the foil wrapper. |
|||
Ipratropium bromide inhalation solution |
U 132897 |
Absolutely hard to
read ingredients. Cannot distinguish
which is which. Serious Patient
Safety Risk. Respiratory therapist
complaining to us. |
|||
Ipratropium bromide inhalation solution |
M 128923 |
The packaging on
the above mentioned medications almost identical. The problem is compounded by the fact that the labeling is
embossed making it extremely difficult to read. If there was a way to color code the containers or if the
labels were printed so they could be easily read, it would correct the
problem. |
|
U 023801 |
The labeling is
imprinted into the clear plastic container making it very difficult to
read. The reporter suggests that a
painted label be applied. |
Proventil Solution for inhalation |
U 008130 |
Label is very
difficult to read. It looks like 25
mg/3 mL rather than 2.5 mg/3 mL |
Pulmicort Respules Inhalation
suspension |
M130437 |
Budesonide 0.5 mg
respules dispensed and administered instead of 0.25 mg respules because of
poor labeling; strength is a clear imprint on clear plastic and is very
small, making it difficult to read. |
Roxanol UD Oral solution |
D 109832 |
Container too
similar in design to saline containers by Wyeth and Alupent containers made by Boehringer Ingelheim. Expiration date on container impossible to
read easily. Reporter’s nurses are
having to draw up solutions in syringes over concern of accuracy of actual
volume in container. |
Sodium Chloride |
D 111575 |
Individual unit
dose NaCl containers contain unreadable end crimp expiration due to color of
plastic. |
Ventolin Inhalation Solution |
U 016233 |
The problem
occurred on 1-7-1993. The product
“label” consists of imprint of text into plastic unit-dose container. It is extremely difficult to read. |
|
018240 |
The respiratory
therapy department has complained about “how hard it is to squeeze the
dropper” (their complaint is how well the elderly could use the dropper while
at home). Additional information per
call to reporter 11-30-1993.
Therapists have also complained that because the label goes completely
around the container, it is difficult to tell how much solution is in the
container. |
Ventolin Nebules Solution Inhalation |
M 112337 |
The product
information is printed on a clear plastic container and it is very difficult
to read. Potential error with other
medications with similar packaging. |
|
U 017687 |
The problem
occurred on 8-3-1993. Poor labeling
of the product. Name of the product
is hard to read as it consists of only raised lettering on the plastic
vials. Very easy to mix up with
Normal Saline for respiratory use.
Interestingly, Roxane Laboratories also manufacturers the normal saline
the reporter uses and this product is labeled in such a way that the product
is easily identifiable. The product
brochure for the Ventolin solution
shows a clearly labeled vial.
However, the product does not possess the clear labeling as in the
brochure. See file for the photocopy
of the product’s label. |
|
019041 |
The problem
occurred in 3-1994. Current nebules
are prepackaged in opaque plastic.
The label consists of raised lettering in the same material. Therefore, the product identification can
be very difficult due to low visual contrast between the label and container. |
Xopenex Solution Inhalation |
M 128921 |
Label on Xopenex (levalbuterol) unit dose is
impossible to read – raised plastic lettering. Need clearer identification. |
Xopenex Solution Inhalation |
131036 |
1.25 mg/ 3 mL and
0.63 mg/3 mL – difficult to read imprint on unit dose packages. Possibility of giving incorrect dosage;
suggest color coding or change labeling in both individual unit dose vials. |
|
132242 |
1.25 mg/ 3 mL and
0.63 mg/3 mL - difficult to read imprint on unit dose packages. Possibility of giving incorrect dosage;
suggest color coding or change labeling in both individual unit dose vials. |
|
133174 |
The packaging of
some nebulizer solutions are very difficult to read. Xopenex
and generic Albuterol (Alpharma) are in clear plastic ampules. The companies label the product by using
raised lettering in the plastic.
Beside the fact that one product looks like another, they have to be
angled just right in the light to read it. |
|
U 026514 |
The problem was
observed on all dates. The product is
manufactured in clear plastic vials with the imprint into the plastic
vials. None of the information on the
vial is legible, imprinted clear on clear.
The very real possibility exists that the wrong medication or dose can
be given because none of the information is able to read. Why would the FDA allow anyone to label a
product in this manner? There is also
a problem with the product being light sensitive. It comes in a foil pouch and then any product not used after
two weeks is to be discarded. Why is
the product not in an opaque container to begin with to eliminate the light
sensitivity? The warning to discard
discolored is not on the individual container, and even if it were it
couldn’t be read. The reporter
considers this product to be poorly designed, poorly labeled, and dangerous. |
|
132898 |
Absolutely hard to
read ingredients. Cannot distinguish
which is which. Serious patient
safety risk. Respiratory therapist
complaining to us. |
APPENDIX C - Images of Products
DEY Sterile Water for Inhalation
USP Embossed label |
|
DEY Sodium Chloride Inhalation
Solution USP Embossed label |
|
DEY Paper label |
|
DEY Paper label |
|
Roxane Ipratropium Bromide Embossed label |
|
Roxane Sodium Chloride Paper label |
|
Roxane Cromolyn Sodium Embossed label |
|
Roxane Albuterol Sulfate Embossed label |
|
AstraZeneca Pulmicort Respules Embossed label |
|
DEY DuoNeb Embossed label |
|
Genentech Pulmozyme Embossed label |
|
Sepracor Xopenex Embossed label |
|
Boehringer Ingelheim Alupent Paper label |
|
|
|
|
|
|
|
|
REFERENCES
1
ISMP Medication Safety
Alert! Atrocious labeling of
plastic ampuls needs action now by FDA and manufacturers. Volume 7 Issue 10 May 15, 2002.
2 ISMP Medication Safety Alert! Safety Brief: Xopenex and Ipratropium have look-alike packaging. Volume 5 Issue 7 April 5, 2000.
3 Some product images in Appendix C are from the electronic Physicians Desk Reference (PDR) © 2002 Thomson MICROMEDEX
http://www.thomsonhc.com/pdrel/librarian/PFParentUsageId/1077303
4
Some product images in Appendix C are from ISMP. www.ismp.org