ISMP Acute Care May 9, 2014 - Sullivan University Library

Educating the
healthcare community about
safe medication practices
2014 Institute for
Safe Medication Practices
©
Ò
ISMP
MedicationSafetyAlert!
May 8, 2014
Acute Care
Volume 19 Issue 9
SafetyBriefs
™
Drug hypersensitivity reactions
Allergic reactions second most frequently reported serious event
Decimal commas a problem.
GRANIX (tbo-filgrastim) was approved in
QuarterWatch™ is an ISMP surveilwas second in frequency, only trailing nonlance program that monitors serious,
specific gastrointestinal symptoms. We
2012 by the US Food and Drug Administration
disabling, and fatal adverse drug events
classified 4,045 of these cases as severe,
(FDA). It has become available recently for use as
(ADEs) reported to the US Food and Drug
involving a medical emergency/disability
a leukocyte growth factor. A hospital pharmacist
Administration (FDA) by
(3,079) or death (966). A diverse group of
reported that he noticed something
manufacturers, healthcare
234 drugs were implicated, although only
unusual while evaluating samples of
professionals, and the public.
87 drugs were linked to the most severe
the product as a possible formulary
The latest Quarterhypersensitivity cases. This means that,
replacement for NEUPOGEN
Watch™ examines serin most medical settings, health profes(filgrastim), a similar leukocyte
ious hypersensitivity reactsionals must be alert to the dangers of
growth factor. Both the outer carton
ions reported to the FDA
hypersensitivity reactions with a
and the peel-away prefilled syringe
using data from April 2012 to
diverse group of drugs.
wrappers refer to the syringe volume
March 2013 (most recent
using
Extent of warnings. To determine whether
data available as of last week).
the
The full report also surveys
drugs with 10 or more reported cases of
familiar
newly released case reports for
hypersensitivity had warnings in official
decimal
the first Quarter of 2013, and provides an
prescribing information, we surveyed a
point (e.g., 300 mcg
update on safety issues with anticoagurandom sample of 20 of the 87 suspect
per 0.5 mL). However,
lants. The goal of QuarterWatch™ is to
drugs. The prescribing information for all
increments on the barimprove patient safety through the identifi20 drugs included accurate information
rel of the syringe use
cation of signals that may represent imporabout hypersensitivity, and 14 of 20 (70%)
commas (e.g., 0,5 mL)
tant drug safety issues. The term signal
of the warnings were prominent—3 boxed
to separate the integers
means evidence judged to be substantial
warnings and 11 in the Warnings section.
(Figure 1). This is the
Figure 1. Note comma way decimals are
enough to warrant publication but which
The remainder of the hypersensitivity
Hospital
in place of decimal on
requires
further
investigation
to
determine
descriptions appeared under Precautions or
marked
in
Europe
and
the Granix syringe scale.
its frequency of occurrence and establish a
Adverse Events.
many other countries.
causal relationship to the suspect drug.
Granix is manufactured in Lithuania and is an Israeli
Types of Hypersensitivity
product distributed by Teva Pharmaceuticals USA. On
Hypersensitivity Overview
To analyze the most frequently reported
the surface, it doesn’t seem like a comma would
Report totals. Cases of drug hypersensitivity
severe hypersensitivity reactions, cases
pose much of a problem. However, the decimal
continued on page 2 — SafetyBriefs
reported for the year ending March 2013
were divided into categories: 1) anaphywere screened from among a subset of
lactic shock, 2) severe cutaneous reactions, 3)
Help ISMP update its latest
147,318 serious ADEs reported to FDA
angioedema, and 4) other. The 10 most
high-alert drug list
from which certain reports were excluded
frequently reported suspect drugs in each
It’s been more than 2 years since we last
(e.g., foreign reports, litigation reports,
category are identified in Table 2 (page 2).
surveyed readers and updated ISMP’s List
drugs that require special reporting).
Anaphylactic shock. Anaphylactic shock
of High-Alert Medications. Please take a
Hypersensitivity was a common ADE,
few minutes to complete our short survey by
accounting for 13,042 cases (8.9%) in the
accounted for 1,196 (30%) of the severe
June 20, 2014, at: www.ismp.org/sc?id=358.
study year (Table 1). Of the 93 adverse
hypersensitivity cases, including 133
A copy of the survey appears on pages 4 and 5.
event categories reported, hypersensitivity
cont’d on page 2 — QuarterWatch
We would like to know whether YOU believeHospital
Table 1. Overview of hypersensitivity cases in 12 months ending March 31, 2013
the medications listed in the survey belong on
Standardized Query
Cases
Drugs*
Deaths
our high-alert medication list and whether
Hypersensitivity
13,042
234
YOUR PRACTICE SITE considers them to be
Severe
4,045
87
966
high-alert medications with special precautions
Anaphylactic shock**
1,196
44
133
in place. We are also interested in your opinion
Severe cutaneous
891
20
97
regarding medications that should be added to
Angioedema
894
13
77
ISMP’s list. We appreciate your thoughts on
Other severe
1,316
16
667
this important topic!
*Regularly monitored with 10 or more cases **Drugs could fall into more than 1 category
2
May 8, 2014
Volume 19 Issue 9
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SafetyBriefs continued from page 1
comma is unfamiliar to US health professionals, and
its use has caused problems in the past, so it
shouldn’t be permitted in the US. For example, some
computer systems may not be able to calculate
properly if a comma somehow becomes the decimal
marker in a drug database. We’ve also heard of a
problem in which a period key ( . ) produced a
comma ( , ) whenever it was struck (ISMP Medication
Safety Alert! Safety Brief, April 17, 2002). Thus, an
order for a patient-controlled analgesia dose of
morphine 0.5 mg IV would print on labels and reports
as “morphine,5 mg IV” if a leading zero is omitted
(a dangerous practice by itself). An error happened
when such a label was misread as “morphine, 5 mg.”
We mention this because we imagine the same could
happen if someone types or writes a comma instead
of a decimal point after seeing it on a syringe barrel.
Also, in handwritten orders, the comma can look like
the number 1, allowing “morphine ,5 mg” to look like
“morphine 15 mg.” To prevent unforeseen issues,
we’ve asked FDA to look into this issue with Granix,
and we’ve let Teva know of our concern.
Ten-fold error with trailing
zero. A few weeks ago, a pharmacist
initially misread the maximum IV niCARdipine (CARDENE) dose on the GlobalRPh website as 150 mg per
hour when it actually listed the dose as “15.0 mg/hr.”
GlobalRPh indicated the company was simply
following the text of the official label which reads,
“Initiate therapy at 50 mL/hr (5.0 mg/hr). If desired
blood pressure reduction is not achieved at this dose,
the infusion rate may be increased by 25 mL/hr
(2.5 mg/hr) every 5 minutes (for rapid titration) to
15 minutes (for gradual titration) up to a maximum
of 150 mL/hr (15.0 mg/hr), until desired blood
pressure reduction is achieved.” GlobalRPh has now
changed the way the dose is depicted (www.global
rph.com/nicardipine_dilution.htm), without using
trailing zeros. We’ve asked the US Food and Drug
Administration (FDA) to ask the sponsor to make the
same change in the approved label, as well.
QuarterWatch continued from page 1
deaths. There were 44 drugs with 10 or
more anaphylaxis cases. The most frequently involved drugs (Table 2) included
two of the most widely used non-prescription analgesics, ibuprofen and naproxen.
The drug with the most ADE reports
associated with anaphylactic shock in
the study year, omalizumab (XOLAIR), is a biological product used to
treat children and adults with documented allergy problems causing asthma
or chronic urticaria. In 2007, FDA
required the manufacturer to include a
boxed warning and Medication Guide for
patients citing the risk of anaphylaxis after
124 cases were documented between 2003
and 2006. The reactions occurred any time
during treatment, even after a year of taking
the medication. We identified 59 cases in
the 12-month study period in which the
drug was suspected of causing anaphylactic
Rank Drug
continued on page 3 — SafetyBriefs
May 6 - 12, 2014
cont’d on page 3 — QuarterWatch
# Cases Percent* Rank Drug
Anaphylactic Shock
1
2
3
5
6
Omalizumab
Moxifloxacin
InFLIXimab
Gadopentetate &
Dimeglumine
Cetuximab
Glatiramer
7
AmLODIPine
4
8
9
10
Rank
Ibuprofen
Lisinopril
Naproxen
Drug
# Cases Percent*
Severe Cutaneous Reactions
59
39
35
9.4
17.5
1.2
1
2
3
Telaprevir
LamoTRIgine
Allopurinol
105
55
48
5.6
10.3
43.6
29
19.1
4
DULoxetine
37
3.2
23
22
4.7
2.8
5
6
26
25
10.0
5.8
25
10.4
Vancomycin
LevETIRAcetam
Sulfamethoxazole &
20
3.9
7 Trimethoprim
18
2.2
8 Phenytoin
17
2.4
9 Bendamustine
17
1.8
10 Clindamycin
# Cases Percent* Rank Drug
Angioedema
1
24
5.9
23
5.1
20
12.5
# Cases Percent*
Other
131
18.8
1
Erlotinib
453
15.5
27
27.8
2
Alendronate
85
5.2
20
8.3
3
Heparin
26
11.9
4
5
6
7
8
9
Lisinopril
Hydrochlorothiazide
& Lisinopril
Sulfamethoxazole &
Trimethoprim
Alendronate
Levofloxacin
Moxifloxacin
Enalapril
Telaprevir
Ciprofloxacin
18
18
18
15
15
12
1.1
2.4
8.1
36.6
0.8
2.6
4
5
6
7
8
9
20
19
18
16
16
16
6.8
1.2
4.4
0.6
1.2
2.2
10
Benzoyl Peroxide
11
26.2
10
Digoxin
Bevacizumab
Vemurafenib
InFLIXimab
Interferon alfa
RiTUXimab
Sulfamethoxazole &
Trimethoprim
15
6.2
2
Actiq is not for sore throats!
A hospital reported three events in which
a provider attempted to order ACTIQ (fentaNYL
citrate oral transmucosal lozenge) to treat a sore
throat, mistaking the powerful opioid as a typical
throat lozenge. In two cases, the pharmacist identified
the error and contacted the provider. In the third
case, the provider caught his own error. In each case,
the patients did not have other opioids on their
profiles, or a history of opioid use. Use of this product
in opioid-naïve patients could have resulted in serious,
Severe cutaneous reactions. Skin
eruptions are a common drug side
effect, usually mild. Less frequently, drugs
trigger a potentially life-threatening spectrum of cutaneous reactions including
erythema multiforme, Stevens-Johnson
syndrome (SJS), toxic epidermal necrolysis
(TEN), or drug reaction with eosinophilia
and systemic symptoms (DRESS). In the
most severe variants, SJS and TEN, exfoli-
Table 2. Top 10 drugs associated with severe hypersensitivity by reaction type
HIGH-ALERT
HIGH-ALERT
shock. Although the label includes warnings and a requirement to administer the
drug in a physician’s office, where emergency treatment should be immediately available, almost half the cases in the earlier
FDA study occurred more than 1 hour
after administration. This may explain why
reported hypersensitivity cases still resulted in 2 patient deaths, 3 cases of permanent disability, and 9 hospitalizations.
3
*Percent equals the number of specific adverse events (e.g., anaphylaxis) divided by all serious adverse event cases
reported for the drug during the 12-month study period ending March 2013, multiplied by 100
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3
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SafetyBriefs continued from page 2
harm. The hospital where the events occurred is
considering possible IT changes. The hospital is also
implementing safeguards to prevent further occurrences, including limitations on prescribing to pain
management specialists, anesthesiologists, hematologists, oncologists, palliative care, and hospice
providers. Strict limitations on prescribing, dispensing,
and distributing this drug are required by the
Transmucosal Immediate Release FentaNYL (TIRF)
Risk Evaluation and Mitigation Strategy (REMS), an
FDA-required program designed to ensure informed
risk-benefit decisions before initiating treatment, and
appropriate use while patients are treated. Before
enrollment in the TIRF REMS Access program,
prescribers and pharmacists must review an education program (www.ismp.org/sc?id=357), successfully complete a knowledge assessment with a score
of 100%, and sign acknowledgement statements on
the enrollment form. The hospital where these events
happened is also implementing an automatic medication order form that includes criteria for use of the
product that can’t be bypassed without completing
the form. Due to the risk of fatal respiratory depression, Actiq is contraindicated in opioid-naïve patients.
Special Announcement s ...
ISMP webinar
Join us for our May 28 webinar, Managing
Outcomes and Enhancing Safety: The Role
of Protocol-Driven Care in Today’s Healthcare Environment. Join our guest speakers as
they discuss protocol-driven care for treatment
modalities such as pain management, nutritional
support, and various drug therapies. For details,
visit: www.ismp.org/sc?id=349.
Unique 2-day program
Attend ISMP’s Medication Safety INTENSIVE
workshop in Las Vegas on May 30-31. For
details, visit: www.ismp.org/sc?id=351.
ISMP Medication Safety Alert! Acute Care
(ISSN 1550-6312) ©2014 Institute for Safe
Medication Practices (ISMP). Permission is
granted to subscribers to reproduce material for
internal communications. Other reproduction is
prohibited without permission. Report medication
errors to the ISMP National Medication Errors
Reporting Program (ISMP MERP) at 1-800FAIL-SAF(E) or online at www.ismp.org/MERP.
Unless noted, published errors were received
through the ISMP MERP. ISMP guarantees
confidentiality of information received and
respects reporters' wishes as to the level of detail
included in publications. Editors: Judy Smetzer,
RN, BSN, FISMP; Michael R. Cohen, RPh, MS,
ScD; Russell Jenkins, MD. ISMP, 200 Lakeside
Drive, Suite 200, Horsham, PA 19044. Email:
[email protected]; Tel: 215-947-7797; Fax: 215914-1492. This is a peer reviewed publication.
Volume 19 Issue 9
QuarterWatch continued from page 2
ation and skin detachment occurs over 530% of the body, leading to life-threatening
complications comparable to severe
burn cases. In the 12-month study
period, we identified 891 possible cases
of severe cutaneous reactions, 22% of
the total severe hypersensitivity cases.
These included 97 deaths and 35
cases of permanent disability. The
reactions included 387 cases of SJS/TEN
and 291 cases of DRESS. The 10 most
frequently identified suspect drugs are
shown in Table 2 (page 2).
The drug with the most frequent severe
cutaneous reactions, telaprevir (INCIVEK), was approved in 2011 to treat
chronic hepatitis C in combination with
two other antiviral agents. In the study
period, we identified 131 cases of severe
hypersensitivity with telaprevir, including
14 deaths and 105 cases of severe
cutaneous reactions—more than any other
drug studied. Before the drug was
approved, 60% of previously untreated
patients developed skin rashes during
clinical trials; 16% of these experienced
rashes covering 50% or more of their body.
In 2012, FDA required a boxed warning in
the prescribing information and a strong
patient alert in a mandatory Medication
Guide. However, discontinuation of the
drug is recommended only for systemic
symptoms or progressive, severe rash. The
Infectious Diseases Society of America
notes that treatment with telaprevir is
“markedly inferior to preferred and alternative regimens” because it is “associated with
higher rates of serious adverse events.”
Angioedema. Angioedema is a common
reaction (most often caused by drugs,
foods, and insect bites) with an estimated
lifetime risk of 15-25% in the general
population. Angioedema can be life-threatening if it occurs in the upper airway,
blocking respiration. In the study period, we
identified 891 cases of angioedema classified as severe. The most frequent suspects
among the severe angioedema cases are
shown in Table 2 (page 2). The most
notable signal was for the angiotensinconverting enzyme (ACE) inhibitor lisinopril, both as monotherapy and in combination with hydrochlorothiazide. Another
ACE inhibitor, enalapril (VASOTEC), was
also a frequent suspect, as were three
fluoroquinolone antibiotics: levofloxacin,
moxifloxacin, and ciprofloxacin. Lisinopril
and moxifloxacin were also prominent suspects with cases of anaphylactic shock.
Other severe hypersensitivity. The final
subset includes atypical reactions
that did not fit into the other
categories. The most frequently reported drugs are shown in Table 2 (page 2). It
was notable that 5 of the 10 most frequently reported drugs were biological products rather than small molecule drugs.
Erlotinib (TARCEVA) accounted for more
severe hypersensitivity cases overall than
any other drug. Because this drug is indicated for metastatic non-small cell lung
cancer and pancreatic cancer, where longterm survival is rare, deaths were numerous
(461), as were reports of rash. In clinical
trials before drug approval, 85% of patients
experienced rashes; 14% had rashes
covering 50% or more of the body. Heparininduced thrombocytopenia, ranked third in
Table 2 , is a Type II hypersensitivity.
Conclusion
As noted above, all 20 randomly sampled
drugs included accurate hypersensitivity
information in the prescribing information.
This suggests drug manufacturers were
screening and evaluating the adverse event
cases as received, and updating the
prescribing information as required. In
addition, the drugs with larger numbers of
severe reactions reported generally had
stronger or more prominent warnings.
We hope the drugs listed in Table 2 (page 2)
will be targeted to create meaningful clinical alerts that appear in electronic prescribing and order entry systems, or when
using electronic medication administration
records (MARs), to warn practitioners
about the most serious risks associated with
hypersensitivity. Clinicians should consider
carefully the use of telaprevir to treat hepatitis C given that drugs with better safety
profiles and effectiveness are available.
See the full, referenced QuarterWatch™
report at: www.ismp.org/QuarterWatch/
default.aspx.
Please encourage your patients and staff to visit www.consumermedsafety.org often. It may save a life!
4
May 8, 2014
Volume 19 Issue 9
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ISMP Survey on High-Alert Medications in Hospitals and Other Inpatient Healthcare Settings
Please complete our short survey on high-alert medications in hospitals and other inpatient healthcare settings, and submit your responses by June 20, 2014, at:
www.ismp.org/sc?id=358. High-alert medications bear a heightened risk of causing significant patient harm when they are used in error. Although errors may or may
not be more common with these medications, the consequences of an error are often devastating to both patients and their healthcare providers.
For Section A, indicate whether YOU consider these drugs or drug classes to be high-alert medications. For Section B, indicate whether YOUR PRACTICE SITE considers
these drugs to be high-alert medications. For Section C, please indicate whether you believe your practice site has SPECIAL PRECAUTIONS IN PLACE for these medications, and whether you believe they are EFFECTIVE. Under OTHERS, include additional medications that YOU and/or YOUR PRACTICE SITE consider high-alert medications. There will be ample room to make comments when you enter your responses at the above URL.
Medication or Class of Medications
Current List (Drug Classes or Specific Drugs)
1) Adrenergic agonists, IV (e.g., EPINEPHrine, terbutaline, norepinephrine)
2) Beta-adrenergic antagonists, IV (e.g., propranolol, metoprolol)
3) Anesthetic agents, general, inhaled, IV (e.g., propofol, ketamine)
4) Antiarrhythmics, IV (e.g., amiodarone)
5) Antithrombotic agents
Anticoagulants (e.g., warfarin, heparin)
6) Factor Xa inhibitors (e.g., fondaparinux, apixaban, riveroxaban)
7) Direct thrombin inhibitors (e.g., dabigatran, argatroban, lepirudin)
8) Thrombolytics (e.g., alteplase, tenecteplase)
9) Glycoprotein IIb/IIIa inhibitors (e.g., eptifibatide)
10) Cardioplegia solution
11) Chemotherapeutic agents, parenteral and oral
12) Dextrose, hypertonic, 20% or greater
13) Dialysis solutions, peritoneal and hemodialysis
14) Epidural or intrathecal medications
15) Hypoglycemics, oral
16) Inotropic medications, IV (e.g., digoxin)
17) Liposomal forms of drugs and conventional counterparts
18) Moderate sedation agents, IV (e.g., midazolam)
19) Moderate sedation agents, oral, for children (e.g., midazolam)
20) Opioids, injectable (IM, IV)
21) Opioids, transdermal
22) Opioids, transmucosal and oral, including liquid concentrates and
immediate- or sustained-release products
23) Neuromuscular blocking agents (e.g., succinylcholine, rocuronium)
24) Parenteral nutrition preparations
25) Radiocontrast agents, IV
26) Sterile water for injection, inhalation, and irrigation, in containers of 100
mL or more (excluding pour bottles)
27) Sodium chloride for injection, hypertonic, greater than 0.9% concentration
28) Epoprostenol (Flolan), IV
29) Magnesium sulfate injection
30) Methotrexate, oral, non-oncologic use
31) Opium tincture
32) Oxytocin, IV
33) Insulin, subcutaneous (including use in pen devices and pump devices)
34) Insulin, IV
35) Nitroprusside sodium, IV
Section A
Do YOU consider
this a high-alert
drug?
Yes
No
Section B
Does YOUR
PRACTICE SITE
consider this a
high-alert drug?
Yes
No
Section C
Does YOUR
Do YOU believe
PRACTICE SITE your practice
have special presite’s precautions
cautions in place? are EFFECTIVE?
Yes
No
Yes
No
cont’d on page 5 — Survey
5
May 8, 2014
Volume 19 Issue 9
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Survey continued from page 4
Medication or Class of Medications
Current List (Drug Classes or Specific Drugs)
Section A
Do YOU consider
this a high-alert
drug?
Section B
Does YOUR
PRACTICE SITE
consider this a
high-alert drug?
Section C
Does YOUR
Do YOU believe
PRACTICE SITE your practice
have special presite’s precautions
cautions in place? are EFFECTIVE?
Yes
No
Yes
No
Yes
No
Yes
No
Yes
No
Yes
No
Yes
No
Yes
No
Table continued from page 4
36) Potassium chloride injection concentrate
37) Potassium phosphate injection
38) Promethazine, IV
39) Vasopressin, IV or intraosseous
New Drugs to Consider (Not on ISMP’s List of High-Alert Medications)
40) Insulin, U-500, special emphasis, listed separate from U-100 insulin
41) Antithrombotic agents
Antiplatelet agents (e.g., clopidogrel [Plavix], cilostazol [Pletal])
42) Ergot derivatives (e.g., methylergonovine, dihydroergotamine)
43) Methylergonovine (without other ergot derivatives)
44) Medications administered via an endotracheal tube
45) Intrauterine medications intended for fetus
46) Glacial acetic acid
47) EPINEPHrine, subcutaneous or IM
48) Others: Please list
Please select the categories that best describe your profession (select one), current position (select one), and work setting (select all that apply).
Profession:
Pharmacy technician
Physician
Pharmacist
Physician assistant
Registered nurse
Practical nurse
Other:_________________
Nurse practitioner
Position:
Staff
Manager/Director
Administrator
Other:______________________
Work setting:
Inpatient: oncology
Outpatient: oncology
Inpatient: critical care
Outpatient: critical care
Inpatient: non-critical care
Outpatient: non-critical care
Inpatient: other_________________
Outpatient: other________________
Thank you for participating! Enter your responses by June 20, 2014, at: www.ismp.org/sc?id=358.
Please encourage your patients and staff to visit www.consumermedsafety.org often. It may save a life!

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