| Archives
2002
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Warnings
Clarify CHF Risks With Two
Diabetes Agents
Product labeling for two Type 2 diabetes agents has been
changed to warn more clearly of the risk of fluid retention
that may lead to, or exacerbate, congestive heart failure
(CHF). The two drugs are thiazolidinediones: pioglitazone
HCl (Actos) and rosiglitazone maleate (Avandia). In a
study of 566 patients receiving insulin or insulin plus
pioglitazone, four patients on combination therapy developed
CHF; all had previous cardiovascular conditions. In two
studies of a total of 611 patients given rosiglitazone
plus insulin or insulin alone, 10 patients on combination
therapy developed CHF. They were older and mostly on a
higher 8 mg dose of rosiglitazone, but three of the 10
had no previous CHF or cardiovascular condition. Patients
on either drug should be watched for CHF symptoms and
told to immediately report symptoms such as an unusually
rapid increase in weight, edema, or shortness of breath.
The warnings apply to the use of thiazolidinediones as
monotherapy or with insulin. Rosiglitazone, however, isn’t
approved for combination use with insulin. The drugs should
be stopped if a patient’s cardiac status deteriorates.
U.S.
Food and Drug Administration MedWatch. “Thiazolidinediones
(Actos [pioglitazone HCl], Avandia [rosiglitazone maleate]).”
2002. www.fda.gov/medwatch/SAFETY/2002/summary-actos-avandia.pdf
(21 May 2002)
[TOP]
New
Safety Data And Indication Added To Vioxx Labeling
Several important changes have been made to the labeling
for rofecoxib (Vioxx), a popular COX-2 inhibitor used
to treat pain and osteoarthritis. The changes include
a new indication for the treatment of rheumatoid arthritis,
evidence of reduced GI risks vs. naproxen (Anaprox, Naprosyn,
others), and precautions about cardiovascular risks associated
with rofecoxib. The two key changes on safety are based
on data from a double-blind study in 8,000 patients taking
rofecoxib 50 mg/day—which is twice the highest recommended
maintenance dose—or the standard dose of naproxen
(1,000 mg/day). Rofecoxib demonstrated a significantly
lower incidence of serious GI effects, such as major bleeding,
perforation, and obstruction, but it was associated with
a higher rate of thromboembolic adverse events, including
MI, angina, and peripheral vascular events (1.8% vs. 0.6%
with naproxen). In studies in rheumatoid arthritis patients,
rofecoxib 25 mg/day was also associated with a higher
incidence of hypertension compared to naproxen 1,000 mg/day.
As a result, the drug’s labeling advises providers
to use caution when prescribing rofecoxib for patients
with ischemic heart disease.
U.S.
Food and Drug Administration. “FDA approves new indication
and label changes for the arthritis drug, Vioxx.”
2002. www.fda.gov/bbs/topics/ANSWERS/2002/ANS01145.html
(12 Apr. 2002).
[TOP]
Low-Dose
Weekly Methotrexate Should Be A “High Alert”
Med
Because of the potential for dangerous dosing errors,
the Institute for Safe Medication Practices (ISMP) has
urged clinicians to make low-dose methotrexate sodium
a “high alert” medication. Long used in cancer
chemotherapy, methotrexate is approved in low-dose forms
for rheumatoid arthritis (RA) and psoriasis, and sold
under brand names like Rheumatrex, Folex PFS, and others.
The dosages for these “newer” indications are
weekly, typically starting at 2.5 to 5 mg every 12 hours
for a total of three doses per week, or one 7.5 mg dose
per week. Some deaths have occurred because patients confused
the drug with a daily regimen; but even in hospitals,
the dosage has been erroneously transcribed. ISMP recommends
having systems in place that require confirmations of
dose and indication, as well as written instructions for
patients naming a specific time and day for taking the
drug. Under the brand name Rheumatrex, methotrexate is
sold in weekly dose packs, which can help reinforce the
regimen.
Institute
For Safe Medication Practices (ISMP) Medication Safety
Alert. “Beware of erroneous daily oral methotrexate
dosing.” 2002. www.ismp.org/MSAarticles/Beware.htm
(18 May 2002).
[TOP]
Researchers
Call For Changes To Thwart Rise In Med Errors
A recent analysis of avoidable drug-related deaths concluded
that serious drug errors are bound to increase unless
providers improve their communication skills and facilities
ensure that drug information is available near the point
of use, and automated drug order and administration systems
are implemented. The study examined medication errors
in hospitals and outpatient settings reported to the FDA
from 1993 to 1998. Of the more than 5,000 reports analyzed,
68% involved serious outcomes and 9.8% were fatal; nearly
half of the deaths were in patients over age 60. Almost
55% of the deaths involved CNS drugs, anticancer agents,
and cardiovascular drugs. The most common types of error
were dose-related, followed by giving the wrong drug and
using the wrong route of administration.
Phillips,
J., Beam, S., et al. (2001). Retrospective analysis of
mortalities associated with medication errors. Am J Health-Syst
Pharm, 58(19), 1835.
[TOP]
Product
That Treats Burns Is Approved For Use On Scars
The Integra Dermal Regeneration Template, a bilayer skin
replacement system used to treat severe full-thickness
or deep partial-thickness burns, has been approved as
a treatment for scars caused by burns. To treat scars,
the scar tissue has to first be removed, and then Integra
is placed over the wound. The product’s lower, dermal
layer, which is a matrix of collagen/glycosaminoglycan
fibers, promotes skin re-growth, while its upper epidermal
layer helps close the wound and prevent fluid loss. The
top layer is removed after two to three weeks, and a skin
graft is applied to the wound area. This new use of Integra
was studied at a burn hospital, where 30 scarred areas
resulting from severe burns were treated in 20 patients.
U.S.
Food and Drug Administration. “FDA approves reconstructive
surgery product for patients with severe scarring.”
2002. www.fda.gov/bbs/topics/answers/2002/ans01148.html
(1 May 2002).
[TOP]
New
Arimidex Data Shows Benefits
Vs. Tamoxifen
The FDA has granted an expedited review of new data on
anastrozole (Arimidex) based on benefits seen vs. tamoxifen
(Nolvadex) as adjuvant treatment of early breast cancer
in postmenopausal women. The review may lead to a new
indication for anastrozole, which is currently approved
only for advanced breast cancer. The new data comes from
a study in over 9,300 patients who received anastrozole
alone, tamoxifen alone, or a combination of the two, after
having primary surgery, and radiation therapy and chemotherapy
(if given) for early breast cancer. After about 31 months
of treatment, anastrozole reduced the overall risk of
recurrence by 17% vs. tamoxifen. Only 317 of 3,125 women
given anastrozole had a relapse or died compared with
379 of 3,116 women in the tamoxifen group. Combination
therapy showed no advantages. Anastrozole was associated
with significantly fewer reports of venous thromboembolic
events, vaginal bleeding, and other adverse events, although
women on tamoxifen had fewer musculoskeletal disorders
and fractures.
AstraZeneca
Pharmaceuticals. “AstraZeneca submits supplemental
new drug application to the FDA for Arimidex to treat
early breast cancer.” 2002. www.astrazeneca-us.com/news/article.asp?file=2002030401.htm
(22 May 2002).
Safety
Notice Warns Of Risks Of Improper Abortion Pill Use
Cases of ruptured ectopic pregnancies, sepsis, and an
MI have been reported in women treated with mifepristone
(Mifeprex) in combination with misoprostol (Cytotec) for
termination of early pregnancy (49 days or less). All
the cases, two of which were fatal, involved vaginal administration
of misoprostol—contrary to the FDA-approved dosing,
which is oral. No causal relationship between these events
and the drugs has yet been determined. But the safety
letter, issued by Danco Laboratories, the manufacturer
of mifepristone, alerts clinicians of their responsibility
to report serious adverse events that occur with the treatments,
as well as ongoing pregnancies following treatment. It
also reminds them to use the FDA-approved dosing regimen
and not to use the drug in women with confirmed or suspected
ectopic pregnancy. To access the letter and related FDA
documents, point your browser to www.fda.gov/cder/drug
/infopage/mifepristone.
U.S.
Food and Drug Administration. “Mifepristone information.”
2002. www.fda.gov/cder/drug/infopage/mifepristone (19
Apr. 2002).
Botox
Approved For Use On Frown Lines
The FDA has approved botulinum toxin type A (Botox Cosmetic)
for temporarily improving the appearance of moderate to
severe glabellar lines, the frown lines, or furrows, that
form between the eyebrows. The toxin, produced by the
bacterium Clostridium botulinum, reduces frown lines by
cutting off the signal for muscle to contract, thus paralyzing
or weakening injected muscles. It lasts three to four
months. In placebo-controlled trials, 405 patients received
a single injection of Botox Cosmetic. At 30 days, the
severity of glabellar lines at maximum frown was rated
by investigators as none or mild in 80% of treated patients
vs. 3% of those given placebo. Side effects are generally
temporary but could last a few months. The most common
are headache, respiratory infection, flu syndrome, droopy
eyelids, and nausea. Facial pain, redness at the injection
site, and muscle weakness occurred in 3% of patients.
Botox Cosmetic should not be given more frequently than
once every three months.
U.S.
Food and Drug Administration. “FDA approves Botox
to treat frown lines.” 2002. www.fda.gov/bbs/topics/answers/2002/ans01147.html
(16 Apr. 2002).
PROBLEM
RX
When A “Bug” Won’t Surrender A 16-year-old
male comes to the ED with a severe sore throat and a temperature
of 101° F (38.3° C). A throat swab is obtained,
and a rapid group A streptococcal antigen-detection test
ordered. Two hours later, the test comes back positive.
The patient is prescribed erythromycin 250 mg q6h for
10 days, but on follow-up the infection hasn’t cleared.
A second physician prescribes clindamycin HCl (Cleocin),
which is effective. Why didn’t the first antibiotic
work?
The
patient may have been infected with a strain of group
A streptococci resistant to erythromycin, or he may have
a recurrent infection that was treated repeatedly with
macrolide antibiotics—a class that includes erythromycin
as well as newer agents like azithromycin (Zithromax)—and
a resistant strain developed. When antibiotics are frequently
used empirically, as was done here, and/or excessively,
resistant bugs can eventually emerge. Ideally, all antibiotic
treatments should be based on a susceptibility report.
This can be ordered along with the rapid screen for strep.
Source:
Martin, J. M., Green, M., et al. (2002). Erythromycin-resistant
group A streptococci in schoolchildren in Pittsburgh.
N Engl J Med, 346(16), 1200.
THE
AUTHOR LINDA M. PORTERFIELD, RN, PhD, is a clinical pharmacologist
and director of cardiovascular research at Arrhythmia
Consultants in Memphis. She works with her husband, James
Porterfield, MD, FACC, who is a cardiologist and electrophysiologist.
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