Download December 2012 - APhA DrugInfoLine

December 2012
page 1 / 44
Focus on Asthma Care
Advising on this article: Devra K. Dang
December 4, 2012
Is there a role for as-needed inhaled corticosteroids in asthma
management?
Key Point
In patients with mild to moderate asthma controlled with low-dose inhaled corticosteroids, adjusting the corticosteroid
dose based on asthma symptoms or a biomarker did not avert treatment failure better than physician-based
assessment of asthma symptoms and dose adjustment according to treatment guidelines.
Source URL:
http://www.aphadruginfoline.com/focus-asthma-care/there-role-needed-inhaled-corticosteroids-asthma-management
page 2 / 44
Respiratory
Advising on this article: Devra K. Dang
December 4, 2012
Vitamin D left out in the cold for preventing upper respiratory tract
infections
Key Point
Monthly administration of vitamin D did not decrease the incidence or severity of upper respiratory tract infections
(URTIs) in adults.
Source URL:
http://www.aphadruginfoline.com/respiratory/vitamin-d-left-out-cold-preventing-upper-respiratory-tract-infections
page 3 / 44
Infectious Diseases
Advising on this article: Allana Sucher
December 11, 2012
New strep guidelines emphasize proper diagnosis, antimicrobial
stewardship
Key Point
The Infectious Diseases Society of America (IDSA) updated its 2002 recommendations on the diagnosis and treatment
of Group A Streptococcal (GAS) pharyngitis, highlighting the use of rapid antigen detection tests to help ensure that
only confirmed cases are treated with antibiotics.
Source URL:
http://www.aphadruginfoline.com/infectious-diseases/new-strep-guidelines-emphasize-proper-diagnosis-antimicrobial-s
tewardship
page 4 / 44
Endocrinology
Advising on this article: Frank Pucino
December 11, 2012
Updated guidelines: Levothyroxine okay at bedtime
Key Point
Levothyroxine remains the drug of choice for treating all types of hypothyroidism (i.e., primary or secondary etiologies),
according to updated treatment guidelines. Levothyroxine doses should be administered on an empty stomach in the
morning 30–60 minutes before breakfast or at bedtime 4 hours after the last meal, authors recommended.
Source URL:
http://www.aphadruginfoline.com/endocrinology/updated-guidelines-levothyroxine-okay-bedtime
page 5 / 44
Oncology
Advising on this article: Gary C. Yee
December 18, 2012
New hope: Anti-angiogenic agent for metastatic colorectal cancer
Key Point
In patients with metastatic colorectal cancer previously treated with oxaliplatin, use of ziv-aflibercept (Zaltrap—Sanofi) in
combination with FOLFIRI resulted in an improvement in overall survival and progression-free survival and a greater
response rate compared with FOLFIRI combined with placebo.
Source URL:
http://www.aphadruginfoline.com/oncology/new-hope-anti-angiogenic-agent-metastatic-colorectal-cancer
page 6 / 44
Focus on HIV Care
Advising on this article: Betty J. Dong
December 18, 2012
Universal antiretroviral therapy linked to increased HIV RNA
suppression
Key Point
In a cohort of HIV-infected patients with a CD4 count greater than 500 cells/?L, implementing recommendations to
initiate antiretroviral therapy (ART) in all untreated individuals regardless of CD4 cell count (universal ART) was
associated with increased likelihood of achieving HIV RNA suppression.
Source URL:
http://www.aphadruginfoline.com/focus-hiv-care/universal-antiretroviral-therapy-linked-increased-hiv-rna-suppression
page 7 / 44
OTC Medicines Corner
Advising on this article: R. William Soller
December 18, 2012
OTC cough medications: Do they work?
Key Point
Available evidence does not support a definite beneficial or harmful effect of OTC medicines for treatment of acute
cough in adults or children, according to an updated analysis in the Cochrane Database of Systematic Reviews.
Source URL:
http://www.aphadruginfoline.com/otc-medicines-corner/otc-cough-medications-do-they-work
page 8 / 44
Pharmacogenomics Corner
Advising on this article: Mary W. Roederer
December 26, 2012
PREDICT initiative: A look into the future of personalized medicine
Key Point
In a prospective effort to decrease medication-related adverse events, patients undergoing left heart catheterization at
a large academic health center were stratified to receive usual care (clopidogrel) or alternative therapy based on CYP
2C19 genotyping. Based on genotyping results, approximately 22% of patients received an alternative to usual care.
Source URL:
http://www.aphadruginfoline.com/pharmacogenomics-corner/predict-initiative-look-future-personalized-medicine
page 9 / 44
Gastroenterology
Advising on this article: C. Wayne Weart
December 26, 2012
Does a probiotic a day keep C. difficile away?
Key Point
In adults and children who were taking antibiotics, prophylactic probiotics were associated with decreased risk of
developing Clostridium difficile-associated diarrhea (CDAD) with no increase in clinically important adverse events,
compared with placebo or no treatment.
Source URL:
http://www.aphadruginfoline.com/gastroenterology/does-probiotic-day-keep-c-difficile-away
page 10 / 44
Focus on Immunizations
Advising on this article: John D. Grabenstein
December 28, 2012
Shingles vaccine: Is a booster shot on the horizon?
Key Point
In a follow-up of a 4-year herpes zoster vaccine live (Zostavax—Merck) trial conducted in a cohort of patients monitored
for an additional 3 years, zoster vaccine efficacy decreased over time, but was statistically significant for herpes zoster
incidence and burden of illness through year 5.
Source URL:
http://www.aphadruginfoline.com/focus-immunizations/shingles-vaccine-booster-shot-horizon
page 11 / 44
Alternative Medicines Corner
Advising on this article: Nicole M. Maisch
December 28, 2012
Daily multivitamin disappoints: No decrease in cardiovascular risk,
death
Key Point
Men who took a daily multivitamin for more than a decade did not have lower incidence of major cardiovascular events,
myocardial infarction (MI), stroke, and cardiovascular mortality.
Source URL:
http://www.aphadruginfoline.com/alternative-medicines-corner/daily-multivitamin-disappoints-no-decrease-cardiovascul
ar-risk-death
page 12 / 44
New Drug Approvals
Generic Name (Trade Name—Company)
Uses/Notes
December 1, 2012
Treatment of progressive, metastatic medullary
thyroid cancer
Cabozantinib
In clinical testing, progression-free survival was 11.2
months in patients taking cabozantinib, a significant
increase over the 4.0 months seen with placebo in
patients with this rare form of thyroid cancer. FDA
-approved labeling contains a black-box warning of
increased risks of hemorrhage and colonic perforations
and fistulas.
Approved doses of the drug are 140 mg orally once
daily (one 80 mg capsule and three 20 mg capsules).
Cabozantinib should not be taken with food, and patients
are advised to not eat for at least 2 hours before and at
least 1 hour after taking doses.
In the randomized double-blind controlled EXAM trial of
330 patients with progressive, metastatic medullary
thyroid carcinoma, partial responses were observed only
among patients in the cabozantinib arm (27% of patients
versus 0% with placebo, P < 0.0001). The median
duration of objective responses was 14.7 months (95%
CI, 11.1–19.3) for patients treated with cabozantinib.
There was no statistically significant difference in overall
survival between the treatment arms at the planned
interim analysis, Exelixis said in a news release.
The most commonly reported adverse drug reactions to
cabozantinib, occurring in 25% or more of patients, are
diarrhea, stomatitis, palmar–plantar erythrodysesthesia
syndrome, decreased weight, decreased appetite,
nausea, fatigue, oral pain, hair color changes,
dysgeusia, hypertension, abdominal pain, and
constipation. The most common laboratory abnormalities
(?25%) are increased AST, increased ALT,
lymphopenia, increased alkaline phosphatase,
page 13 / 44
(Cometriq—Exelixis)
Multiple-receptor tyrosine kinase inhibitor approved
for rare thyroid cancer
hypocalcemia, neutropenia, thrombocytopenia,
hypophosphatemia, and hyperbilirubinemia.
Cabozantinib is a CYP 3A4 substrate, and increased
drug levels result if 3A4 inhibitors are used
concomitantly. Inducers of the isoenzyme can lower
cabozantinib levels.
Source URL:
http://www.aphadruginfoline.com/new-drug-approvals/multiple-receptor-tyrosine-kinase-inhibitor-approved-rare-thyroidcancer
page 14 / 44
Product Withdrawals
Generic Name (Trade Name—Company)
Uses/Notes
December 4, 2012
Ondansetron
(Zofran—GlaxoSmithKline, various generics)
High-dose removed from the market
The 32-mg single I.V. dose of ondansetron has been
pulled from the market, FDA announced yesterday,
because of concerns related to cardiac adverse events.
In June, the agency warned that the 32-mg dose should
be avoided because of the risk of QT interval
prolongation, which can lead to torsade de pointes.
Preliminary results of a study ordered by the FDA found
a maximum mean difference in QTcF of 20 ms after the
32 mg intravenous dose, compared with a QTcF
difference of 6 ms for the 8 mg intravenous dose.
FDA noted that removal of the 32-mg dose should not
contribute to a potential ondansetron shortage, as this
dose only made up a small percentage of the current
market. The agency also noted that it will continue to
recommend an I.V. regimen of 0.15 mg/kg administered
every 4 hours for three doses to prevent
chemotherapy-induced nausea and vomiting. Oral
ondansetron was also discussed as an effective
alternative for the management of
chemotherapy-induced nausea and vomiting.
Source URL:
http://www.aphadruginfoline.com/product-withdrawals/high-dose-removed-market
page 15 / 44
Alerts and Recalls
Generic Name (Trade Name—Company)
Uses/Notes
December 5, 2012
Heparin
(No trade name—Multiple manufacturers )
Labeling revised to reduce potential for errors
FDA announced that the labeling of heparin containers
and cartons will be modified to clearly state the total
drug strength. Manufacturers of heparin lock flush
solutions and heparin sodium injections will now need to
list the strength of the entire container of the medication,
followed by how much of the medication is in 1 mL.
These modifications are being made to eliminate the
need for providers to calculate the total amount of
heparin medication in a product containing more than 1
mL, FDA reported, thereby reducing the risk of
miscalculations that may result in medication errors. In
addition, this labeling change will ensure that labels for
heparin products comply with USP’s general
requirements for all small-volume injectable products,
which currently display the total drug content.
FDA noted that there will be a transition period before
and after the official implementation date on May 1,
2013, during which both the current heparin container
labels and the revised heparin container labels will be
available in the marketplace. During this time, the
agency recommended separating current and revised
labeled heparin products to minimize confusion and the
potential for medication errors.
Source URL:
http://www.aphadruginfoline.com/alerts-and-recalls/labeling-revised-reduce-potential-errors
page 16 / 44
Alerts and Recalls
Generic Name (Trade Name—Company)
Uses/Notes
December 6, 2012
Hydrocodone bitartrate/acetaminophen
(No trade name—Qualitest)
Oversized tablets prompts recall of more than 100
lots
Qualitest announced that it will conduct a voluntary
nationwide recall for 101 lots of hydrocodone bitartrate
and acetaminophen tablets 10 mg/500 mg. The
company announced this recall because the affected
lots may contain tablets that exceed the weight
requirement and could exceed the label claim potency
requirements for hydrocodone and acetaminophen. If
patients consume excess amounts of acetaminophen,
liver toxicity may occur, especially in patients with liver
dysfunction or who consume more than three alcoholic
beverages a day. Qualitest noted that if excess
hydrocodone is taken, the severity or frequency of
adverse events, such as sedation or respiratory
depression, could increase in select patients.
The affected lots were distributed between February 20,
2012, and November 19, 2012, to wholesale distributors
and retail pharmacies nationwide. Patients who have
purchased products from the affected lots should contact
Qualitest at 800-444-4011; those who are unsure if they
have products from those lots or have any concerns
about their product should consult their pharmacy or a
health professional. In addition, pharmacists and
wholesalers should check their inventories for the
affected lots, segregate any material from the lots, and
contact MedTurn at 800-967-5952 for instructions on
product return.
Source URL:
http://www.aphadruginfoline.com/alerts-and-recalls/oversized-tablets-prompts-recall-more-100-lots
page 17 / 44
Supplemental Approvals
Generic Name (Trade Name—Company)
Uses/Notes
December 9, 2012
Metastatic prostate cancer
Abiraterone
FDA announced today that abiraterone has been
approved to be used in men late-stage (metastatic),
castration-resistant prostate cancer prior to receiving
chemotherapy. The drug was initially approved last year
to be used in men whose prostate cancer progressed
after treatment with docetaxel. This new indication was
granted under the agency’s priority review program.
(Zytiga—Janssen)
Now approved for use prior to chemotherapy
Approval was based on a double-blind study involving
1,088 men with late-stage, castration-resistant prostate
cancer who had not previously received chemotherapy.
Patients were randomized to abiraterone 1,000 mg plus
prednisone 5 mg twice daily or placebo plus prednisone.
Results from the trial, which were published online today
in the New England Journal of Medicine, showed that
radiographic progression-free survival was 16.5 months
with abiraterone and 8.3 months with prednisone alone
(P < 0.001). In addition, over a median follow-up period
of 22.2 months, overall survival was improved with
abiraterone (median not reached vs. 27.2 months for
prednisone alone, P = 0.01). In terms of safety, Grade 3
or 4 mineralocorticoid-related adverse events and
abnormalities on liver-function testing were more
common with abiraterone.
Source URL:
http://www.aphadruginfoline.com/supplemental-approvals/now-approved-use-prior-chemotherapy
page 18 / 44
Supplemental Approvals
Generic Name (Trade Name—Company)
Uses/Notes
December 11, 2012
Management of moderate to severe pain
Oxymorphone
Endo announced the launch of its reformulated,
crush-resistant oxymorphone extended-release tablets
in two new strengths, 7.5 mg and 15 mg. According to
surveillance data, the reformulated design correlated to
reduced abuse rates when compared with the
non-crush-resistant version that was discontinued in
May. The launch of these two additional dosage
strengths add to the five reformulated crush-resistant
strengths already on the market: 5 mg, 10 mg, 20 mg,
30 mg, and 40 mg.
(Opana ER—Endo)
New crush-resistant formulation launched
Oxymorphone extended-release is indicated for
moderate to severe pain when the use of a continuous,
around-the-clock opioid is required for an extended
period of time.
Source URL:
http://www.aphadruginfoline.com/supplemental-approvals/new-crush-resistant-formulation-launched
page 19 / 44
Alerts and Recalls
Generic Name (Trade Name—Company)
Uses/Notes
December 11, 2012
Varenicline
(Chantix—Pfizer)
Updated CV safety data released
FDA released an updated safety communication today
regarding the cardiovascular safety of varenicline. The
agency first notified the public about a possible
increased risk of cardiovascular adverse events with
varenicline in June 2011. The new information comes
from a meta-analysis which included data from 7,002
patients (4,190 varenicline and 2,812 placebo) that were
enrolled in 15 Pfizer-sponsored, randomized,
double-blind, placebo-controlled clinical trials of at least
12 weeks treatment duration. The primary
cardiovascular safety assessment included an analysis
of the occurrence and timing of major adverse
cardiovascular events (MACE). The MACE composite
outcome included cardiovascular-related death, nonfatal
myocardial infarction, and nonfatal stroke.
The analysis showed that there was a low incidence of
MACE occurring within 30 days of treatment
discontinuation (varenicline 0.31% [13/4,190] vs.
placebo 0.21% [6/2,812]). Exposure to varenicline
resulted in an adjusted hazard ratio for MACE of 1.95
(95% CI 0.79–4.82) based on trials reporting at least one
MACE. Although the findings were not statistically
significant, they were consistent with higher rates of
composite outcomes in patients on varenicline relative to
placebo across different time frames and prespecified
sensitivity analyses.
FDA advised that health care providers weigh the risks
of varenicline against the benefits of its use. In addition,
the agency advised patients to contact their health care
provider if they experience new or worsening symptoms
of cardiovascular disease, such as chest pain, shortness
of breath, calf pain when walking, or sudden onset of
weakness, numbness, or difficulty speaking.
Source URL:
http://www.aphadruginfoline.com/alerts-and-recalls/updated-cv-safety-data-released
page 20 / 44
Alerts and Recalls
Generic Name (Trade Name—Company)
Uses/Notes
December 11, 2012
No generic name
(Protandim—LifeVantage)
Metal fragments prompt recall
LifeVantage announced that it will conduct a voluntary
recall of select lots of Protandim, a dietary supplement,
because of the possible inclusion of small metal
fragments in the final product. The fragments were
originally discovered in batches of turmeric extract, an
ingredient in Protandim that was purchased from a third
party supplier. The 10 affected lot numbers and their
respective expiration dates are listed on FDA’s website.
The lots were distributed in the United States and Japan
between July 2012 and November 2012.
To date, the company has not received any reports of
health problems related to this issue. Patients who have
received bottles of Protandim from the affected lot
numbers are encouraged to stop using the product and
call the company with any questions at 866-912-9051.
Source URL:
http://www.aphadruginfoline.com/alerts-and-recalls/metal-fragments-prompt-recall
page 21 / 44
New Drug Approvals
Generic Name (Trade Name—Company)
Uses/Notes
December 13, 2012
Management of adults with CML and Ph+ ALL
Ponatinib
FDA announced today the approval of ponatinib, a third
generation tyrosine kinase inhibitor (TKI), to treat adults
with chronic myeloid leukemia (CML) and Philadelphia
chromosome–positive acute lymphoblastic leukemia
(Ph+ ALL) whose leukemia is resistant or intolerant to
TKIs. The agent is unique in that it targets cells that
have a T315I mutation, which makes these cells
resistant to currently approved TKIs. This approval
comes 3 months before the product’s scheduled
prescription user fee goal date of March 27, 2013.
(Iclusig—ARIAD Pharmaceuticals)
New treatment for TKI-resistant leukemia
Approval was based on data from a single clinical trial
of 449 patients with various phases of CML and Ph+
ALL; all participants were treated with ponatinib. Major
cytogenetic response occurred in 54% of all patients and
70% of patients with the T315I mutation. In addition,
52% of patients with accelerated phase CML
experienced major hematologic response (MaHR) for a
median duration of 9.5 months, 31% of patients with
blast phase CML achieved MaHR for a median duration
of 4.7 months, and 41% percent of patients with Ph+
ALL achieved MaHR for a median duration of 3.2
months.
FDA noted that ponatinib was approved with a boxed
warning that the drug can cause blood clots and liver
toxicity. The most common adverse events reported
during clinical trials were elevations in blood pressure,
rash, abdominal pain, fatigue, headache, dry skin,
constipation, fever, joint pain, and nausea.
Source URL:
http://www.aphadruginfoline.com/new-drug-approvals/new-treatment-tki-resistant-leukemia
page 22 / 44
New Drug Approvals
Generic Name (Trade Name—Company)
Uses/Notes
December 16, 2012
Management of inhalational anthrax
Raxibacumab
FDA announced on Friday the approval of raxibacumab
for the treatment of adult and pediatric patients with
inhalational anthrax due to Bacillus anthracis in
combination with appropriate antibacterial drugs and for
prophylaxis of inhalational anthrax when alternative
therapies are not available or are not appropriate.
Raxibacumab is a monoclonal antibody that works by
neutralizing toxins produced by B. anthracis that can
cause massive and irreversible tissue injury and death.
(No trade name—GlaxoSmithKline)
First monoclonal antibody approved under Animal
Efficacy Rule
FDA noted that raxibacumab is the first monoclonal
antibody approved using the Animal Efficacy Rule, which
allows efficacy findings from adequate and
well-controlled animal studies to support agency
approval when it is not feasible or ethical to conduct
trials in humans.
In the case of raxibacumab, effectiveness for
inhalational anthrax was demonstrated in one study in
monkeys and three studies in rabbits. All animals were
administered aerosolized B. anthracis spores, and
efficacy was determined by survival at the end of the
studies. Results from these studies demonstrated that
64% of animals in the monkey study and 44% of animals
in one rabbit study who received a 40 mg/kg dose of
raxibacumab survived exposure to anthrax, compared
with none in the placebo groups. In addition, data from
another study in rabbits showed that 82% of animals
treated with antibiotics and raxibacumab survived
exposure to anthrax, compared with 65% of animals
receiving antibiotic treatment alone.
Rash, extremity pain, itching, and drowsiness were the
most common adverse events observed in a safety
study involving 326 healthy adult human volunteers.
Source URL:
http://www.aphadruginfoline.com/new-drug-approvals/first-monoclonal-antibody-approved-under-animal-efficacy-rule
page 23 / 44
New Drug Approvals
Generic Name (Trade Name—Company)
Uses/Notes
December 16, 2012
Management of Cushing disease
Pasireotide
FDA announced on Friday the approval of pasireotide
injection for the treatment of patients with Cushing
disease for whom pituitary surgery is not an option or
has not been curative. Pasireotide is a somatostatin
analog which is administered as a subcutaneous
injection twice daily. According to the manufacturer, the
product is expected to be available in March in the 0.3
mg/mL, 0.6 mg/mL, and 0.9 mg/mL strengths.
(Signifor—Novartis)
Orphan drug approved for endocrine disease
Approval was based on data from a Phase III,
multicenter, 6-month randomized study conducted in
162 patients with persistent or recurrent Cushing
disease despite pituitary surgery or de novo patients for
whom surgery was not indicated or who had refused
surgery. Patients were given a dosage of either 0.6 mg
twice daily or 0.9 mg twice daily, with doses increased
after 3 months if indicated. After 6 months of therapy,
15% and 26% of patients in the 0.6 mg and 0.9 mg
groups, respectively, reached the primary endpoint of
normalization of mean 24-hour urinary free cortisol
(UFC) levels. In addition, the percentages of patients
with mean UFC no greater than the upper limit of normal
or at least a 50% reduction from baseline, a less
stringent endpoint than the primary endpoint, were 34%
in the 0.6 mg and 41% in the 0.9 mg groups,
respectively.
The most common adverse reactions occurring in at
least 20% of patients were diarrhea, nausea,
hyperglycemia, cholelithiasis, headache, abdominal
pain, fatigue, and diabetes. FDA noted that it is requiring
three postmarketing studies for pasireotide: a clinical
trial to assess hyperglycemia management, a long-term
prospective observational cohort study and registry of
patients with Cushing disease treated with pasireotide,
and focused safety monitoring for reports of serious
hyperglycemia, acute liver injury, and adrenal
insufficiency.
Source URL:
http://www.aphadruginfoline.com/new-drug-approvals/orphan-drug-approved-endocrine-disease
page 24 / 44
Alerts and Recalls
Generic Name (Trade Name—Company)
Uses/Notes
December 16, 2012
Carboplatin
(No trade name—Hospira)
Three lots recalled due to visible particulates
Hospira released further information about a previously
communicated voluntary user-level recall of three lots of
carboplatin injection because of visible particulates.
These particles have been identified as carboplatin
crystals. Hospira noted that if particulate matter is
injected into a patient, there may be the potential for
serious and/or life-threatening patient injury, such as
obstruction of a blood vessel.
The affected products include: carboplatin injection, 450
mg/45 mL, 10 mg/mL, 45 mL multidose vial, lot
Z011711AA; carboplatin injection, 600 mg/60 mL, 10
mg/mL, 60 mL multidose vial, lot Z021650AA; and
carboplatin injection, 450 mg/45 mL, 10 mg/mL, 45 mL
multidose vial, NOVAPLUS, lot Z011711AB. All of the
products have an expiration date of August 2013 and
were distributed nationwide and in Puerto Rico between
March 2012 and September 2012.
Hospira recommended that anyone with an existing
inventory should stop use and distribution, quarantine
the product immediately, and call Stericycle
(877-650-8362) to arrange for the return of the product.
Source URL:
http://www.aphadruginfoline.com/alerts-and-recalls/three-lots-recalled-due-visible-particulates
page 25 / 44
Alerts and Recalls
Generic Name (Trade Name—Company)
Uses/Notes
December 16, 2012
Sodium oxybate
(Xyrem—Jazz)
FDA cautions against use with CNS-depressing
agents
FDA released a safety communication today warning
providers to avoid using sodium oxybate with alcohol or
central nervous system (CNS) depressant drugs
because these combinations may markedly impair
consciousness and may lead to respiratory depression.
The agency noted that it has added a new
contraindication to the sodium oxybate label warning
against its use with alcohol.
CNS-depressing medications that should be avoided
include agents such as opioid analgesics,
benzodiazepines, sedating antidepressants or
antipsychotics, general anesthetics, and muscle
relaxants. FDA noted that a statement has also been
added to the label recommending that when concomitant
use of sodium oxybate with a CNS depressant is
required, a reduction in dose or discontinuation of one or
more CNS depressants (including sodium oxybate)
should be considered. It further recommends
considering interruption of sodium oxybate treatment if
short-term opioid treatment is required.
This safety communication stems from FDA’s review of
postmarketing adverse event reports submitted to the
agency’s Adverse Event Reporting System or to the
manufacturer. The evaluation of case reports of patient
deaths in those taking sodium oxybate revealed that a
number of deaths occurred in those who were reported
to be concomitantly taking one or more potentially
CNS-depressing medications. The agency noted,
however, that the exact cause of these deaths is not
clear because the reports contained incomplete
information and did not adequately address confounding
factors.
Source URL:
http://www.aphadruginfoline.com/alerts-and-recalls/fda-cautions-against-use-cns-depressing-agents
page 26 / 44
Supplemental Approvals
Generic Name (Trade Name—Company)
Uses/Notes
December 16, 2012
Prevention of influenza
Influenza virus vaccine
GlaxoSmithKline announced today the approval of
Fluarix Quadrivalent, the first intramuscular vaccine to
protect against four influenza strains. The immunization
is approved for children 3 years and older and adults to
help prevent disease caused by seasonal influenza virus
subtypes A and type B contained in the vaccine. Current
vaccines are trivalent and protect against two A-virus
strains most common in humans and the B strain
expected to be predominant in a given year.
(Fluarix Quadrivalent—GlaxoSmithKline)
Four-strain influenza vaccine approved
The manufacturer noted that since the year 2000, two B
virus strains (Victoria and Yamagata) have cocirculated
to varying degrees each season, with various degrees of
mismatch in the trivalent vaccines. Therefore, use of the
new quadrivalent vaccine is ideal because it will help
protect individuals against both B strains and may help
decrease the burden of disease.
Fluarix Quadrivalent will be available in time for the
2013–14 flu season, according to GlaxoSmithKline.
Source URL:
http://www.aphadruginfoline.com/supplemental-approvals/four-strain-influenza-vaccine-approved
page 27 / 44
Alerts and Recalls
Generic Name (Trade Name—Company)
Uses/Notes
December 17, 2012
No generic names
(Multiple trade names—Performance Plus
Marketing)
Undeclared ingredients prompt recall
Performance Plus Marketing announced that it is
conducting a voluntary nationwide recall of Libigrow,
Libigrow XXXtreme, Blue Diamond, Blue Diamond
Platinum, Mojo Nights, Mojo Nights Supreme, and
Casanova because they contain undeclared
sulfoaildenafil and thioaildenafil. These two ingredients
are analogues of sildenafil and can cause serious
adverse events if taken by patients who are concurrently
consuming nitrates.
These products are marketed as sexual enhancers for
men and were sold to distributors and retail stores
nationwide and via the internet. A full list of affected lot
numbers and corresponding expiration dates can be
accessed on FDA’s website. The manufacturer
recommended that patients not consume any of these
products and return them immediately to the place of
purchase for a full refund.
Source URL:
http://www.aphadruginfoline.com/alerts-and-recalls/undeclared-ingredients-prompt-recall-0
page 28 / 44
Alerts and Recalls
Generic Name (Trade Name—Company)
Uses/Notes
December 18, 2012
No generic name
(Zicam Extreme Congestion Relief—Matrixx)
Bacterial contamination prompts recall
Matrixx announced that one lot of Zicam Extreme
Congestion Relief nasal gel (lot number 2123, expiration
date September 15) is being recalled because
Burkholderia cepacia was found in a single sample of
the product taken from the affected lot. Additional tests
on samples from the same lot showed no evidence of
the organism.
Matrixx noted that B. cepacia poses little medical risk to
healthy individuals; however, the prescenece of B.
cepacia in a nasal spray could cause upper airway
colonization and secondarily lead to respiratory
infections in individuals with a compromised immune
system or those with chronic lung conditions.
The product was distributed to retailers nationwide
throughout the United States. Distributors and retail
customers are urged to return the product, and patients
that have the affected lot of Zicam Extreme Congestion
Relief nasal gel should stop using the product and
contact Matrixx for a full refund.
Source URL:
http://www.aphadruginfoline.com/alerts-and-recalls/bacterial-contamination-prompts-recall-0
page 29 / 44
Alerts and Recalls
Generic Name (Trade Name—Company)
Uses/Notes
December 18, 2012
FDA released a safety communication today
announcing that it has received reports of serious skin
(Incivek—Vertex)
reactions, some fatal, in patients taking telaprevir in
combination with peginterferon alfa and ribavirin. The
Skin reactions, some fatal, with combination therapy agency noted that some patients died when they
continued to receive telaprevir combination treatment
after developing a worsening or progressive rash and
systemic symptoms.
Telaprevir
The alert is a result of reports received to FDA’s
Adverse Event Reporting System database of serious
skin reactions, including 92 cases of drug reaction with
eosinophilia and systemic symptoms (DRESS) and 20
cases of Stevens–Johnson syndrome (SJS) in patients
taking telaprevir combination treatment. These reports
were received from May 23, 2011, through June 19,
2012. The agency noted that it also received reports of
two cases of toxic epidermal necrolysis (TEN) from
Japan. FDA reported that two of these patients with
serious skin reactions died.
All patients who receive telaprevir and develop serious
skin reactions should receive urgent medical care, FDA
advised, and telaprevir combination treatment including
peginterferon alfa and ribavirin should be immediately
discontinued. In addition, the patient's health
professional should consider stopping any other
medications that may be associated with serious skin
reactions.
FDA has added a boxed warning to the telaprevir label
describing this serious adverse event and providing
recommendations for managing patients who experience
it. Patients receiving telaprevir should be educated to
call their health care provider immediately if they
develop any of the following signs or symptoms: rash
with or without itching; severe rash with raised bumps,
blisters, or ulcerations; rash that does not improve after
2 or 3 days; rash that gets progressively worse; fever;
nausea; diarrhea; mouth sores or ulcers; swelling of the
face; or red or inflamed eyes.
Source URL:
page 30 / 44
http://www.aphadruginfoline.com/alerts-and-recalls/skin-reactions-some-fatal-combination-therapy
page 31 / 44
Alerts and Recalls
Generic Name (Trade Name—Company)
Uses/Notes
December 19, 2012
Dabigatran
(Pradaxa—Boehringer-Ingelheim)
Do not use in patients with mechanical heart valves
FDA warned yesterday that dabigatran should not be
used in patients with mechanical heart valves, because
use in this patient population has been associated with
an increased risk of major thromboembolic events. The
alert is a result of data from the RE-ALIGN trial, which
showed that patients given dabigatran were more likely
to experience strokes, myocardial infarctions, and blood
clots forming on mechanical heart valves compared with
those treated with warfarin. In addition, more bleeding
events were observed after mechanical heart valve
surgery in the dabigatran group than in the warfarin
group.
RE-ALIGN was a European clinical trial which was
terminated early once adverse events were observed in
the dabigatran arm. In this trial, patients with bileaflet
mechanical prosthetic heart valves were randomized to
dose-adjusted warfarin (international normalized ratio
[INR] 2–3.5) or to dabigatran 150 mg, 220 mg, or 300
mg twice a day. The investigators reported that use of
dabigatran was associated with significantly more
thromboembolic events, such as valve thrombosis (2.5%
vs. 0%), stroke (5.0% vs. 0%), and myocardial infarction
(1.9% vs. 0), and major bleeding (3.8% vs. 1.1%),
compared with the warfarin treatment arm. The major
bleeding was predominantly postoperative pericardial
effusions requiring intervention for hemodynamic
compromise and was reported in patients who were
initiated on dabigatran postoperatively within 3 days
after mechanical bileaflet valve implantation and in those
whose valves had been implanted more than 3 months
previously.
FDA has added a contraindication stating that
dabigatran should not be used in patients with
mechanical heart valves. In addition, the agency
recommended that providers promptly transition any
patient with a mechanical heart valve who is taking
dabigatran to another medication. The use of dabigatran
is also not recommended for those with other types of
heart valves.
Source URL:
page 32 / 44
http://www.aphadruginfoline.com/alerts-and-recalls/do-not-use-patients-mechanical-heart-valves
page 33 / 44
Supplemental Approvals
Generic Name (Trade Name—Company)
Uses/Notes
December 19, 2012
Management of primary humoral immunodeficiency
Immune globulin
Biotest announced FDA approval of immune globulin
intravenous (human) 10% liquid for the treatment of
patients with primary humoral immunodeficiency (PI).
The product is a sugar-free, glycine-stabilized, I.V.
immune globulin available in 50-mL (5-g) and 100-mL
(10-g) tamper-evident vials. In addition, Biotest noted
that the product uses a label with an integrated hanger
and the packaging material is latex free.
(Bivigam—Biotest)
New formulation manufactured in US
The approval was based on a Phase III, open-label,
multicenter study in 63 patients with PI. Patients were
treated every 3 or 4 weeks with 300–800 mg/kg of
immune globulin for 1 year. The primary efficacy
endpoint was demonstration that the rate of acute
serious bacterial infections was less than 1.0 per
person–year during regular administration of the
product. The study achieved its primary endpoint for
efficacy and was also shown to be safe and tolerable.
Biotest also noted that this is the first polyspecific
intravenous immune globulin they are manufacturing in
the United States. They plan to eventually produce up to
1.5 million g (1.5 tons) of immune globulin in the U.S.
facility.
Source URL:
http://www.aphadruginfoline.com/supplemental-approvals/new-formulation-manufactured-us
page 34 / 44
New Drug Approvals
Generic Name (Trade Name—Company)
Uses/Notes
December 20, 2012
Management of short bowel syndrome
Teduglutide
FDA announced today the approval of teduglutide to
treat short bowel syndrome in adult patients who need
additional nutrition from intravenous parenteral nutrition.
The drug acts by improving intestinal absorption of fluids
and nutrients, thereby reducing the frequency and
volume of parenteral nutrition. The agency noted that
this is the third drug approved to treat adults with short
bowel syndrome receiving nutritional support.
(Gattex—NPS)
New drug enhances intestinal absorption
Approval was based on data from two clinical trials and
two extension studies. Patients in these trials were
randomized to teduglutide or placebo. Results from the
two clinical trials showed that 46% and 63% of patients
treated with teduglutide achieved a clinical response,
defined as achieving at least a 20% reduction in the
volume of weekly parenteral nutrition, compared with 6%
and 30% of patients in the placebo group. In addition,
results showed a mean reduction in parenteral nutrition
of 2.5 L/wk and 4.4 L/wk in teduglutide-treated patients,
compared with 0.9 L/wk and 2.3 L/wk reductions in
placebo-treated patients.
Data from the two extension studies showed that
patients treated with teduglutide experienced a 4.9 L/wk
and 5.2 L/wk mean reduction in parenteral nutrition after
1 year of continuous treatment, and six patients in the
extension studies were weaned off parenteral nutrition
while on teduglutide.
Abdominal pain, injection-site reactions, nausea,
headaches, abdominal distension, and upper respiratory
tract infection were the most common adverse events in
the trials. In addition, teduglutide may be associated with
an increased risk of developing cancer and polyps in the
intestine, obstructions in the intestine, gallbladder
disease, biliary tract disease, and pancreatic disease.
FDA noted that the drug is being approved with a Risk
Evaluation and Mitigation Strategy to ensure that the
benefits of therapy outweigh the risks.
Source URL:
page 35 / 44
http://www.aphadruginfoline.com/new-drug-approvals/new-drug-enhances-intestinal-absorption
page 36 / 44
Alerts and Recalls
Generic Name (Trade Name—Company)
Uses/Notes
December 20, 2012
No generic name
(Slimdia Revolution—P&J Trading)
Sibutramine found in dietary supplement
P&J Trading announced that it is conducting a voluntary
recall of all lots of Slimdia Revolution products after FDA
testing found that the products contained sibutramine.
This ingredient was withdrawn from the U.S. market
because it has been shown to substantially increase
blood pressure and/or pulse rate in some patients and
may present a significant risk to patients with a history of
coronary artery disease, congestive heart failure,
arrhythmias, or stroke.
Slimdia Revolution has been distributed nationwide in
the United States from March 2012 to December 2012.
Patients in possession of Slimdia Revolution products
are advised to return any unused product to the
company directly for a full refund.
Source URL:
http://www.aphadruginfoline.com/alerts-and-recalls/sibutramine-found-dietary-supplement
page 37 / 44
Alerts and Recalls
Generic Name (Trade Name—Company)
Uses/Notes
December 20, 2012
Hydrocodone bitartrate/acetaminophen
(No trade name—Mylan)
Oversized tablets result in another recall
Mylan announced that it is conducting a voluntary
nationwide recall to the retail level of three lots of
hydrocodone bitartrate/acetaminophen tablets 10
mg/500 mg (lots 3037841, 3040859 and 3042573). The
products are being recalled because of the possibility
that a small number of tablets from the affected lots may
exceed the weight requirement and could exceed the
label claim potency requirements for the ingredients.
The three lots were manufactured by Qualitest, and
Mylan repackaged and distributed the product in unit
dose (CD100) under the UDL Laboratories label.
Qualitest first initiated this recall on December 6, 2012.
Source URL:
http://www.aphadruginfoline.com/alerts-and-recalls/oversized-tablets-result-another-recall
page 38 / 44
Supplemental Approvals
Generic Name (Trade Name—Company)
Uses/Notes
December 20, 2012
Treatment of influenza
Oseltamivir
FDA announced today that it has expanded the
approval of oseltamivir to treat pediatric patients as
young as 2 weeks who have shown symptoms of
influenza for no longer than 2 days. The agency noted
that the drug is not approved to prevent influenza in this
population.
(Tamiflu—Roche)
Expanded approval to as young as 2 weeks
The expanded approval was based on extrapolation of
data from previous study results in adults and older
children, as well as additional supporting safety and
pharmacokinetic studies sponsored by both the National
Institutes of Health and Roche. FDA noted that
pharmacokinetic data indicated that a dose of 3 mg/kg
twice daily provided concentrations of oseltamivir similar
to those observed in older children and adults and is
expected to provide similar efficacy in this very young
age group. Results from safety studies showed the
safety profile in children younger than 1 year to be
consistent with the established safety profile of adults
and older children. The most common adverse events
reported in this age group included vomiting and
diarrhea.
FDA noted that dosing for children younger than 1 year
must be calculated for each patient based on their exact
weight. These children should receive 3 mg/kg twice
daily for 5 days. These smaller doses will require a
different dispenser than what is currently copackaged
with the drug.
Osetamivir was originally approved to treat adults
infected with influenza who have shown symptoms for
no longer than 2 days, and was subsequently approved
to treat patients 1 year and older. In addition, the drug is
approved to prevent influenza in adults and children 1
year and older.
Source URL:
http://www.aphadruginfoline.com/supplemental-approvals/expanded-approval-young-2-weeks
page 39 / 44
New Drug Approvals
Generic Name (Trade Name—Company)
Uses/Notes
December 20, 2012
Reduce the severity of chicken pox infections
Varicella zoster immune globulin
FDA announced the approval of varicella zoster
immune globulin for reducing the severity of chickenpox
infections in high-risk individuals when given within 4
days after exposure. It is approved for
immune-compromised children and adults, newborns,
pregnant women, premature infants, children younger
than 1 year old, and adults with no immunity to varicella
zoster virus (VZV).
(Varizig—Cangene)
New therapy to reduce chickenpox symptoms
Varicella zoster immune globulin is an antibody
preparation manufactured from plasma of healthy
donors with high anti-VZV antibody levels. It is
administered in two or more injections, depending on the
weight of the recipient, within 96 hours after exposure.
FDA noted that the product has been available under an
investigational expanded access protocol during the
licensing process.
Studies have shown the product to be comparable to a
previously marketed varicella zoster immune globulin in
preventing infection during pregnancy. In addition, data
collected from individuals treated under the expanded
access protocol showed a low rate of severe VZV
infection in susceptible individuals, compared with the
rate in untreated individuals. The studies also showed
the product to be safe for its intended use, with the most
common adverse effects being pain at the injection site
and headache.
Source URL:
http://www.aphadruginfoline.com/new-drug-approvals/new-therapy-reduce-chickenpox-symptoms
page 40 / 44
New Drug Approvals
Generic Name (Trade Name—Company)
Uses/Notes
December 25, 2012
Management of homozygous familial
hypercholesterolemia
Lomitapide
Aegerion announced FDA approval of lomitapide
capsules as an adjunct to a low-fat diet and other
lipid-lowering treatments, including low-density
lipoprotein (LDL) apheresis where available, to reduce
LDL-C, total cholesterol (TC), apolipoprotein B (apo B),
and non- high-density-lipoprotein cholesterol (non-HDL)
in patients with homozygous familial
hypercholesterolemia. Patients with this rare genetic
lipid disorder have impairment of receptors that remove
LDL from the body, resulting in extremely high levels
and development of premature and progressive
atherosclerosis.
Lomitapide is a microsomal triglyceride transfer protein
(MTP) inhibitor. Inhibiting MTP reduces the level of
cholesterol that the liver and intestines assemble and
secrete into the bloodstream. This is the first MTP
inhibitor approved by the FDA for any indication.
Approval was based on data from a Phase III,
single-arm, open-label trial that evaluated the use of
lomitapide in 29 adult patients with homozygous familial
hypercholesterolemia. Patients were treated with
lomitapide at an initial dose of 5 mg daily and gradually
escalated to doses of 10 mg, 20 mg, 40 mg, up to 60
mg, based on tolerability and acceptable liver enzymes
levels. Results from the study showed that when
lomitapide was added onto existing lipid-lowering
treatment, LDL cholesterol was significantly reduced
from a baseline average of 336 mg/dL to 190 mg/dL
(40% reduction) at week 26. In 23 patients, LDL
cholesterol was reduced by an average of 50% at week
26. Some of the more common adverse events
observed in this trial included diarrhea, nausea,
vomiting, dyspepsia, and abdominal pain.
Aegerion noted that the drug has been approved with a
boxed warning citing the risk of hepatotoxicity. Because
of the risk of liver toxicity, lomitapide will only be
available through the restricted Juxtapid Risk Evaluation
page 41 / 44
(Juxtapid—Aegerion)
Novel lipid treatment for rare disorder
and Mitigation Strategy Program. Aegerion will certify all
health care providers who prescribe the drug and
pharmacies that dispense the medicine.
Source URL:
http://www.aphadruginfoline.com/new-drug-approvals/novel-lipid-treatment-rare-disorder
page 42 / 44
Supplemental Approvals
Generic Name (Trade Name—Company)
Uses/Notes
December 25, 2012
Acute treatment of agitation
Loxapine
Alexza announced FDA approval of loxapine inhalation
powder for the acute treatment of agitation associated
with schizophrenia or bipolar I disorder in adults.
Loxapine is an antipsychotic agent that is already
marketed in capsule form. Alexza noted that this new
formulation of loxapine uses the company’s proprietary
Staccato delivery system, which is a hand-held inhaler
that delivers a drug aerosol to the deep lung that results
in rapid systemic delivery and absorption.
(Adasuve—Alexza)
First inhalation powder for agitation
Approval was based on data from more than 1,600
patients. In two Phase III trials, loxapine 10 mg
inhalation powder was found to be effective in the acute
treatment of agitation in adults with schizophrenia or
bipolar I disorder. Treatment resulted in statistically
significant reductions in agitation as compared with
placebo at the 2-hour post-dose time point. Rapid effects
were noted with the drug in agitated patients, with
statistically significant reductions in agitation apparent
starting at 10 minutes following administration of a dose
versus placebo.
Alexza noted that loxapine inhalation powder can cause
bronchospasm that has the potential to lead to
respiratory distress and respiratory arrest. The drug will
only be available through a restricted program under a
Risk Evaluation and Mitigation Strategy (REMS) called
the Adasuve REMS. The product can only be
administered in health care facilities with immediate
access to on-site equipment and personnel trained to
manage acute bronchospasm.
Source URL:
http://www.aphadruginfoline.com/supplemental-approvals/first-inhalation-powder-agitation
page 43 / 44
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