Download Express Scripts Drug Information & Wellness Center Drug Information Updates

March 2013
Volume 5 Issue 2
Express Scripts Drug Information & Wellness Center
Drug Information Updates
In the News:
New Recommendation: No Daily Vitamin D/Calcium Postmenopause
 There is insufficient evidence to support the use of vitamin D and calcium supplementation to prevent
fractures in community-dwelling men and premenopausal women without decreased bone mineral
density.
 In 2 systematic reviews and a meta-analysis, vitamin D and calcium supplementation had no effect
on the frequency of bone fractures among community-dwelling adults.
 The Women’s Health Initiative (WHI) reported a slightly increased risk for nephrolithiasis associated
with vitamin D and calcium supplementation in a trial with 36,282 healthy postmenopausal women.
 The US Preventive Services Task Force (USPSTF) encourages clinicians to think carefully before
recommending vitamin D and calcium supplementation for healthy patients.
Azithromycin Poses Fatal Cardiac Risk, FDA Warns
 FDA warrants a careful screening of patients for azithromycin due to the risk of potentially fatal irregular heart rhythm.
 Patients at risk for azithromycin-induced arrhythmia include individuals who already have a prolonged
QT interval, low blood levels of potassium or magnesium, abnormally slow heart rate, or take drugs to
treat arrhythmias.
 The announcement follows a study that reported a small, increased risk for sudden cardiac death in
patients taking a 5-day course of azithromycin compared to patients taking amoxicillin or no antibiotics.
 The label of azithromycin has been updated to warn of the risk for QT interval prolongation and torsades de pointes.
Special points of interest:
 In the News
 New Formulations and Indications
 Newly Approved Drugs
 Apps of the Month
 New Generic Approvals
 Drug Safety Recalls
 Resolved Drug Shortages
 New Drug Shortages
 Drug Information Question
$63 Million Won by Teenager from Massachusetts from Johnson & Johnson
 Samantha Reckis experienced the adverse reaction toxic epidermal necrosis in 2003 after taking
Motrin for fever.
 Samantha, now 16, suffered brain damage, lost 90% of her skin, and went blind from the reaction.
 The lawsuit alleged that Johnson & Johnson failed to properly warn consumers in the labeling that Motrin could
cause life-threatening reactions.
 A similar case involving Children’s Motrin in 2011 awarded a Pennsylvania girl $10 million dollars after suffering
toxic epidermal necrosis.
March is National Colorectal Cancer Awareness Month!

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

Colorectal cancer was the second leading cause of cancer-related deaths in 2009.
The US Preventative Services Task Force recommend that adults get a colonoscopy
every 10 years starting at age 50.
Screening helps prevent cancer by identifying and removing precancerous polyps,
or by being able to treat colorectal cancer in its early stages.
Make sure your family and patients aren’t among the 37% of patients who are not
getting screened as recommended!
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Express Scripts Drug Information & Wellness Center
Volume 5 Issue 2
New Formulations and Indications
Delzicol (mesalamine) delayed release capsule (2/1/13)
Indication: mild to moderate ulcerative colitis (UC), or UC in remission
Dosing: 800 mg three times daily for active UC, or 1.6 g in divided doses
New ly Approved Drugs
for UC in remission.
MOA: unknown, but may topically block cyclooxygenase and inhibit prosta- Ravicti (glycerol phenylbutyrate) oral liquid by Hyperion Therapeutics,
glandin production in the colon.
Inc. (2/1/13)
New Formulation: delayed release capsule
Versacloz (clozapine) oral suspension (2/6/13)
Indications: treatment-resistant schizophrenia and reducing suicidal behavior in patients with schizophrenia or schizoaffective disorder.
Dosing: target dose of 300-400 mg daily in divided doses.
MOA: antagonism of dopamine type 2 and serotonin type 2a receptors
New Formulation: oral suspension
Vituz (hydrocodone bitartarate and chlorpheniramine maleate) oral
solution (2/20/13)
Indication: cough and symptoms associated with upper respiratory allergies or a common cold.
Dosing: 5 mL (5 mg hydrocodone/4 mg chlorpheniramine) every 4 - 6
hours as needed.
Mechanism of Action: Hydrocodone: unknown, but is believed to act
directly on the cough center.
Chlorpheniramine: H1 receptor antagonist with anticholinergic and
sedative activity.
New Combination
Stivarga (regorafenib) tablets by Bayer HealthCare Pharmaceuticals
Inc. (2/25/13)
Indication: metastatic colorectal cancer.
Dosing: 160 mg daily for the first 21 days of each 28-day cycle.
MOA: inhibits kinases involved in normal cellular functions and in pathologic processes such as oncogenesis, tumor angiogenesis, and maintenance
of tumor environment.
New Indication: locally advanced, unresectable or metastatic gastrointestinal stromal tumor
Indication: Urea Cycle Disorders
Dosing: 4.5 – 11.2 mL (5 – 12.4 g)/m2 divided among three daily doses
Mechanism of Action: Provides an alternate route for excretion of waste
nitrogen by conjugating with glutamate, which contains two molecules
of nitrogen, via acetylation. It is then excreted renally.
Pomalyst (pomalidomide) capsules by Celgene Corporation
(2/8/13)
Indication: multiple myeloma
Dosing: 4 mg daily on days 1-12 of repeated 28-day cycles until disease
progression
MOA: exerts antineoplastic activity by enhancing T cell- and natural
killer cell-mediated immunity and inhibiting proliferation of
pro-inflammatory cytokines.
Kadcyla (ado-trastuzumab emtansine) for injection by Genetech,
Inc. (2/22/13)
Indication: HER2-positive metastatic breast cancer
Dosing: 3.6 mg/kg as an IV infusion every 3 weeks
MOA: binds to the HER2 receptor and is internalized by the cell and
degraded to release the cytotoxin DM1, disrupting microtubule networks
in the cell and resulting in cell death.
Osphena (ospemifene) tablets by Penn Pharmaceutical Services
Ltd. (2/26/13)
Indication: moderate to severe dyspareunia
Dosing: 60 mg daily with food
MOA: estrogen agonist/antagonist with tissue selective effects
Abilify Maintena (aripirazole) injectable solution by Otsuka America
Pharmaceutical, Inc. (2/28/13)
Indication: schizophrenia.
Dosing: 400 mg IM monthly. Dose range of 160 – 300 mg for poor metabolizers or concomitant CYP450 inhibitors.
W
NE
!
MOA: unknown, but may be through partial agonist activity at D2 and 5HT1A receptors and antagonist activity at 5-HT2A receptors.
New Formulation: once monthly extended release injection
Apps of the Month The following applications for smartphones has been reviewed and critiqued by students and pharmacists:
Name: LactMed
Cost: Free
Name: Google Translate
Cost: Free
Content: Provides information on drug level in breast milk, Rating (1-5):
effects in infants, and effects on lactation for thousands of
medications and herbal supplements. References from the
literature are cited for all information provided. Information
in this app comes from the National Library of Medicine’s
Toxicology Data Network.
Content: Never let the language barrier get between you Rating (1-5):
and your patients again! Provides the ability to translate
text in 65 languages as well as speaking the text in 40
languages.
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Volume 5 Issue 2
Express Scripts Drug Information & Wellness Center
2013 New Drug Shortages
Resolved Drug Shortages
Aminocaproic Acid Injection by Hospira Inc. (03/08/2013)
Products:
 250 mg/mL (20 mL vials)
Reason: No reason provided
Related Information: Shortage per manufacturer due to capacity restraints.
Next delivery available in April with full recovery estimated by June 2013.
Calcitriol 1 mcg/mL Injection by Abbott Laboratories
Related Information: Abbott has supplies available for ordering.
Ammonium Chloride Injection by Hospira Inc. (03/08/2013)
Products:
 5 mEq/mL (20 mL vial)
Reason: Manufacturing delay
Related Information: Hospira anticipates a release date and full recovery to
occur in the second quarter of 2013.
Oxsoralen-Ultra (methoxsalen) 10 mg Capsules by
Valeant Pharmaceuticals International
Related Information: No further supply issues anticipated.
Cytarabine Injection by Bedford, APP, and Hospira Inc.
Related Information: APP and Hospira report good supply and no further
supply issues are anticipated. Beford is working to increase supplies as well.
Propofol Injection by Hospira Inc. and APP
Related Information: No further supply issues anticipated.
Streptomycin for Injection, USP by X-Gen Pharmaceuticals
Related Information: X-Gen now has streptomycin injection available.
Vasopressin Injection by American Regent/Luitpold, JHP, and APP
Related Information: No further supply issues anticipated.
2013 Drug Safety Recalls
New Generic Approvals
Acetylcysteine Solution, USP by Bedford
Reason/Problem: Visible glass particle found in a vial.
Generic
1) Betamethasone/
Calcipotriete Ointment
Brand
Taclonex
Ointment
Lo/Ovral-28 by Pfizer, Inc.
Reason/Problem: Some blister packs may contain an inexact count of inert
or active ingredient tablets and the tablets may be out of sequence.
2) Mupirocin Cream
Bactroban Cream January 24, 2013
3) Rosiglitazone Tablets
Avandia
January 25, 2013
Aveeno® Baby Calming Comfort® by Johnson and Johnson
Reason/Problem: The lot exceeded bacterial specifications
4) Doxurubicin Injection
Doxil
February 4, 2013
5) Mafenide Topical Solution Sulfamylon
February 12, 2013
Treanda (bendamustine HCl) for Injection by Cephalon
Reason/Problem: Presence of particulate matter in vial identified as glass
fragments.
6) Buprenorphine/Naloxone Suboxone
Sublingual Tablets
February 22, 2013
7) Travoprost Opthalmic
Solution
March 1, 2013
Hair Regrowth Products by Perfect Image Solutions, LLC
Reason/Problem: Unapproved new drug products that may present potential
health hazards.
Vagifresh Ball and Gel by USA Far Ocean Group
Reason/Problem: Vagifresh Gel contains benzocaine and Vagifresh Ball
contains numerous bacteria.
Polymyxin B for Injection, USP and Vecuronium Bromide by Bedford
Reason/Problem: Vials may contain visible glass particulates.
Excedrin, NoDoz, Bufferin, and Gas-X by Novartis
Reason/Problem: Products may contain stray tablets, capsules, or caplets
from Novartis products, or contain broken or chipped tablets.
Motrin IB Coated Tablets and Caplets by McNeil
Reason/Problem: May not dissolve as quickly as intended.
Travatan Z
Date Approved
January 14, 2013
8) Zoledronic Acid Injection Zometa
March 4, 2013
9) Desvenalfaxine Extended Pristiq
March 4, 2013
Volume 5 Issue 2
Page 4
Drug Information Question
Why does the African American patient population experience angiotensin converting enzyme inhibitor (ACEi) induced
cough and angioedema at a higher rate relative to other patient populations?
The exact mechanism of ACEi induced cough and angioedema is unclear; however, increased levels of bradykinin (bK)
has been proposed as a possible cause of the side effects. Bradykinin is a potent vasodilator that causes decreased blood pressure.
ACE inhibitors work to decrease blood pressure by inhibiting the breakdown of bradykinin. Gainer et al. investigated the relationship between bK, ethnicity, and ACE inhibitors. Gainer et al. hypothesized that bK sensitivity may play a role in the rate of angioedema seen in African Americans (AA) based on evidence that AA with hypertension have lower levels of urinary kallikrein (an
enzyme which cleaves bK from kininogen) than Caucasians (CC). With lower levels of kallikrein, patients would have a decreased ability to break down bK and would be at greater risk of developing an adverse event from the higher bK levels. Gainer
tested this hypothesis by measuring a wheal response to two separate intradermal doses of bK in hypertensive (N = 47 AA and 41
CC) and normotensive (N = 36 AA and 33 CC) subjects. The doses, 1 µg and 10 µg, were administered on separate days. Both
normotensive and hypertensive AA, at low doses, displayed significantly greater wheal size (p < 0.02 & p < 0.03, respectively)
than their CC comparators. High dose wheal size in normotensive AA was significantly higher than in CC (p < 0.03). Higher doses of bK were associated with greater wheal size in all 4 groups (p < 0.001). Furthermore, AA with hypertension have been shown
to have higher levels of ACE than CC with hypertension. ACE inhibitors prevent ACE from degrading bK. Gainer et al. proposed
that in response to an increase in bK levels seen with ACE inhibitors, AA may have up regulation in bK receptors, thus leading to
an increased sensitivity to bK. (1)
A second Gainer et al. article builds on the results of the 1996 article and goes a step further to investigate if genetic variations that effect intrinsic levels of ACE, seen in different ethnicities, effect the response to exogenous bK increases. As mentioned prior, bK is a potent endogenous vasodilator. Forearm blood flow (FBF), a validated measure of vasodilator response, was
used to determine patient response to exogenous bK. FBF was measured in 14 white and 14 black patients after receiving bK
(100, 200, and 400 ng/min), acetylcholine (15, 30, and 60 µg/min), and sodium nitroprusside (0.8, 1.6, and 3.2 µg/min). Each patient received 1 ml/minute for 5 minutes. FBF was measured over the last 2 minutes of each infusion. Patients were unaware of
their ACE genotype (insertion/deletion variations). No differences existed between gene loci at baseline between groups. Homozygous ACE deletion polymorphism has been shown to result in increased bK degradation. The results of this study show that
normotensive AA patients with homozygous ACE deletion polymorphism, had increased forearm blood flow compared to heterozygous counterparts (p = 0.01). This outcome further supports the hypothesis that exogenous bK may cause an up regulation in bK
receptors in patients whom have typically low bK levels, further detailing how ACE inhibitor induced increase of circulating bK
could lead to increased response to bK side effects. The outcomes of this study also showed that CC ACE heterozygous insertion/
deletion patients had clinically significant higher response (p < 0.001) to exogenous bK than did AA ACE heterozygous insertion/
deletion patients; this result indicates that response to bK is a race specific anomaly that has not been physiologically identified
yet. (2)
The cause of increased rate of ACE inhibitor induced cough and angioedema in African American patients is not immediately clear, although it has been proposed that bK levels play a role. Studies have shown a clinically significant difference between AA and CC in endogenous bK levels as well as in their responses to exogenous bK. Therefore, the adverse reactions such
as angioedema and dry cough manifested in African American patients on ACE inhibitors may be due to an increased up regulation of bK because of lower endogenous levels compared to CC patients.
1: Gainer JV, Nadeau JH, Ryder D, Brown NJ. Increased sensitivity to bradykinin among African Americans. J Allergy Clin Immunol. 1996 Aug;98(2):283-7.
2. Gainer JV, Stein CM, Neal T, et al. Interactive effect of ethnicity and ACE insertion/deletion polymorphism on vascular reactivity. Hypertension 2001;37 (1): 46-51.
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