Download Express Scripts Drug Information & Wellness Center Drug Information Updates

July 2012
Volume 4 Issue 4
Express Scripts Drug Information & Wellness Center
Drug Information Updates
In the News
Special points of interest:
 In the News
Cefepime and Seizure Risk

On June 26th 2012, the FDA reminded health-care providers about the need to adjust the dose of
cefepime in patients with renal impairment due to the increased risk of seizures.

The FDA’s Adverse Events Reporting Database revealed that from 1996 through February 2012,
59 cases of nonconvulsive status epilepticus had been reported.

According to FDA’s research, these patients were typically over the age of 50, had underlying renal
dysfunction, and had not received appropriate dosage adjustment.
 New Drug Approvals
Health-care professionals are advised to adjust cefepime doses in patients with a creatinine clearance of < 60 mL/min. If seizures associated with cefepime therapy occur, consider discontinuing
 New Generic Approvals
cefepime or making appropriate dose adjustments in patients with renal impairment.
 Drug Information Question
The cefepime package insert is being revised to highlight this risk.


Ondansetron and Prolonged QT Interval


 Drug Recalls
 New Formulations and
Indications
 Drug Shortages
On June 29th 2012, the FDA notified health-care professionals about the results of a study showing  Apps of the Month
that a single intravenous dose of 32 mg of ondansetron may prolong the QT interval by 20 milliseconds when compared with placebo.
 Recent Guideline Updates
GlaxoSmithKline (GSK) has announced changes to ondansetron labeling to remove the 32 mg
single intravenous dose.

Updated labeling will state that ondansetron 0.15 mg/kg can still be used for chemotherapy-induced
nausea and vomiting in adults and children, but no single intravenous dose should exceed 16 mg.

The FDA will evaluate the final results of the study when available and will work with GSK in order
find an alternative single dose regimen that is both safe and effective for chemotherapy-induced
nausea and vomiting.
Drug Recalls
Leucovorin Calcium 500 mg Injection, by Bedford Laboratories (07/03/12)
Reason/Problem:
 Lots 2038374, 2038374A, and 2017620 (expiration dates of February 2013 and January 2013)
were voluntarily recalled due to the discovery of visible crystalline particulate matter in a small
number of the vials. The crystalline matter has been identified as active drug and foreign material.
Vecuronium Bromide 20 mg Vials, by Bedford Laboratories (06/28/12)
Reason/Problem:
 Lot 2067134 (expiration May 2013) was voluntarily recalled after the discovery of particulate matter
in a small number of the vials. The matter has been recognized as a potential health hazard.
Introvale® by Sandoz (06/05/12)
Reason/Problem:
 Lots LF00478C, LF00479C, LF00551C, LF00552C, LF00687C, LF00688C, LF00763C, LF00764C,
LF00765C and LF01261C were voluntarily recalled after the discovery of a packaging flaw where
the white placebo tablets were mistakenly in the ninth row (labeled "Week 9") of the 13-row blister
card, rather than in the correct position in the 13th and final row (labeled "Week 13").
Created by: Saima Farooqui, Steven Gibson, and Michael Sheppard,
PharmD Candidates
Page 2
Volume 4 Issue 4
Express Scripts Drug Information & Wellness Center
New Formulations and Indications
Combivir (lamivudine and zidovudine) tablets for oral suspension by
VIIV Healthcare
Class: Antiretroviral agent
Indication: HIV infection
MOA: Combivir inhibits reverse transcriptase by DNA chain termination
after nucleoside analogue incorporation.
New Formulation: Tablets for oral suspension (30 mg/60 mg)
Durezol (difluprednate opthalmic emulsion) by Alcon Vision
Class: Adrenal Glucocorticoid
Indication: Inflammation and pain associated with ocular injury
MOA: Durezol is a topical corticosteroid that inhibits the inflammatory
response to a variety of agents that may delay or slow healing.
New Indication: Treatment of endogenous anterior uveitis
Erbitux (cetuximab) by Imclone
Class: Monoclonal Antibody
Indication: Metastatic Colorectal Cancer (EGFR expressing)
MOA: Erbitux specifically binds to EGFR blocking phosphorylation and
activation of receptor–associated kinases, resulting in inhibition of growth
and survival of tumor cells that over-express the EGFR.
New Indication: KRAS mutation negative, EGFR expressive, metastatic
colorectal cancer in combination with the chemotherapy regimen FOLFIRI
(irinotecan, 5-fluorouracil, leucovorin)
Lyrica (pregabalin) by Pfizer
Class: Gamma aminobutyric acid analog
Indication: Fibromyalgia and management of neuropathic pain for diabetic
peripheral neuropathy
MOA: Lyrica is a GABA analog and binds to the alpha (2) delta site in
CNS tissues. It also decreases the calcium dependent release of pronociceptive neurotransmitters, possibly by modulation of calcium channel
function.
New Indication: Neuropathic pain associated with spinal cord injury
New Drug Approvals
Belviq (lorcaserin hydrochloride) by Arena Pharms:
(06/27/12)
Class: Selective serotonin receptor 2C agonist
Indication: Obesity
MOA: Belviq’s exact mechanism is unknown, but it is believed to
promote satiety and decrease food intake by activating the 5HT
(2C) receptors on anorexigenic pro-melanocortin neurons in the
hypothalamus.
Dosing: 10 mg orally twice daily
Myrbetriq (Mirabegron) by Astellas Pharma:
(06/28/12)
Class: Beta-3 adrenoreceptor agonist
Indication: Bladder muscle dysfunction
MOA: Myrbetriq activates the beta-3 adrenoreceptor on the detrusor muscle of the bladder resulting in increased bladder filling; the
amplitude of bladder contractions during micturition is not suppressed.
Dosing: 25 mg orally daily
Perjeta (Pertuzumab) by Genetech:
(06/08/12)
Class: Monoclonal antibody
Indication: Metastatic breast cancer with HER2 overexpression
MOA: Perjecta binds to the extracellular domain of the HER2
protein. This inhibition of ligand-initiated intracellular signaling
results in cell growth arrest and apoptosis.
Dosing: Initial dose: 840 mg IV over 60 minutes, then every three
weeks 420 mg IV infusion over 30-60 minutes
New Generic Approvals
Generic
Clindamycin Phosphate/Benzoyl Peroxide
Clopidogrel
Dextromethorphan Polistirex
Diclofenac Sodium/Misoprostol
Levonorgestrol
Pregabalin
Tolterodine Tartrate
Approval Date
06/26/12
05/17/12
05/31/12
07/09/12
07/12/12
07/03/12
06/26/12
Brand
Duac
Plavix
Delsym
Arthrotec
Plan-B One-Step
Lyrica
Detrol
Page 3
Express Scripts
Drug Information & Wellness Center
Southern Illinois University Edwardsville
Monday — Friday
8 a.m. — 4 p.m.
Drug Information Question
A patient states that they cannot take albuterol due to the development of hives, but they tolerate levalbuterol (Xopenex) with no complications. Is there any evidence that supports that this could be related to the active ingredient?
Micromedex DrugDex states that a hypersensitivity reaction to albuterol is a contraindication to the use of levalbuterol. As a precaution,
it also states that both albuterol and levalbuterol can cause immediate hypersensitivity reactions that can manifest as urticaria. However, the
incidence of these reactions does in fact differ between the 2 medications. The incidence is described as approximately 6% for albuterol compared to “rare” for levalbuterol.
Foye’s Principles of Medicinal Chemistry was consulted to compare the isomer to the racemate.1 It states that levalbuterol is only composed of the (R)-isomer, and the (S)-isomer (found in racemic albuterol) may actually oppose the bronchodilation effects of levalbuterol. The (S)enantiomer is pro-inflammatory and achieves higher and prolonged tissue concentrations compared to levalbuterol. Removal of the (S)-isomer
increases the clinical potency of levalbuterol and may provide a reduction in side effects.
Google and Scopus were used to ascertain the (S)-isomer’s role in allergic reactions. Google provided a discussion between two experts at the 2002 American Society of Consultant Pharmacists Midyear Conference.2 They stated that (S)-albuterol increases eosinophil activation, histamine release, mucus production, and the release of several other chemical mediators. An abstract of a review article discovered
through Scopus confirmed that (S)-albuterol is generally considered inert in terms of bronchodilation, but does enhance eosinophil activation and
histamine-induced influx of fluid, proteins, and neutrophils into the airspaces.3 Additionally, a Scopus search provided a murine trial concluding
that (S)-albuterol activates mast cells to produce inflammatory mediators such as histamine.4
In conclusion, it seems that there is some scientific evidence to support this reaction. Because the (S)-isomer of albuterol causes increased histamine release, the presence of urticaria with the racemate is plausible. However, there is no clinical evidence (case reports, descriptions of events in the literature) that a patient who has a histamine-like reaction with albuterol will be able to tolerate levalbuterol.
References:
1. Lemke TL, Williams DA, editors. Foye’s Priniciples of Medicinal Chemistry. 6th ed. Philadelphia: Lippincott Williams & Wilkins; 2008.
2. Improved Chemical Entities: From Bench to Bedside. Available From: http://www.cmecorner.com/macmcm/ascp/ascp2002_01.htm. Accessed
July 17, 2012.
3. Handley DA, Anderson AJ, Koester J, Snider ME. New millennium bronchodilators for asthma: single-isomer beta agonists. Curr Opin Pulm
Med. 2000 Jan;6(1):43-9.
4. Cho SH, Hartleroad JY, Oh CK. (S)-albuterol increases the production of histamine and IL-4 in mast cells. Int Arch Allergy Immunol. 2001
Apr;124(4):478-84.
Drug Shortages
Dextroamphetamine by Teva
 Products: Dextroamphetamine 5 mg and 10 mg tablets
 Reason: Manufacturing delays
 Related information: Teva has dextroamphetamine 5 mg and 10
mg, 100 count packages available on intermittent back order
through mid-2012
Furosemide 10 mg/mL Injection by Hospira, APP, and American
Regent/ Luitpold
 Products: Furosemide 2 mL, 4 mL, 10 mL
 Reason: Manufacturing delays
 Related information: Check with the wholesaler for available inventory
Diazepam Injection by Hospira
 Products: Diazepam 5 mg/mL and the 2 mL Carpuject
 Reason: Manufacturing delays
 Related information: Hospira expects the next delivery to be sometime in July
Ketorolac 15 mg/mL and 30 mg/mL Injection by many manufacturers
 Products: Ketorolac 1 mL and 2 mL
 Reason: Manufacturing delays/raw material shortage
 Related information: Check with the wholesaler for available inventory
Page 4
Apps of the Month
The following applications have been reviewed and critiqued by students and pharmacists:
Name
Micromedex
Drug Information
Calculate by QxMD
Cost
Content
Free
Drug monographs, ability to search by drug name or
class, no internet access required, listed drug interactions. App does not provide the depth of Micromedex DrugDex nor does it include an interaction checker.
Free
More than 150 unique calculators and decision support tools, grouped by specialty, able to view recently used equations and favorite equations, equations
fully explained and referenced.
Rating (1-5)
Recent Guideline Updates
The Infectious Diseases Society of America has released updated guidelines on the diagnosis and treatment of diabetic foot infections.
The general recommendations include the following:




Clinically uninfected wounds should NOT be treated with antibiotic therapy.
Cultures should be obtained from infected wounds before empiric antibiotic therapy, if possible.
Antibiotic therapy is appropriate for all infected wounds, but is usually insufficient unless combined with appropriate wound care.
For mild to moderate infections in patients who have NOT recently received an antibiotic, empiric therapy should target aerobic gram
-positive cocci.



For severe infections, empiric therapy should target MRSA .
If patient has received an antibiotic within the last month, agents against gram-negative bacilli should be included in regimen.
Antibiotic course of therapy should be 1-2 weeks for mild infections and 2-3 weeks for moderate to severe infections.
The Centers for Disease Control and Prevention has updated its evidence-based recommendations for the management of hepatitis B
virus-infected health-care providers and students. The recommendations include the following:

HBV infection alone should not disqualify infected persons from the practice or study of surgery, dentistry, medicine or allied health
fields.

There is no clear justification or benefit from notification of the HBV infection status of a health-care provider to his or her patient
with the exception of instances in which an infected provider transmits HBV to one or more patients or documented instances in
which a provider exposes a patient to a bloodborne infection.

Providers or students with an active HBV infection who do not perform exposure-prone procedures but who practice non– or mini
mally invasive procedures should not be subject to any restrictions of their activities or study.
The American Association for the Study of Liver Diseases has released updated guidelines on the diagnosis and management of nonalcoholic fatty liver disease (NAFLD). Among the recommendations for pharmacologic agents:

Metformin has no significant effects on liver histology and is not recommended as a specific treatment for liver disease in adults with
non-alcoholic steatohepatitis (NASH).

Pioglitazone can be used in patients with biopsy-proven NASH, but the majority of patients in clinical trials were non-diabetic and
long-term safety and efficacy has yet to be established.

Vitamin E administered at a daily dose of 800 IU improves liver histology in non-diabetic adults with biopsy-proven NASH and
therefore should be considered first-line pharmacotherapy for this patient population.

Statins can be used to treat dyslipidemia in patients with NAFLD and NASH.