Download Express Scripts Drug Information & Wellness Center Drug Information Updates

February 2013
Volume 5 Issue 1
Express Scripts Drug Information & Wellness Center
Drug Information Updates
In the News
Special points of interest:
FDA Warns on Insomnia Drugs, Suggests Lower Doses
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Due to next-day impaired alertness and driving, US health regulators recommend that bed-time
doses of zolpidem are decreased
 In the News
 Drug Recalls
The FDA warns that any drug taken for insomnia, particularly ER formulations, can impair any activity that requires alertness after use
 New Formulations and
Indications
Women maybe more susceptible to this risk due to slower elimination rates of zolpidem
The regulator suggested that manufacturers lower the recommended doses of zolpidem along with
its brands (Ambien, Ambien CR, Edluar, and Zolpimist)
Study: Vitamin C supplements tied to kidney stones in men
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A Swedish study concluded that men who take vitamin C supplements are at higher-than-average
risk of developing kidney stones
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The study included middle-aged to elderly Swedish men who answered questions on their diet,
lifestyle, with an 11 year follow-up period (907 vitamin C users, 22,000 non-vitamin C users)
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Swedish supplements usually contain 1,000 mg of vitamin C per tablet
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Vitamin C users were more likely to develop kidney stones for the first time during the study compared to non vitamin C users (Vitamin C users: 31 of 907 participants (3.4%); Non-vitamin C users:
405 of 22,448 participants (1.8%) ), with men taking supplements at least once daily having the
highest risk
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Researches state that results do not prove that use of vitamin C triggers kidney stones to form
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However, patients with history of kidney stones should weigh the possible risk versus benefits of
regular vitamin C use
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More research is needed to determine whether more reasonable doses of vitamin C would increase
risk for kidney stone development
 New Drug Approvals
 New Generic Approvals
 Drug Information Question
 Drug Shortages
 Apps of the Month
 Recent Guideline Updates
Drug Recalls
Lactated Ringers and 5% Dextrose Injection, USP, by Hospira, Inc. (01/25/2013)
Reason/Problem:
 May contain spore like particulate
Super Power, Dietary Supplement, by D&S Herbals, LLC, d/b/a Freedom Trading (01/24/2013)
Reason/Problem:
 Unapproved drug
Ferrous Sulfate Tablets, 325 mg, by Advance Pharmaceutical Inc (01/17/2013)
Reason/Problem:
 Bottle of Ferrous Sulfate Tablets, 325 mg, may actually contain Meclizine HCl 25 mg tablets
Mitosol, Mitomycin for solution, by MobiusTherapeutics, LLC (01/10/2013)
Reason/Problem:

May be non-sterile
Created by: Debbie Carlson and Emily Powers, PharmD Candidates
Express Scripts Drug
Page 2
Volume 5 Issue 1
New Drug Approvals
Kynamro (mipomersen sodium): by Cambridge, Genzyme Corp
(01/29/2013)
Class: second generation antisense oligonucleotide
Indication: homozygous familial hypercholesterolemia (HoFH)
MOA: Works with other lipid-lowering medications and diet to impair the
creation of the lipid particles that ultimately give rise to LDL-C
Dosing: 200 mg subcutaneous injection once weekly
Note: Due to possible risk of steatohepatitis and cirrhosis of the liver, mipomersen sodium is only available through REMS (Kynamro™ REMS)
New Formulations and Indications
Nesina (alogliptin): by Takeda Pharmaceuticals (01/28/2013)
Class: Dipeptidyl peptidase-4 (DPP-4) inhibitor
Indication: treatment of type 2 diabetes in adults as adjunct to diet and
exercise
MOA: lower blood glucose by preventing the breakdown of glucagon-like
peptide-1 (GLP-1)
Dosing: 12.5 and 25 mg once daily by mouth
*dose adjustment based on renal function
Oseni (alogliptin/pioglitazone): by Takeda Pharmaceuticals
(01/28/2013)
Class: Dipeptidyl peptidase-4 (DPP-4) inhibitor/ Thiazolidinedione
Indication: treatment of type 2 diabetes in adults as adjunct to diet and
exercise
MOA: lower blood glucose by preventing the breakdown of glucagon-like
peptide-1 (GLP-1) and by improving target cell response to insulin by acting on PPARgamma
Dosing:
Initial dose: Alogliptin 25 mg/pioglitazone 15 mg or alogliptin 25 mg/
pioglitazone 30 mg
Max dose: Alogliptin 25 mg/pioglitazone 45 mg once daily by mouth
*dose adjustment based on renal function
Kazano (alogliptin/metformin hydrochloride) by Takeda Pharmaceuticals (01/28/2013)
Class: Dipeptidyl peptidase-4 (DPP-4) inhibitor/ Biguanide
Indication: treatment of type 2 diabetes in adults as adjunct to diet and
exercise
MOA: lower blood glucose by preventing the breakdown of glucagon-like
peptide-1 (GLP-1) and by decreasing hepatic glucose production, intestinal
absorption, and by improving insulin sensitivity
Dosing: 12.5 mg alogliptin and 500 mg metformin HCl or 12.5 mg alogliptin
and 1000 mg metformin HCl twice daily by mouth
*Max dose 25 mg alogliptin and 2000 mg metformin HCl
Exjade (deferasirox) tablets East Hanover, N.J.-based Novartis
(01/23/2013)
Class: Selective for iron chelator
Indication: treatment of chronic iron overload caused by blood transfusions (transfusional hemosiderosis) in patients 2 years and older
MOA: It’s tridentate ligand that binds iron with high affinity to iron in a
2:1 ratio
New Indication: treatment of patients ages 10 years and older who have
chronic iron overload resulting from a genetic blood disorder called nontransfusion-dependent thalassemia (NTDT)
Prevnar 13 (pneumococcal 13-valent conjugate vaccine) by Pfizer
(02/05/2013)
Indications:
Children 6 wk– 5yo: for active immunization for the prevention of otitis
media, and invasive disease caused by Streptococcus pneumoniae
serotypes
Adults +50yo: prevention of pneumonia and S. pneumonia invasive
disease caused by the 13 Streptococcus pneumoniae serotypes
MOA: PCV13, composed of polysaccharides of S. pneumoniae serotypes conjugated to a carrier protein (CRM197), elicits a T-cell–
dependent immune response. Protein carrier–specific T cells provide
the signals needed for maturation of the B-cell response.
New Indication: Vaccine-naive children and adolescents 6 to 17 years of
age for active immunization for the prevention of invasive disease
caused by the 13 Streptococcus pneumoniae serotypes contained in
the vaccine
Gleevec (imatinib) by Novartis (01/28/2013)
Class: Tyrosine Kinase Inhibitor
Indication: relapsed or refractory Ph+ ALL, aggressive systemic mastocytosis, dermatofibrosarcoma protuberans, GI stromal tumors, hypereosinophilic syndrome and/or chronic eosinophilic leukemia, and myelodysplastic/myeloproliferative diseases in adults, as well as Ph+ chronic
myeloid leukemia in adults and pediatric patients
MOA: Inhibits Bcr-Abl tyrosine kinase, the constitutive abnormal gene
product of the Philadelphia chromosome in chronic myeloid leukemia
(CML)
New Indication: treatment of children with newly diagnosed Philadelphia
chromosome positive (Ph+) acute lymphoblastic leukemia (ALL)
New Generic Approvals
Generic Name
Doxorubicin hydrochloride liposome injection
Candesartan Cilexetil and HCTZ
Phenytoin Chewable Tablet
Lamotrigine ER Tablet
Tranexamic Acid Tablet
Sildenafil 20 mg Tablet
Acetylcysteine Injection
Single use vials (200 mg/ml)
Tretinoin Capsules
Approval Date
02/04/2013
12/4/2012
12/26/2012
12/26/2012
12/27/2012
11/6/2012
11/7/2012
Brand
Doxil
Atacand-HCT Tablets
Dilantin Chewable Tablet
Lamictal XR ER Tablet
Lysteda Tablet
Revatio Tablet
Acetadote Injection
10/24/2012
Vesanoid Capsules
Page 3
Drug Information Question
Do NSAIDs cause delayed bone healing after fractures? If so, how long following a fracture should NSAIDs be avoided? Are any NSAID
better or worse for this?
COX-2 effects endochondral ossification by signaling the production of pro-inflammatory prostaglandins. Also, COX-2 messenger RNA
has been shown to be locally elevated for the first fourteen days after a fracture, suggesting that it plays an important role in the early stages of
bone repair. Therefore, COX inhibiting agents (NSAIDs) may directly impact bone repair. (1)The occurrence of nonunion of bone in fractures has
been reported with both COX-2 selective and nonselective agents. (2) In one study, fracture healing failed in rats treated with COX-2 selective
NSAIDS (celecoxib, rofecoxib). (3) The 1976 work of Bo et al. suggested that doses >2mg/kg/day of indomethacin inhibited bone repair, but not
lower dosages. Animal studies using high-dosage regimens of diclofenac, celecoxib, rofecoxib, parecoxib, ketorolac, tenoxicam, and etodolac have
all been studied and shown a delay in fracture healing. (1)
There is abundant evidence in animal studies that demonstrates suppression of bone repair after controlled injury with both short and
long term NSAID use. Unfortunately, there are many disparities among the studies and the results have yet to be proven in human subjects. Evidence from human studies primarily consists of uncontrolled retrospective analyses. Currently, there are no strong studies that have explored the
head-to-head effect of short and long-term NSAID use on fracture-repair. Recent evidence suggests that NSAID administration within 90 days of
injury in an older population is significantly associated with nonunion of fractures of long-bones (relative risk, 3.7; 95% confidence interval, 2.4 to
5.6) and that long-duration oral administration significantly reduces local bone formation by up to 58%. It is important to note that patients who are
most likely to have required long-duration NSAID therapy after injury are those who are considered “high-risk” because of additional barriers to the
normal healing process (smoking status, weight, microvascular disease, etc.). Some studies have reported the prevalence of delayed union and
nonunion following long-bone fracture to be as high as 10% without the use of NSAIDs.
When choosing an NSAID, keep in mind the controversy with COX-2 selective agents. These agents are controversial because of their
potentially serious adverse events related to cardiovascular events. Outside of this information, it is unclear whether the effects on bone repair are
class related or agent specific.
In summary, major differences arise in the type of fracture and patient characteristics in the available literature which make it difficult to
extrapolate previous study results. Previous studies conclude that there is an association between NSAID use and delayed healing of spinal fractures, long bone, and stress fractures in humans. Patients at the highest risk for delayed fracture healing include those who are smokers, overweight, diabetic, and those with cardiovascular disease or more traumatic fractures. While COX-2 specific suppression of fracture-healing in animal
studies is evident, the effect in humans is less clear. Whether the effect on bone healing is related to COX-2 specific agents or non-specific
NSAIDs is not well defined. Overall, there is not enough clinical support to avoid NSAIDs in patients with simple fractures. It may be wise to recommend avoiding NSAID use in “high-risk” patients.
References:
1. Kurmis AP, Kurmis TP, O’Brien JX, Dalén T. The Effect of Nonsteroidal Anti-Inflammatory Drug Administration on Acute Phase Fracture-Healing: A Review. J Bone Joint Surg Am.
2012 May 2;94(9):815-23.
2. Solomon DH. Nonselective NSAIDs: overview of adverse effects [internet]. UptoDate, Inc. c2013 [updated 2012 May 9; cited 2013 Jan 23]. Available from: http://www.uptodate.com/
contents/nonselective-nsaids-overview-of-adverse-effects?source=search_result&search=NSAIDs+and+fracture+healing&selectedTitle=1~150
3. Simon AM, Manigrasso MB, O'Connor JP. Cyclo-oxygenase 2 function is essential for bone fracture healing. J Bone Miner Res. 2002 Jun;17(6):963-76.
Drug Shortages
Amytal Sodium Injection by Marathon
 Products: Amytal Sodium Injection USP 0.5 g, 10 ml via
 Reason: Manufacturing
 Related information: Marathon expects next available delivery 4-13
Doxycycline Hyclate by Mutual, Watson, and West-Ward
 Products: 20, 50, 100 mg tablets and capsules
 Reason: Manufacturing delays, limited
 Related information: Product is currently available on an allocated
basis
Sodium Phosphate Injection by American Regent/Luitpold and Hospira
 Products: Sodium Phosphate 3 mmol/mL, all vials
 Reason: Demand increase for drug
 Related information: Hospira expects next delivery in February
Dexamethasone Sodium Phosphate Injection by APP, Pfizer, WestWard and American Regent
 Products: Various strengths/products
 Reason: Backordered or unavailable
 Related information: West-ward expects delivery by end of February, American Regent is currently not manufacturing this product
Express Scripts
Drug Information & Wellness Center
Southern Illinois University Edwardsville
Monday — Friday
8 a.m. — 4 p.m.
(618) 650-5142
Page 4
App of the Month
The following application has been reviewed and critiqued by students and pharmacists:
Name
Cost
AACP Immunization
Advisor
Free
Content
Rating (1-5)
Search vaccine recommendations by age, condition, occupation, travel destinations, sexual activity, addictions,
living arrangements, and family planning. Vaccine library
includes indications, contraindications, administration,
possible side effects, storage and handling, pregnancy/
nursing, boosters, and coding for billing. ACP news updates and vaccine schedules available with an option for e
-mail sign up. The information in this app may be limited
by frequency of updates. The current information is based
on the 2012 ACIP Adult Immunization Schedule.
Recent Guideline Updates
The American Heart Association has released updated guidelines for treatment, management, and secondary prevention of
Ischemic Stroke.
The revised recommendations include the following:
 Eligible patients presenting to the hospital with ischemic stroke should receive intravenous recombinant tissue plasminogen activator (rTPA) within 60 minutes of arrival. TPA administration should not be delayed by waiting for baseline ECG, troponin, and CXR. Only blood glucose checks and a non-contrast enhanced CT or MRI are required prior
to TPA.
 Intravenous fibrinolysis may be considered in patients with mild stroke deficits, rapidly improving stroke symptoms,
major surgery in the prior 3 months, and recent myocardial infarction.
 New guidelines aim to improve outcomes through the expansion of stroke care delivery by utilizing “telestroke” communication with Comprehensive Stroke Centers.
2013 Diabetes Guidelines are now available!
The revised recommendations include the following:
 Blood pressure goal has been changed to < 140/80, based on multiple meta-analyses showing little benefit with
lower targets
 Clarification on when patients requiring multiple daily insulin injections or insulin pumps should test their blood
glucose includes: prior to meals and snacks, occasionally after eating, at bedtime, before exercise, when they
suspect low blood glucose, after treating low blood glucose levels until they return to normal and “prior to critical
tasks such as driving.”
 ADA has not changed LDL goals (LDL cholesterol,100 mg/dL, HDL cholesterol, 50 mg/dL, and triglycerides, 150
mg/dL)
 Abnormal urinary albumin excretion is no longer being differentiated as microalbuminuria or macroalbuminuria.
Any value > 30 is now being described as “increased urinary albumin excretion.”
 Screening for peripheral arterial disease is recommended.
American Academy of Pediatrics, New Guidelines for the management of T2DM in children:
 Recommends lifestyle modifications, such as diet and exercise, with medication for patients ages 10 to 18
 Providers should discuss nutrition with patients when they are diagnosed and during treatment, and if possible,
refer patients to a registered dietitian with expertise in the nutritional needs of youths with type 2 diabetes.
 These guidelines call for further research on whether the associated comorbidities and complications of diabetes
are more aggressive in pediatric populations than among adults.