Dual antiplatelet therapy with a thieno-

pyridine, such as clopidogrel or prasugrel, and

aspirin is the current standard of care after

vascular occlusion requiring stent placement.

When a drug-eluting stent is used, the current

recommended length of therapy is at least one

year to prevent stent thrombosis, which is as-

sociated with myocardial infarction. Although

there still may be a risk of stent thrombosis

even after one year of treatment it has been

controversial if treatment with dual antiplatelet

therapy beyond one year reduces the risk of

myocardial infarction, or if risk reduction was

present if it would outweigh the risk of bleed-

ing. There have not been adequately powered,

randomized trials to look into this until now.

Mauri, et al. conducted an internation-

al, multi-center, randomized, placebo-

controlled trial looking at aspi-

rin+thienopyridine vs. aspirin+placebo after the

standard of therapy for one year had been

completed until thirty months after placement

of the drug-eluting stent. Eligible patients to be

included in the study were those that complet-

ed one year of dual antiplatelet therapy with

clopidogrel dosed at 75mg daily or prasugrel

dosed at 10mg daily, unless the patient

weighed less than 60kg in which case a dose

of 5mg daily was used, alongside aspirin dosed

at 75-162mg daily. During the year of standard

therapy, patients could not have had a major

adverse cardiovascular or cerebrovascular

event, repeat revascularization, or moderate or

severe bleeding and must have been adherent

to thienopyridine therapy. After completion of the study, results

of the primary endpoints of stent thrombosis

and major adverse cardiovascular/

cerebrovascular events were determined. Look-

ing at stent thrombosis, the group randomized

to continue thienopyridine therapy with asprin

had a lower incidence than placebo (0.4% vs.

1.4%; hazard ratio 0.29; 95% CI 0.17-0.48;

p<0.001). Comparing major adverse cardio/

cerebrovascular events, thienopyridine treat-

ment had a lower incidence compared to pla-

cebo (4.3% vs 5.9%; hazard ratio 0.71; 95% CI

0.59-0.85; p<0.001). Thienopyridine therapy

also had lower incidence of myocardial infarc-

tion. The rate of death from both cardiac and

vascular causes and the rate of stroke were

similar for the two groups. The rate of death

from any cause was higher in the thieno-

pyridine group (2.0% vs. 1.5%; hazard ratio

1.36; 95% CI 1.00-1.85; p=0.05). The com-

bined safety endpoint of moderate or severe

bleeding during the randomized part of the trial

found that the thienopyridine group had this

occurrence at a higher frequency (2.5% vs.

1.6%; hazard ratio 1.61; 95% CI 1.21-2.16;

p=0.001) although this was not significant with

respect to fatal bleeding or severe bleeding

alone.

When assessing this study some limi-

tations should be considered. First, patients

had to make it through a year of the standard

therapy without thombosis or moderate to se-

vere bleeding. This may have selected for pa-

tients who were at a lower risk of adverse

events. Also, it did not randomize between

drugs or stents used which could confound

comparisons. Another point to look at is the

rate of deaths from any cause, being higher in

the thienopyridine group. This was attributed

to bleeding, mainly from fatal trauma, and can-

cer-related deaths mediated by bleeding - with

more deaths coming from the cancer cohort.

The authors attributed this to an imbalance of

patients with history of cancer randomly as-

signed to the thenopyridine group by 22 pa-

tients but this difference is not statistically sig-

nificant [488(9.8%) vs. 466(9.5%);p=0.63].

This study was a large, randomized,

placebo-controlled trial looking at the differ-

ence in length of dual antiplatelet therapy after

drug-eluting stent placement. It was of good

design and adequate power. After reviewing

this study, I would recommend prolonging dual

antiplatelet therapy to 30 months in all pa-

tients completing a year of therapy that do not

have a history of cancer.

Written By: Steven Apa

Reference: Mauri L, Kereiakes DJ, Yeh RW, et al. Twelve or 30

Months of Dual Antiplatelet Therapy after Drug-

Eluting Stents. NEJM. 2014. 371(23): 2155-2166

Duration of Dual Antiplatelet Therapy after Drug-Eluting Stent Placement: 12 versus 30 Months

NorthCrest Medical Center

February 2015

Volume 28, Number 22

Pharmacy & Therapeutics B♦U♦L♦L♦E♦T♦I♦N

FORMULARY UDATE

The Pharmacy and

Therapeutics Committee will

meet on February 24th in the

ABC Conference room.

Full Documentation from

meetings are available upon

request.

Approved Additions —

none

Deletions — see agenda

MUE—

Sedation of mechanically

ventilated patients in CCU

Mycamine

Inside this issue:

Drug-Eluting Stents 1

Drug Shortages: Causes

and Management

2

Impact of Increasing Rates of

Neonatal Absentee Syndrome 3

P&T Agenda 4

Current Drug Shortages 5

Shortages of drugs pose a significant public health

threat, delaying or denying critically needed care for patients.

The number of drug shortages quadrupled from 2005 to

2011, jumping from 61 to 2511. In 2010 and 2011, almost

75% of shortages were sterile injectable drugs, which are the

foundation of life-saving cancer treatments, antibiotics, emer-

gency room medications and electrolytes needed for IV feed-

ing. Beginning in 2012, the number of drug shortages has

started to decline thanks to the FDA Safety and Innovation Act

(FDASIA), which gave the agency new authority to deal with

drug shortages by requiring early notification from manufac-

turers. In 2011, the FDA was able to help prevent 195 drug

shortages, and in 2012, 282 drug shortages were prevented2.

In spite of these improvements, shortages involving sterile

injectable drugs are still a problem.

According to most recent ASHP Guidelines on Manag-

ing Drug Product Shortages in Hospitals and Health Systems

(2009), there are many contributing factors to shortages: raw

and bulk material unavailability, manufacturing difficulties

and regulatory issues, voluntary recalls, changes in formula-

tions, manufacturer’s production economics, industry consoli-

dations, restricted drug product distribution, inventory practic-

es, unexpected increases in demand, and shifts in clinical

practice3. Discontinuation is a major contributor to drug short-

ages. Older drugs are discontinued by companies in favor of

newer, more profitable drugs. When one manufacturer discon-

tinues a drug, the remaining manufacturers have a hard time

increasing production quickly and a shortage occurs. The sup-

pliers of raw material are also limited in the amount they can

make due to capacity issues at their facilities. The small num-

ber of manufacturers and limited production capacity for ster-

ile injectables, combined with the complexity of the manufac-

turing injectable drugs, results in exacerbation of drug short-

ages.

Just as we plan for worst scenarios in case of fires,

storms, code blue or pink, etc., we also need to plan for drug

shortages to minimize the impact on patient care and phar-

macy operations. The ASHP has put in place a three-phase

approach to effectively manage and also prevent shortages

(see figure below). The first phase consists of the identifica-

tion of shortages by the purchasing agent and the assess-

ment of the extent and potential effects of these shortages.

Figuring out the inventory usage patterns is useful at this

stage. In the second phase, hospital pharmacies should iden-

tify therapeutic alternatives, communicate with other clinical

staff, establish a collaborative agreement with other health

systems, if appropriate, and prioritize the drugs for a specific

patient population. In the last phase, pharmacies should pre-

pare for potential litigation from patients who might have suf-

fered an adverse event as a result of delays or alternative

therapies. Finally, hospital pharmacies should also consider

the financial implications of expensive alternatives and budg-

et for similar future expenditures.

Managing drug shortages is a complex task for health

systems pharmacies. However, the pharmacy department

must take a leadership role in developing and implementing

appropriate steps to minimize the impact on patient care and

contain costs.

Written by Florentina Eller

References:

1. FDA, DHHS. A Review of FDA’s Approach to Medical Product Shortages.

9/2011. http://www.fda.gov/downloads/AboutFDA/ReportsManualsForms/

Reports/UCM277755.pdf. Accessed 1/24/2015

2. US Food and Drug Administration. Frequently Asked Questions about the

Drug Shortages Program. http://www.fda.gov/Drugs/DrugSafety/

DrugShortages/ucm050796.htm. Accessed 1/24/2015

3. Fox E, Birt A, James K, et al. ASHP Guidelines on Managing Drug Product

Shortages in Hospitals and Health Systems. Am J Health-Syst Pharm. 2009;

66:1399-406.

Drug Shortages: Causes and Management

Page 2 Pharmacy & Therapeutics

Impact of Increasing Rates of Neonatal Abstinence Syndrome

Page 3

The incidence of Neonatal Abstinence

Syndrome (NAS) has increased dramatically

over the past 15 years. Once recent study

in the Journal of Pediatrics found that in

>5% of births, mothers tested positive for

opiates on UDS. There has been almost a 3

fold increase in incidents of NAS in the past

5 years according the data from the Cincin-

nati Children’s Hospital. Among other is-

sues opiate use in expecting mothers has

been linked to premature birth, respiratory

complications, GI dysfunction, and

CNS irritability.

Tools for assessing withdrawal

manifestations are used to quantify severity

and determine the initiation of pharmalogic

therapy and drug titrations. Examples of

some tools are the Finnegan scoring

system, Lipsitz Tool, Neonatal Narcotic

Withdrawal Index, Ostrea System, and

Neonatal Withdrawal Inventory. Every insti-

tution should have a chosen assessment

tool and nurses should be trained to ade-

quately and routinely preform these

assessments.

Another complicating issue is that

management of NAS can vary greatly

because of the lack of evidence for one

clear treatment strategy and lack of a

control population. As of right now either

morphine or methadone is the

recommended treatment for NAS.

Traditionally there have been other options

but paregoric and tincture of opium are

falling out of favor due to their unwanted

adverse effects and other safety concerns.

The pharmacokinetic issue of methadone,

which has a long and variable half-life,

makes it less preferred compared to

morphine.

Other treatment options that are lacking

evidence but are promising include

clonidine and buprenorphine. Both are

viable options for neonates that are failing

treatment of NAS with morphine.

Traditionally, phenobarbital was used as

adjunct therapy and in some institutions is

still the primary drug of choice but as new

evidence emerges a trend to adopt

alternative therapies can be seen.

Therapies including benzodiazepines have

been studied as well because they

suppress neurological excitability.

Diazepam is the most common

benzodiazepine studied as of now.

The use of non-pharmalogical therapy is an

adjunctive imperative treatment that has

evidence to support its use. As new

evidence emerges, drug therapies will

change and although studies are

lacking, there has been a sharp rise in

interest in NAS because of the quick rise in

the incidence of NAS in the past few years.

Wexelblatt SL, Ward LP, Torok K, Tisdale E, Meinzen-derr JK,

Greenberg JM. Universal Maternal Drug Testing in a High-

Prevalence Region of Prescription Opiate Abuse. J Pediatr.

2014

Parlier AB, Fagan B, Ramage M, Galvin S. Prenatal care,

pregnancy outcomes, and postpartum birth control plans

among pregnant women with opiate addictions. South Med J.

2014;107(11):676-83.

Volume 28, Number 22

Pharmacy & Therapeutics Page 4

PHARMACY & THERAPEUTICS COMMITTEE

AGENDA

February 24th 2015 12:00 noon

1. Review and approval of October 28, 2014 minutes

Old Business (yellow tab) – PowerPoint NPSG3 Compliance – warfarin/enoxaparin dosing guidelines – pharmacy Renal Dosing Report – pharmacy interventions

New Business (red tab) – PowerPoint unless noted Formulary Additions and Deletions Additions – none Deletions:

Uroblue

Tetracyline

Moduretic

Minocycline

Carbamazepine suspension

Cefaclor 250mg po

Candida albicans skin test

Aminocaproic acid 500mg

Amiloride & HCTZ tablet 5-50mg

Chlorzoxazone tablet 500mg

Aridol (PFT testing-no longer available)

Phophasal

PNU-23 (pneumonia vaccine)

Large Volume Fluid Shortage – attached Propofol Shortage

MUE Propofol (Diprivan) Micafungin (Mycamine)

Protocols (green tab) – attached * PNU-23 and Flu vaccine admission protocol COPD

Policies (blue tab) *

Adult Massive Transfusion

Therapeutic Hypothermia

Order Reconciliation

Approval of Outsource Pharmacies

NorthCrest—Current Drug Shortages (1/28/15)

Volume 28, Number 21 Page 5

Out of Stock/Unavailable Legend

added new

RED Restriction:

ER/CCU/OR

Yellow Order with Caution

Green Good Supply

Out of Stock/Unavailable Out

Atropine Pediatric 0.5mg/5ml PFS

Caffeine/sodium benzoate 2 ml vial

Calcium Gluconate

Chloroprocaine 20mg/ ml 20ML

Digoxin 0.5mg / 2ml inj

Diltiazem ADD-VANTAGE 100mg

Epinephrine 1:1000 (PF) 1ml inj

Indigo Carmine -

Morrhuate inj 50mg/1ml

Pancuronium inj

Protonix IV

Phentolamine 5mg/ 1ml

Vecuronium 20mg inj

Restricted Use

Tuberculin Skin Test

Critical Low

2000 ml Sterile Water

0.9% Sodium Chloride 250ADV added new

0.9% Sodium Chloride 3000ml

Hydralazine 20mg/1ml inj

HydrOXYzine injection 50mg /1ml

Ketorolac Injection added new

Multitrace injection

Multivitamin 10 ml inj

Phenylephrine Opth Drops 10%

Phenylephrine Opth Drops 2.5 %

Proparacaine 0.5% /15 ml

0.9% Sodium Chloride 250 ml added new

Vancomycin

Good Supply

https://www.ashp.org/menu/DrugShortages/CurrentShortages

Volume 28, No 22February 2015

This publication is produced by the

Department of Pharmacy

Services and the Pharmacy and

Therapeutics Committee at

NorthCrest.

Editor Jeremy Felker, PharmD. and

Brian Barnes, PharmD.

Director of Pharmacy Services

Keith Kuboske, PharmD. DPh

Chairman, Pharmacy &

Therapeutics Committee

Ronnie Jackson, MD

100 NorthCrest Drive

Springfield, TN 32610-0316

Phone: 615-384-1553

NorthCrest Medical Center Department of Pharmacy

Drug Information Questions?

Contact the Pharmacy: Call 384-1523 or

1-800-599-8870 after hours

This service for physicians and other healthcare

professionals taking care of NorthCrest Medical

Center patients.

All answers are thoroughly researched

and referenced