Don’t Let the Bed Bugs Bite...Really

Bed bugs used to be a problem only in devel-

oping countries. However, they have been

spreading rapidly in parts of the US, Canada,

UK, and other developed countries. Bed bug

infestations can occur in houses, dormitories,

apartments, homeless shelters, hotels, cruise

ships, buses, and trains.

Bed bugs are a public health pest, but do not

spread disease. The presence of bed bugs

does not mean a room is not clean; bed bugs

have been found in five-star hotels and resorts.

Adult bed bugs are long and brown about the

size of an apple seed with a flat, oval-shaped

body. Young bed bugs are smaller and translu-

cent or whitish yellow color. Bed bug eggs are

about the size of a pinhead and pearl-white in

color.

When bed bugs bite...

Bed bug bites can look like mosquito bites,

rashes, or hives. Itching, welts, or swelling

usually occur one to several days after the

initial bite. Some people do not react to the

bites and do not develop any signs of bites.

To detect bed bugs:

Bed bugs generally avoid light. They hide

during the day and feed at night. Bed bugs

deposit their eggs in crevices of walls, floors,

bedding, and furniture.

A sweet, musty odor in sleeping areas may

indicate a heavy bed bug infestation. Look

Volume

November 2015

We welcome any comments

and suggestions for future

newsletter topics.

Editors in Chief:

Sherrill Brown, DVM, Pharm.D, BCPS

Micah Miller, PharmD

Varubi™ (rolapitant)

2

Patient Information: Acne

3

Patient Information: Smoking Cessation

4

Corlanor® (ivabradine)

5

Addyi™ (felbanserin)

7

Inside this issue:

DIS News Col lege of Heal th Professions and Biomedica l Sc iences

Drug Informa tion Service

closely at blankets, sheets, and mattress pads for

blood specks or shell-like bed bug remains.

Don’t let the bed bugs bite...

Do not pack or unpack luggage on the bed

or floor. Use racks o prevent bed bugs from

attaching to your belongings.

Reduce clutter at home to keep bed bugs

from finding a hiding place.

Vacuuming frequently helps to reduce the

bed bug infestations.

Seal cracks and crevices around baseboards

to reduce bed bug hiding places.

Dry bedding and clothing at high tempera-

tures for 30 minutes to kill bed bugs.

Contact a pest management professional if

the bed bug infestation persists.

To treat bed bug bites:

Wash bites with soap and water to prevent

infection and decrease itching.

Reduce itching with over-the-counter medi-

cations—oral antihistamines or topical anti-

histamine or corticosteroid creams

Bacterial infections can occur due to exces-

sive scratching and broken skin. Talk to

your medical provider if you notice blisters,

swollen red skin, or oozing sores.

By David Hernández Ángeles, PharmD Candi-

date

Adult bed bug http://www2.epa.gov/sites/production/files/styles/large/

public/2014-01/bed-bug-size-millimeters.png?

itok=WLBvG24C

Bed bug eggs https://www.epa.gov/sites/production/files/2013-09/bed-

bug-eggs-221px_0.jpg

References on Page 6

Page 2

Varubi™ (rolapitant) is a promising new NK-1 receptor antagonist for reducing the incidence of chemotherapy-induced nausea

and vomiting (CINV) in the delayed phase of the at-risk period (24-120 hours after chemotherapy).1-4 Its long half-life and dura-

tion of action allow for a single oral dose (along with concomitant antiemetic administration) to prevent CINV during the entire at

-risk period. Unlike other NK-1 antagonists, rolapitant does not appear to exhibit strong inductive or inhibitory effects on

CYP3A4, which significantly reduces its potential for interactions with many other medications. Rolapitant is a safe, effective

alternative for patients undergoing moderately or highly emetogenic chemotherapy.1-4

Rolapitant disrupts the signaling pathway responsible for causing delayed phase CINV. Co-administration of rolapitant with oth-

er antiemetics provides complete prophylaxis for the entire 120-hour CINV at-risk period.1-4

One oral dose of rolapitant 180 mg (2 tablets) should be administered 1 to 2 hours prior to the start of moderately or highly emeto-

genic chemotherapy. Dexamethasone and a 5-HT3 antagonist should be administered concomitantly with rolapitant.1-4

MEC/AC Trial: Rolapitant was more likely to result in a complete response than placebo in cancer patients on moderately

emetogenic chemotherapy (MEC) regimens (including anthracycline and cyclophosphamide, AC, which are now classified as

highly emetogenic).2 The rolapitant group received a single dose of rolapitant, while the control group received an identical pla-

cebo. Both groups also received granisetron and dexamethasone in accordance with recommendations for CINV prophylaxis. A

complete response (defined as no vomiting or use of rescue medication) occurred in significantly more rolapitant patients than

placebo patients (71.3% vs. 61.6%; p=0.0002).2

The MEC/AC study may not be generalizable to other populations because the study population was mostly female. Use of pa-

tient-reported events may have affected study results due to potential reporting bias.2

HEC-1/HEC-2 Trials: Rolapitant was also more effective than placebo in achieving delayed phase CINV response in cancer

patients receiving cisplatin-based highly emetogenic chemotherapy (HEC).3 In two similar studies, patients received either rolapi-

tant or placebo in addition to appropriate doses of granisetron and dexamethasone for CINV prophylaxis. Significantly more pa-

tients achieved a complete response during the delayed phase in the rolapitant group than in the control group in both HEC trials.

Pooled analysis of both HEC trials demonstrated a better response in rolapitant patients compared to placebo patients (71% vs.

60%; p = 0.0001).3

The study populations in both HEC trials were primarily male, which may limit the generalizability of their results. Additionally,

the primary endpoint was tracked by patients using a using a daily journal, which may have biased the results.3

The rolapitant trials did not compare rolapitant to other available NK-1 antagonists, so no con-

clusions can be drawn regarding the comparative efficacy of individual NK-1 antagonists for

the treatment of CINV.2,3 Studies with active comparator drugs and more diverse patient popu-

lations are needed to fully determine the efficacy of rolapitant.

By Curtis Johnson, PharmD Candidate

REFERENCES:

1. Varubi [package insert]. Waltham, MA: Tesaro, Inc.; September 2015.

2. Schwartzberg LS, Modiano MR, Rapoport BL, et al. Safety and efficacy of rolapitant for

prevention of chemotherapy-induced nausea and vomiting after administration of moder-

ately emetogenic chemotherapy or anthracycline and cyclophosphamide regimens in patients with cancer: a randomised,

active-controlled, double-blind, phase 3 trial. Lancet Oncol 2015;16(9):1071-1078.

3. Rapoport BL, Chasen MR, Gridelli C, et al. Safety and efficacy of rolapitant for prevention of chemotherapy-induced nausea

and vomiting after administration of cisplatin-based highly emetogenic chemotherapy in patients with cancer: two random-

ized, active-controlled, double-blind, phase 3 trials. Lancet Oncol 2015;16(9):1079-1089.

4. Rolapitant. Drug Facts and Comparisons. Facts & Comparisons® eAnswers [online]. St. Louis, MO: Wolters Kluwer

Health, Inc. October 2015. Accessed October 15, 2015.

Varubi™ (rolapitant): Prophylaxis for Delayed CINV

Prevention of Acne: Choosing an Acne Product:

Page 3 DIS News

See Your Healthcare Provider If:

PATIENT INFORMATION: Don’t Pick Acne — Prevent and Treat It!

By Chris Selph,

PharmD Candidate

References on Page 6

Stress Can make acne worse, so find a relaxing

activity like exercise, yoga or meditation

Sun Can cause damage to the skin, so prevent

sunburns

Apply generous amount 15 minutes before

going outside and at least every 2 hours

Clothing Tight fitting clothing can cause irritation and

prevents air flow

Cosmetics Avoid products with oils

Gel Dries skin

Remains on skin for longest time

Non-greasy: good for oily skin

Apply only to affected skin

Solution Dries Skin

Non greasy: Good for oily Skin

Cream and Lo-

tion

Less effective than gels

Less drying than gels or solutions

Best for sensitive skin or dry winter

months

There are many types of acne treatments. Each treatment has different benefits and different side effects. Read below to

find out what is best for you.

Benzoyl Peroxide

Most effective over-the-counter agent; kills bacteria and cleans pores

Works well for acne that is red or swollen

Comes in many strengths

Higher strengths are more likely to irritate skin, so use the lowest strength to prevent prob-

lems

Directions:

Test the product on a small areas of affected skin for 3 days

Then wash 1 time per day with 2 weeks

Then increase in to 2 times per day

If irritation occurs, decrease the strength or how often you use the medication

Can make skin more sensitive to the sun, so use sunscreen

Can bleach hair and fabrics (clothing, pillow covers, and towels)

Salicylic Acid

Removes skin cells and cleans pores

Works well for blackheads and whiteheads

Available in many strengths

Higher strengths may help clear pores better, but may cause more side effects

Directions: use 1 to 2 times per day

If irritating, use only once daily

Less irritating than benzoyl peroxide

Sulfur products

Prevents bacterial growth and cleans pores

Directions: use 1 to 3 times per day

Unpleasant smell

Does not work as well as benzoyl peroxide

You use medications that are thought to cause acne

You have acne that is mostly red and swollen

You have many blackheads and whiteheads with some

red or swollen pimples

Your acne does not improve after 6 weeks of over-the-

counter treatment

Page 4

Tricks and Tips

Delay: most cravings last 5-10 minutes—make yourself wait 10 more minutes.

Avoid triggers: stay away from places and situations where you used to smoke.

Support: ask family and fr iends for help; join a suppor t group (online or in

person).

Distraction: chew something such as gum or car rots, take up a hobby, or try

relaxation techniques such as yoga or meditation.

PATIENT INFORMATION:

Smoking Cessation—It’s Never Too Late To Quit!

Exercise: 30 minutes of moderate

physical activity can stop a craving.

Nicotine Replacement Therapy (NRT)

Options: lozenges, gum, patches.

Do not smoke or use other forms on

tobacco while using NRT.

Consult with a doctor if you have

heart issues, high blood pressure, or

stomach ulcers or are pregnant,

breastfeeding, or <18years of age.

Resources to help you quit

Talk to your health care provider

about counseling resources in your

area.

≥25 cigarettes per day: 4mg <25 cigarettes per day: 2mg

To use: Slowly chew. At first sign of flavor , “park” piece between cheek and

gum. When flavor disappears, chew gum until tingling or flavor returns then “park” in

a different place in the mouth. Do not use > 24 pieces per day. Do not eat or drink

within 15 minutes of using gum.

1st cigarette after waking? ≤30 min: 4 mg >30 min: 2 mg

To use: Allow lozenge to dissolve in mouth. Do not chew or swal-

low. Occasionally move the lozenge around in mouth. Do not use >

5 lozenges in 6 hours or 20 lozenges per day. Do not eat or drink

within 15 minutes of using lozenge.

Weeks 1-6 1 piece or lozenge every 1-2 hours

Weeks 7-9 1 piece or lozenge every 2-4 hours

Weeks 10-12 1 piece or lozenge every 4-8 hours

>10 cigarettes/day ≤10 cigarettes/day To use: Apply to clean, dry, hair less area on upper body or arm. Ro-

tate application area each day. Firmly apply the patch, holding down for

10 seconds. Do not leave on skin for more than 24 hours. Do not cut patch

in half. You may shower , swim, and exercise while wear ing the patch.

21 mg/day for 6 weeks 14 mg/day for 6 weeks

14 mg/day for 2 weeks 7 mg/day for 2 weeks

7 mg/day for 2 weeks

Starting Dose for Nicotine Gum:

Starting Dose for Nicotine Lozenges:

Dosing Schedule for Gum and Lozenges:

Dosing Guide for Nicotine Patches:

By Mary Van Allen, PharmD Candidate

References on Page 6

Page 5

Corlanor® (ivabradine) is new option in the

cardiologist’s toolkit. Ivabradine demon-

strated morbidity and mortality reductions

in patients with heart failure, but not in pa-

tients with a heart rate < 70 beats per minute

(BPM) or an ejection fraction > 40%.2

Ivabradine was used in combination with

beta-blockers in 83-90% of subjects in all

major studies. Most studied patients were

on guideline-directed therapy in conjunction

with ivabradine.3-5

Ivabradine is a negative chronotrope and

inhibits hyperpolarization-activated cyclic

nucleotide-gated channels (HCN), ultimate-

ly regulating HR via the If current or ‘funny’

current.2 The most prominent effects of

ivabradine are observed within the SA node,

as well as prolongation of the AH and PR

intervals. QT prolongation via rate correc-

tion has not occurred in clinical trials, de-

spite an increase in the uncorrected QT in-

terval. Ivabradine does not affect repolariza-

tion. Several factors influence therapeutic

response to ivabradine, including ivabradine

dose and the patient’s baseline resting HR.

In two clinical trials (BEAUTIFUL and

SHIFT), patients with a higher baseline HR

had a more profound therapeutic response

than patients with a lower HR.2-4

SHIFT:

Ivabradine effectively treated patients with

heart failure in the SHIFT study, a 32-

month, multi-center, randomized, double-

blind, placebo-controlled trial.3 Included

patients had an ejection fraction < 35%, a

resting heart rate (HR) > 70 BPM in normal

sinus rhythm, and at least one hospital ad-

mission for heart failure within the previous

year. All patients were also on background

therapy for heart failure. Ivabradine was

started at 5 mg twice daily, with dose titra-

tion based on HR response (dose reduction

for HR < 50 BPM and dose increase for HR

> 60 BPM).3

Patients on ivabradine had lower cardiovas-

cular mortality and fewer hospital admis-

sions due to heart failure (24%) compared to

patients on placebo (29%). Heart failure

deaths were less common in the ivabradine

group (3% vs. 5%). All-cause hospital ad-

missions were also lower in the ivabradine

group (38% vs. 42%).Excluding bradycar-

Corlanor® (Ivabradine): A Funny Tool for Heart Failure

dia, few patients in the ivabra-

dine group experienced seri-

ous adverse events and few

withdrew from the study due

to adverse reactions.3

The results of this study are

applicable only to patients in

normal sinus rhythm with a

HR of 70 BPM. Because

patients with atrial fibrillation

and flutter were excluded from the study

and few geriatric patients were included,

the data are not applicable to those popu-

lations. Because ivabradine was used in

conjunction with beta-blockers, the ef-

fect of ivabradine monotherapy is un-

known. In addition, optimal doses of

guideline-directed therapy were often not

achieved, so the efficacy of ivabradine

under those conditions cannot be extrap-

olated from the results of the SHIFT

study.3

BEAUTIFUL:

Ivabradine treatment did not improve

morbidity/mortality in the BEAUTIFUL

trial, a 24-month, multicenter, random-

ized, double-blind, placebo-controlled

study.4 However, re-analysis of patients

with a HR > 70 BPM revealed a reduc-

tion in morbidity endpoints with ivabra-

dine treatment. Of nearly 11,000 enrolled

patients, 74-94% currently used beta-

blockers and other guideline-directed

therapies. Ivabradine starting dose was 5

mg twice daily, which was then titrated

based on HR response.4

Rates of cardiovascular death and hospi-

talization due to myocardial infarction or

heart failure were similar between the

ivabradine and placebo groups. Patients

with a resting HR > 70 BPM had a sig-

nificant reduction in coronary revascu-

larization when treated with ivabradine

(2.8% vs. 4.0%). Hospitalizations due to

myocardial infarction or unstable angina

were also reduced with ivabradine treat-

ment when compared to placebo.4

Limitations of the study included con-

comitant use of beta-blockers, which

prevents the determination of the mortal-

ity and morbidity effects of ivabradine

alone. Exclusion of patients not in nor-

mal sinus rhythm, patients with heart

failure or anginal-related hospitaliza-

tions in the previous three months, and

patients younger than 55 years of age

means that the study results may not be

generalizable to patients in these popu-

lations.4

Ivabradine did not improve cardiovas-

cular morbidity or mortality in the SIG-

NIFY 42-month trial.5 Initial ivabra-

dine doses were higher in this study;

patients were started on 7.5 mg twice

daily (5 mg twice daily for patients ≥

75 years). Dose titration was based on

heart rate as in the SHIFT and BEAU-

TIFUL trials. Limitations were similar

to the other studies and included the

use of concomitant beta-blockers in

83.1% of patients, exclusion of patients

with sinus arrhythmias, and inclusion

of patients ≥ 55 years of age.5

During clinical trials, the treatment

groups experienced few adverse ef-

fects, although bradycardia occurred in

10% of patients.2 With 80-90% of pa-

tients taking concurrent beta-blockers

in conjunction to ivabradine, bradycar-

dia was expected.3-5 Due to potential

inhibition of the retinal IH current, some

patients may develop phosphenes

(temporary increased brightness within

select areas of the visual field).2 Visual

changes, hypersensitivity reactions,

hypotension, and angioedema have

been reported in post-marketing sur-

veillance.2

Ivabradine metabolism is mostly

through CYP3A4, so drug interactions

Continued on Page 5

Page 6

may occur. Concurrent use of CYP3A4 in-

hibitors can result in bradycardia and inap-

propriate conduction. Ivabradine dose does

not need to be adjusted for creatinine clear-

ance of 15-60 mL/min or mild to moderate

hepatic impairment. However, severe hepat-

ic impairment (Childs-Pugh C) is a contrain-

dication to use of ivabradine.2

Additional studies are warranted to deter-

mine the morbidity and mortality data of

ivabradine without concomitant beta-blocker

therapy and in patients with dysrhythmias.

By Matt Slagle, PharmD Candidate

REFERENCES:

1. FDA approves Corlanor to treat heart

failure (7/6/2015). FDA Web site. Avail-

able at: http://www.fda.

NewsEvents/Newsroom/Pr essAn-

nouncements/ucm4429 78.htm. Accessed

September 10, 2015.

2. Corlanor [package insert]. Thousand

Oaks, CA: Amgen Inc; April 2015.

3. Swedberg K, Komajda M, Böhm M, et

al. Ivabradine and outcomes in chronic

heart failure (SHIFT): a randomised pla-

cebo-controlled study. Lancet 2010;376

(9744):875-885.

4. Fox K, Ford I, Steg PG, Tendera M, Fer-

rari R. Ivabradine for patients with sta-

ble coronary artery disease and left-

ventricular systolic dysfunction

(BEAUTIFUL): a randomised, double-

blind, placebo-controlled trial. Lancet

2008;372(9641):807-816.

5. Fox K, Ford I, Steg PG, et al. Ivabradine

in stable coronary artery disease without

clinical heart failure. N Engl J Med

2014;371(12):1091-1099.

Ivabradine (Cont.)

1. Foster KT, Coffey CW. Acne. In:

Krinksky DL, Ferreri SP Hemstreet

BA, et al., editors. Handbook of

Nonprescription Drugs: An Interac-

tive Approach to Self-Care. 18th ed.

Washington (D.C.): American Phar-

macists Association;2015:685-697.

2. The effects of stress on acne (2015).

Acne Organization Web site. Avail-

able at: http://www.acne.org/spf-

sunscreen.html. Accessed Septem-

ber 10, 2015.

3. Sunscreen and acne (2015). Acne

Organization Web site. Available at:

http://www.acne.org/spf-

sunscreen.html. Accessed Septem-

ber 10, 2015.

4. Over-the counter acne products:

what works and why (7/9/2015).

Mayo Clinic Web site. Available at:

http://www.mayoclinic.org/diseases-

conditions/acne/in-depth/acne-

products/art-20045814 Accessed

September 10, 2015.

1. Bed bugs: get them out and keep

them out (3/13/2015). EPA Web

site. Available at: https://

www.epa.gov/bedbugs. Accessed

October 9, 2015.

2. Bed bug bites (n.d.). Orkin Web

site. Available at: http://

www.orkin.com/other/bed-bugs/

bedbug-bites/. Accessed April 19,

2016.

3. Parasites - bed bugs (1/10/2010).

CDC Web site. Available at: http://

www.cdc.gov/parasites/bedbugs/

faqs.html. Accessed October 10,

2015.

4. Buff W, Powell PH. Insect bites and

stings and pediculosis. In: Krinsky

DL, Berardi RR, Ferreri SP, et al.,

editors. Handbook of Nonprescrip-

tion Drugs. An Interactive Ap-

proach to Self-Care. 17th ed. Wash-

ington (DC): APhA;2012:675-691.

5. Goddard J, DeShazo R. Bed bugs

(Cimex lectularius) and clinical

consequences of their bites. JAMA

2009;301:1358-1366.

6. Thomas I, Kihiczak GG, Schwartz

RA. Bedbug bites: a review. Int J

Dermatol 2004;43:430-433.

7. Bed bugs: diagnosis, treatment and

outcome (2015). American Acade-

my of Dermatology Web site.

Available at: https://www.aad.org/

dermatology-a-to-z/diseases-and-

treatments/a---d/bedbugs/diagnosis-

treatmentbugs. Accessed October

11, 2015.

8. Battling bed bugs (6/2012). Federal

Trade Commission Web site. Avail-

able at:

www.consumer.ftc.gov/

articles/0139-battling-bed-bugs.

Accessed October 12, 2015.

Acne References Bed Bugs References

Smoking Cessation

References

1. Hudmon KS, Kroon LA, Corelli RL.

Smoking cessation. In: Krinsky

DL, Berardi RR, Ferreri SP, et al,

editors. Handbook of Nonprescrip-

tion Drugs: An Interactive Guide to

Self-Care. 17th ed. Washington

(DC): American Pharmacist Associ-

ation;2012:885-907.

2. Quitting smoking: 10 ways to resist

tobacco cravings (3/5/2014). Mayo

Clinic Web site. Available at:

http://www.mayoclinic.org/healthy-

lifestyle/quit-smoking/in-depth/

nicotine-craving/art-20045454?

pg=1. Accessed October 12, 2015.

The University of Montana

Skaggs School of Pharmacy

32 Campus Drive

Missoula, MT 59812-1522

College of Health Professions and Biomedical Sciences

Drug Information Service

Phone: 406-243-5254

Fax: 406-243-5256

Email: druginfo@umontana.edu

www.health.umt.edu/DIS

Addyi™ (flibanserin)—”The Female Viagra®”?

Addyi™ (flibanserin), deemed “the

female Viagra®”, is a new female libi-

do drug.1 However, filbanserin’s nick-

name is a misnomer. Unlike Viagra®,

which treats a physical sexual dysfunc-

tion with as needed administration,

filbanserin treats a psychological cause

of low libido and requires chronic ad-

ministration.2

Filbanserin is indicated for the treat-

ment of hypoactive sexual desire disor-

der (HSDD) in premenopausal wom-

en.2 HSDD is characterized by a lack

of sexual desire that cannot be ac-

counted for by a medication, relation-

ship status, or physical or psychologi-

cal dysfunction. Filbanserin’s mecha-

nism of action for increasing libido is

unknown. It is mainly a 5-HT1A re-

ceptor agonist and 5-HT2A receptor

antagonist. It is also a moderate antag-

onist for 5-HT2B, 5-HT2C, and dopa-

mine D4 receptors.2

Filbanserin improved sexual desire

compared to placebo in one study.

Premenopausal women with HSDD

who were in heterosexual monoga-

mous relationships were treated with

either filbanserin or placebo for 24

weeks. Patients on filbanserin had an

average of one more satisfying sexual

encounters per month compared to

patients on placebo (p<0.0001). Dis-

tress due to low libido was also low-

ered with use of filbanserin. The patient-

reported subjective data may have biased

the results of this study. In addition, the

clinical significance of the improvements

seen in patients on filbanserin has been

questioned.3

Filbanserin use was associated with sys-

tolic hypotension when administered con-

comitantly with alchohol. Systolic blood

pressure decreased by up to 54 mmHg in

male and female patients taking two

glasses of wine with filbanserin.4 There-

fore, patients are advised to abstain from

alcohol consumption to reduce the risk of

severe hypotension and syncope.2,4

Somnolence, nausea, and dizziness were

the most common side effects reported

during the 3 filbanserin clinical trials

which included 3009 subjects. These side

effects are all consistent with filbanserin’s

mechanism of action.2,3 Filbanserin is

only available through a REMS pro-

gram.2,4

By Micah Nevin, PharmD Candidate

REFERENCES:

1. Edney A. Female libido pill caused

dissent in FDA ranks, memo shows

(9/17/2015). FDA Web site. Availa-

ble at: http://www.bloomberg.com/

news/articles/2015-09-17/pink-

female-libido-pill-caused-dissent-in-

fda-ranks-memo-shows. Accessed

September 16, 2015.

2. Addyi [package insert]. Raleigh, NC:

Sprout Pharmaceuticals Inc; 2015

August.

3. Katz M, DeRogatis LR, Ackerman R,

et al. Efficacy of flibanserin in wom-

en with hypoactive sexual desire dis-

order: results from the BEGONIA

trial. J Sex Med 2013;10(7):1807-

1815.

4. Addyi risk evaluation and mitigation

strategy (8/2015). FDA Web site.

Available at: http://www.accessd

ata.fda.gov/drugsatfda_docs/lab

el/2015/022526REMS.pdf. Accessed

September 16, 2015.