The medical letter on drugs and therapeutics june 23 2014

PHARMACOLOGY — Maximum plasma concentra-tions of luliconazole were low but measurable after topi-cal application of about 3.5 grams of cream daily for 15 days in patients with moderat

The Medical Letter ®

On Drugs and Therapeutics

Published by The Medical Letter, Inc • 145 Huguenot Street, New Rochelle, NY 10801 • A Nonprofi t Publication

IN THIS ISSUE (starts on next page)

Luliconazole Cream (Luzu) for Tinea Infections p 50

The Medical Letter® publications are protected by US and international copyright laws Forwarding, copying or any distribution of this material is prohibited.

Sharing a password with a non-subscriber or otherwise making the contents of this site available

to third parties is strictly prohibited.

By accessing and reading the attached content I agree to comply with US and international copyright laws and these terms and conditions of The Medical Letter, Inc.

For further information click: Subscriptions, Site Licenses, Reprints

or call customer service at: 800-211-2769

Important Copyright Message

FORWARDING OR COPYING IS A VIOLATION OF U.S AND INTERNATIONAL COPYRIGHT LAWS

The Medical Letter ®

On Drugs and Therapeutics

Published by The Medical Letter, Inc • 145 Huguenot Street, New Rochelle, NY 10801 • A Nonprofi t Publication

ALSO IN THIS ISSUE

Luliconazole Cream (Luzu) for Tinea

Infections p 50

Tobramycin Inhalation Solution (Bethkis)

for Cystic Fibrosis p 51

Low-Dose Aspirin for Prevention

of Preeclampsia

The American College of Obstetricians and

Gynecolo-gists (ACOG) and the US Preventive Services Task

Force (USPSTF) have recommended that women at

risk for preeclampsia take low-dose aspirin daily after

the fi rst trimester.1,2

PREECLAMPSIA — Preeclampsia is a multisystem

disorder characterized by hypertension and proteinuria

that occurs after 20 weeks’ gestation and can result in

signifi cant maternal and fetal morbidity and mortality

In severe cases, the mother may have severe

headache, visual disturbances, thrombocytopenia,

renal insuffi ciency, and impaired liver function, with

an increased risk of seizures (eclampsia), pulmonary

edema, stroke, and death In the fetus, preeclampsia can

cause intrauterine growth restriction, premature delivery,

and death Delivery is the only defi nitive treatment

A NEW REVIEW — An analysis of 21 randomized

con-trolled trials and 2 observational studies in women at

high or average risk for preeclampsia found that daily

low-dose aspirin (50-150 mg/day) started as early as

the second trimester was associated with absolute risk

reductions of 2-5% for preeclampsia, 1-5% for

intra-uterine growth restriction, and 2-4% for preterm birth

None of these reductions were statistically signifi cant.3

RECOMMENDATIONS — ACOG recommends

low-dose aspirin (60-80 mg/day) beginning in the late fi rst

trimester for women with a history of early-onset

pre-eclampsia and preterm delivery at <34 weeks’ gestation

or preeclampsia in more than one prior pregnancy.1

The USPSTF has released a preliminary statement recommending low-dose aspirin (81 mg/day) for patients with ≥1 high-risk factors (prior preeclampsia, multiple gestation pregnancy, chronic hypertension, diabetes, kidney disease, or autoimmune disease)

or several moderate-risk factors (nulliparity, obesity, family history of preeclampsia, African American race, low socioeconomic status, age >35 years, previous adverse pregnancy outcome, >10-year interval between pregnancies, or mother who was born with a low birth weight or was small for gestational age).2

ADVERSE EFFECTS — Low-dose aspirin taken after

the fi rst trimester has not been shown to increase the risk of antepartum or postpartum bleeding in the mother

or the newborn infant The largest available controlled trial of low-dose aspirin in pregnancy found no increase

in bleeding and no effect on the development of the infant up to age 18 months.4

CONCLUSION — The evidence that low-dose aspirin

(81 mg/day) taken after 12 weeks’ gestation reduces the risk of preeclampsia in women at risk for this disorder

is limited, but use of low-dose aspirin for this indication generally appears to be safe □

1 The American College of Obstetricians and Gynecologists Hypertension in pregnancy Available at: http://www.acog.org/ Resources_And_Publications/Task_Force_and_Work_Group_ Reports/Hypertension_in_Pregnancy Accessed June 16, 2014.

2 U.S Preventive Services Task Force Low-dose aspirin for the prevention of morbidity and mortality from preeclampsia: U.S Preventive Services Task Force recommendation statement draft Available at: http://www.uspreventiveservicestaskforce.org/ uspstf14/asprpreg/asprpregdraftrec.htm Accessed June 16, 2014.

3 JT Henderson et al Low-dose aspirin for prevention of morbidity and mortality from preeclampsia: a systematic evidence review for the U.S Preventive Services Task Force Ann Intern Med 2014; 160:695

4 CLASP (Collaborative Low-dose Aspirin Study in Pregnancy) Collaborative Group CLASP: a randomised trial of low-dose as-pirin for the prevention and treatment of pre-eclampsia among

9364 pregnant women Lancet 1994; 343:619.

The Medical Letter publications are protected by US and international copyright laws.

Forwarding, copying or any other distribution of this material is strictly prohibited.

For further information call: 800-211-2769

50 The Medical Letter • Volume 56 • Issue 1445 • June 23, 2014

The FDA has approved luliconazole (Luzu Cream, 1% –

Valeant) for treatment of tinea pedis, tinea cruris, and

tinea corporis infections

DRUGS FOR TINEA PEDIS — Tinea pedis is the most

common form of tinea infection It is generally treated

with a topical allylamine, benzylamine, or imidazole

antifungal for 4 weeks (see Table 1) Allylamines

are more active in vitro than imidazoles against the

dermatophytes that cause the disease, but cure rates

for allylamines, benzylamines, and imidazoles have

generally been similar Cure rates have been lower

with tolnaftate, and nystatin is not effective Relapse is

common with all of these drugs

PHARMACOLOGY — Maximum plasma

concentra-tions of luliconazole were low but measurable after

topi-cal application of about 3.5 grams of cream daily for 15

days in patients with moderate to severe tinea pedis

or tinea cruris and were about 8-fold higher in patients

treated for tinea cruris.

Table 1 Some Topical Antifungals for Tinea Pedis Infection

Allylamines

Benzylamines

Imidazoles

Other

1 Other formulations may be available for other indications

2 Dosing schedule may vary based on formulation

3 Approximate wholesale acquisition cost (WAC) for the number of tubes of cream or gel or bottles of powder spray needed for one course of treatment at the lowest usual dosage (about 0.5 g/application) Source: Analy$ource® Monthly (Selected from FDB MedKnowledge™) June 5, 2014 Reprinted with permission by FDB, Inc All rights reserved ©2014 www.fdbhealth.com/policies/drug-pricing-policy Actual retail prices may be higher

4 Four weeks for the 1% cream or gel; 2 weeks for the 2% formulations The 1% gel should be applied bid

5 Cost of a 45-g tube of Naftin 2% cream.

6 Available without a prescription

7 One week between the toes; 2 weeks on bottom or sides of foot

8 Cost of 60 g

9 Cost of 100 g

Luliconazole Cream (Luzu) for Tinea

Infections

CLINICAL STUDIES — Luliconazole applied once

daily for 14 days was compared to its vehicle alone in 2 unpublished, randomized, double-blind trials (summarized

in the package insert) in a total of 423 patients with culture-proven tinea pedis Complete clearance (clinical and mycological cure) at 4 weeks post-treatment (the primary endpoint) occurred in the 2 studies in 26% and 14% of patients treated with the active drug compared

to 2% and 3% of those treated with the vehicle alone Mycological cure occurred in the 2 studies in 62% and 56% of patients treated with the active drug compared to 18% and 27% of those treated with the vehicle alone In one similar published trial, 11 of 41 patients (27%) treated for 2 weeks with luliconazole and 2 of 22 (9%) treated with the vehicle alone achieved complete clearance at 2 weeks post-treatment (the primary endpoint).1

A randomized, double-blind, controlled trial of luliconazole once daily for 7 days in 256 patients with tinea cruris found that 35 of 165 patients (21%) treated with the active drug and 4 of 91 (4%) treated with the vehicle alone achieved complete clearance at 21 days post-treatment Mycologi-cal cure occurred in 78% of those treated with luliconazole compared to 45% of those treated with the vehicle alone.2

The FDA has approved another solution of the

aminoglycoside antibiotic tobramycin (Bethkis –

Chiesi/Cornerstone) for oral inhalation via a nebulizer

for management of cystic fi brosis (CF) patients with

Pseudomonas aeruginosa.

INHALED ANTIBIOTICS FOR CF — Inhaled

antibiot-ics, which can achieve high concentrations in the lung

with minimal systemic side effects, are probably the

most effective therapy available for chronic P

aeru-ginosa infection in patients with CF.1 Tobramycin and

aztreonam (Cayston) are the only 2 antibiotics that are

FDA-approved for such use Bethkis delivers the same

dose of tobramycin as an older formulation (Tobi, and

generics), but in a more concentrated solution An

orally inhaled dry powder formulation of tobramycin

(Tobi Podhaler) was approved by the FDA in 2013 It

is more convenient to administer than the nebulizer

solution, which may improve patient adherence, but it

can cause more cough, dysphonia, and dysgeusia.2,3

Inhaled tobramycin is generally preferred over inhaled

Tobramycin Inhalation Solution

(Bethkis) for Cystic Fibrosis

ADVERSE EFFECTS — Luliconazole was well tolerated

in the clinical trials; adverse effects were similar to those

reported with use of the vehicle alone Mild application

site reactions occurred in a few patients Safety trials

in animals found that luliconazole cream had minimal

potential for irritation and did not show a potential

for sensitization, phototoxicity, or photoallergenicity

Luliconazole is classifi ed as category C (embryofetal

toxicity in animals at high doses; no adequate human

studies) for use during pregnancy.

DOSAGE AND ADMINISTRATION — Luzu is available

in 30- and 60-gram tubes For treatment of tinea pedis,

it should be applied to affected areas and to about

1 inch of the adjacent areas once daily for 2 weeks

Table 1 Inhaled Antibiotics for Cystic Fibrosis

Tobi (Novartis) 300 mg/5 mL ampule Inhalation via nebulizer ≥6 yrs: 300 mg bid3 7337.70

Tobi Podhaler (Novartis) 28 mg capsule Inhalation via dry powder ≥6 yrs: 112 mg (4 caps) 6676.90

Aztreonam lysine – Cayston 75 mg vial of lyophilized powder Inhalation via nebulizer ≥7 yrs: 75 mg tid 6070.80

1 One cycle consists of 28 days on treatment followed by 28 days off treatment

2 Approximate wholesale acquisition cost for one treatment cycle Source: Analy$ource® Monthly (Selected from FDB MedKnowledge™) June 5, 2014 Reprinted with permission by FDB, Inc All rights reserved ©2014 www.fdbhealth.com/policies/drug-pricing-policy Actual retail prices may be higher

3 Doses should be inhaled as close to 12 hours apart as possible and not less than 6 hours apart

Application instructions are the same for tinea cruris and tinea corporis, but the recommended treatment duration is one week

CONCLUSION — Luliconazole (Luzu Cream, 1%)

ap-pears to be moderately effective for treatment of tinea pedis and tinea cruris infections There is no evidence that it is more effective than other topical antifungals that are available generically or over the counter at a much lower cost □

1 M Jarratt et al Luliconazole for the treatment of interdigital tinea pedis: A double-blind, vehicle-controlled study Cutis 2013; 91:203.

2 TM Jones et al A randomized, multicenter, double-blind, vehicle-controlled study evaluating the effi cacy and safety of luliconazole cream 1% once daily for 7 days in patients aged >12 years with tinea cruris J Drugs Dermatol 2014; 13:32.

aztreonam because more long-term data are available supporting its safety and effi cacy.

CLINICAL STUDIES — In two unpublished

double-blind trials (summarized in the package insert), a total

of 306 CF patients with P aeruginosa infection were

randomized to receive the new tobramycin inhalation solution or placebo for 1 cycle (28 days on treatment followed by 28 days off) in study 1 and for 3 cycles in study 2 All patients had a baseline forced expiratory volume in one second (FEV1) between 40% and 80%

of predicted normal Patients who received tobramycin inhalation solution had statistically signifi cant

increas-es in FEV1 in both studies: 16% vs 5% with placebo in study 1 and 7% vs 1% in study 2.

In one published study, Bethkis was compared to

Tobi inhalation solution in a randomized, open-label,

non-inferiority trial in 324 CF patients >6 years old

with chronic P aeruginosa infection After 28 days

of treatment, FEV1 increased by 7.0% with the new

formulation and by 7.5% with Tobi ; adverse events

were similar with the two formulations In a 48-week extension phase, improvements in lung function were

52 The Medical Letter • Volume 56 • Issue 1445 • June 23, 2014

On Drugs and Therapeutics

EDITOR IN CHIEF: Mark Abramowicz, M.D

EXECUTIVE EDITOR: Gianna Zuccotti, M.D., M.P.H., F.A.C.P., Harvard Medical School EDITOR: Jean-Marie Pfl omm, Pharm.D

ASSISTANT EDITORS, DRUG INFORMATION: Susan M Daron, Pharm.D.,

Corinne Z Morrison, Pharm.D., Michael P Viscusi, Pharm.D.

CONSULTING EDITORS: Brinda M Shah, Pharm.D., F Peter Swanson, M.D CONTRIBUTING EDITORS:

Carl W Bazil, M.D., Ph.D., Columbia University College of Physicians and Surgeons Vanessa K Dalton, M.D., M.P.H., University of Michigan Medical School Eric J Epstein, M.D., Albert Einstein College of Medicine

Jane P Gagliardi, M.D., M.H.S., F.A.C.P Duke University School of Medicine Jules Hirsch, M.D., Rockefeller University

David N Juurlink, BPhm, M.D., Ph.D., Sunnybrook Health Sciences Centre Richard B Kim, M.D., University of Western Ontario

Hans Meinertz, M.D., University Hospital, Copenhagen Sandip K Mukherjee, M.D., F.A.C.C., Yale School of Medicine Dan M Roden, M.D., Vanderbilt University School of Medicine Esperance A.K Schaefer, M.D., M.P.H., Harvard Medical School

F Estelle R Simons, M.D., University of Manitoba Neal H Steigbigel, M.D., New York University School of Medicine Arthur M F Yee, M.D., Ph.D., F.A.C.R., Weill Medical College of Cornell University SENIOR ASSOCIATE EDITOR: Amy Faucard

MANAGING EDITOR: Susie Wong ASSISTANT MANAGING EDITOR: Liz Donohue PRODUCTION COORDINATOR: Cheryl Brown EXECUTIVE DIRECTOR OF SALES: Gene Carbona FULFILLMENT & SYSTEMS MANAGER: Cristine Romatowski DIRECTOR OF MARKETING COMMUNICATIONS: Joanne F Valentino VICE PRESIDENT AND PUBLISHER: Yosef Wissner-Levy

Founded in 1959 by Arthur Kallet and Harold Aaron, M.D

Copyright and Disclaimer: The Medical Letter is an independent nonprofi t organization that provides health care professionals with unbiased drug prescribing recommendations The edi-torial process used for its publications relies on a review of published and unpublished litera-ture, with an emphasis on controlled clinical trials, and on the opinions of its consultants The Medical Letter is supported solely by subscription fees and accepts no advertising, grants, or donations No part of the material may be reproduced or transmitted by any process in whole

in this publication is accurate and complete in every respect The editors shall not be held responsible for any damage resulting from any error, inaccuracy, or omission

Subscription Services

Mailing Address:

The Medical Letter, Inc

145 Huguenot St Ste 312 New Rochelle, NY 10801-7537

Customer Service:

Call: 800-211-2769 or 914-235-0500 Fax: 914-632-1733

Web Site: www.medicalletter.org E-mail: custserv@medicalletter.org

Permissions:

To reproduce any portion of this issue, please e-mail your request to:

permissions@medicalletter.org

Subscriptions (US):

1 year - $98; 2 years - $189;

3 years - $279 $49.00 per year for students, interns, residents, and fellows in the US and Canada

E-mail site license inquiries to:

info@medicalletter.org or call 800-211-2769 x315

Special fees for bulk subscriptions Special classroom rates are available Back issues are $12 each Major credit cards accepted

Copyright 2014 ISSN 1523-2859

Coming Soon in The Medical Letter:

Treatment of Atrial Fibrillation

In Brief: Esomeprazole Strontium Ceritinib (Zykadia) for Non-Small Cell Lung Cancer

RNS Stimulator Device for Epilepsy

Dalbavancin (Dalvance) for Skin and Skin Structure Infections Propanolol (Hemangeol) for Infantile Hemangiomas

Oxycodone/Acetaminophen (Xartemis XR) for Pain

maintained in patients who continued to take the new

formulation, and no new safety issues were reported.4

ADVERSE EFFECTS — In the controlled clinical trials,

adverse effects occurring in >3% of patients treated with

the new product and more often than with placebo

in-cluded a decrease in FEV1, rales, dysphonia, wheezing,

and epistaxis Bronchospasm can occur Voice alteration

and tinnitus have been reported with use of the older

formulation of tobramycin inhalation solution Systemic

aminoglycosides can be nephrotoxic and possibly

oto-toxic, but the low serum concentrations associated with

oral inhalation of tobramycin make these effects unlikely.

Aminoglycosides are classifi ed as category D (positive

evidence of fetal harm) for use during pregnancy Whether

inhalation of tobramycin could harm a fetus is unknown.

USE WITH AZITHROMYCIN — Concomitant use of

oral azithromycin may antagonize the therapeutic effect

of inhaled tobramycin.5

DOSAGE AND ADMINISTRATION — The contents of

one 300 mg/4 mL ampule of tobramycin solution should

be inhaled by mouth via a nebulizer twice daily The

doses should be taken as close to 12 hours apart as

possible, and not less than 6 hours apart.

Bethkis should be administered using the hand-held

PARI LC PLUS reusable nebulizer with a PARI Vios air

compressor over a period of about 15 minutes Each

cy-cle consists of 28 days on treatment followed by 28 days

off Bethkis is supplied in cartons of 7 or 14 foil pouches,

each containing 4 single-use 300 mg/4 mL ampules,

which should be refrigerated and protected from light

CONCLUSION — A new, more concentrated tobramycin

inhalation solution (Bethkis) for cystic fi brosis patients

with Pseudomonas aeruginosa appears to be similar in

effi cacy and safety to the older tobramycin nebulizer

so-lution (Tobi) How it compares to tobramycin inhalation

powder (Tobi Podhaler) or aztreonam inhalation solution

(Cayston) for this indication remains to be determined □

1 L Máiz et al Inhaled antibiotics for the treatment of chronic

bron-chopulmonary Pseudomonas aeruginosa infection in cystic fi

bro-sis: systematic review of randomised controlled trials Expert Opin

Pharmacother 2013; 14:1135.

2 Tobramycin inhalation powder (Tobi Podhaler) for cystic fi brosis

Med Lett Drugs Ther 2013; 55:51.

3 MJ Harrison et al Inhaled versus nebulised tobramycin: a real world

comparison in adult cystic fi brosis (CF) J Cyst Fibros 2014 May 9

(epub).

4 H Mazurek et al Long-term effi cacy and safety of aerosolized

tobramy-cin 300 mg/4 ml in cystic fi brosis Pediatr Pulmonol 2014 Jan 24 (epub).

5 JA Nick et al Azithromycin may antagonize inhaled tobramycin

when targeting Pseudomonas aeruginosa in cystic fi brosis Ann

Am Thorac Soc 2014; 11:342.

The Medical Letter®

Online Continuing Medical Education

To take CME exams and earn credit, go to:

medicalletter.org/CMEstatus

Issue 1445 Questions

(Correspond to questions #73-78 in Comprehensive Exam #70, available July 2014)

Low-Dose Aspirin for Prevention of Preeclampsia

1 Which of the following are considered high-risk factors for preeclampsia?

c autoimmune disease

d all of the above

2 Taking low-dose aspirin daily throughout the second and third trimesters of pregnancy has been shown to reduce the absolute risk of preeclampsia by

as much as:

Luliconazole Cream (Luzu) for Tinea Infections

3 In the published trial, complete clearance of tinea pedis (clinical and

mycological cure) 2 weeks post-treatment with luliconazole occurred in about what percentage of patients?

4 A 20-year-old college basketball player with tinea pedis and no health

insurance has been given a sample tube and a prescription for Luzu cream

but is concerned about the cost You could tell him that:

a Luliconazole has been shown to be more effective than most

other topical products for treatment of tinea pedis.

b Luliconazole is an imidazole antifungal, and this class of topical

antifungals has been shown to be more effective than any other, but he could use a less expensive imidazole product.

c Luliconazole has been shown in clinical trials to be more

effective than other imidazole antifungals.

d Cure rates have generally been similar with all topical antifungals

used to treat tinea pedis, and there is no good reason to pay for

an expensive brand name product for this condition.

Tobramycin Inhalation Solution (Bethkis) for Cystic Fibrosis

5 Compared to the older tobramycin inhalation solution (Tobi), Bethkis:

a is easier to administer

b is more concentrated

c has been shown to be more effective in eradicating

Pseudomonas aeruginosa

d all of the above

6 Concomitant use of which of the following may antagonize the therapeutic effect of inhaled tobramycin?

a inhaled albuterol

b oral aztreonam

c oral azithromycin

d an inhaled anticholinergic

Earn Up to 26 Category 1 AMA PRA credits

Choose CME from The Medical Letter in the format that’s right for you!

Comprehensive Exam – Available online or in print to Medical Letter subscribers, this 78 question test enables you to earn 13 credits immediately upon successful completion of the test A score of 70% or greater is required to pass the exam Our Comprehensive exams allow you to test at your own pace in the comfort of your home or offi ce

Comprehensive tests are offered every January and July enabling you to earn up to 26 credits per year $49.00/13

credits

Free Individual Exams – Free to active subscribers of The Medical Letter Answer six questions per issue and submit answers online Earn one credit/exam

Paid Individual Exams – Available to non-subscribers Answer six questions per issue and submit answers online Earn one credit/exam $12.00/exam

DO NOT FAX OR MAIL THIS FLAP For more information: medicalletter.org/cme or call 800-211-2769

ACCREDITATION INFORMATION:

ACCME: The Medical Letter is accredited by the Accreditation Council for Continuing Medical Education to provide

continuing medical education for physicians The Medical Letter designates this enduring material for a maximum of

1 AMA PRA Category 1 Credit(s)™ Physicians should claim only the credit commensurate with the extent of their

participation in the activity This CME activity was planned and produced in accordance with the ACCME Essentials and Policies

AAFP: This enduring material activity, The Medical Letter Continuing Medical Education Program, has been reviewed

and is acceptable for up to 39 Prescribed credits by the American Academy of Family Physicians AAFP certifi cation begins January 1, 2014 Term of approval is for one year from this date with the option of yearly renewal Credit may be claimed for one year from the date of each issue Physicians should claim only the credit commensurate with the extent

of their participation in the activity

ACPE: The Medical Letter is accredited by the Accreditation Council for Pharmacy Education as a provider of continuing

pharmacy education This exam is acceptable for 1.0 hour(s) of knowledge-based continuing education credit (0.1 CEU) The comprehensive exam is acceptable for 13.0 hour(s) of knowledge-based continuing education credit (1.3 CEU)

The American Academy of Nurse Practitioners (AANP) and the American Academy of Physician Assistants

(AAPA) accept AMA Category 1 credit for the Physician’s Recognition Award from organizations accredited by the

ACCME

This activity, being ACCME (AMA) approved, is acceptable for Category 2-B credit by the American Osteopathic

Association (AOA)

Physician Assistants: The National Commission on Certifi cation of Physician Assistants (NCCPA) accepts AMA

PRA Category 1 Credit(s)™ from organizations accredited by ACCME NCCPA also accepts AAFP Prescribed credits

for recertifi cation The Medical Letter is accredited by both ACCME and AAFP.

Physicians in Canada: Members of The College of Family Physicians of Canada are eligible to receive Mainpro-M1

credits (equivalent to AAFP Prescribed credits) as per our reciprocal agreement with the American Academy of Family Physicians

Physicians, nurse practitioners, pharmacists, and physician assistants may earn 1 credit with this exam

MISSION:

The mission of The Medical Letter’s Continuing Medical Education Program is to support the professional development

of healthcare professionals including physicians, nurse practitioners, pharmacists, and physician assistants by providing independent, unbiased drug information and prescribing recommendations that are free of industry infl uence The program content includes current information and unbiased reviews of FDA-approved and off-label uses of drugs, their mechanisms

of action, clinical trials, dosage and administration, adverse effects, and drug interactions The Medical Letter delivers educational content in the form of self-study material

The expected outcome of the CME Program is to increase the participant’s ability to know, or apply knowledge into

practice after assimilating, information presented in materials contained in The Medical Letter.

The Medical Letter will strive to continually improve the CME program through periodic assessment of the program and activities The Medical Letter aims to be a leader in supporting the professional development of healthcare professionals through Core Competencies by providing continuing medical education that is unbiased and free of industry infl uence The Medical Letter is supported solely by subscription fees and accepts no advertising, grants, or donations

GOAL:

Through this program, The Medical Letter expects to provide the healthcare community with unbiased, reliable, and timely educational content that they will use to make independent and informed therapeutic choices in their practice

LEARNING OBJECTIVES:

Activity participants will read and assimilate unbiased reviews of FDA-approved and off-label uses of drugs and other treatment modalities Activity participants will be able to select and prescribe, or confi rm the appropriateness

of the prescribed usage of, the drugs and other therapeutic modalities discussed in The Medical Letter with specifi c

attention to clinical trials, pathophysiology, dosage and administration, drug metabolism and interactions, and patient management Activity participants will make independent and informed therapeutic choices in their practice

Upon completion of this program, the participant will be able to:

1 Explain the evidence supporting the use of low-dose aspirin for prevention of preeclampsia

2 Review the effi cacy and safety of luliconazole cream (Luzu) for treatment of tinea infections.

3 Review the effi cacy and safety of tobramycin inhalation solution (Bethkis) for treatment of cystic fi brosis patients with

Pseudomonas aeruginosa and explain how it compares to other available inhaled antibiotics for this indication.

Privacy and Confi dentiality: The Medical Letter guarantees our fi rm commitment to your privacy We do not sell any

of your information Secure server software (SSL) is used for commerce transactions through VeriSign, Inc No credit card information is stored

IT Requirements: Windows XP/Vista/7/8, Mac OS X+; current versions of Microsoft IE, Mozilla Firefox, Google Chrome,

Safari or any other compatible Web browser High-speed connection

Have any questions? Call us at 800-211-2769 or 914-235-0500 or e-mail us at: custserv@medicalletter.org

Continuing Medical Education Program

medicalletter.org/cme