• 145 Huguenot Street, New Rochelle, NY 10801 • A Nonprofi t Publication IN THIS ISSUE starts on next page In Brief: Testosterone and Cardiovascular Risk ...p 17 Riociguat Adempas for Pu
Trang 1The 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)
In Brief: Testosterone and Cardiovascular Risk p 17
Riociguat (Adempas) for Pulmonary Hypertension p 17
Low-Dose Diclofenac (Zorvolex) for Pain p 19
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
Trang 2The Medical Letter®
On Drugs and Therapeutics Published by The Medical Letter, Inc • 145 Huguenot Street, New Rochelle, NY 10801 • A Nonprofi t Publication
FORWARDING OR COPYING IS A VIOLATION OF U.S AND INTERNATIONAL COPYRIGHT LAWS 17
ALSO IN THIS ISSUE
Low-Dose Diclofenac (Zorvolex)
for Pain p 19
IN BRIEF
Testosterone and Cardiovascular Risk
Prompted by the recent publication of 2 retrospective
stud-ies, the FDA has announced that it is investigating the risk
of stroke, heart attack, and death in men taking
FDA-ap-proved testosterone products.1
The fi rst study examined the records of 8709 men with
low testosterone levels (<300 ng/dL) who underwent
coronary angiography between 2005 and 2011; 1223 of
these men started testosterone therapy after a median
of 531 days following coronary angiography Three years
after coronary angiography, the Kaplan-Meier estimated
cumulative percentages of men who died or had a
myo-cardial infarction (MI) or ischemic stroke were 26% of
those treated with testosterone and 20% of those who
were not treated with the hormone, a hazard ratio of 1.29
(95% CI 1.04-1.58; P=0.02).2
The second study compared the rate of nonfatal MI
dur-ing the 90 days after fi lldur-ing a prescription with the rate
in the prior year in 56,000 men given a prescription for
testosterone and in 167,000 given a phosphodiesterase
type 5 inhibitor (sildenafi l [Viagra] or tadalafi l [Cialis]) In
the testosterone group as a whole, the
post/pre-prescrip-tion rate ratio was 1.36, but in men >65 years old it was
2.19 and in younger men with a history of heart disease
it was 2.90 In men who received a prescription for
silde-nafi l or tadalafi l, the rate ratio was 1.08 for all ages, 1.15
for those >65 years old, and 1.40 for younger men with a
history of heart disease.3
A recent meta-analysis of randomized, placebo-controlled
trials of testosterone therapy also found an increased risk of
cardiovascular-related events in men treated with the
hor-mone (odds ratio [OR] 1.54; 95% CI 1.09-2.18); an analysis
by funding source found that the risk was greater in trials not
funded by the pharmaceutical industry (OR 2.06 vs 0.89).4
1 FDA Drug Safety Communication January 31, 2014: FDA evalu-ating risk of stroke, heart attack and death with FDA-approved testosterone products Available at www.fda.gov/drugs/drugsafe-ty/ucm383904.htm Accessed February 24, 2014.
2 R Vigen et al Association of testosterone therapy with mortality, myocardial infarction, and stroke in men with low testosterone levels JAMA 2013; 310:1829.
3 WD Finkle et al Increased risk of non-fatal myocardial infarction following testosterone therapy prescription in men PLoS One 2014; 9:e85805.
4 L Xu et al Testosterone therapy and cardiovascular events among men: a systematic review and meta-analysis of placebo-controlled randomized trials BMC Med 2013; 11:108.
The FDA has approved the sGC stimulator riociguat
(rye” oh sig’ ue at; Adempas – Bayer) for oral
treat-ment of pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH) following surgery or when surgery is not an option It is the fi rst drug to be approved for treatment
of CTEPH
Riociguat (Adempas) for Pulmonary
Hypertension
Table 1 Pharmacology
Drug class Soluble guanylate cyclase (sGC) stimulator Route Oral
Formulation 0.5, 1, 1.5, 2, 2.5 mg tablets Tmax 1.5 hrs Metabolism Primarily by CYP1A1, 3A, 2C8 and 2J2 Elimination Feces (53%); urine (40%)
Elimination half-life 12 hrs (patients), 7 hrs (healthy subjects)
DRUGS FOR PAH — Current management of PAH
usually includes warfarin (Coumadin, and others) and furosemide (Lasix, and generics) Oral drugs approved
for PAH include the phosphodiesterase type 5 (PDE5)
inhibitors sildenafi l (Revatio, and generics) and tadalafi l (Adcirca), the endothelin receptor antagonists bosen-tan (Tracleer), ambrisenbosen-tan (Letairis), and, most
recent-ly, macitentan (Opsumit), a nonselective endothelin
re-ceptor antagonist derived from bosentan.1 Patients with more advanced disease can be treated with a systemic prostacyclin (see Table 2)
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
Trang 318 The Medical Letter • Volume 56 • Issue 1437 • March 3, 2014
Table 2 Some Drugs for Pulmonary Arterial Hypertension
Soluble Guanylate Cyclase (sGC) Stimulator
Riociguat – Adempas (Bayer) Oral 0.5, 1, 1.5, 2, 2.5 mg tabs 1-2.5 mg tid $7500.00
Endothelin Receptor Antagonists
Nonselective
Macitentan – Opsumit (Actelion) Oral 10 mg tabs 10 mg once/day 6840.00
Bosentan – Tracleer Oral 62.5, 125 mg tabs 62.5 mg bid (for 4 wks) 7050.00 (Actelion) then 125 mg bid
Selective
Ambrisentan – Letairis (Gilead) Oral 5, 10 mg tabs 5-10 mg once/day 6893.30
Phosphodiesterase 5 (PDE5) Inhibitors
S ildenafi l – generic Oral 20 mg tabs 20 mg tid 239.40
Revatio2
Tadalafi l – Adcirca (Eli Lilly) Oral 20 mg tabs 40 mg once/day 1899.00
Prostacyclins
Iloprost – Ventavis (Actelion) Inhalation 10 and 20 mcg ampules 2.5-5 mcg/inhalation 6-9 times/day 15,210.00 3
Epoprostenol – generic Continuous IV 0.5 and 1.5 mg in 17 mL 20-40 ng/kg/min 4
1145.54 5
Flolan (Gilead) infusion single-use vials 1850.74 5
Veletri (Actelion) 0.5 and 1.5 mg in 10 mL 1849.92 5
single-use vials Treprostinil 6 –
Remodulin (United Therapeutics) Continuous SC or IV 1, 2.5, 5, 10 mg/mL 40-160 ng/kg/min 7 7132.95 5
infusion multi-dose vials
Tyvaso (United Therapeutics) Inhalation 1.74 mg/2.9 mL ampules 8
9 breaths (54 mcg) qid 13,018.00 9
1 Approximate wholesale acquisition cost (WAC) for 30 days’ treatment at the lowest usual dosage Source: Analy$ource® Monthly (Selected from FDB MedKnowledge™) February 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 Ancillary costs will substantially increase the cost of non-oral drugs.
2 Also available in an IV formulation for patients on oral sildenafi l who are temporarily unable to take oral medication Also approved in a powder for oral suspension.
3 Cost of 180 ampules of either strength.
4 Initial dosage recommended is 2 ng/kg/min with subsequent increases of 2 ng/kg/min every 15 minutes or longer as tolerated Dosage requirements tend to increase over time Average dosage after 6 months is about 20-40 ng/kg/min
5 Cost for a 70-kg patient
6 The FDA recently approved an extended-release oral formulation of treprostinil (Orenitram) that will be available soon.
7 Initial dosage recommended is 1.25 ng/kg/min, or half if poorly tolerated, with subsequent increases of 1.25 ng/kg/min weekly for the fi rst 4 weeks, then 2.5 ng/kg/min weekly thereafter Average dosage after 9 months is about 60 ng/kg/min
8 Initial dosage is 3 breaths (18 mcg) 4 times daily, or 1-2 breaths if poorly tolerated then increasing to 3 breaths The dosage should be increased by an additional 3 breaths
at 1-2 week intervals as tolerated The target and maximum dosage is 9 breaths (54 mcg) 4 times daily.
9 Cost of 7 foil pouches containing 4 ampules each.
TREATMENT OF CTEPH — In CTEPH, residual
thromboemboli obstruct pulmonary arteries, leading to
an increase in pulmonary vascular resistance and
sub-sequently to progressive pulmonary hypertension and
right heart failure The treatment of choice is
pulmo-nary endarterectomy, which can be curative but is not
an option in many patients because of distal occlusion
or comorbidities About 10% of patients who undergo
surgery continue to experience pulmonary
hyperten-sion.2 Drugs for PAH have been used off-label to treat
patients with CTEPH.3
MECHANISM OF ACTION — Riociguat is a soluble
guanylate cyclase (sGC) stimulator sGC binds to
nitric oxide (NO), forming an enzyme that promotes
synthesis of the signaling molecule cyclic guanosine
monophosphate (cGMP) Pulmonary hypertension
is associated with impaired synthesis of NO and
in-suffi cient stimulation of the NO-sGC-cGMP pathway
Riociguat acts both by directly stimulating sGC
inde-pendently of NO, and by increasing the sensitivity of sGC to NO
CLINICAL STUDIES — PAH – In a 12-week,
double-blind trial (PATENT-1), 443 patients with symptomatic PAH were randomized to individually adjusted dos-ages of riociguat capped at either 1.5 or 2.5 mg 3 times daily, or to placebo.4 At the end of the study, the mean 6-minute walk distance was longer by 31 meters in the 1.5-mg group and by 30 meters in the 2.5-mg group, compared to a decrease of 6 meters in the placebo group Time to clinical worsening, a sec-ondary endpoint, was also longer in patients treated with riociguat
CTEPH – A 16-week, double-blind trial (CHEST-1) in
261 patients with inoperable CTEPH or persistent or re-current pulmonary hypertension despite surgery found that riociguat titrated to a maximum of 2.5 mg 3 times daily increased 6-minute walk distance by 39 meters, compared to a decrease of 6 meters with placebo.5
Trang 419 The Medical Letter • Volume 56 • Issue 1437 • March 3, 2014
Low-Dose Diclofenac (Zorvolex) for Pain
The FDA has approved Zorvolex (Iroko), a low-dose
oral formulation of the relatively COX-2 selective NSAID diclofenac, for treatment of mild-to-moderate acute pain
in adults
Zorvolex is available as 18- and 35-mg capsules
Oth-er oral formulations of diclofenac include immediate-release, extended-immediate-release, and enteric-coated tablets and capsules in strengths ranging from 25 to 100 mg Diclofenac is also available topically as a transdermal
patch (Flector), a gel (Voltaren Gel), and a solution (Pennsaid).
THE NEW FORMULATION — Each capsule of Zorvolex
contains diclofenac as submicron particles The reduction
in particle size increases surface area, leading to faster dissolution and absorption of the drug A single-dose crossover study compared the new 35-mg formulation
of diclofenac to diclofenac potassium 50 mg in healthy subjects Taken without food, Tmax was about 1 hour for both formulations; Cmax and AUC were about 26% and 23% lower, respectively, with the new formulation Taking
Zorvolex with food delayed its Tmax by 2.32 hours and
reduced its Cmax by 60% and its AUC by 11%
CLINICAL STUDIES — Approval of Zorvolex was
based on the results of a double-blind clinical trial in
428 patients with moderate-to-severe pain following bunionectomy Patients were randomized to diclofenac
18 mg or 35 mg 3 times daily, celecoxib 200 mg twice daily after a 400-mg loading dose, or placebo At 12 hours, pain intensity with diclofenac 18 and 35 mg was reduced from baseline by 48% and 51%, respectively, compared to 24% with placebo At 24 hours, pain in-tensity was reduced by 69% and 73% versus 52% All
of these differences from placebo were statistically sig-nifi cant Compared with celecoxib, overall reductions in pain intensity were greater with diclofenac 35 mg and similar with diclofenac 18 mg.1
Extension Trials – In long-term extensions of both
tri-als (PATENT-2 and CHEST-2), treatment was unblinded
after 8 weeks Exploratory analyses at 12 weeks found
that patients taking riociguat increased their 6-minute
walk distance from the original baseline by 53 meters in
PATENT-2 and by 63 meters in CHEST-2.4,5
ADVERSE EFFECTS — Adverse effects of riociguat
(>5%) that occurred more frequently than with placebo
in clinical trials were headache, dyspepsia/gastritis,
dizziness, nausea, diarrhea, hypotension, vomiting,
anemia, gastroesophageal refl ux, and constipation
Hypotension occurred in 10% of patients taking
rio-ciguat compared to 4% of those taking placebo
Seri-ous hemorrhagic events, including one fatal case,
oc-curred in 2.4% of patients treated with the drug and in
none with placebo
PREGNANCY — Riociguat is contraindicated for use
during pregnancy (category X) It is available for women
only through a restricted access program
DRUG INTERACTIONS — Because of the risk of
hy-potension, riociguat is contraindicated for use with
ni-trates, nitric oxide donors (such as amyl nitrite), PDE5
inhibitors (such as sildenafi l) and nonspecifi c PDE
in-hibitors (such as dipyridamole or theophylline)
Concomitant use of riociguat with strong CYP and
P-glycoprotein/breast cancer resistance protein (P-gp/
BCRP) inhibitors (such as ketoconazole, itraconazole,
and ritonavir) can increase riociguat serum
concentra-tions and the risk of hypotension
Plasma concentrations of riociguat are reduced by
50-60% in smokers compared to nonsmokers Antacids
such as aluminum hydroxide/magnesium hydroxide
re-duce absorption of riociguat
DOSAGE AND ADMINISTRATION — The
recom-mended starting dosage of riociguat is 1 mg 3 times
daily The dose can be increased by 0.5 mg every 2
weeks up to the maximum of 2.5 mg 3 times daily
In patients who cannot tolerate the drug’s hypotensive
effects, or in those taking concomitant strong CYP and
P-gp/BCRP inhibitors, the starting dosage can be
low-ered to 0.5 mg 3 times daily Riociguat dosages higher
than 2.5 mg 3 times daily may be considered for
pa-tients who smoke Dosage reductions may be
neces-sary for patients who stop smoking Antacids should not
be taken within 1 hour of taking riociguat
CONCLUSION — Riociguat (Adempas) can improve
exercise capacity in patients with pulmonary arterial
hypertension (PAH) and in those with chronic thrombo-embolic pulmonary hypertension (CTEPH) □
1 Macitentan (Opsumit) for pulmonary arterial hypertension Med Lett Drugs Ther 2014; 56:15.
2 J Pepke-Zaba et al Chronic thromboembolic pulmonary hyperten-sion (CTEPH): results from an international prospective registry Circulation 2011; 124:1973.
3 M Delcroix Chronic post-embolic pulmonary hypertension: a new target for medical therapies? Eur Respir Rev 2013; 22:258
4 HA Ghofrani et al Riociguat for the treatment of pulmonary arterial hypertension N Engl J Med 2013; 369:330.
5 HA Ghofrani et al Riociguat for the treatment of chronic thrombo-embolic pulmonary hypertension N Engl J Med 2013; 369:319.
Trang 5On 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
or in part without prior permission in writing The editors do not warrant that all the material
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
The Medical Letter • Volume 56 • Issue 1437 • March 3, 2014
Coming Soon in The Medical Letter:
Golimumab (Simponi) for Ulcerative Colitis
Drugs for Gout
Tobramycin Inhalation (Bethkis) for Cystic Fibrosis
Coming Soon in Treatment Guidelines:
Drugs for Peptic Ulcer Disease and GERD Drugs for Hypertension
In a randomized, double-blind trial in 305 patients with
osteoarthritis, diclofenac 35 mg three times daily for 12
weeks was signifi cantly more effective than placebo
in relieving pain; twice-daily administration of the drug
was not signifi cantly better than placebo.2
ADVERSE EFFECTS — NSAIDs frequently cause
small increases in aminotransferase activity; serious
hepatotoxicity is rare, but may occur more frequently
with diclofenac An increased risk of serious
cardio-vascular events has been reported with some NSAIDs;
the risk appeared to be highest with diclofenac.3 In the
12-week osteoarthritis trial, no serious gastrointestinal,
cardiovascular, or renal adverse events were reported
with diclofenac 35 mg 3 times daily.4
DRUG INTERACTIONS — Diclofenac is metabolized
primarily by CYP2C9; co-administration with CYP2C9
inhibitors (such as fl uconazole) may increase its serum
concentrations and toxicity.5 Like other NSAIDs,
diclof-enac may decrease the effectiveness of diuretics, beta
blockers, ACE inhibitors and some other
antihyperten-sive drugs, may increase the toxicity of lithium,
metho-trexate, and cyclosporine, and may increase the risk of
gastrointestinal bleeding in patients taking warfarin
DOSAGE, ADMINISTRATION, AND COST — The
rec-ommended dosage of Zorvolex is 18 mg or 35 mg three
times daily It can be taken with or without food, but its
effectiveness may be reduced when taken with food A
single Zorvolex capsule of either strength costs $2.50,
compared to about $0.70 for one 50-mg tablet of
ge-neric diclofenac potassium.6
CONCLUSION — NSAIDs can cause serious adverse
effects and should be used in the lowest effective dosage
Zorvolex, a new low-dose oral formulation of diclofenac,
is more effective than placebo in relieving acute pain
How it compares in effi cacy or safety to oral
immediate-release diclofenac potassium, which is available
generi-cally, or to any other traditional NSAID, is unknown □
1 A Gibofsky et al Lower-dose diclofenac submicron particle capsules
provide early and sustained acute patient pain relief in a phase 3
study Postgrad Med 2013; 125:130.
2 A Gibofsky et al A phase 3 study of lower-dose diclofenac submicron
particle capsules demonstrates effective pain relief in patients with
os-teoarthritis Osteoarthritis Cartilage 2013; 21(4) suppl:S267 Abs 518.
3 Drugs for pain Treat Guidel Med Lett 2013; 11:31.
4 C Young and MC Hochberg Safety of lower-dose diclofenac
sub-micron particle capsules dosed up to 12 weeks in patients with
os-teoarthritis Arthritis Rheum 2013; 65(10) suppl:S915 Abs 2149.
5 Inhibitors and inducers of CYP enzymes and P-glycoprotein Med
Lett Drugs Ther 2013; 55:e44.
6 Approximate wholesale acquisition cost (WAC) Source: Analy$ource
Monthly (Selected from FDB MedKnowledge ™ ) February 5, 2014
Re-printed with permission by FDB, Inc All rights reserved © 2014
www.fdb-health.com/policies/drug-pricing-policy Actual retail prices may be higher.
Trang 6ACPE UPN: Per Issue Exam: 0379-0000-14-437-H01-P; Release: March 3, 2014, Expire: March 3, 2015 Comprehensive Exam 70: 0379-0000-14-070-H01-P; Release: July 2014, Expire: July 2015
Over
Online Continuing Medical Education
To take CME exams and earn credit, go to:
medicalletter.org/CMEstatus
Issue 1437 Questions
(Correspond to questions #25-30 in Comprehensive Exam #70, available July 2014)
Riociguat (Adempas) for Pulmonary Hypertension
1 Which of the following are used to manage PAH?
c sildenafi l
d all of the above
2 Riociguat taken for 12 weeks increased the 6-minute walk distance from baseline by about:
3 In clinical trials, 10% of patients treated with riociguat experienced:
Low-Dose Diclofenac (Zorvolex) for Pain
4 Compared to diclofenac potassium 50 mg, the AUC and Cmax of Zorvolex
35 mg were about:
5 A 56-year-old woman with mild osteoarthritis of the knee treated fairly
successfully with acetaminophen has seen advertisements for Zorvolex and
asks if she could try it instead She has had atrial fi brillation for 10 years, for which she takes warfarin and a beta blocker You could tell her that:
a Zorvolex may be less convenient than acetaminophen because
taking it with food could decrease its effectiveness
b diclofenac could increase the risk of gastrointestinal bleeding in
patients taking warfarin
c diclofenac could decrease the effectiveness of the beta blocker
d all of the above
6 Compared to other NSAIDs, diclofenac is more likely to cause:
a gastric ulcer
b renal toxicity
c serious hepatotoxicity
d all of the above
Trang 7Earn 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 $44.50/13
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 Review the effi cacy and safety of riociquat (Adempas) for treatment of pulmonary arterial hypertension.
2 Review the effi cacy and safety of a new lower-dose formulation of diclofenac (Zorvolex) for treatment of pain.
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 98/NT/2000/XP/Vista/7/8, Pentium+ processor, Mac OS X+ w/compatible processor;
Microsoft IE 6.0+, Mozilla Firefox 2.0+ or any other compatible Web browser Dial-up/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