The medical letter on drugs and therapeutics january 5 2015

The Medical Letter

®

on Drugs and Therapeutics
Objective Drug Reviews Since 1959
Volume 57

ISSUE
ISSUE
No.

1433
1459
Volume 56

January 5, 2015

IN THIS ISSUE

In Brief: Influenza in 2015 ....................................................................................... p 1
Olodaterol (Striverdi Respimat) for COPD ................................................................ p 1
Oritavancin (Orbactiv) for Skin and Skin Structure Infections ................................... p 3
Trumenba: A Serogroup B Meningococcal Vaccine .................................................. p 5
Triumeq: A 3-Drug Combination for HIV .................................................................. p 7
Siltuximab (Sylvant) for Treatment of Multicentric Castleman’s Disease ........ online only

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The Medical Letter

®

on Drugs and Therapeutics
Objective Drug Reviews Since 1959
Volume 57

ISSUE

ISSUE No.

1433
1459

Volume 56

January 5, 2015
Take CME Exams
ALSO IN THIS ISSUE

Oritavancin (Orbactiv) for Skin and Skin Structure Infections ......................................... p 3
Trumenba: A Serogroup B Meningococcal Vaccine ....................................................... p 5
Triumeq: A 3-Drug Combination for HIV ....................................................................... p 7
Siltuximab (Sylvant) for Treatment of Multicentric Castleman's Disease ............ online only

▶

IN BRIEF

Influenza in 2015
The CDC has announced that the most common
influenza viruses circulating now are influenza A
H3N2, which tend to cause more severe disease,
and that about half of these viruses are antigenically
different from the H3N2 strain in this year’s flu
vaccine.1 Vaccination may still have a protective
effect, even against drifted variants, and patients
who have not received this year’s vaccine2 should be
encouraged to do so.
Prompt treatment of confirmed or suspected influenza illness with antiviral drugs is recommended
for hospitalized patients, for those with severe,
complicated, or progressive illness, and for persons
at high risk of complications: children <2 years old,
adults ≥65 years old, women who are pregnant

or ≤2 weeks postpartum, persons <19 years old
receiving long-term aspirin therapy, morbidly obese
patients (BMI ≥40), persons of American Indian/
Alaskan Native heritage, residents of nursing homes
or chronic-care facilities, and patients who are
immunosuppressed or have chronic diseases such
as asthma, diabetes, or heart, lung, or kidney disease.
The neuraminidase inhibitors oseltamivir (Tamiflu),
which is taken orally, and zanamivir (Relenza),
which is inhaled, taken within 48 hours after the
onset of illness can decrease the duration of fever
and symptoms in uncomplicated influenza and
may reduce the incidence of pneumonia and death
in high-risk patients.3 All of the influenza viruses
tested to date for resistance to neuraminidase
inhibitors this season have been susceptible to both
oseltamivir and zanamivir.1 ■
1. CDC health advisory regarding the potential for circulation of drifted influenza A (H3N2) viruses. Available at .
gov/han/han00374.asp. Accessed December 18, 2014.
2. Influenza vaccine for 2014-2015. Med Lett Drugs Ther 2014; 56:97.
3. Antiviral drugs for seasonal influenza 2014-2015. Med Lett Drugs
Ther 2014; 56:121.

Olodaterol (Striverdi Respimat) for
COPD

Olodaterol (Striverdi Respimat – Boehringer Ingelheim),
a new inhaled long-acting beta2-agonist, has been
approved by the FDA for once-daily maintenance
treatment of airflow obstruction in patients with

chronic obstructive pulmonary disease (COPD). It is
not approved for treatment of acute exacerbations of
COPD or for treatment of asthma. Olodaterol is the third
long-acting beta2-agonist to be approved by the FDA
for once-daily use; indacaterol (Arcapta Neohaler),1
which is available as a single agent, and vilanterol,
which is available only in fixed-dose combinations
with the long-acting anticholinergic umeclidinium
(Anoro Ellipta) or the corticosteroid fluticasone furoate
(Breo Ellipta), were approved earlier.2,3
Pronunciation Key
Olodaterol: oh" loe da' ter ol
Striverdi Respimat: stri ver' dee res' pi mat

MAINTENANCE TREATMENT — In patients with
moderate to severe COPD, regular treatment with an
inhaled long-acting bronchodilator (a beta2-agonist or
an anticholinergic) can relieve symptoms, improve lung
function, and reduce the frequency of exacerbations. A
combination of a beta2-agonist and an anticholinergic
can be used for patients inadequately controlled with
Table 1. Pharmacology
Drug class

Long-acting beta2-adrenergic agonist

Formulation

Inhalation spray, 4 g cartridges

Route

Oral inhalation

Tmax

10-20 minutes

Metabolism

Glucuronidation (UGT2B7, 1A1, 1A7, 1A9) and
O-demethylation (mainly CYP2C9; also 2C8 and
3A4), followed by conjugation

Effective half-life

7.5 hours in COPD patients

Elimination

Feces (84%), urine (9%) after oral administration

1

Published by The Medical Letter, Inc. • A Nonprofit Organization


The Medical Letter

Vol. 57 (1459)

®

January 5, 2015

Table 2. Some Drugs for Maintenance Treatment of COPD
Drug

Formulations

Inhaled Long-Acting Beta2-Agonists
Olodaterol – Striverdi Respimat
2.5 mcg/inhalation
(Boehringer Ingelheim)
Indacaterol – Arcapta Neohaler (Novartis)
75 mcg/capsule
Salmeterol – Serevent Diskus (GSK)
50 mcg/blister
Formoterol – Foradil Aerolizer (MSD)
12 mcg/capsule
Perforomist (Mylan)
20 mcg/2 mL soln
Arformoterol – Brovana (Sunovion)
15 mcg/2 mL soln
Inhaled Long-Acting Anticholinergics
Tiotropium – Spiriva HandiHaler
18 mcg/capsule
(Boehringer Ingelheim)
Spiriva Respimat (Boehringer Ingelheim)
2.5 mcg/inhalation

Aclidinium – Tudorza Pressair (Actavis)
400 mcg/inhalation
Umeclidinium – Incruse Ellipta (GSK)
62.5 mcg/inhalation
Inhaled Long-Acting Anticholinergic/Long-Acting Beta2-Agonist Combination
Umeclidinium/vilanterol – Anoro Ellipta
62.5 mcg/25 mcg/blister
(GSK/Theravance)
Inhaled Corticosteroid/Long-Acting Beta2-Agonist Combinations
Fluticasone propionate/salmeterol –
100, 250, 500 mcg/
Advair Diskus (GSK)
50 mcg/blister2
Fluticasone furoate/vilanterol –
100 mcg/25 mcg/
Breo Ellipta (GSK/Theravance)
blister
Budesonide/formoterol – Symbicort
80, 160 mcg/
(AstraZeneca)
4.5 mcg/inhalation3

Delivery Device

Usual Adult Dosage

Cost1

MDI (28, 60 inh/unit)

5 mcg once/day

$155.70

DPI (30 inh/unit)
DPI (28, 60 inh/unit)
DPI (12, 60 inh/unit)
Nebulizer
Nebulizer

75 mcg once/day
50 mcg bid
12 mcg bid
20 mcg bid
15 mcg bid

183.40
221.80
221.10
618.60
598.80

DPI (5, 30, 90 inh/unit)

18 mcg once/day

297.80

MDI (28, 60 inh/unit)
DPI (30, 60 inh/unit)

DPI (7, 30 inh/unit)

5 mcg once/day
400 mcg bid
62.5 mcg once/day

297.80
256.00
N.A.

DPI (7, 30 inh/unit)

62.5/25 mcg once/day

281.00

DPI (14, 60 inh/unit)

250/50 mcg bid

DPI (14, 30 inh/unit)

100/25 mcg once/day

MDI (60, 120 inh/unit)

320/9 mcg bid

283.70
267.70

254.40

DPI = dry powder inhaler; MDI = metered-dose inhaler; inh = inhalation; soln = solution; N.A. = Cost not yet available
1. Approximate WAC for 30 days’ treatment. WAC = wholesaler acquisition cost, or manufacturer’s published price to wholesalers; WAC represents published
catalogue or list prices and may not represent actual transactional prices. Source: AnalySource® Monthly. December 5, 2014. Reprinted with permission by
First Databank, Inc. All rights reserved. ©2014. www.fdbhealth.com/policies/drug-pricing-policy.
2. Only the 250/50 mcg strength is FDA-approved for use in COPD.
3. Only the 160/4.5 mcg strength is FDA-approved for use in COPD.

a single agent. For patients with severe COPD who
experience frequent exacerbations despite treatment with a long-acting beta2-agonist/anticholinergic
combination, addition of an inhaled corticosteroid is
recommended.4
CLINICAL STUDIES — Two identical randomized,
double-blind, crossover studies in a total of 199
patients with moderate to very severe COPD compared
the forced expiratory volume in 1 second (FEV1)
24-hour time profile of once-daily olodaterol with
twice-daily formoterol and placebo after 6 weeks of
treatment. Both active drugs were superior to placebo.
Mean increases from baseline in FEV1 area under the
curve (AUC) were similar with olodaterol and formoterol
over 0-12 hours and 0-24 hours. Peak bronchodilation
occurred within 30 minutes after a dose of olodaterol
or formoterol.5
The efficacy of olodaterol was also evaluated in four
randomized, double-blind, placebo-controlled 48week trials in 3104 patients with moderate to very
severe COPD, most of whom were also taking other
pulmonary medications. Twice-daily formoterol was
included as an active comparator in 2 of the trials.

Compared to placebo, once-daily olodaterol 5 mcg
significantly increased FEV1 AUC over 0-3 hours at
2

12 weeks and 24 weeks in all 4 trials. Trough (predose) FEV1 increased significantly in 3 of 4 trials at
week 12 and in all 4 trials at week 24. Improvements
were maintained through 48 weeks. Efficacy and
adverse effects of formoterol were not significantly
different from those with olodaterol. Patients taking
olodaterol also reported improvements in respiratory
symptoms and reductions in daytime and nighttime
use of rescue medication, compared to those taking
placebo.6,7
Olodaterol has not been directly compared with indacaterol for treatment of COPD, but one meta-analysis
of eighteen randomized, controlled clinical trials of the
two drugs found them to be similarly effective.8
ADVERSE EFFECTS — In clinical trials of olodaterol,
common adverse effects (reported in >2% of patients
and more frequently than with placebo) included
nasopharyngitis, upper respiratory tract infection,
bronchitis, urinary tract infection, cough, dizziness,
rash, diarrhea, back pain, and arthralgia. Systemic
adverse effects of inhaled beta2-agonists are generally
mild, but can include skeletal muscle tremors,
insomnia, palpitations, tachycardia, QTc interval
prolongation, hypokalemia, and hyperglycemia.
Tolerance can occur with chronic use.


The Medical Letter

®

All US products that contain a long-acting beta2-agonist, including olodaterol, are required to have a boxed
safety warning in their labeling indicating that they may
increase the risk of asthma-related death; there is no
evidence to date that patients with COPD are at risk.
PREGNANCY — Olodaterol is classified as category C
(teratogenic effects in animals at very high doses; no
adequate studies in women) for use during pregnancy.
DRUG INTERACTIONS — As with other beta2-agonists,
use of olodaterol with non-potassium-sparing
diuretics can exacerbate hypokalemia and ECG
changes, and concurrent use with MAO inhibitors,
tricyclic antidepressants, or other drugs that prolong
the QTc interval (www.crediblemeds.org) can result
in additive cardiovascular effects. Olodaterol is
extensively metabolized, mainly by CYP2C9, and is
a P-glycoprotein (P-gp) substrate, but no dosage
adjustment is required when it is co-administered with
a CYP and/or P-gp inhibitor.
DOSAGE AND ADMINISTRATION — Striverdi Respimat
inhalation spray is supplied in cartons containing one
inhaler and one olodaterol hydrochloride cartridge.
The recommended dosage is two 2.5-mcg inhalations
once daily. Before using the inhaler for the first time, a
cartridge must be inserted and primed. If the inhaler is
not used for 21 days, the cartridge must be re-primed.
Some older patients may need assistance assembling
the cartridge and inhaler. Pictures of the device and

instructions for use are available at www.striverdi.com.
CONCLUSION — Once-daily inhalation of olodaterol
(Striverdi Respimat) can improve lung function in
patients with moderate to severe COPD. Its efficacy
and safety appear to be similar to those of twicedaily formoterol (Foradil Aerolizer) and once-daily
indacaterol (Arcapta Neohaler). ■
1. Indacaterol (Arcapta Neohaler) for COPD. Med Lett Drugs Ther
2012; 54:33.
2. Anoro Ellipta: an inhaled umeclidinium/vilanterol combination
for COPD. Med Lett Drugs Ther 2014; 56:30.
3. Breo Ellipta: an inhaled fluticasone/vilanterol combination for
COPD. Med Lett Drugs Ther 2013; 55:69.
4. Drugs for asthma and COPD. Treat Guidel Med Lett 2013; 11:75.
5. GJ Feldman et al. The 24-h FEV1 time profile of olodaterol once
daily via Respimat and formoterol twice daily via Aerolizer in
patients with GOLD 2-4 COPD: results from two 6-week crossover studies. Springerplus 2014; 3:419.
6. GT Ferguson et al. Efficacy and safety of olodaterol once daily
delivered via Respimat in patients with GOLD 2-4 COPD: results
from two replicate 48-week studies. Int J Chron Obstruct Pulmon Dis 2014; 9:629.
7. A Koch et al. Lung function efficacy and symptomatic benefit
of olodaterol once daily delivered via Respimat versus placebo
and formoterol twice daily in patients with GOLD 2-4 COPD: results from two replicate 48-week studies. Int J Chron Obstruct

Vol. 57 (1459)

January 5, 2015

Pulmon Dis 2014; 9:697.
8. NS Roskell et al. Once-daily long-acting beta-agonists for chronic
obstructive pulmonary disease: an indirect comparison of olodaterol and indacaterol. Int J Chron Obstruct Pulmon Dis 2014; 9:813.

▶

Oritavancin (Orbactiv) for Skin and
Skin Structure Infections

The FDA has approved oritavancin (Orbactiv – The
Medicines Company), a long-acting lipoglycopeptide
antibiotic given as a single intravenous (IV) dose, for
treatment of acute bacterial skin and skin structure
infections caused by susceptible gram-positive
bacteria in adults. It is the third lipoglycopeptide
antibiotic to be marketed in the US; telavancin (Vibativ)
and dalbavancin (Dalvance) were approved earlier.1,2
Pronunciation Key
Oritavancin: or it" a van' sin
Orbactiv: or bak' tiv

STANDARD TREATMENT – Purulent skin and softtissue infections are now caused predominantly by
methicillin-resistant Staphylococcus aureus (MRSA)
in many parts of the US. Patients hospitalized for
complicated skin and soft-tissue infections suspected
to be caused by MRSA are usually treated empirically
with IV vancomycin. Some alternatives are listed in
Table 3. For less serious MRSA infections, incision and
drainage alone or in combination with oral trimethoprim/
sulfamethoxazole or doxycycline is usually effective.3
For patients hospitalized for non-purulent skin and
soft-tissue infections, which are often caused by
streptococci, treatment with IV penicillin, cefazolin,

ceftriaxone, or clindamycin is recommended.4
Table 1. Pharmacology
Class
Route
Formulation
Distribution
Metabolism
Excretion
Half-life (terminal)

Lipoglycopeptide antibiotic
IV infusion
400 mg single-use vials
85% protein bound
Not metabolized
Slow; unchanged (urine [5%], feces [<1%]
in 14 days)
~10 days

MECHANISM OF ACTION – Oritavancin inhibits cell
wall synthesis and disrupts bacterial membrane integrity, leading to cell death.
ACTIVITY – Oritavancin has concentration-dependent
bactericidal activity against S. aureus, Streptococcus
pyogenes, and Enterococcus faecalis. It is active both
clinically and in vitro against S. aureus (including MRSA),
S. pyogenes, Streptococcus agalactiae, Streptococcus
anginosus group, Streptococcus dysgalactiae, and
3

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January 5, 2015

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®

vancomycin-susceptible isolates of E. faecalis.
Oritavancin has also demonstrated in vitro activity
against vancomycin-susceptible and vancomycinresistant isolates of Enterococcus faecium.5
CLINICAL STUDIES – FDA approval of oritavancin was
based on 2 randomized, double-blind, non-inferiority
trials (SOLO I and SOLO II) that compared a single 1200mg dose of IV oritavancin with IV vancomycin given
twice daily for 7 to 10 days in adults with acute bacterial
skin and skin structure infections.6,7 Oritavancin was
found to be noninferior to vancomycin in achieving the
primary composite end point, which was defined as
no increase from baseline in the size of the infected
area, absence of fever, and no rescue antibiotic use at
48-72 hours after initiation of therapy. The percentage
of patients achieving a ≥20% reduction from baseline
in lesion size 48-72 hours after initiation of therapy
and the proportion considered to be clinically cured
7-14 days after treatment, two secondary endpoints,
were similar in the two groups. S. aureus was the
predominant pathogen in both studies; the two drugs
appeared to be similarly effective in achieving the
primary endpoint in patients infected with methicillinsusceptible and methicillin-resistant strains.
The prescribing information for oritavancin includes

a warning about a higher incidence of osteomyelitis in
patients treated with the drug in phase III trials. Whether
osteomyelitis was due to failure to diagnose it at baseline
or progression of skin infection due to lack of efficacy of
oritavancin is not known.

Table 2. Oritavancin Clinical Trials
Oritavancin

Vancomycin

SOLO I (n=954)1
Primary Composite Endpoint2 82.3% (391/475)
Reduction in Lesion Area3
86.9% (413/475)
Clinical Cure4
79.6% (378/475)

78.9% (378/479)
82.9% (397/479)
80.0% (383/479)

SOLO II (n=1005)5
Primary Composite Endpoint2 80.1% (403/503)
Reduction in Lesion Area3
85.9% (432/503)
Clinical Cure4
82.7% (416/503)

82.9% (416/502)

85.3% (428/502)
80.5% (404/502)

1. GR Corey et al. N Engl J Med 2014; 370:2180.
2. Defined as no increase from baseline in the size of the infected area, absence of fever, and no rescue antibiotic use at 48-72 hours after initiation
of therapy.
3. Reduction from baseline of ≥20% in lesion surface area 48-72 hours after
initiation of therapy, a secondary endpoint.
4. Investigator assessed at 7-14 days post treatment, a secondary endpoint.
5. GR Corey et al. Clin Infect Dis 2014 October 6 (epub).

ADVERSE EFFECTS – The most common adverse
effects of oritavancin were nausea (9.9%), headache
(7.1%), vomiting (4.6%), limb and subcutaneous abscess
(3.8%), and diarrhea (3.7%). Serious hypersensitivity
reactions have been reported; the long half-life of the
drug can further complicate these reactions. Patients
with a history of a hypersensitivity reaction to another
glycopeptide (vancomycin, teicoplanin, telavancin, or
dalbavancin) may be at increased risk. Infusion-related
reactions such as pruritus, urticaria, and flushing have
also been reported. Oritavancin, unlike telavancin, does
not prolong the QT interval.
Oritavancin appears to be better tolerated than
telavancin. The adverse effects of telavancin, which
include taste disturbances, nausea, vomiting, and

Table 3. Some IV Antibiotics for MRSA Skin and Skin Structure Infections
Drug
Glycopeptides

Vancomycin – generic
Dalbavancin4 – Dalvance (Durata)
Oritavancin4 – Orbactiv (Medicines Co.)
Telavancin4 – Vibativ (Theravance)
Oxazolidinones
Linezolid – Zyvox (Pfizer)
Tedizolid phosphate4 – Sivextro (Cubist)
Others
Ceftaroline fosamil4 – Teflaro (Forest)
Daptomycin4 – Cubicin (Cubist)

Some Available Formulations

Usual Adult Dosage

Cost1

500, 750 mg, 1, 5, 10 g vials
500 mg single-use vials
400 mg single-use vials
250, 750 mg single-use vials

15-20 mg/kg (max 2 g) q12h x 7-14 days2,3 $16.50
1000 mg x 1, then 500 mg 1 wk later2
2980.005
1200 mg once
2900.006
10 mg/kg q24h x 7-14 days2
309.50

200, 600 mg infusion bags7
200 mg single-use vials9

600 mg q12h x 10-14 days8
200 mg q24h x 6 days

278.90
235.00

400, 600 mg single-use vials
500 mg single-use vials

600 mg q12h x 5-14 days2
4 mg/kg q24h x 7-14 days2

252.70
354.7010

1. Approximate wholesale acquisition cost (WAC) for 1 day’s treatment of a 70-kg patient with the lowest usual dosage. WAC = wholesaler acquisition cost or
manufacturer’s published price to wholesalers; WAC represents a published catalogue or list price and may not represent an actual transactional price. Source:
AnalySource® Monthly (Selected from FDB MedKnowledge™) December 5, 2014. Reprinted with permission by First Data Bank, Inc. All rights reserved. ©2014.
www.fdbhealth.com/policies/drug-pricing-policy.
2. Dosage adjustment may be needed for renal or hepatic impairment.
3. Dose may be too low to achieve adequate trough concentrations in many patients with normal renal function. Some experts recommend 15-20 mg/kg q8-12
hours (M Rybak et al. Am J Health Syst Pharm 2009; 66:82). Initial pediatric dosage is 10-15 mg/kg q6h.
4. Not FDA-approved for use in children.
5. Cost for two 500-mg vials.
6. Cost for three 400-mg vials.
7. Also available for oral administration in 600-mg tabs and a 100 mg/5 mL oral suspension.
8. Dosage for children <12 years old is 10 mg/kg q8h.

9. Also available for oral administration in 200-mg tabs.
10. Cost for one 500-mg vial.

4


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January 5, 2015

nephrotoxicity, have limited its use. The adverse
effect profiles of oritavancin and dalbavancin appear
to be similar.

▶

PREGNANCY – Oritavancin is classified as category C
(no fetal toxicity in animals at low concentrations; no
adequate studies in women) for use during pregnancy.

The FDA has approved Trumenba (Pfizer), a vaccine
that protects against invasive meningococcal disease
caused by Neisseria meningitidis serogroup B, for use
in adolescents and young adults 10-25 years old.

DRUG INTERACTIONS – Use of IV unfractionated

heparin is contraindicated for 48 hours after
administration of oritavancin because the drug can
falsely elevate activated partial thromboplastin time
(aPTT) for up to 48 hours. It also artificially prolongs
prothrombin time (PT) and INR for up to 24 hours
after administration. Oritavancin is a weak inhibitor of
CYP2C19; coadministration with warfarin (Coumadin,
and others), a substrate of 2C19, can increase warfarin
serum concentrations and the risk of bleeding.

SEROGROUP B MENINGOCOCCAL VACCINES — Until
recently, no serogroup B meningococcal vaccine was
available in the US because the polysaccharide capsule
of the B serogroup is only weakly immunogenic. A
different meningococcal B vaccine (4CMenB; Bexsero)
has been approved for use in Canada, the European
Union, and Australia. In late 2013 and early 2014,
the FDA and the CDC permitted the importation and
investigational use of Bexsero in two outbreaks of
serogroup B meningococcal disease.1

DOSAGE AND ADMINISTRATION – Oritavancin is
administered as a single 1200-mg dose infused
intravenously over 3 hours. No dosage adjustments
are needed for renal or hepatic impairment. The drug
is available in single-use vials containing 400 mg of
lyophilized powder, which must be reconstituted and
mixed in 1 liter of D5W prior to infusion.

MENINGOCOCCAL DISEASE — Five major serogroups

(A, B, C, Y, and W-135) of N. meningitidis cause most
invasive meningococcal disease worldwide. Rates
of meningococcal disease are highest in infancy. A
second peak occurs in adolescents and young adults,
and a third occurs in adults ≥65 years old.2 Three FDAapproved vaccines (Menomune, Menactra, Menveo)3,4
protect against serogroups A, C, Y, and W-135 and a
combination meningococcal/Haemophilus influenzae
type b vaccine (MenHibrix),5 which is FDA-approved
only for use in children 6 weeks to 18 months old,
protects against serogroups C and Y. According
to the CDC, serogroup B causes about 60% of all
meningococcal disease in US children <5 years
old and about 30% of meningococcal disease in
US adolescents and young adults. Meningococcal
disease rates have been declining in recent years,
including rates of serogroup B disease. In 2012, the
CDC reported 551 cases of meningococcal disease, of
which 110 were caused by serogroup B.6

CONCLUSION – Oritavancin (Orbactiv) appears
to be as effective as vancomycin for treatment of
acute bacterial skin and skin structure infections,
including those caused by MRSA. Use of a single
dose of oritavancin may permit outpatient treatment
of infections that previously required hospitalization,
but its long half-life could prolong allergic and other
adverse reactions if they occur. The efficacy of
oritavancin for treatment of more invasive infections,
including pneumonia and bacteremia, is unknown.
Until more data are available, older, less expensive

alternatives are preferred. ■
1. Telavancin (Vibativ) for gram-positive skin infections. Med Lett
Drugs Ther 2010; 52:1.
2. Two new drugs for skin and skin structure infections. Med Lett
Drugs Ther 2014; 56:73.
3. Drugs for MRSA skin and soft-tissue infections. Med Lett Drugs
Ther 2014; 56:39.
4. DL Stevens et al. Practice guidelines for the diagnosis and
management of skin and soft tissue infections: 2014 update
by the Infectious Diseases Society of America. Clin Infect Dis
2014; 59:147.
5. CA Arias et al. Unmet needs and prospects for oritavancin in the
management of vancomycin-resistant enterococcal infections.
Clin Infect Dis 2012; 54 suppl 3:5233.
6. GR Corey et al. Single-dose oritavancin in the treatment of
acute bacterial skin infections. N Engl J Med 2014; 370:2180.
7. GR Corey et al. Single-dose oritavancin versus 7-10 days of
vancomycin in the treatment of gram-positive acute bacterial
skin and skin structure infections: the SOLO II noninferiority
study. Clin Infect Dis 2014 October 6 (epub).

Trumenba: A Serogroup B
Meningococcal Vaccine

THE NEW VACCINE — Administration of Trumenba
generates serum bactericidal antibodies.7,8 A 0.5-mL
dose contains 60 mcg each of two recombinant
lipidated factor H binding protein (fHBP) variants
(grown in E. coli ) from N. meningitidis serogroup B.
fHBP, which is one of several proteins expressed on

the surface of meningococci, binds to human
factor H and interferes with complement-mediated
bacteriolysis, which is the primary mechanism for
clearing N. meningitidis from the blood. The efficacy
of the vaccine depends on the antigenic similarity
between bacterial and vaccine fHBP and the amount
of fHBP expressed on the surface of the invading
meningococci.
5


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January 5, 2015

Table 1. Meningococcal Vaccines in the US
Vaccine

Type

Serogroups

FDA-Approved
Age/Dose

Schedule

Cost1

Trumenba
(Pfizer)

Factor H
binding protein

B

10-25 yrs: 0.5 mL IM

3 doses (0, 2, and 6 mos)

$115.00

Menomune
(Sanofi Pasteur)

Unconjugated,
polyscaccharide

A, C, Y, W-135

≥2 yrs: 0.5 mL SC

1 dose2

116.60

Menactra
(Sanofi Pasteur)

Conjugated,
polysaccharide

A, C, Y, W-135

9 mos-55 yrs: 0.5 ML IM3

9-23 mos: 2 doses 3 mos apart2
2-55 yrs: 1 dose2,3

112.20

Menveo
(Novartis)

Conjugated,
polysaccharide

A, C, Y, W-135

2 mos-55 yrs: 0.5 mL IM

2 mos: 4 doses (2, 4, 6, and
12 mos old)2
7-23 mos: 2 doses at least
3 mos apart, second dose

at >12 mos old2
2-55 yrs: 1 dose2

116.70

MenHibrix4
(GSK)

Conjugated,
polysaccharide

C, Y

6 wks-18 mos: 0.5 mL IM

4 doses (2, 4, 6, and
12-15 mos old5)2

22.10

1. Approximate WAC for 1 dose. WAC = wholesaler acquisition cost or manufacturer’s published price to wholesalers; WAC represents a published catalogue or
list price and may not represent an actual transactional price. Source: AnalySource® Monthly. December 5, 2014. Reprinted with permission by First Databank,
Inc. All rights reserved. ©2014. www.fdbhealth.com/policies/drug-pricing-policy.
2. The US Advisory Committee on Immunization Practices (ACIP) recommends routine immunization of adolescents with a single dose of Menactra or Menveo at
11 or 12 years of age with a booster dose at age 16 years (the booster dose should be given between 16 and 18 years of age if the first dose was administered
at age 13-15). The ACIP also recommends routine immunization for persons ≥2 mos old with an increased risk of developing invasive meningococcal disease,
including those with anatomic or functional asplenia or persistent complement deficiencies, first-year college students living in dormitories, those at risk of
exposure during a community outbreak, travelers (≥9 mos old) to a country where meningococcal disease is hyperendemic or epidemic, and laboratory personnel routinely exposed to isolates of N. meningitidis (MenHibrix is recommended for infants 2-18 months old; Menactra or Menveo is recommended for those
9 months to 55 years old and for those ≥56 years old previously vaccinated with Menactra or Menveo; Menomune is recommended for vaccine-naive persons
≥56 years old who will require only a single dose). Those who received a primary series at 2 mos-6 years of age should receive an additional dose after 3 years

and then every 5 years thereafter; those who completed a primary series at ≥7 years of age should receive booster doses every 5 years (AC Cohn et al. MMWR
Recomm Rep 2013; 62[RR-2]:1).
3. A single booster dose of Menactra given ≥4 years after the previous dose is FDA-approved for persons 15-55 years old at continued risk.
4. MenHibrix also protects against Haemophilus influenzae type b.
5. The first dose can be given as early as 6 weeks and the fourth as late as 18 months.

CLINICAL STUDY — The immunogenicity of a 3-dose
series of the new vaccine was established in an
unpublished study (summarized in the package insert)
in adolescents 11 to 17 years old that measured serum
bactericidal activity against 4 serogroup B strains
prevalent in the US. After the third dose, the percentage
of adolescents with protective antibody levels against
the 4 strains was 84% when the meningococcal B
vaccine was given alone and 81% when it was given with
a quadrivalent human papilloma virus (HPV) vaccine.
ADVERSE EFFECTS — In clinical trials in subjects
11-25 years old, most patients (85-93%) experienced
injection site reactions; other common adverse effects
were fatigue (43-64%), headache (35-57%), muscle
pain (31-42%), and chills (16-30%). The incidence of
adverse effects was highest with the first dose of the
vaccine.
CONCLUSION — Trumenba is the first vaccine against
Neisseria meningitidis serogroup B to be approved in
the US. Based on immunogenicity studies, it should
be effective in preventing serogroup B meningococcal
disease in adolescents and young adults
10-25 years old. The duration of protection with the
new vaccine is unknown. To date, the US Advisory

6

Committee on Immunization Practices (ACIP) has
not published any recommendations for its use. How
Trumenba compares to 4CMenB (Bexsero), another
meningococcal B vaccine that has been used as an
investigational drug in the US but is not yet approved,
remains to be determined. ■
1. In brief: Prevention of meningococcal B disease. Med Lett
Drugs Ther 2013; 55:97.
2. AC Cohn et al. Prevention and control of meningococcal
disease: recommendations of the Advisory Committee on
Immunization Practices (ACIP). MMWR Recomm Rep 2013;
62(RR-2):1.
3. Menactra: A meningococcal conjugate vaccine. Med Lett Drugs
Ther 2005; 47:29.
4. A new conjugate meningococcal vaccine (Menveo). Med Lett
Drugs Ther 2010; 52:59.
5. In brief: Meningococcal vaccine for infants. Med Lett Drugs
Ther 2013; 55:92.
6. DA Adams et al. Summary of notifiable diseases-United States,
2012. MMWR Morb Mortal Wkly Rep 2014; 61(53):1.
7. PC Richmond et al. Safety, immunogenicity, and tolerability
of meningococcal serogroup B bivalent recombinant lipoprotein 2086 vaccine in healthy adolescents: a randomised,
single-blind, placebo-controlled, phase 2 trial. Lancet Infect
Dis 2012; 12:597.
8. LK McNeil et al. Role of factor H binding protein in Neisseria
meningitidis virulence and its potential as a vaccine candidate
to broadly protect against meningococcal disease. Microbiol

Mol Biol Rev 2013; 77:234.


The Medical Letter

▶

®

Triumeq: A 3-Drug Combination
for HIV

The FDA has approved Triumeq (Viiv Healthcare),
a fixed-dose combination of the integrase strand
transfer inhibitor (INSTI) dolutegravir and the
nucleoside reverse transcriptase inhibitors (NRTIs)
abacavir and lamivudine, for once-daily treatment of
HIV-1 infection. Dolutegravir (Tivicay) was approved
as a single agent in 2013.1
Pronunciation Key
Abacavir: a bak' a veer
Lamivudine: la miv' ue deen
Dolutegravir: doll ue teg' rah veer Triumeq: trye' ue mek

Vol. 57 (1459)

January 5, 2015

Table 1. Regimens for Treatment-Naive Patients1
NNRTI-Based Regimens

Efavirenz2/tenofovir DF3/emtricitabine4
*
Recommended Efavirenz2 + abacavir5/lamivudine4
Rilpivirine6/tenofovir DF3/emtricitabine4
PI-Based Regimens
Recommended

Recommended

Atazanavir/ritonavir7 + tenofovir DF3/
emtricitabine4
Darunavir/ritonavir (once daily)
+ tenofovir DF3/emtricitabine4

Recommended* Atazanavir/ritonavir7 + abacavir5/lamivudine4
Alternative

Darunavir/ritonavir + abacavir5/lamivudine4
Lopinavir/ritonavir (once or twice daily)
+ either abacavir5/lamivudine4 or
tenofovir DF3/emtricitabine4

INSTI-Based Regimens

TREATMENT OF HIV – First-line therapy for HIV usually
consists of two NRTIs in combination with a third
antiretroviral drug from one of three drug classes: a
non-nucleoside reverse transcriptase inhibitor (NNRTI),
a protease inhibitor (PI) boosted with ritonavir, or an
INSTI.2,3 Dolutegravir plus abacavir and lamivudine is

a recommended INSTI-based regimen for treatmentnaive patients (Table 1).
CLINICAL STUDIES – FDA approval of Triumeq was
based on a double-blind trial in 833 treatment-naive
patients that compared dolutegravir plus fixeddose abacavir/lamivudine once daily with efavirenz/
tenofovir disoproxil fumarate/emtricitabine (Atripla)
once daily. After 48 weeks, 88% of patients treated with
the dolutegravir-based regimen had achieved an HIV-1
RNA level of <50 copies/mL, the primary endpoint,
compared to 81% of those taking the efavirenz-based
regimen.4 At week 96, 80% of patients taking the
dolutegravir-based regimen and 72% of those taking
the efavirenz-based regimen had achieved an HIV-1
RNA level of <50 copies/mL. The differences in efficacy
were primarily due to a higher rate of discontinuation
due to adverse effects in the efavirenz group (11%)
than in the dolutegravir group (3%). NNRTI resistance
mutations occurred in 6 patients taking efavirenz; no
INSTI resistance mutations occurred in those taking
dolutegravir.5
ADVERSE EFFECTS – The most common adverse
effects of dolutegravir/abacavir/lamivudine have
been insomnia (3%), headache (2%), and fatigue (2%).
Severe and sometimes fatal hypersensitivity reactions
have been associated with abacavir; Triumeq should
be not be started in patients with a previous reaction
to abacavir and should be discontinued permanently
if a hypersensitivity reaction occurs. Screening
for the HLA-B*5701 allele, which is associated
with a higher risk of developing a hypersensitivity

Recommended

Dolutegravir + either abacavir5/lamivudine4 or
tenofovir DF3/emtricitabine4
Elvitegravir/cobicistat/tenofovir DF3/emtricitabine8
Raltegravir + tenofovir DF3/emtricitabine4

Alternative

Raltegravir + abacavir5/lamivudine4

*Recommended only if pretreatment viral load is <100,000 copies/mL.
1. For non-pregnant adults and adolescents. An NNRTI-, PI- or INSTI-based
regimen is preferred for initial therapy. Adapted from HHS guidelines
available at Accessed December
18, 2014. “Recommended regimens” are those regimens studied in
randomized controlled trials and shown to have optimal and durable
virologic efficacy, favorable tolerability and toxicity profiles, and ease of
use. “Alternative regimens” are those regimens that are effective, but have
potential disadvantages when compared with recommended regimens.
2. Women who might become pregnant should not be started on efavirenz.
Efavirenz can be used during pregnancy if it is started after the 8th week
of pregnancy. Women with optimal viral suppression with efavirenz who
become pregnant can continue taking it.
3. Use with caution in patients with renal insufficiency.
4. Emtricitabine can be substituted for lamivudine and vice versa.
5. For patients who test negative for HLA-B*5701. Abacavir should be used
with caution in patients with a pretreatment viral load >100,000 copies/
mL or in those who are at high risk for cardiovascular disease.
6. Use of proton pump inhibitors is contraindicated.

7. Not recommended for patients who require >20 mg/d omeprazole equivalent.
8. Should not be started in patients with CrCl <70 mL/min and should be
changed to an alternative regimen if CrCl falls to <50 mL/min during
treatment.

reaction, is recommended before starting Triumeq.
Hypersensitivity reactions have also occurred with
dolutegravir.
Lactic acidosis and severe hepatomegaly with
steatosis have occurred with abacavir and lamivudine.
Elevated liver transaminases have been reported in
patients co-infected with hepatitis B or C being treated
with dolutegravir.
PREGNANCY – Triumeq is classified as category C
(embryofetal toxicity in animals; no adequate studies
in women) for use during pregnancy.
DRUG INTERACTIONS – Drugs containing polyvalent
cations (sucralfate, buffered medications, and calcium,
magnesium, or iron supplements) can decrease the absorption of dolutegravir. Triumeq should be taken 2 hours
before or 6 hours after any of these agents, if possible. It
can be taken simultaneously with supplements containing calcium and/or iron, if taken with food.
7


The Medical Letter

January 5, 2015

Vol. 57 (1459)

®

Table 2. Integrase Strand Transfer Inhibitors (INSTIs)
Drug

Formulations

Usual Adult Dosage

Abacavir/dolutegravir/lamivudine –
Triumeq (Viiv Healthcare)

600/50/300 mg tabs

1 tab once/d

Dolutegravir –
Tivicay (Viiv Healthcare)

50 mg tabs

1 tab once/d3

Elvitegravir/cobicistat/emtricitabine/tenofovir –
Stribild (Gilead)

150/150/200/300 mg tabs

1 tab once/d4

Elvitegravir – Vitekta (Gilead)

85, 150 mg tabs

85-150 mg once/d5,6

Raltegravir – Isentress (Merck)

400 mg tabs7

400 mg bid

Cost1

2

$2207.40
1233.00
2457.30
N.A.
1126.70

N.A. = Cost not yet available.
1. Approximate WAC for 30 days’ treatment. WAC = wholesaler acquisition cost, or manufacturer's published price to wholesalers; WAC represents published
catalogue or list prices and may not represent actual transactional prices. Source: AnalySource® Monthly. December 5, 2014. Reprinted with permission by
First Databank, Inc. All rights reserved. ©2014. www.fdbhealth.com/policies/drug-pricing-policy.
2. Not recommended for use in patients with CrCl <50 mL/min.
3. Dose for INSTI-naive patients.
4. Should not be started in patients with CrCl <70 mL/min and should be changed to an alternative regimen if CrCl falls to <50 mL/min during treatment.
5. Taken with food.

6. Must be taken in combination with a protease inhibitor coadministered with ritonavir and another antiretroviral drug.
7. Also available as 25, 100 mg chewable tabs and 100 mg packets. Formulations are not bioequivalent and cannot be substituted.

Dolutegravir inhibits the renal organic cation
transporter (OCT) 2 and can inhibit tubular secretion
of serum creatinine and drugs eliminated by OCT2,
such as metformin and the antiarrhythmic drug
dofetilide; concurrent use of Triumeq and dofetilide
is contraindicated. Drugs that induce UGT1A1 and/
or CYP3A,6 such as rifampin, efavirenz, or etravirine,
can reduce serum concentrations of dolutegravir
and decrease its effectiveness. Other antiretrovirals
that can decrease dolutegravir serum concentrations
include nevirapine and the protease inhibitors
fosamprenavir/ritonavir and tipranavir/ritonavir.
Abacavir may increase the clearance of methadone;
an increase in the dose of methadone may be needed
in some patients. Elimination of abacavir is decreased
by ethanol.
DOSAGE AND ADMINISTRATION – The recommended
dosage of Triumeq is one tablet (abacavir 600 mg/
dolutegravir 50 mg/lamivudine 300 mg) once daily
with or without food. Before starting treatment
with Triumeq, patients should be screened for the
HLA-B*5701 allele; those who test positive for the
allele should not be treated with Triumeq. The drug is
not recommended for patients with CrCl <50 mL/min.
An additional 50-mg dose of dolutegravir, separated by
12 hours from Triumeq, is recommended for patients
concurrently taking efavirenz, fosamprenavir/ritonavir,

tipranavir/ritonavir, or rifampin. Use of Triumeq alone
is not recommended in patients who have INSTIassociated resistance mutations or suspected
INSTI resistance because the recommended dose of
dolutegravir for such patients is 50 mg twice daily.

8

CONCLUSION – The integrase strand transfer inhibitor
(INSTI)-based fixed-dose combination of abacavir/
dolutegravir/lamivudine (Triumeq) is effective for
treatment of HIV-1 infection in treatment-naive
patients and is well tolerated. Taking one tablet daily
of the new combination is more convenient than taking
the components separately. ■
1. Dolutegravir (Tivicay) for HIV. Med Lett Drugs Ther 2013; 55:77.
2. Drugs for HIV infection. Treat Guidel Med Lett 2014; 12:7.
3. Panel on Antiretroviral Guidelines for Adults and Adolescents.
Guidelines for the use of antiretroviral agents in HIV-1-infected
adults and adolescents. Department of Health and Human Services. November 13, 2014. Available at />guidelines. Accessed December 18, 2014.
4. SL Walmsley et al. Dolutegravir plus abacavir-lamivudine for
the treatment of HIV-1 infection. N Engl J Med 2013; 369:1807.
5. S Walmsley et al. Dolutegravir regimen statistically superior
to efavirenz/tenofovir/emtricitabine: 96-week results from the
SINGLE study (ING114467). 21st Conference on Retroviruses
and Opportunistic Infections; Boston, MA; March 3-6, 2014.
Abstract 543. Available at www.croiconference.org/sites/all/
abstracts/543.pdf. Accessed December 18, 2014.
6. Inhibitors and inducers of CYP enzymes and P-glycoprotein.
Med Lett Drugs Ther 2013; 55:e44.

2014 Year-End Index
For an electronic copy of the 2014 index, go to:
www.medicalletter.org/downloads/tmlindex2014.pdf

Coming Soon in The Medical Letter:
Drugs for Chronic Heart Failure
Suvorexant (Belsomra) for Insomnia
Buprenorphine/naloxone (Bunavail) for Opioid Dependence


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The Medical Letter

®

on Drugs and Therapeutics
Objective Drug Reviews Since 1959
Volume 57 (Issue 1459)

▶

January 5, 2015

Siltuximab (Sylvant) for Treatment
of Multicentric Castleman's
Disease

The FDA has approved the interleukin-6 (IL-6) antagonist siltuximab (Sylvant – Janssen), a recombinant
chimeric (human-mouse) monoclonal antibody, for
treatment of multicentric Castleman’s disease (MCD) in
patients who are HIV negative and human herpesvirus-8
(HHV-8) negative. It is the first drug to be approved for
this indication.
Pronunciation Key
Siltuximab: sil tux' i mab
Sylvant: sill vant

receiving siltuximab was 383 days. The median time to
treatment failure, 134 days in the placebo group, was
not reached in the siltuximab group after a median
follow-up of 422 days.3
ADVERSE EFFECTS — Common adverse effects of
siltuximab in the controlled clinical trial (reported at
least 10% more frequently than with placebo) included
rash, pruritus, weight gain, hyperuricemia, and upper
respiratory tract infection. In an interim analysis of
a long-term safety study in 19 patients with MCD
receiving chronic siltuximab therapy, no cumulative
toxicities were identified and there were no deaths
after a median follow-up of 5.1 years.4

MULTICENTRIC CASTLEMAN’S DISEASE — MCD is a
rare lymphoproliferative disorder that is associated
with excessive release of IL-6 and other proinflammatory cytokines.1 HHV-8 causes the elevated
levels of cytokines in many patients with MCD,
particularly those who are HIV positive. The etiology of
HIV- and HHV-8-negative MCD is unknown.2 Patients

usually present with generalized lymphadenopathy,
which may be accompanied by hepatosplenomegaly in
severe cases. There is no standard treatment for MCD.
Unicentric (localized) Castleman’s disease, which is
more common, can usually be cured with surgery.

DOSAGE AND COST — Sylvant is supplied in 100- and
400-mg single-use vials. The recommended dosage is
11 mg/kg given by intravenous infusion over 1 hour
every 3 weeks. One treatment for a patient weighing 70
kg (two 400-mg vials) costs $6664.5

MECHANISM OF ACTION — Siltuximab binds human
IL-6 and prevents its binding to IL-6 receptors. It
was not studied in HIV- and HHV-8-positive patients
because, according to the manufacturer, it did not bind
to virally produced IL-6 in a nonclinical study.

1. A Dispenzieri et al. The clinical spectrum of Castleman’s disease. Am J Hematol 2012; 87:997.
2. DC Fajgenbaum et al. HHV-8-negative, idiopathic multicentric
Castleman disease: novel insights into biology, pathogenesis,
and therapy. Blood 2014; 123:2924.
3. F van Rhee et al. Siltuximab for multicentric Castleman’s disease: a randomised, double-blind, placebo-controlled trial.
Lancet Oncol 2014; 15:966.
4. F van Rhee et al. An open-label, phase 2, multicenter study of
the safety of long-term treatment with siltuximab (an anti-interleukin-6 monoclonal antibody) in patients with multicentric
Castleman’s disease. Blood 2013; 122 (21):1806.
5. Approximate wholesale acquisition cost (WAC). WAC = wholesaler acquisition cost or manufacturer’s published price to
wholesalers; WAC represents a published catalogue or list price
and may not represent an actual transactional price. Source:

AnalySource® Monthly (Selected from FDB MedKnowledge™)
December 5, 2014. Reprinted with permission by First Data
Bank, Inc. All rights reserved. ©2014. www.fdbhealth.com/policies/drug-pricing-policy.

CLINICAL STUDY — Approval of siltuximab was based
on the results of a double-blind study in 79 patients
with MCD who were HIV and HHV-8 negative. Patients
were randomized to receive supportive care plus
either siltuximab or placebo by IV infusion every 3
weeks until treatment failure. A durable tumor and
symptomatic response for at least 18 weeks, the
primary endpoint, occurred in 18 of 53 patients (34%)
treated with siltuximab (one complete and 17 partial
responses) compared to 0 of 26 (0%) who received a
placebo; the median duration of response in patients

CONCLUSION — Siltuximab (Sylvant) can reduce
tumor size and improve symptoms in about one-third
of HIV- and human herpesvirus-8-negative patients
with multicentric Castleman’s disease. Patients who
respond will probably require chronic treatment with
this expensive drug. ■

e8

Published by The Medical Letter, Inc. • A Nonprofit Organization


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Discuss the recommendations for use of influenza vaccine and antiviral drugs based on the strains of influenza circulating this year.
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3.
Review the efficacy and safety of oritavancin (Orbactiv) for treatment of acute bacterial skin and skin structure infections.
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Issue 1459 Questions
(Correspond to questions #1-10 in Comprehensive Exam #72, available July 2015)
Influenza in 2015
1. Prompt treatment of confirmed or suspected influenza is
recommended for:
a. hospitalized patients
b. patients with severe, complicated, or progressive illness
c. persons at high risk of complications
d. all of the above
Olodaterol (Striverdi Respimat) for COPD
2. Olodaterol is FDA-approved for:
a. asthma

b. maintenance treatment of COPD
c. treatment of acute exacerbations of COPD
d. all of the above

6. A major concern with the use of oritavancin is:
a. thrombocytopenia
b. nephrotoxicity
c. prolonged allergic reactions
d. all of the above
7. Oritavancin affects which of the following laboratory tests?
a. aPTT
b. PT
c. INR
d. all of the above
Trumenba: A Serogroup B Meningococcal Vaccine

3. In clinical studies that included both drugs, results with olodaterol
were similar to those with:
a. formoterol
b. indacaterol
c. umeclidinium
d. all of the above
Oritavancin (Orbactiv) for Skin and Skin Structure Infections
4. Oritavancin is administered:
a. once weekly
b. as a single dose
c. once daily
d. twice daily
5. A 65-year-old woman presents to the emergency room with a
large abscess on her leg. You think she needs parenteral therapy

following incision and drainage and you decide to treat her with
oritavancin because she refuses to be admitted to the hospital
for treatment. Her serum creatinine is 2.5 mg/dL. Which of the
following statements is true?
a. The dose of oritavancin should be reduced based on her
diminished renal function.
b. She should receive an IV infusion of oritavancin today and
another one in 7 days.
c. Coverage for MRSA with oritavancin is not necessary
because her infection is most likely streptococcal.
d. The infusion of oritavancin will take 3 hours.

8. The effectiveness of the new meningococcal serogroup B
vaccine was established by:
a. immunogenicity as measured by serum bactericidal activity
b. controlled clinical trials in Europe
c. clinical efficacy in a controlled clinical trial in the US
d. all of the above
Triumeq: A 3-Drug Combination for HIV
9. In the clinical trial comparing the combination of dolutegravir and
abacavir/lamivudine to efavirenz/tenofovir disoproxil fumarate/
emtricitabine, more patients receiving the efavirenz-based
regimen:
a. achieved an HIV-1 RNA level <50 copies/mL at 48 weeks
b. achieved an HIV-1 RNA level <50 copies/mL at 96 weeks
c. withdrew due to adverse effects
d. none of the above
10. Which of the following tests should be performed before
prescribing Triumeq for a treatment-naive 24-year-old man with
newly diagnosed HIV-1 infection?

a. baseline INSTI resistance testing
b. serum creatinine
c. screening for HLA-B*5701 allele
d. all of the above

ACPE UPN: Per Issue Exam: 0379-0000-15-459-H01-P; Release: January 5, 2015 Expire: January 5, 2016
Comprehensive Exam 72: 0379-0000-15-072-H01-P; Release: July 2015, Expire: July 2016
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 Pflomm, 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; SENIOR ASSOCIATE EDITOR: Amy Faucard
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
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VICE PRESIDENT AND PUBLISHER: Yosef Wissner-Levy
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Arthur Kallet and Harold Aaron, M.D.
Copyright and Disclaimer: The Medical Letter, Inc. is an independent nonprofit organization that provides healthcare professionals with unbiased drug prescribing recommendations. The editorial
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