Prehospital antibiotics improved sepsis care How to manage workplace violence

80 Pages·2017·13.53 MB·English

SLEEP MEDICINE CRITICAL CARE MEDICINE CARDIOTHORACIC SURGERY PULMONARY MEDICINE
Nasal pillows versus standard masks Positive outcomes of a corticosteroid More hope for patients with end- Good news and bad news about
for OSA patients // 14 combo in septic shock // 24 stage heart failure // 29 tuberculosis numbers// 49
VOL. 13 • NO. 4 • APRIL 2018
Prehospital
antibiotics
improved
sepsis care
BY ANDREW D. BOWSER
Frontline Medical News
SAN ANTONIO – Training EMS personnel in
ws
Ne early recognition of sepsis improved some as-
cal pects of care within the acute care chain, but did
di
Me not reduce mortality, according to results of a
ontline ranEdmoemrgieznedc yt rmiael.dical service (EMS) personnel
Fr
r/ were able to recognize sepsis more quickly, ob-
Bowse “Workplace violence is not just active shooter – it’s ubiquitous, tain blood cultures, and give antibiotics after the
w training, reported investigator Prabath Nanayak-
re and we only know a little bit about it,” noted Dr. Lewis J. Kaplan.
nd kara, MD, PhD, FRCP, at the Society of Critical
A
Care Medicine’s Critical Care Congress.
How to manage workplace
However, the hypothesis that this training
would lead to increased survival was not met,
violence noted Dr. Nanayakkara, of the acute medicine
section of the department of internal medicine
at VU University Medical Center, Amsterdam.
At 28 days, 120 patients (8%) in the prehospital
BY ANDREW D. BOWSER To actively prepare for premeditated events, antibiotics group had died, compared with 93
Frontline Medical News clinicians should develop partnerships with lo- patients (8%) in the usual care group (relative
cal law enforcement officials and initiate active risk, 0.95; 95% confidence interval, 0.74-1.24),
SAN ANTONIO – Active-shooter events and oth- training that involves anyone who could come according to the study’s results that were simulta-
er episodes of workplace violence can be better into contact with an active shooter, Dr. Kaplan neously published online in Lancet Respiratory
managed with proper planning and training by recommended. PREHOSPITAL ANTIBIOTICS // continued on page 7
hospitals and staff, Lewis J. Kaplan, MD, said in There are many steps that can be taken to
INSIDE HIGHLIGHT
a late-breaking session at the Critical Care Con- protect the facility, including visitor screening
gress. and management, security that extends to the NEWS FROM CHEST
“Workplace violence is not just active shooter – perimeter of the facility, building design that
Bringing
it’s ubiquitous, and we only know a little bit about limits access to specific places in the facility, and
respiratory care
it,” noted Dr. Kaplan, section chief, surgical critical deployment of firearm-detection canines, Dr.
care, Corporal Michael J. Crescenz VA Medical Kaplan said, during the session at the congress, for asthma to
Center, Philadelphia. “The facility and everyone in sponsored by the Society of Critical Care Medi- Guyana
the health care team have a role in being an active cine.
Page 76
participant, rather than a passive one.” WORKPLACE VIOLENCE // continued on page 6
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Indication placebo group; 2.2% of patients in the Esbriet 2403 mg/day
group discontinued treatment due to a gastrointestinal event, as
Esbriet® (pirfenidone) is indicated for the treatment of
compared to 1.0% in the placebo group. The most common (>2%)
idiopathic pulmonary fi brosis (IPF).
gastrointestinal events that led to dosage reduction or interruption were
Select Important Safety Information nausea, diarrhea, vomiting, and dyspepsia. Dosage modifi cations may be
necessary in some cases.
Elevated liver enzymes: Increases in ALT and AST >3× ULN
have been reported in patients treated with Esbriet. In some Adverse reactions: The most common adverse reactions (≥10%)
cases these have been associated with concomitant elevations are nausea, rash, abdominal pain, upper respiratory tract infection,
in bilirubin. Patients treated with Esbriet had a higher incidence diarrhea, fatigue, headache, dyspepsia, dizziness, vomiting, anorexia,
of elevations in ALT or AST than placebo patients (3.7% vs 0.8%, gastroesophageal refl ux disease, sinusitis, insomnia, weight
respectively). No cases of liver transplant or death due to liver decreased, and arthralgia.
failure that were related to Esbriet have been reported. However,
Drug interactions: Concomitant administration with strong inhibitors
the combination of transaminase elevations and elevated bilirubin
of CYP1A2 (eg, fl uvoxamine) signifi cantly increases systemic exposure of
without evidence of obstruction is generally recognized as an
Esbriet and is not recommended. Discontinue prior to administration of
important predictor of severe liver injury that could lead to death
Esbriet. If strong CYP1A2 inhibitors cannot be avoided, dosage reductions
or the need for liver transplants in some patients. Conduct liver
of Esbriet are recommended. Monitor for adverse reactions and consider
function tests (ALT, AST, and bilirubin) prior to initiating Esbriet, then
discontinuation of Esbriet as needed.
monthly for the fi rst 6 months and every 3 months thereafter. Dosage
Concomitant administration of Esbriet and ciprofl oxacin (a moderate
modifi cations or interruption may be necessary.
inhibitor of CYP1A2) moderately increases exposure to Esbriet. If
Photosensitivity reaction or rash: Patients treated with Esbriet
ciprofl oxacin at the dosage of 750 mg twice daily cannot be avoided,
had a higher incidence of photosensitivity reactions (9%) compared
dosage reductions are recommended. Monitor patients closely when
with patients treated with placebo (1%). Patients should avoid or
ciprofl oxacin is used.
minimize exposure to sunlight (including sunlamps), use a sunblock
Agents that are moderate or strong inhibitors of both CYP1A2 and
(SPF 50 or higher), and wear clothing that protects against sun
CYP isoenzymes involved in the metabolism of Esbriet should be avoided
exposure. Patients should avoid concomitant medications that
during treatment.
cause photosensitivity. Dosage reduction or discontinuation may
be necessary. The concomitant use of a CYP1A2 inducer may decrease the
exposure of Esbriet, and may lead to loss of effi cacy. Concomitant use of
Gastrointestinal disorders: Gastrointestinal events of nausea,
strong CYP1A2 inducers should be avoided.
diarrhea, dyspepsia, vomiting, gastroesophageal refl ux disease,
and abdominal pain were more frequently reported in patients Specifi c populations: Esbriet should be used with caution in patients
treated with Esbriet. Dosage reduction or interruption for with mild to moderate (Child Pugh Class A and B) hepatic impairment.
gastrointestinal events was required in 18.5% of patients in the Monitor for adverse reactions and consider dosage modifi cation
2403 mg/day group, as compared to 5.8% of patients in the or discontinuation of Esbriet as needed. The safety, effi cacy, and
© 2017 Genentech USA, Inc. All rights reserved. ESB/021215/0039(1)a(3) 08/17
CHPH_2.indd 2 8/30/2017 12:51:51 PM
WE WON’T BACK DOWN FROM IPF
Help preserve more lung function. Reduce lung function decline.1– 4
STUDIED IN A DEMONSTRATED ESTABLISHED COMMITTED WORLDWIDE
RANGE OF EFFICACY SAFETY AND TO PATIENTS PATIENT
PATIENTS TOLERABILITY EXPERIENCE
Clinical trials In clinical trials, The safety and Genentech offers a More than
included patients Esbriet preserved tolerability of breadth of patient 31,000 patients
with IPF with a more lung function Esbriet were support and have taken
range of clinical by delaying disease evaluated based assistance services pirfenidone
characteristics, progression for on 1247 patients to help your patients worldwide1§
select comorbidities, patients with IPF 1–4* in 3 randomized, with IPF‡
and concomitant controlled trials2†
medications1
pharmacokinetics of Esbriet have not been studied in patients with severe IPF=idiopathic pulmonary fi brosis.
hepatic impairment. Esbriet is not recommended for use in patients with *T he safety and effi cacy of Esbriet were evaluated in three phase 3,
severe (Child Pugh Class C) hepatic impairment. randomized, double-blind, placebo-controlled, multicenter trials in
which 1247 patients were randomized to receive Esbriet (n=623) or
Esbriet should be used with caution in patients with mild (CL 50–80 mL/
cr placebo (n=624).2 In ASCEND, 555 patients with IPF were randomized
min), moderate (CL 30–50 mL/min), or severe (CL less than 30 mL/min)
cr cr to receive Esbriet 2403 mg/day or placebo for 52 weeks. Eligible patients
renal impairment. Monitor for adverse reactions and consider dosage
had percent predicted forced vital capacity (%FVC) between 50%–90%
modifi cation or discontinuation of Esbriet as needed. The safety, effi cacy,
and percent predicted diffusing capacity of lung for carbon monoxide
and pharmacokinetics of Esbriet have not been studied in patients with
(%DL ) between 30%–90%. The primary endpoint was change in %FVC
end-stage renal disease requiring dialysis. Use of Esbriet in patients with co
from baseline at 52 weeks.3 In CAPACITY 004, 348 patients with IPF were
end-stage renal diseases requiring dialysis is not recommended. randomized to receive Esbriet 2403 mg/day or placebo. Eligible patients
Smoking causes decreased exposure to Esbriet, which may alter the had %FVC ≥50% and %DL ≥35%. In CAPACITY 006, 344 patients with
co
effi cacy profi le of Esbriet. Instruct patients to stop smoking prior to IPF were randomized to receive Esbriet 2403 mg/day or placebo. Eligible
patients had %FVC ≥50% and %DL ≥35%. For both CAPACITY trials,
treatment with Esbriet and to avoid smoking when using Esbriet. co
the primary endpoint was change in %FVC from baseline at 72 weeks.4
You may report side effects to the FDA at 1-800-FDA-1088 or Esbriet had a signifi cant impact on lung function decline and delayed
www.fda.gov/medwatch. You may also report side effects progression of IPF vs placebo in ASCEND.2,3 Esbriet demonstrated a
to Genentech at 1-888-835-2555. signifi cant effect on lung function for up to 72 weeks in CAPACITY 004,
Please see Brief Summary of Prescribing Information on adjacent as measured by %FVC and mean change in FVC (mL).1,2,4 No statistically
signifi cant difference vs placebo in change in %FVC or decline
pages for additional Important Safety Information.
in FVC volume from baseline to 72 weeks was observed in
CAPACITY 006.2,4
References: 1. Data on fi le. Genentech, Inc. 2016. 2. Esbriet Prescribing
† I n clinical trials, serious adverse reactions, including elevated liver
Information. Genentech, Inc. January 2017. 3. King TE Jr, Bradford WZ,
enzymes, photosensitivity reactions, and gastrointestinal disorders, have
Castro-Bernardini S, et al; for the ASCEND Study Group. A phase 3 trial
been reported with Esbriet. Some adverse reactions with Esbriet occurred
of pirfenidone in patients with idiopathic pulmonary fi brosis [published
early and/or decreased over time (ie, photosensitivity reactions and
correction appears in N Engl J Med. 2014;371(12):1172]. N Engl J Med.
gastrointestinal events).2
2014;370(22):2083–2092. 4. Noble PW, Albera C, Bradford WZ, et al;
‡E sbriet Access Solutions offers a range of access and reimbursement
for the CAPACITY Study Group. Pirfenidone in patients with idiopathic
pulmonary fi brosis (CAPACITY): two randomised trials. Lancet. 2011; support for your patients and practice. Clinical Coordinators are available
to educate patients with IPF. The Esbriet® Inspiration Program™ motivates
377(9779):1760–1769.
patients to stay on treatment.
Learn more about Esbriet and how to access medication §T he safety of pirfenidone has been evaluated in more than 1400
at EsbrietHCP.com subjects, with over 170 subjects exposed to pirfenidone for more
than 5 years in clinical trials.2
CHPH_3.indd 3 8/30/2017 12:53:21 PM
NEWS
Climate change is worsening allergies, expert says
BY THOMAS R. COLLINS lives with increasingly powerful and Immunology and the World the air by wildfires are some of the
Frontline Medical News hurricanes, but appears to be con- Asthma Organization. concerns that should be alarming
tributing to increases in allergy and Longer pollen seasons, allergens physicians and policy makers, said
ORLANDO – Climate change is not asthma, an expert told the audience unleashed by felled trees and ripped- Nelson A. Rosario, MD, PhD, profes-
just eroding coastlines and threat- at the joint congress of the Amer- up plants, mold growth following sor of pediatrics at Federal University
ening seaside cities and taking ican Academy of Allergy, Asthma, floods, and irritants launched into of Paraná (Brazil).
ESBRIET® (pirfenidone)
(Studies 1, 2, and 3) in which a total of 623 patients received 2403 mg/day
of ESBRIET and 624 patients received placebo. Subjects ages ranged from 40 to
80 years (mean age of 67 years). Most patients were male (74%) and Caucasian
Rx only (95%). The mean duration of exposure to ESBRIET was 62 weeks (range: 2 to
118 weeks) in these 3 trials.
BRIEF SUMMARY
At the recommended dosage of 2403 mg/day, 14.6% of patients on ESBRIET
The following is a brief summary of the full Prescribing Information for compared to 9.6% on placebo permanently discontinued treatment because
ESBRIET® (pirfenidone). Please review the full Prescribing Information prior of an adverse event. The most common (>1%) adverse reactions leading
to prescribing ESBRIET. to discontinuation were rash and nausea. The most common (>3%) adverse
reactions leading to dosage reduction or interruption were rash, nausea, diarrhea,
1 INDICATIONS AND USAGE and photosensitivity reaction.
ESBRIET is indicated for the treatment of idiopathic pulmonary fibrosis (IPF). The most common adverse reactions with an incidence of ≥10% and more
frequent in the ESBRIET than placebo treatment group are listed in Table 2.
4 CONTRAINDICATIONS
None. Table 2. Adverse Reactions Occurring in ≥10% of ESBRIET-Treated
Patients and More Commonly Than Placebo in Studies 1, 2, and 3
5 WARNINGS AND PRECAUTIONS
% of Patients (0 to 118 Weeks)
5.1 Elevated Liver Enzymes
Increases in ALT and AST >3 × ULN have been reported in patients treated with Adverse Reaction ESBRIET Placebo
ESBRIET. In some cases these have been associated with concomitant elevations 2403 mg/day
(N = 624)
in bilirubin. Patients treated with ESBRIET 2403 mg/day in the three Phase 3 trials (N = 623)
had a higher incidence of elevations in ALT or AST ≥3 × ULN than placebo patients
Nausea 36% 16%
(3.7% vs. 0.8%, respectively). Elevations ≥10 × ULN in ALT or AST occurred
in 0.3% of patients in the ESBRIET 2403 mg/day group and in 0.2% of patients in Rash 30% 10%
the placebo group. Increases in ALT and AST ≥3 × ULN were reversible with
dose modification or treatment discontinuation. No cases of liver transplant Abdominal Pain1 24% 15%
or death due to liver failure that were related to ESBRIET have been reported.
However, the combination of transaminase elevations and elevated bilirubin Upper Respiratory Tract Infection 27% 25%
without evidence of obstruction is generally recognized as an important predictor
Diarrhea 26% 20%
of severe liver injury, that could lead to death or the need for liver transplants
in some patients. Conduct liver function tests (ALT, AST, and bilirubin) prior to Fatigue 26% 19%
the initiation of therapy with ESBRIET in all patients, then monthly for the first
6 months and every 3 months thereafter. Dosage modifications or interruption Headache 22% 19%
may be necessary for liver enzyme elevations [see Dosage and Administration
sections 2.1 and 2.3 in full Prescribing Information]. Dyspepsia 19% 7%
Dizziness 18% 11%
5.2 Photosensitivity Reaction or Rash
Patients treated with ESBRIET 2403 mg/day in the three Phase 3 studies had Vomiting 13% 6%
a higher incidence of photosensitivity reactions (9%) compared with patients
treated with placebo (1%). The majority of the photosensitivity reactions occurred Anorexia 13% 5%
during the initial 6 months. Instruct patients to avoid or minimize exposure to
Gastro-esophageal Reflux Disease 11% 7%
sunlight (including sunlamps), to use a sunblock (SPF 50 or higher), and to wear
clothing that protects against sun exposure. Additionally, instruct patients to avoid Sinusitis 11% 10%
concomitant medications known to cause photosensitivity. Dosage reduction
or discontinuation may be necessary in some cases of photosensitivity reaction or Insomnia 10% 7%
rash [see Dosage and Administration section 2.3 in full Prescribing Information].
Weight Decreased 10% 5%
5.3 Gastrointestinal Disorders
Arthralgia 10% 7%
In the clinical studies, gastrointestinal events of nausea, diarrhea, dyspepsia,
vomiting, gastro-esophageal reflux disease, and abdominal pain were more 1 Includes abdominal pain, upper abdominal pain, abdominal distension, and stomach discomfort.
frequently reported by patients in the ESBRIET treatment groups than in those
taking placebo. Dosage reduction or interruption for gastrointestinal events was Adverse reactions occurring in ≥5 to <10% of ESBRIET-treated patients and more
required in 18.5% of patients in the 2403 mg/day group, as compared to 5.8% commonly than placebo are photosensitivity reaction (9% vs. 1%), decreased
of patients in the placebo group; 2.2% of patients in the ESBRIET 2403 mg/day appetite (8% vs. 3%), pruritus (8% vs. 5%), asthenia (6% vs. 4%), dysgeusia
group discontinued treatment due to a gastrointestinal event, as compared to (6% vs. 2%), and non-cardiac chest pain (5% vs. 4%).
1.0% in the placebo group. The most common (>2%) gastrointestinal events that 6.2 Postmarketing Experience
led to dosage reduction or interruption were nausea, diarrhea, vomiting, and In addition to adverse reactions identified from clinical trials the following adverse
dyspepsia. The incidence of gastrointestinal events was highest early in the reactions have been identified during post-approval use of pirfenidone. Because
course of treatment (with highest incidence occurring during the initial 3 months) these reactions are reported voluntarily from a population of uncertain size, it is
and decreased over time. Dosage modifications may be necessary in some cases not always possible to reliably estimate their frequency.
of gastrointestinal adverse reactions [see Dosage and Administration section 2.3
in full Prescribing Information]. Blood and Lymphatic System Disorders
Agranulocytosis
6 ADVERSE REACTIONS Immune System Disorders
The following adverse reactions are discussed in greater detail in other sections Angioedema
of the labeling:
Hepatobiliary Disorders
• Liver Enzyme Elevations [see Warnings and Precautions (5.1)] Bilirubin increased in combination with increases of ALT and AST
• Photosensitivity Reaction or Rash [see Warnings and Precautions (5.2)]
7 DRUG INTERACTIONS
• Gastrointestinal Disorders [see Warnings and Precautions (5.3)]
7.1 CYP1A2 Inhibitors
6.1 Clinical Trials Experience Pirfenidone is metabolized primarily (70 to 80%) via CYP1A2 with minor
contributions from other CYP isoenzymes including CYP2C9, 2C19, 2D6 and 2E1.
Because clinical trials are conducted under widely varying conditions, adverse reaction
rates observed in the clinical trials of a drug cannot be directly compared to rates in Strong CYP1A2 Inhibitors
the clinical trials of another drug and may not reflect the rates observed in practice. The concomitant administration of ESBRIET and fluvoxamine or other strong
The safety of pirfenidone has been evaluated in more than 1400 subjects with CYP1A2 inhibitors (e.g., enoxacin) is not recommended because it significantly
over 170 subjects exposed to pirfenidone for more than 5 years in clinical trials. increases exposure to ESBRIET [see Clinical Pharmacology section 12.3 in full
Prescribing Information]. Use of fluvoxamine or other strong CYP1A2 inhibitors
ESBRIET was studied in 3 randomized, double-blind, placebo-controlled trials should be discontinued prior to administration of ESBRIET and avoided during
4
• APRIL 2018 • CHEST PHYSICIAN
“This is related to disease,” he uting to their symptoms.
said. “I’m trying to convince you In a survey published in 2016,
that something is happening. This is 63% of AAAAI members said that
not a matter of believe it or not.” climate change was relevant to pa-
And evidence suggests that his tient care either “a great deal” or in
k
fellow allergists and their patients oc “a moderate amount.” Only 11% said
agree. kst that climate change wasn’t relevant
n
hi
A 2015 international survey T at all. Asked how patients have been
a/
h
found that 80% of rhinitis patients k affected by climate change, about
u
blamed climate change for contrib- Gilit two-thirds said “increased care for
allergic sensitization and symptoms
on exposure to plants or mold.”
ESBRIET® (pirfenidone) ESBRIET® (pirfenidone)
Science supports these views, Dr.
ESBRIET treatment. In the event that fluvoxamine or other strong CYP1A2 inhibitors 8.4 Pediatric Use Rosario said.
are the only drug of choice, dosage reductions are recommended. Monitor for Safety and effectiveness of ESBRIET in pediatric patients have not been established. A 2011 study of North American
adverse reactions and consider discontinuation of ESBRIET as needed [see Dosage
and Administration section 2.4 in full Prescribing Information]. 8.5 Geriatric Use pollen seasons found that some
Of the total number of subjects in the clinical studies receiving ESBRIET, 714 cities had signif-
Moderate CYP1A2 Inhibitors
(67%) were 65 years old and over, while 231 (22%) were 75 years old and over.
Concomitant administration of ESBRIET and ciprofloxacin (a moderate inhibitor of No overall differences in safety or effectiveness were observed between icant increases
CYP1A2) moderately increases exposure to ESBRIET [see Clinical Pharmacology older and younger patients. No dosage adjustment is required based upon age. of 11-27 days,
section 12.3 in full Prescribing Information]. If ciprofloxacin at the dosage of 750 mg
twice daily cannot be avoided, dosage reductions are recommended [see Dosage 8.6 Hepatic Impairment compared with
and Administration section 2.4 in full Prescribing Information]. Monitor patients ESBRIET should be used with caution in patients with mild (Child Pugh Class A) to 15 years before.
closely when ciprofloxacin is used at a dosage of 250 mg or 500 mg once daily. moderate (Child Pugh Class B) hepatic impairment. Monitor for adverse reactions
This year, a
and consider dosage modification or discontinuation of ESBRIET as needed [see
Concomitant CYP1A2 and other CYP Inhibitors
Dosage and Administration section 2.3 in full Prescribing Information]. New England
Agents or combinations of agents that are moderate or strong inhibitors of both
The safety, efficacy, and pharmacokinetics of ESBRIET have not been studied Journal of Med-
CYP1A2 and one or more other CYP isoenzymes involved in the metabolism of
in patients with severe hepatic impairment. ESBRIET is not recommended for
ESBRIET (i.e., CYP2C9, 2C19, 2D6, and 2E1) should be discontinued prior to and use in patients with severe (Child Pugh Class C) hepatic impairment [see Clinical icine (2018 Mar
avoided during ESBRIET treatment. Pharmacology section 12.3 in full Prescribing Information]. 8;378[10]:881-3)
7.2 CYP1A2 Inducers 8.7 Renal Impairment DR. ROSARIO article pointed
The concomitant use of ESBRIET and a CYP1A2 inducer may decrease ESBRIET should be used with caution in patients with mild (CL 50–80 mL/min),
cr out the respira-
the exposure of ESBRIET and this may lead to loss of efficacy. Therefore, moderate (CL 30–50 mL/min), or severe (CL less than 30 mL/min) renal
discontinue use of strong CYP1A2 inducers prior to ESBRIET treatment and impairment [secer Clinical Pharmacology section 12.3cr in full Prescribing Information]. tory dangers of increasing wildfires,
avoid the concomitant use of ESBRIET and a strong CYP1A2 inducer [see Clinical Monitor for adverse reactions and consider dosage modification or discontinuation noting the carbon dioxide, partic-
Pharmacology section 12.3 in full Prescribing Information]. of ESBRIET as needed [see Dosage and Administration section 2.3 in full Prescribing
Information]. The safety, efficacy, and pharmacokinetics of ESBRIET have not been ulate matter, trace minerals, and
8 USE IN SPECIFIC POPULATIONS studied in patients with end-stage renal disease requiring dialysis. Use of ESBRIET thousands of other compounds that
in patients with end-stage renal diseases requiring dialysis is not recommended.
8.1 Pregnancy are unleashed.
8.8 Smokers
Risk Summary Smoking causes decreased exposure to ESBRIET [see Clinical Pharmacology
section 12.3 in full Prescribing Information], which may alter the efficacy profile
The data with ESBRIET use in pregnant women are insufficient to inform on drug of ESBRIET. Instruct patients to stop smoking prior to treatment with ESBRIET
“This is related to disease. ...
associated risks for major birth defects and miscarriage. In animal reproduction and to avoid smoking when using ESBRIET.
studies, pirfenidone was not teratogenic in rats and rabbits at oral doses up to
3 and 2 times, respectively, the maximum recommended daily dose (MRDD) in 10 OVERDOSAGE This is not a matter of believe
adults [see Data]. There is limited clinical experience with overdosage. Multiple dosages of ESBRIET up
to a maximum tolerated dose of 4005 mg per day were administered as five 267 mg it or not,” Dr. Rosario said.
In the U.S. general population, the estimated background risk of major birth capsules three times daily to healthy adult volunteers over a 12-day dose escalation.
defects and miscarriage in clinically recognized pregnancies is 2–4% and
In the event of a suspected overdosage, appropriate supportive medical care
15–20%, respectively.
should be provided, including monitoring of vital signs and observation of the
Data clinical status of the patient.
And a 2017 review noted the im-
Animal Data 17 PATIENT COUNSELING INFORMATION pacts of the consequences of climate
Animal reproductive studies were conducted in rats and rabbits. In a combined Advise the patient to read the FDA-approved patient labeling (Patient Information).
change, from increased allergies
fertility and embryofetal development study, female rats received pirfenidone Liver Enzyme Elevations
at oral doses of 0, 50, 150, 450, and 1000 mg/kg/day from 2 weeks prior to due to heavy precipitation events,
Advise patients that they may be required to undergo liver function testing
mating, during the mating phase, and throughout the periods of early embryonic
periodically. Instruct patients to immediately report any symptoms of a liver asthma prompted by intense tropical
development from gestation days (GD) 0 to 5 and organogenesis from GD 6 to
problem (e.g., skin or the white of eyes turn yellow, urine turns dark or brown
17. In an embryofetal development study, pregnant rabbits received pirfenidone cyclones, and allergic conditions
[tea colored], pain on the right side of stomach, bleed or bruise more easily than
at oral doses of 0, 30, 100, and 300 mg/kg/day throughout the period of normal, lethargy) [see Warnings and Precautions (5.1)]. caused by extremely high sea levels.
organogenesis from GD 6 to 18. In these studies, pirfenidone at doses up to
3 and 2 times, respectively, the maximum recommended daily dose (MRDD) in Photosensitivity Reaction or Rash Dr. Rosario suggested that, rather
adults (on mg/m2 basis at maternal oral doses up to 1000 mg/kg/day in rats Advise patients to avoid or minimize exposure to sunlight (including sunlamps) than wait for official agencies to take
and 300 mg/kg/day in rabbits, respectively) revealed no evidence of impaired during use of ESBRIET because of concern for photosensitivity reactions or rash.
fertility or harm to the fetus due to pirfenidone. In the presence of maternal Instruct patients to use a sunblock and to wear clothing that protects against sun action, physicians need to adapt and
toxicity, acyclic/irregular cycles (e.g., prolonged estrous cycle) were seen in rats exposure. Instruct patients to report symptoms of photosensitivity reaction or help their patients adapt. A team
at doses approximately equal to and higher than the MRDD in adults (on a mg/m2 rash to their physician. Temporary dosage reductions or discontinuations may
basis at maternal doses of 450 mg/kg/day and higher). In a pre- and post-natal be required [see Warnings and Precautions (5.2)]. of doctors wrote in 2013 that while
development study, female rats received pirfenidone at oral doses of 0, 100, 300, Gastrointestinal Events “improved governmental controls”
and 1000 mg/kg/day from GD 7 to lactation day 20. Prolongation of the gestation
Instruct patients to report symptoms of persistent gastrointestinal effects could lead to cleaner air, they “meet
period, decreased numbers of live newborn, and reduced pup viability and body
weights were seen in rats at an oral dosage approximately 3 times the MRDD in including nausea, diarrhea, dyspepsia, vomiting, gastro-esophageal reflux disease, strong opposition because of their
and abdominal pain. Temporary dosage reductions or discontinuations may be
adults (on a mg/m2 basis at a maternal oral dose of 1000 mg/kg/day). required [see Warnings and Precautions (5.3)]. effect on business and productivity.”
8.2 Lactation Smokers So, they said, the allergy community

Encourage patients to stop smoking prior to treatment with ESBRIET and to should adjust, by “anticipating the
Risk Summary
avoid smoking when using ESBRIET [see Clinical Pharmacology section 12.3 in
needs of patients and by adopting
No information is available on the presence of pirfenidone in human milk, full Prescribing Information].
the effects of the drug on the breastfed infant, or the effects of the drug on Take with Food practices and research methods to
milk production. The lack of clinical data during lactation precludes clear Instruct patients to take ESBRIET with food to help decrease nausea and dizziness. meet changing environmental con-
determination of the risk of ESBRIET to an infant during lactation; therefore, the
developmental and health benefits of breastfeeding should be considered along Distributed by: ditions.”
with the mother’s clinical need for ESBRIET and the potential adverse effects Genentech USA, Inc. Dr. Rosario urged physicians to
on the breastfed child from ESBRIET or from the underlying maternal condition. A Member of the Roche Group think of the climate-change effects
1 DNA Way, South San Francisco, CA 94080-4990
Data
on allergy and asthma as a “collec-
Animal Data tive action” problem, not an individ-
A study with radio-labeled pirfenidone in rats has shown that pirfenidone or its ual one.
metabolites are excreted in milk. There are no data on the presence of pirfenidone
or its metabolites in human milk, the effects of pirfenidone on the breastfed child, ESBRIET® is a registered U.S. trademark of Genentech, Inc. “The consequences will come,” he
or its effects on milk production. © 2017 Genentech, Inc. All rights reserved. ESB/100115/0470(2) 2/17 said. “There must be international
cooperation.”
[email protected]
5
CHESTPHYSICIAN.ORG • APRIL 2018 •
NEWS FROM CHEST // 69
CHEST NETWORKS // 69
CHEST PHYSICIAN
IS ONLINE
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Workplace violence
// continued from page 1 Critical Care Commentary information contained in this publication, including
any claims related to products, drugs, or services
Christopher Lettieri, MD, FCCP
mentioned herein.
In all, Dr. Kaplan listed 19 steps In a 2017 survey of 150 trauma Sleep Strategies POSTMASTER: Send change
that facilities could take to avert nurses, 67% said they had been the of address (with old mailing
label) to
a planned attack, drawing in part victim of physical violence at work,
Editorial Advisory Board CHEST Physician,
on recommendations from the FBI though many did not report the Subscription Service, 151
G. Hossein Almassi, MD, FCCP, Wisconsin
Fairchild Ave., Suite 2,
publication, Workplace violence: Is- incidents, Dr. Kaplan noted. Some Jennifer Cox, MD, FCCP, Florida Plainview, NY 11803-1709. Scan this QR
sues in response. reasons nurses gave for not reporting Jacques-Pierre Fontaine, MD, FCCP, Florida
CHEST PHYSICIAN Code to visit
“This is a lot, and you don’t need violence included the feeling that it Eric Gartman, MD, FCCP, Rhode Island (ISSN 1558-6200) is chestnet.org/
Octavian C. Ioachimescu, MD, PhD, FCCP, published monthly for chestphysician
to do all of it,” Dr. Kaplan said. “But was “just part of the job” in 27% of
Georgia the American College of
you need to have an internally con- cases, and concerns about patient sat- Jason Lazar, MD, FCCP, New York Chest Physicians by Frontline Medical
sistent plan for how you will do this isfaction scores in 10% of the cases. Susan Millard, MD, FCCP, Michigan Communications Inc., 7 Century Drive,
Suite 302, Parsippany, NJ 07054-4609.
at your facility, and it must involve Active-shooter events in the Michael E. Nelson, MD, FCCP, Kansas Subscription price is $244.00 per year.
everyone. They all need to be able to workplace are of particular concern, Daniel Ouellette, MD, FCCP, Michigan Phone [phone], fax [phone].
be part of your team.” though they are relatively rare; one Frank Podbielski, MD, FCCP, Massachusetts EDITORIAL OFFICES 2275 Research Blvd,
M. Patricia Rivera, MD, FCCP, North Carolina Suite 400, Rockville, MD 20850, 240-221-
recent report identified 160 events Nirmal S. Sharma, MD, California 2400, fax [phone]
Recent data on that occurred during 2000-2013 in Krishna Sundar, MD, FCCP, Utah ADVERTISING OFFICES 7 Century Drive,
Suite 302, Parsippany, NJ 07054-4609
workplace violence which 1,043 individuals were injured, E-mail: [email protected] 973-206-3434, fax [phone]
The latest data show that the great according to Dr. Kaplan. ©Copyright 2018, by the American
majority of workplace violence is Other presentations in the College of Chest Physicians
perpetrated by individuals out- late-breaking session covered issues
side the organization. According related to disaster preparedness and FRONTLINE MEDICAL COMMUNICATIONS
to the International Association the Charlie Gard case. CHAIRMAN Stephen Stoneburn
for Healthcare Security and Safety “We picked these three topics Frontline Medical PRESIDENT/CEO Alan J. Imhoff
Foundation 2017 Healthcare Crime to be in a late-breaker session not Communications CFO Douglas E. Grose
Survey, 89% of events involved a only because of the recent events Society Partners PRESIDENT, DIGITAL Douglas E. Grose
CHIEF DIGITAL OFFICER Lee Schweizer
customer or patient of the work- that had happened, but because VP/GROUP PUBLISHER; DIRECTOR, VICE PRESIDENT, DIGITAL PUBLISHING Amy Pfeiffer
FMC SOCIETY PARTNERS Mark Branca
place or employees. they have a common thread – it’s EDITOR IN CHIEF Mary Jo M. Dales PRESIDENT, CUSTOM SOLUTIONS JoAnn Wahl
In-hospital violence is prevalent, not a matter of if it will happen, but EXECUTIVE EDITORS Denise Fulton, VICE PRESIDENT, CUSTOM PROGRAMS Carol Nathan
Kathy Scarbeck VICE PRESIDENT, CUSTOM SOLUTIONS Wendy
according to 2016 data from Occupa- when will it happen, and are you Raupers
EDITOR Katie Wagner Lennon
tional Safety and Health Administra- ready and how do we prepare,” said CREATIVE DIRECTOR Louise A. Koenig SENIOR VICE PRESIDENT, FINANCE Steven J. Resnick
tion that identified 24,000 workplace session chair Gloria M. Rodriguez DIRECTOR, PRODUCTION/MANUFACTURING VICE PRESIDENT, HUMAN RESOURCES & FACILITY
Rebecca Slebodnik OPERATIONS Carolyn Caccavelli
assaults in a 3-year span covering Vega, MD.
DIRECTOR, BUSINESS DEVELOPMENT VICE PRESIDENT, MARKETING & CUSTOMER ADVOCACY
2013-2015, including 33 homicides, “One of the things I learned as a Angela Labrozzi, 973-206-8971, Jim McDonough
30 assaults, and 74 rapes. fellow was that part of the success in cell 917-455-6071, alabrozzi@ VICE PRESIDENT, OPERATIONS Jim Chicca
frontlinemedcom.com VICE PRESIDENT, SALES Mike Guire
Many in-hospital incidents are critical care was attention to detail VICE PRESIDENT, SOCIETY PARTNERS Mark Branca
marked by failures in communication, and layers of safety,” said Dr. Ro- ReyDI GVIaTlAdLi vAiCaC O9U7N3T -M2A0N6A-G8E0R9 4 CIRCULATION DIRECTOR Jared Sonners
CORPORATE DIRECTOR, RESEARCH & COMMUNICATIONS
patient observation, noncompliance driguez Vega, an intensivist in Bay- [email protected] Lori Raskin
with workplace violence policies or amon, Puerto Rico. “I think you can CLASSIFIED SALES REPRESENTATIVE EDITOR IN CHIEF Mary Jo M. Dales
Drew Endy 215-657-2319,
lack of such policies, and perhaps most apply that to all these situations.” cell 267-481-0133 dendy@ In affiliation with Global Academy for Medical
Education, LLC
importantly, an inadequate assessment Dr. Kaplan had no industry dis- frontlinemedcom.com
VICE PRESIDENT, MEDICAL EDUCATION & CONFERENCES
for the violent potential of the perpe- closures related to his presentation. SENIOR DIRECTOR OF CLASSIFIED SALES Sylvia H. Reitman, MBA
Tim LaPella, 484-921-5001, VICE PRESIDENT, EVENTS David J. Small, MBA
trator, according to Dr. Kaplan. [email protected] [email protected]
6
• APRIL 2018 • CHEST PHYSICIAN
NEWS
ICU corticosteroid insufficiency guidelines explained
BY ANDREW D. BOWSER shock, acute respiratory distress Memorial Sloan Kettering Cancer severe the sepsis, the more septic
Frontline Medical News syndrome, and major trauma (Crit Center, New York. “We only re- shock the patient was in, the more
Care Med. 2017 Dec;45[12]:2078- quired 80% of the panelists to agree likely the corticosteroids were likely
SAN ANTONIO – When corticoste- 88). Part two of the guidelines, that these were the recommenda- to help those patients,” Dr. Pastores
roids are used for septic shock, the published separately, covers other tions and statements that we were explained.
dose should be low to moderate, syndromes, such as influenza, going to go by.” Accordingly, the guidelines fur-
the timing should be early, and the meningitis, burns, and other con- The guidelines recommend ther suggest using long-course,
duration should be at least 3 days, ditions that at least 80% of the task against the use of corticosteroids in low-dose corticosteroid treatment,
said a speaker at the Critical Care force members agreed were asso- adult patients who have sepsis with- namely intravenous hydrocortisone
Congress sponsored by the Society ciated with CIRCI (Crit Care Med. out shock, Dr. Pastores noted. at no more than 400 mg/day for at
for Critical Care. 2018 Jan;46[1]:146-8). In contrast, the guidelines do sug- least 3 days.
Dosing, timing, and duration are During his presentation, Dr. Pa- gest using corticosteroids for hos- The expert panel specifically rec-
“three critical questions” critical care stores limited his remarks to dis- pitalized adults patients with septic ommended hydrocortisone as the
specialists face that are answered cussion of sepsis and septic shock shock that is not responsive to fluid corticosteroid of choice in this set-
by the new critical illness–related with corticosteroids. He cautioned and moderate- to high-dose vaso- ting, according to Dr. Pastores. That
corticosteroid insufficiency (CIRCI) that, despite careful deliberations pressor therapy. recommendation was based in part
guidelines, continued Stephen M. by the panel, the level of evidence In an analysis of available data on a recent systematic review and
Pastores, MD, a cochair of the task behind some of the recommenda- from randomized clinical trials in- meta-analysis showing that hydro-
force that developed guidelines for tions was “low to moderate and cluding patients with septic shock, cortisone, given as a bolus or an in-
the diagnosis and management of never high” and that not all task corticosteroids significantly reduced fusion, was more likely than placebo
CIRCI in critically ill patients. force members agreed with all rec- 28-day mortality when compared or methylprednisolone to result in
The recently published guide- ommendations. with placebo, Dr. Pastores said. shock reversal.
lines come in two parts. The “There were a lot of back and That survival benefit seems to be Dr. Pastores reported disclosures
first takes into account the most forth disagreements behind these dependent on several factors: dose related to Theravance Biopharma,
current evidence on the use of recommendations,” said Dr. Pa- of the corticosteroids (hydrocorti- Bayer HealthCare Pharmaceu-
corticosteroids in disorders that stores, who is the director of the sone less than 400 mg/day), longer ticals, Spectral Diagnostics, and
most clinicians associate with critical care medicine fellowship duration (at least 3 or more days), Asahi-Kasei.
CIRCI, including sepsis/septic training and research programs at and severity of sepsis. “The more [email protected]
Prehospital antibiotics
// continued from page 1
Medicine.
The intervention group received antibiotics a
median of 26 minutes prior to emergency depart-
ment arrival. In the usual care group, median time
to antibiotics after ED arrival was 70 minutes,
versus 93 minutes prior to the sepsis recognition
training (P = .142), the report further says.
“We do not advise prehospital antibiotics at the
moment for patients with suspected sepsis,” Dr.
Nanayakkara said, during his presentation at the
conference. ws
Ne
Other countries might see different results, he al
c
cautioned. Medi
In the Netherlands, ambulances reach the ne
emergency scene within 15 minutes 93% of the ntli
o
time, and the average time from dispatch call to r/Fr
ED arrival is 40 minutes, Dr. Nanayakkara noted wse
o
in the report. D. B
“In part, due to the relatively short response w
re
times in the Netherlands, we don’t know if there nd
A
are other countries with longer response times “[We] don’t know if there are other countries with longer response times that would have other results,
that would have other results, and whether they and whether they should use antibiotics in their ambulances,” Dr. Prabath Nanayakkara (left) noted.
should use antibiotics in their ambulances,” Dr.
Nanayakkara said in his presentation. The primary end point of the study was all-cause ing to Dr. Vincent.
The study was the first-ever prospective random- mortality at 28 days. “After this initial experience, I believe that a
ized, controlled open-label trial to compare early The negative mortality results of this trial are randomized, controlled trial could be done to
prehospital antibiotics with standard care. “not surprising,” given that the trial’s inclusion assess the potential benefit of early antibiotic ad-
Before the study was started, EMS personnel at criteria allowed individuals with suspected in- ministration in the ambulance for patients with
10 large regional ambulance services serving 34 fection but without organ dysfunction, said organ dysfunction associated with infection,” Dr.
secondary or tertiary hospitals were trained in Jean-Louis Vincent, MD, PhD, of Erasmus Hos- Vincent wrote in his editorial.
recognizing sepsis, the report says. pital, Brussels, in a related editorial appearing in Dr. Nanayakkara and his coauthors declared no
A total of 2,672 patients with suspected sepsis were the Lancet Respiratory Medicine (2018 Jan. doi: competing interests related to their study.
included in the intention-to-treat analysis, of whom 10.1016/S2213-2600[17]30446-0). [email protected]
1,535 were randomized to receive prehospital antibi- Recent consensus definitions of sepsis recog-
otics and 1,137 to usual EMS care, which consisted of nize that sepsis is the association of an infection SOURCE: Alam N et al. Lancet Respir Med. 2018
fluid resuscitation and supplementary oxygen. with some degree of organ dysfunction, accord- Jan;6(1):40-50.
7
CHESTPHYSICIAN.ORG • APRIL 2018 •
FDA
FDA proposes lower nicotine levels in cigarettes
BY GREGORY TWACHTMAN ment on potential unintended are aware of, and we characterize the arettes but also the negative health
Frontline Medical News effects of lowering the amount of studies that have been done to date effects of nicotine addiction, FDA
nicotine in cigarettes, such as turn- in trying to find out what that right experts wrote in a perspective piece
Nicotine levels in cigarettes ing to other combustible tobacco level is,” Mitch Zeller, director of the published March 15 in the New
could see a significant reduc- products including cigars in con- FDA Center for Tobacco Products, England Journal of Medicine (doi:
tion under regulatory options junction with or as a replacement said during a March 15 press call. 10.1065/NEJMsr1714617).
being considered by the Food and for cigarette use; increasing the He said that the FDA aiming to “Our findings show that reducing
Drug Administration. number of cigarettes smoked; or make sure the level is low enough the nicotine level in cigarettes has the
Cigarettes “are the only legal con- potential to substantially reduce the
sumer product that, when used as enormous burden of smoking-related
intended, will kill half all long-term death and disease,” Benjamin J. Apel-
users,” FDA Commissioner Scott berg, PhD, director of the Division
Gottlieb, MD, said in a statement of Population Health Science, Office
announcing the effort. of Science, within the FDA Center
The agency is seeking comment for Tobacco Products, and his col-
on a proposed regulation regard- leagues, wrote in the report.
ing “a potential maximum nicotine Modeling for the implementation
level that would be appropriate for of a lower nicotine level policy sug-
a
the protection of public health, in otoli gests that smoking prevalence will
light of scientific evidence about r/f decline from a median of 12.8% in
8f
the addictive properties of nicotine _6 baseline scenario to a median of
ky
in cigarettes.” An advance notice of c 10.8% within a year of implemen-
ri
proposed rule making was posted tation, with the increase related to
online March 15 and published in seeking comparable nicotine from that it cannot be compensated for smoking cessation.
the Federal Register on March 16. noncombustible tobacco sources. by smoking more or inhaling deeper “We estimate that approximately
The FDA also is seeking comments At this time, FDA is not suggest- and holding the breath in longer, 5 million additional smokers would
on a number of other areas to help ing what the target might be on a much like how smokers compensat- quit smoking within a year after
inform potential regulatory action specific nicotine level. While the ed when they smoked “light” ciga- implementation of the hypothetical
down the road, including whether advanced notice asks specifically rettes in the unregulated market. policy,” Dr. Apelberg and his col-
a new standard for lower nicotine about the “merits of nicotine levels Mr. Zeller said that seeking com- leagues wrote. “By 2060, smoking
levels should be implemented at once like 0.3, 0.4, and 0.5 mg nicotine/g ments on those levels is based on prevalence drops from 7.9% in the
or whether a phased-in approach of tobacco filler,” it is not suggest- the scientific evidence that is laid baseline scenario to 1.4% in the pol-
should be taken; whether FDA ing that this is the range being con- out in the advanced notice, but it icy scenario.”
should specify a method for man- sidered. is not necessarily foreshadowing Their analysis is based on a nic-
ufacturers to use in order to detect “Not to prejudge any possible pro- where the standard will be set. otine level that is “so low that there
nicotine levels in their products; and posed rule that we would do or any Drastically reducing the amount would not be enough nicotine avail-
whether the proposed lower level is possible level, that is the purpose of of nicotine in cigarettes is expected able in cigarette tobacco for smokers
technically achievable. an advanced proposed rule making, to significantly lower not only the to sustain addiction,” they noted.
The agency also is seeking com- but we share all the science that we number of people addicted to cig- [email protected]
FDA wants data on flavored tobacco products
BY GREGORY TWACHTMAN “Youth consistently report product flavoring as smoking by the age of 18, it’s imperative we look
Frontline Medical News a leading reason for using tobacco products,” Dr. at new ways we can ensure that kids don’t prog-
Gottlieb noted. “In fact, there is evidence indicat- ress from experimentation to regular use,” Com-
The Food and Drug Administration is seeking ing that youth tobacco users who reported their missioner Gottlieb said.
data on the role that flavors, including menthol, first tobacco was flavored had a higher preva- The American Heart Association called the ac-
in tobacco products play in the initiation, use, and lence of current tobacco product use, compared tion “long overdue.”
cessation of tobacco products, with an emphasis to youth whose product was not flavored.” “We encourage the FDA to quickly move be-
on how flavoring impacts young people. The advance notice calls for information across a yond information gathering and develop a strong
“In the spirit of our commitment to preventing number of areas, including the role of flavors other flavoring product standard,” CEO Nancy Brown
kids from using tobacco, we are taking a clos- than tobacco in tobacco products; flavors and ini- said in a statement. “There is already clear evi-
er look at flavors in tobacco products to better tiation and patterns of tobacco product use, partic- dence that flavored tobacco products, including
understand their level of impact on youth initi- ularly among youths and young adults; and flavors menthol, harm the public health. To make it
ation,” FDA Commissioner Scott Gottlieb, MD, and cessation, dual-use, and relapse among current worse, fruit- and candy-flavored e-cigarettes,
said in statement. It is important “that we also and former tobacco product users. cigars, and other tobacco products are highly at-
explore how flavors, under a properly regulat- It also is seeking comment on whether standards tractive to kids and make it more likely that they
ed framework that protects youth, may also be should be set on tobacco flavoring, including will take up this addiction.”
helping some currently addicted adult cigarette whether there should a prohibition or restriction The action comes less than a week after FDA
smokers switch to certain noncombustible forms on flavors and to which types of products these published an advance notice seeking information
of tobacco products.” standards should apply. The notice specifically asks comments on reducing nicotine levels in ciga-
The agency issued an advance notice of pro- about menthol and its role in cigarette initiation rettes to help combat nicotine addiction.
posed rule making March 20 that seeks informa- and whether limitations on menthol could lead to The advance notice was published in March in
tion on flavoring in tobacco products to inform use of other tobacco products. the Federal Register.
future policy making. “Because almost 90% of adult smokers started [email protected]
8
• APRIL 2018 • CHEST PHYSICIAN
SYMBICORT—
SPEED
THE
THEY WANT
CONTROL
WITH THE
THEY NEED
SPEED
– Majority of patients’ FEV* improvement
1
occurred at 5 minutes in COPD1-3
CONTROL
–Reduced COPD exacerbations3
* 1-hour postdose FEV.
1
SYMBICORT is NOT a rescue medication
and does NOT replace fast-acting
inhalers to treat acute symptoms
Please see study designs on following pages.
 SYMBICORT 160/4.5 for the maintenance treatment of COPD, and for reducing COPD exacerbations
IMPORTANT SAFETY INFORMATION

Use of long-acting beta -adrenergic agonists (LABA) as monotherapy

2
160/4.5
(without inhaled corticosteroids [ICS]) for asthma is associated with an
increased risk of asthma-related death. These fi ndings are considered a
class effect of LABA. When LABA are used in fi xed dose combination
(budesonide/formoterol fumarate
with ICS, data from large clinical trials do not show a signifi cant increase
dihydrate) Inhalation Aerosol
in the risk of serious asthma-related events (hospitalizations, intubations,
death) compared to ICS alone
Please see additional Important Safety Information throughout
and Brief Summary of full Prescribing Information on following pages.
CHPH_9.indd 1 2/28/2018 8:16:17 AM
SYMBICORT 160/4.5 for the maintenance treatment of COPD
THE SPEED THEY WANT...
BETTER BREATHING—FAST1-3
The majority of
FEV improvement
1
 In a serial spirometry subset of patients taking SYMBICORT 160/4.5* occurred at:
in the SUN Study, the majority of patients’ 1-hour postdose FEV
1
improvement occurred at 5 minutes on day of randomization,
at month 6, and end of treatment1-3
 Sustained improvement in lung function was demonstrated in a
12-month effi cacy and safety study1,2
SYMBICORT is NOT a rescue medication and does NOT replace
fast-acting inhalers to treat acute symptoms
SYMBICORT 160/4.5 for reducing COPD exacerbations
...THE CONTROL THEY NEED
REDUCTION IN COPD EXACERBATIONS
 In a 12-month exacerbation clinical trial (Study 4), SYMBICORT 160/4.5*
significantly reduced the annual rate of moderate/severe COPD
exacerbations by 35% vs formoterol (Estimate Rate Ratio=0.65; REDUCTION IN
EXACERBATION RATE
95% CI: 0.53, 0.80; p<.0001)3,4
– Annual rate estimate was 0.68 for SYMBICORT 160/4.5 mcg*
(n=404) vs 1.05 for formoterol 4.5 mcg* (n=403)
 In a second exacerbation clinical trial of 6-month duration (Study 3),
SYMBICORT 160/4.5 signifi cantly reduced the annual rate of
moderate/severe COPD exacerbations by 26% vs formoterol
(Estimate Rate Ratio=0.74; 95% CI: 0.61, 0.91; p=.004)3,4
– Annual rate estimate was 0.94 for SYMBICORT 160/4.5 mcg*
(n=606) vs 1.27 for formoterol 4.5 mcg* (n=613)
 The most common adverse reactions ≥3% reported in COPD lung function clinical trials included nasopharyngitis,
oral candidiasis, bronchitis, sinusitis, and upper respiratory tract infection. The safety findings from the two
exacerbation clinical trials were consistent with the lung function studies
Please see additional Important Safety Information throughout and
Brief Summary of full Prescribing Information on following pages. *Administered as 2 inhalations twice daily.
IMPORTANT SAFETY INFORMATION (CONT’D)
 SYMBICORT is NOT a rescue medication and does NOT  Localized infections of the mouth and pharynx with
replace fast-acting inhalers to treat acute symptoms Candida albicans has occurred in patients treated with
SYMBICORT. Patients should rinse the mouth after
SYMBICORT should not be initiated in patients during

inhalation of SYMBICORT
rapidly deteriorating episodes of asthma or COPD

Patients who are receiving SYMBICORT should not use  Lower respiratory tract infections, including pneumonia,

have been reported following the administration of ICS
additional formoterol or other LABA for any reason
CHPH_10.indd 2 2/28/2018 8:24:51 AM