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2011 Updates in Therapeutics:

The Pharmacotherapy Preparatory Review &


Recertification Course
Ambulatory Care
Ila M. Harris, Pharm.D., FCCP, BCPS
University of Minnesota

Conflict of Interest Disclosures

Ila M. Harris, Pharm.D.:


I have no conflicts of interest to disclose

Learning Objectives
Select acute & preventative treatment for adult patients with
asthma, COPD & conditions requiring anticoagulation.
Classify a patient according to asthma severity class, and
assess his/her control, according to NHLBI guidelines.
Di
Discuss iindications
di i ffor warfarin
f i and
d goall INR ffor specific
ifi
patients, and adjust therapy according to INR, other clinical
findings and/or patient factors.
Design a treatment plan for a patient receiving warfarin who
needs to undergo an invasive procedure
Determine appropriate immunizations for an adult.

1
Ambulatory Topics Covered

Asthma
COPD
Anticoagulation
Adult Immunizations

ASTHMA

In adolescents and adults >12 years of age

Page 190

Patient Case 1

BW is a 20-year-old woman who started


attending aerobics class twice weekly to try to
lose weight. She never exercised before.
She has been having a cough and some trouble
breathing during each class but it does not limit
her activity.
What asthma severity class is BW in?

Page 191

2
Classifying Asthma Severity > age 12 Page 190

Mild Moderate Severe


Intermittent
Persistent Persistent Persistent
Impairment
2 days / >2 days / wk Throughout the
Symptoms Daily
week but not daily day
Night >once / week Often
2 x / month 3-4 x / month
Awakenings but not nightly 7 x / week
2 days / wk > 2 days / Several times per
-agonist
agonist Use Daily
weekk d
day
Interference
None Minor Some Extreme
with activity
FEV1 60-80% FEV1<60%
Lung Function Normal Normal
FEV1/FVC 5% FEV1/FVC >5%
Risk
Systemic
<2 x / yr 2 / yr 2 / yr 2 / yr
Steroids

Treatment Step to Initiate

Step 1 Step 2 Step 3 Step 4 or 5

Patient Case 1

A. Intermittent
B. Mild persistent
C. Moderate persistent
D. Severe persistent

Need to consider exercise-induced asthma

Page 224

Patient Case 2

Which of the following medications is best to


recommend for B.W. (intermittent asthma), in
addition to albuterol MDI 1 or 2 puffs prior to
exercise?
A. Albuterol MDI 1-2 puffs QID PRN
B. Montelukast 10 mg daily
C. Omalizumab 150 mg SC Q4 weeks
D. Mometasone MDI 220 mcg 1 puff daily
Page 192

3
Page 190
Classifying Asthma Severity > age 12
Mild Moderate Severe
Intermittent
Persistent Persistent Persistent
Impairment
2 days / >2 days / wk Throughout the
Symptoms Daily
week but not daily day
Night >once / week Often
2 x / month 3-4 x / month
Awakenings but not nightly 7 x / week
-agonist Use 2 days / wk > 2 days / Several times per
Daily
f Symptoms
for S t weekk d
day
Interference
None Minor Some Extreme
with Activity
FEV1 60-80% FEV1<60%
Lung Function Normal Normal
FEV1/FVC 5% FEV1/FVC >5%
Risk
Systemic
<2 x / yr 2 / yr 2 / yr 2 / yr
Steroids

Treatment Step to Initiate

Step 1 Step 2 Step 3 Step 4 or 5

Stepwise Therapy for Asthma


for > 12 years of age
Intermittent Persistent Asthma
Asthma

Therapy Step 6
Step 5
Step 4
Step 3
Step 2
Step 1
Preferred SABA prn Low Dose Low Dose Medium High
Hi hDDose High Dose
ICS ICS + Dose ICS + ICS +
LABA OR ICS + LABA LABA +
medium- LABA AND OCS
dose ICS Consider AND
omalizumab Consider
for patients omalizumab
Alternative Low-dose with for patients
LTRA or ICS + Medium- allergies with
theophylline LTRA, dose ICS + allergies
theophylline LTRA,
or zileuton theophylline
or zileuton

Page 192
Cromolyn&nedocromil: were alternatives for Step 2 but have been D/Ced by manufacturers

Patient Case 2

Which of the following medications is best to


recommend for B.W. (intermittent asthma), in
addition to albuterol MDI 1 or 2 puffs prior to
exercise?
A. Albuterol MDI 1-2 puffs QID PRN
B. Montelukast 10 mg daily
C. Omalizumab 150 mg SC Q4 weeks
D. Mometasone MDI 220 mcg 1 puff daily
Page 224

4
Patient Case 3

Your recommendation has slightly improvedB.W.s


symptoms. However, now she started coughing at
night about once weekly. What is the preferred
medication to add?

A. Budesonide-formoterol MDI 80/4.5 2 puffs BID


B. Montelukast 10 mg daily
C. Salmeterol MDI 2 puffs BID
D. Fluticasone 110 mcg/puff 1 puff BID
Page 192

Assessing Control in Adults


Not Well Very Poorly
Well Controlled Controlled Controlled
Symptoms
2 days/week >2 days/week Throughout the day
Nighttime
2 x/month 1-3x/week 4 days/week
Awakenings
Interference Some Limitation Extremely Limited
Impairment with Activity None

SABA use for >2 days/week Several times/day


2 days/week
Symptoms
Lung function
FEV1 >80% 60% - 80% >60 %
Exacerbations 2 /year 2 /year
Risk <2/year
requiring OCS
Same regimen;
Consider short
F/U 1-6 mo.
Step up 1 step; course OCS;
Action Can step down
F/U 2-6 weeks Step up 1-2 steps
if stable for > 3
F/U 2 weeks
mo.
Page 191

Stepwise Therapy for Asthma


for > 12 years of age
Intermittent Persistent Asthma
Asthma

Therapy Step 6
Step 5
Step 4
Step 3
Step 2
Step 1
Preferred SABA prn Low Dose Low Dose Medium High
Hi hDDose High Dose
ICS ICS + Dose ICS + ICS +
LABA OR ICS + LABA LABA +
medium- LABA AND OCS
dose ICS Consider AND
omalizumab Consider
for patients omalizumab
Alternative Low-dose with for patients
LTRA or ICS + Medium- allergies with
theophylline LTRA, dose ICS + allergies
theophylline LTRA,
or zileuton theophylline
or zileuton

Page 192

5
ICS Comparative Daily Doses >12 y/o Page 197

Drug Low Dose Medium Dose High Dose


Step 2 3 Step 3 4 Step 5 6
Budesonide DPI 180 600 >600 1,200 mcg > 1,200 mcg
(Pulmicort 90,180) mcg
Flunisolide MDI 320 mcg >320 - 640 mcg > 640 mcg
(AeroBid HFA 80)
Fluticasone MDI 88 264 mcg >264 440 mcg > 440 mcg
(Flovent 44,110,220)

Beclomethasone MDI 80 240 mcg >240 480 mcg > 480 mcg
(QVAR 40, 80)
Mometasone DPI 220 mcg 440 mcg > 440 mcg
(Asmanex 110, 220)
Ciclesonide MDI 160 mcg 320 mcg 640 mcg
(Alvesco 80, 160)

Patient Case 3

Your recommendation has slightly


improvedB.W.ssymptoms. However, now she started
coughing at night about once weekly. What is the
preferred medication to add?
p

A. Budesonide-formoterol MDI 80/4.5 2 puffs BID


B. Montelukast 10 mg daily
C. Salmeterol MDI 2 puff BID
D. Fluticasone 110 mcg/puff 1 puff BID
Page 224

Patient Case 4
BW returns one month later. No longer awakening at
night. Uses albuterol MDI 2 puffs once per week to
treat symptoms. She also uses albuterol MDI 2 puffs 5
days per week prior to working out at the gym; she does
not have symptoms while working out. Which of the
f ll i is
following i correct??
A. No medication change needed
B. Increase fluticasone to 110mcg 2 puffs BID
C. Add formoterol inhalation BID
D. Add montelukast 10 mg/d

Page 192

6
Assessing Control in Adults
Not Well Very Poorly
Well Controlled Controlled Controlled
Symptoms
2 days/week >2 days/week Throughout the day
Nighttime
2 x/month 1-3x/week 4 days/week
Awakenings
Interference Some Limitation Extremely Limited
Impairment with activity None

SABA use for >2 days/week Several times/day


2 days/week
symptoms
Lung function
FEV1 >80% 60% - 80% >60 %
Exacerbations 2 /year 2 /year
Risk <2/year
requiring OCS
Same regimen;
Consider short
F/U 1-6 mo.
Step up 1 step; course OCS;
Action Can step down
F/U 2-6 weeks Step up 1-2 steps
if stable for > 3
F/U 2 weeks
mo.
Page 191

Patient Case 4
BW returns one month later. No longer awakening at
night. Uses albuterol MDI 2 puffs once per week to
treat symptoms. She also uses albuterol MDI 2 puffs 5
days per week prior to working out at the gym; she does
not have symptoms while working out. Which of the
f ll i is
following i correct??
A. No medication change needed
B. Increase fluticasone to 110mcg 2 puffs BID
C. Add formoterol inhalation BID
D. Add montelukast 10 mg/d
Page 224

Patient Case 5
D.B is a 16 year old boy with asthma symptoms 1-
2 x/week. He is awakened twice weekly at night
with coughing and trouble breathing. What is his
asthma severity classification?
A. Intermittent
B. Mild persistent
C. Moderate persistent
D. Severe persistent

Page 196

7
Page 190
Classifying Asthma Severity> age 12
Mild Moderate Severe
Intermittent
Persistent Persistent Persistent
Impairment
2 days / >2 days / wk Throughout the
Symptoms Daily
week but not daily day
Night >once / week Often
2 x / month 3-4 x / month
Awakenings but not nightly 7 x / week
2 days / wk > 2 days / Several times per
-agonist
g Use Daily
y
weekk d
day
Interference
None Minor Some Extreme
with activity
FEV1 60-80% FEV1<60%
Lung Function Normal Normal
FEV1/FVC 5% FEV1/FVC >5%
Risk
Systemic
<2 x / yr 2 / yr 2 / yr 2 / yr
Steroids

Treatment Step to Initiate

Step 1 Step 2 Step 3 Step 4 or 5

Patient Case 5
D.B. is a 16 year old boy with asthma symptoms 1-
2x/week. He is awakened twice per week at night
with coughing and trouble breathing. What is his
asthma severity classification?
A. Intermittent
B. Mild persistent
C. Moderate persistent
D. Severe persistent

Page 224

Patient Case 6

In addition to albuterol MDI 1-2 puffs every 4-6


hours as needed, which is best for D.Bs initial
therapy?

A. Beclomethasone 80 mcg/puff 2 puffs BID


B. Montelukast 10 mg daily
C. Mometasone-formoterol 200/5mcg 2 puffs
BID
D. Fluticasone 110 mcg/puff 1 puff BID
Page 196

8
Classifying Asthma Severity > age 12 Page 190

Mild Moderate Severe


Intermittent
Persistent Persistent Persistent
Impairment
2 days / >2 days / wk Throughout the
Symptoms Daily
week but not daily day
Night >once / week Often
2 x / month 3-4 x / month
Awakenings but not nightly 7 x / week
2 days / wk > 2 days / Several times per
-agonist
agonist Use Daily
weekk d
day
Interference
None Minor Some Extreme
with activity
FEV1 60-80% FEV1<60%
Lung Function Normal Normal
FEV1/FVC 5% FEV1/FVC >5%
Risk
Systemic
<2 x / yr 2 / yr 2 / yr 2 / yr
Steroids

Treatment Step to Initiate

Step 1 Step 2 Step 3 Step 4 or 5

Stepwise Therapy for Asthma


for > 12 years of age
Intermittent Persistent Asthma
Asthma

Therapy Step 6
Step 5
Step 4
Step 3
Step 2
Step 1
Preferred SABA prn Low Dose Low Dose Medium High
Hi hDDose High Dose
ICS ICS + Dose ICS + ICS +
LABA OR ICS + LABA LABA +
medium- LABA AND OCS
dose ICS Consider AND
omalizumab Consider
for patients omalizumab
Alternative Low-dose with for patients
LTRA or ICS + Medium- allergies with
theophylline LTRA, dose ICS + allergies
theophylline LTRA,
or zileuton theophylline
or zileuton

Page 192

ICS Comparative Daily Doses >12 y/o Page 197

Drug Low Dose Medium Dose High Dose


Step 2 3 Step 3 4 Step 5 6
Budesonide DPI 180 600 >600 1,200 mcg > 1,200 mcg
(Pulmicort 90,180) mcg
Flunisolide MDI 320 mcg >320 - 640 mcg > 640 mcg
(AeroBid HFA 80)
Fluticasone MDI 88 264 mcg >264 440 mcg > 440 mcg
(Flovent 44,110,220)

Beclomethasone MDI 80 240 mcg >240 480 mcg > 480 mcg
(QVAR 40, 80)
Mometasone DPI 220 mcg 440 mcg > 440 mcg
(Asmanex 110, 220)
Ciclesonide MDI 160 mcg 320 mcg 640 mcg
(Alvesco 80, 160)

9
Patient Case 6

What should D.Bs initial therapy be, in addition


to albuterol MDI 1-2 puffs every 4-6 hours as
needed?

A. Beclomethasone 80 mcg/puff 2 puffs BID


B. Montelukast 10 mg daily
C. Mometasone-formoterol 200/5mcg 2 puffs
BID
D. Fluticasone 110 mcg/puff 1 puff BID
Page 224

Long-Acting Beta Agonists


February 18, 2010
FDA issued a safety announcement due to safety
concerns with LABA
LABA contraindicated without concomitant controller
Long-term LABA should only be used in patients who
are inadequately controlled on controllers
Use LABA short-term when possible and attempt to
discontinue after control is achieved
Pediatric/adolescent patients who require LABA should
use a combination product
Page 196

Anticholinergic (Tiotropium) for


Chronic Asthma
Ipratropium is used in combination with albuterol
for acute asthma exacerbations
A recent study in patients uncontrolled on low dose
ICS evaluated:
ICS; l d
Adding tiotropium vs. LABA vs. doubling dose of ICS
3-way crossover; 14 weeks each treatment

Peters SP, et al. TALC study. N Engl J Med 2010;363:171526.

Page 196

10
Anticholinergic (Tiotropium) for
Chronic Asthma
RESULTS:
Adding tiotropium group: significantly greater
improvements in PEF & FEV1, better symptom control
& more asthma control daysy than doublingg ICS dose
Tiotropium non-inferior to adding LABA for all
outcomes; and it increased pre-bronchodilator FEV1
more than LABA (p=0.003)
Additional studies needed before using routinely in
clinical practice
Page 196

Asthma Action Plan

Asthma Action Plan (AAP)


Previously used peak-flow/zone based; now
moving towards symptom based

Pages 197-198

Patient Case 7 Page 198

JH is a 25 year old woman is using Advair


(fluticasone/salmeterol) 250/50 1 puff BID and
albuterol HFA 1-2 puffs q 4-6 hr PRN. You are
developing an asthma action plan for her. What are
her green zone instructions?
A. Discontinue fluticasone/salmeterol
B. Use fluticasone/salmeterol regularly; may use albuterol
HFA 1-2 puffs q 4-6 hr PRN
C. Use albuterol HFA 2 puffs; repeat in 20 minutes if
needed, then reasses.
D. Use albuterol HFA 6 puffs; repeat in 20 minutes; start
prednisone 50mg QD x 5 days

11
Asthma Action Plan (Adults):
Green Zone
Doing well, no symptoms
Take controller drug only
Use 2 puffs of SABA 55-15
15 min before exercise
if exercise-induced asthma
May use SABA as needed for periodic mild
symptoms

Page 197

Asthma Action Plan: Adults

Green Zone

Advair 250/50 1 puff twice daily

Choice B is correct
Page 224

Patient Case 8
What are J.H.syellow zone instructions?

A. Albuterol HFA 1-2 puffs every 4-6 hr if needed


B. Albuterol HFA 2 p puffs;; repeat
p in 20 min,, if
needed, then reassess
C. Albuterol HFA 6 puffs; repeat in 20 min; start
prednisone 50mg QD x 5 days, then reassess
D. Albuterol HFA 10 puffs; repeat every 20 min x 4
hours; start prednisone 50mg QD x 5 days, then
reassess
Page 198

12
Asthma Action Plan (Adults):
Yellow Zone
Getting worse; some symptoms of wheezing and
dyspnea
Use SABA 2-6
2 6 puffs by MDI or 1 neb treatment;
may repeat in 20 minutes if needed
Use fewer puffs if mild exacerbation (e.g., 2 puffs)

Page 197

AAP: Yellow Zone Page 197

1 hour after initial treatment


Complete Consider OCS burst
Response Contact clinician for f/u

Incomplete R
Repeatt SABA;
SABA add dd OCS burst
b t
Response Contact clinician that day

Repeat SABA; add OCS burst


Poor
Response Contact clinician immediately; go
to ER/call 911 if severe distress
May continue SABA every 3-4 hr regularly for 1-2 days
OCS burst: prednisone 40-60mg/d x 5-10 days

Asthma Action Plan: Adults


Yellow Zone

ProAir 2 puffs repeat in


20 min, then reassess

X X

Doubling dose of ICS does not help


Choice B is correct
Page 224

13
Patient Case 9
What are J.H.sred zone instructions?

A. Albuterol HFA 1-2 puffs every 4-6 hr if needed


B. Albuterol HFA 2 p puffs; repeat
p in 20 min, if
needed, then reassess
C. Albuterol HFA 6 puffs; repeat in 20 min; start
prednisone 50mg QD x 5 days, then reassess
D. Albuterol HFA 10 puffs; repeat every 20 min x 4
hours; start prednisone 50mg QD x 5 days, then
reassess
Page 198

Asthma Action Plan (Adults):


Red Zone
Medical alert; marked wheezing and dyspnea,
inability to speak more than short phrases, use of
accessory muscles, drowsiness
Use SABA: 2-6 puffs (higher dose of 4-6 puffs
usually recommended) by MDI or 1 neb tx; repeat
in 20 minutes; if incomplete or poor response,
repeat SABA again in 20 minutes
Add OCS burst (prednisone 40-60mg/d x 5-10 d)
Pages 197-198

Asthma Action Plan (Adults):


Red Zone
Proceed to ED or call 911 if distress is severe
and unresponsive to treatment
Call 911 or go to ED immediately if lips or
fi
fingernails
il are blue
bl or gray, or if trouble
bl
walking or talking due to SOB
Contact clinician immediately
Continue SABA every 3-4 hr regularly for 1-2
days
Pages 197-198

14
Asthma Action Plan: Adults

Red Zone

ProAir 6 puffs,
puffs repeat in 20 min
min. then reassess
Prednisone 50mg once daily for 5 days

X
X X
X

-Provide prescription to patient ahead of time and have them fill

Choice C is correct Page 224

Patient Case 10
R.D. is a 25 y/o male presenting to the ED with SOB at
rest. He is having trouble with conversation. He used 4
puffs of his albuterol MDI at home but it didnt seem to
help completely. FEV1 is checked and it is 38%
predicted.
di t d WhWhatt is
i his
hi severity
it off asthma
th exacerbation?
b ti ?
A.Mild
B. Moderate
C. Severe
D. Life-threatening
Page 201

Classifying Asthma Exacerbations in


Urgent or ED Setting
Symptoms/Signs Initial FEV1/ PEF (%
predicted or personal best)

Mild Dyspnea only with activity > 70%

Moderate Dyspnea limits or interferes 40-69%


with usual activity

Severe Dyspnea at rest; interferes < 40%


with conversation

Life- Too dyspneic to speak; < 40%


threatening perspiring

Page 199

15
Patient Case 10
R.D. is a 25 y/o male presenting to the ED with SOB at
rest. He is having trouble with conversation. He used 4
puffs of his albuterol MDI at home but it didnt seem to
help completely. FEV1 is checked and it is 38%
predicted.
di t d WhWhatt is
i his
hi severity
it off asthma
th exacerbation?
b ti ?
A. Mild
B. Moderate
C. Severe
D. Life-threatening
Page 224

Patient Case 11
What is the best initial therapy for R.D. in the ED, in
addition to oxygen?

A. Oxygen alone is sufficient


B. Inhaled albuterol MDI 8 puffs every 20 minutes for 1
hour
C. Inhaled albuterol plus ipratropium via nebulizer every 20
minutes for 1 hour plus IV corticosteroids
D. Inhaled albuterol plus ipratropium via nebulizer every 20
minutes for 1 hour plus OCS
Page 201

Initial Management of Exacerbation: ED


or Hospital Page 199

Severity of Initial Management


Exacerbation
Mild-moderate -Oxygen to achieve SaO2> 90%
(FEV1> 40%) -Inhaled SABA (MDI /spacer or neb) up to 3 doses in 1st hour
-OCS if no response immediately or if patient recently took OCS
Severe - Oxygen to achieve SaO2> 90%
(FEV1 < 40%) - High-dose inhaled SABA plusipratropium (MDI/spacer or neb) q
20 min or continuously for 1 hour
- OCS
-Consider adjunctive therapies (IV magnesium or heliox) if still
not responsive
Life- -Intubation and mechanical ventilation with oxygen 100%
threatening/Impen -Nebulized SABA plus ipratropium
ding respiratory -Intravenous corticosteroids
arrest -Consider adjunctive therapies (IV magnesium or heliox) if still
not responsive
-Admit to intensive care

16
Patient Case 11
What is the best initial therapy for R.D. in the ED, in
addition to oxygen?

A. Oxygen alone is sufficient


B. Inhaled albuterol MDI 8 puffs every 20 minutes for 1
hour
C. Inhaled albuterol plus ipratropium via nebulizer every 20
minutes for 1 hour plus IV corticosteroids
D. Inhaled albuterol plus ipratropium via nebulizer every
20 minutes for 1 hour plus OCS
Pages 224-225

COPD

Page 201

Diagnosis
Consider COPD and perform spirometry
if>40 years old with any of the following:

Dyspnea
Chronic cough
Chronic sputum production

History of exposure to risk factors

*2010 GOLD COPD guidelines were released in 2011; no significant


changes regarding pharmacotherapy
Page 202

17
Diagnosis

Criteria for diagnosis of COPD:

FEV1/FVC < 70% *


FEV1 not significantly reversible after
bronchodilator (rules out asthma)

* Hallmark of COPD Page 202

Patient Case 12 Page 205

S.H. is a 50 year old male smoker with recent


diagnosis of COPD. Spirometry showed:
FEV1/FVC: 60%; Pre-bronchodilator FEV1 : 70%
predicted; Post-bronchodilator FEV1: 72% predicted
What is the severity classification (stage) of S.Hs
COPD?
A. Stage I: Mild
B. Stage II: Moderate
C. Stage III. Severe
D. Stage IV: Very Severe

Severity Classification of COPD

0: At Risk I: Mild II: Moderate III: Severe IV: Very Severe

Symptoms FEV1/FVC < 70% FEV1/FVC < 70% FEV1/FVC < 70% FEV1/FVC < 70%
Risk factor FEV1 80% 50% < FEV1 < 80% 30% < FEV1 < 50% FEV1 < 30% or
exposure FEV1 < 50% predicted
Normal plus chronic respiratory
spirometry failure

B. Stage II; Moderate COPD

Page 204 and 225

18
Patient Case 13
Which of the following is the most appropriate
for S.H. to be started on, in addition to albuterol
MDI 2 puffs q 4-6 hr PRN?

A. Albuterol PRN alone is sufficient


B. Formoterol inhale 1 cap BID
C. Salmeterol/fluticasone 50/500 1 puff BID
D. Salmeterol/fluticasone 50/500 1 puff BID plus
home oxygen

Page 205

Therapy at Each Stage of COPD


0: At Risk I: Mild II: Moderate III: Severe IV: Very Severe

Symptoms FEV1/FVC < 70% FEV1/FVC < 70% FEV1/FVC < 70% FEV1/FVC < 70%
Risk factor FEV1 80% 50% < FEV1 < 80% 30% < FEV1 < 50% FEV1 < 30% or
exposure FEV1 < 50% predicted
Normal plus chronic respiratory
spirometry failure

Avoidance of risk factor(s); influenza vaccination


Add short-acting bronchodilator when needed
Addregular treatment with one or more long-
acting bronchodilators; Add rehab
Add inhaled corticosteroids if
repeated exacerbations

Addlong-term
oxygen if chronic
respiratory failure
Consider surgical
Page 204 treatments

Patient Case 13
Which of the following is the most appropriate
for S.H. to be started on, in addition to albuterol
MDI 2 puffs q 4-6 hr PRN?

A.
A Albuteroll PRN iis sufficient
Alb ffi i
B. Formoterol inhale 1 cap BID
C. Salmeterol/fluticasone 50/500 1 puff BID
D. Salmeterol/fluticasone 50/500 1 puff BID plus
home oxygen

Page 225

19
Long-Acting Bronchodilators

The choice of specific long-acting


bronchodilators depends on availability and
individual response in symptom relief and adverse
effects (one not favored over another).
another)
BUT: New data may favor tiotropium over
salmeterol in moderate-severe COPD with
exacerbations

Page 203

Long-Acting Bronchodilators
POET-COPD study
7376 patients with moderate-severe COPD and
1 exacerbation in past year; 1 year
randomized, double-blind, parallel-group trial
Tiotropium vs. salmeterol
Primary endpoint: Time to first exacerbation
Moderate exacerbation: treated with OCS, antibiotics
or both
Severe exacerbation: hospitalized
NEJM 2011;364:1093-103.

Long-Acting Bronchodilators
Results:
Tiotropium (vs. salmeterol) significantly:
Increased time to first exacerbation
187 days vs. 145 days (42 day difference)
B th moderate
Both d t andd severe exacerbations
b ti were significant
i ifi t
Reduced annual number of exacerbations
Rate of both moderate and severe exacerbations was significant
Benefit was consistent in all major subgroups and
independent of concomitant ICS
Benefit evident in 1 month and maintained over 1 year
Sig. fewer patients taking tiotropium withdrew early

20
Patient Case 14
K.R. is a 60 y/0 man with COPD. Smokes ppd.
Gradual worsening of SOB. FEV1/FVC: 55% ;
FEV1: 63%. Meds: tiotropium (Spiriva) QD and
albuterol HFA prn. Which is most appropriate?

A. Add salmeterol 1 puff BID


B. Change tiotropium to salmeterol 1 puff BID
C. Add fluticasone 110 mcg 2 puffs BID
D. D/C tiotropium& start Advair 250/50

Page 205

Therapy at Each Stage of COPD


0: At Risk I: Mild II: Moderate III: Severe IV: Very Severe

Symptoms FEV1/FVC < 70% FEV1/FVC < 70% FEV1/FVC < 70% FEV1/FVC < 70%
Risk factor FEV1 80% 50% < FEV1 < 80% 30% < FEV1 < 50% FEV1 < 30% or
exposure FEV1 < 50% predicted
Normal plus chronic respiratory
spirometry failure

Avoidance of risk factor(s); influenza vaccination


Add short-acting bronchodilator when needed
Addregular treatment with one or more long-
acting bronchodilators; Add rehab
Add inhaled corticosteroids if
repeated exacerbations

Addlong-term
oxygen if chronic
respiratory failure
Consider surgical
Page 204 treatments

Patient Case 14
K.R. is a 60 y/o man with COPD. Smokes ppd.
Gradually worsening SOB. FEV1/FVC: 55% ;
FEV1: 63%. Meds: tiotropium (Spiriva) QD and
albuterol HFA prn. Which is most appropriate?

A. Add salmeterol 1 puff BID


B. Change tiotropium to salmeterol 1 puff BID
C. Add fluticasone 110 mcg 2 puffs BID
D. D/C tiotropium& start Advair 250/50

Page 225

21
Page 205
-blockers in COPD
New observational data suggests long-term
treatment with-blockers (mostly cardioselective)
reduces the risk of exacerbations and improves
survival, even in patients without overt CVD.
More than half of the patients had CV risk factors
or CAD
Too early to use beta-blockers in the treatment of
COPD, but do not withhold in patients who also
have CAD or CHF.
Rutten et al. Arch Intern Med 2010;170:880-7.

Patient Case 15
M.J. is a 56 y/o man with Stage II (moderate) COPD and
HTN who presents to clinic with worsening SOB, coughing
& production of purulent sputum (much more sputum than
usual). Pulse ox 95%. In addition to
nebulizedalbuterol/ipratropiumq
p p q 1-4 hours,, what else
should be added?
A. No additional therapy needed
B. Add oral prednisone 60 mg once daily for 10 days
C. Add TMP/SMX DS 1 tablet BID for 7 days
D. Add oral predisone 60 mg once daily for 10 days and
TMP/SMX DS 1 tablet BID for 7 days.
Page 207

Managing Exacerbations

Short-acting albuterol is effective (Evidence A)


2.5mg via nebulizer every 1-4 hours or
4-8 puffs via MDI/holding chamber every 1-4 hr
G
Generally,
ll short
h t acting
ti ipratropium
ip t pi i also
is l given
i
Systemic corticosteroids are effective (Evidence A)
Outpatients: Use if baseline FEV1 is < 50%
Use in all patients hospitalized for severe exacerbations
MJ has moderate COPD (FEV1 50-80%)
so oral corticosteroids are not indicated.
Page 206

22
Managing Exacerbations
o Patients experiencing COPD exacerbations with
clinical signs of airway infection may benefit
from antibiotic treatment (Evidence B).
o Cardinal Symptoms:
o Increased sputum purulence
o Increased sputum volume
o Increased dyspnea

Page 206

Managing Exacerbations
o Antibiotics should be given if:
o COPD exacerbation with allTHREE cardinal
symptoms (Evidence B)
o COPD exacerbation with TWO cardinal
symptoms, if one is increased sputum
purluence (Evidence C)
o Severe COPD exacerbation requiring
mechanical ventilation (Evidence B)

Page 206

Managing Exacerbations

Empiric antibiotics are used to cover the most


common pathogens: Streptococcus pneumonia,
Hemophilusinfluenzae and Moraxellacatarrhalis.
U l antibiotic
Usual ibi i treatment iis 3 7 days
d

Page 207

23
Exacerbation Preferred Oral Alternative Oral Page 207
Group Antibiotics Antibiotics
Group A Doxycycline, Amoxicillin/clavulanate,
Mild trimethoprim/sulfam azithromycin, clarithromycin,
No risk factors ethoxazole second- or third-generation
for poor cephalosporin
outcome
Group B Amoxicillin/clavulan Levofloxacin, moxifloxacin
Moderate ate
Risk factors for
poor outcome
Group C Ciprofloxacin or
Severe Levofloxacin (at
Risk factorsfor least 750mg)
P. aeruginosa
Risk factors for poor outcome: comorbid diseases, severe COPD,> 3 exacerbations/year, antibiotic
use in past 3 months.
Risk factors for P. aeruginosa: Recent hospitalization, frequent antibiotics (4 courses in last year),
h/o severe COPD exacerbations, isolation of P. aeruginosan previous exacerbation

Patient Case 15
M.J. is a 56 y/o man with Stage II (moderate) COPD and
HTN who presents to clinic with worsening SOB, coughing
& production of purulent sputum (much more sputum than
usual). Pulse ox 95%. In addition to
nebulizedalbuterol/ipratropiumq 11-44 hours, what else
should be added?
A. No additional therapy needed
B. Add oral prednisone 60 mg once daily for 10 days
C. Add TMP/SMX DS 1 tablet BID for 7 days
D. Add oral predisone 60 mg once daily for 10 days and
TMP/SMX DS 1 tablet BID for 7 days. Page 225

ANTICOAGULATION

Page 208

24
Patient Case 16
J.J. is a 30 y/o woman receiving warfarin for a
proximal DVT. She was taking oral
contraceptives at the time her DVT was
diagnosed; they have since been discontinued.
Which of the follo
following
ing is correct with
ith regards to
recommended duration of warfarin?
A. 3 months
B. 6 months
C. 1 year
D. Indefinite
Page 212

Anticoagulation for VTE Page 208

TYPE OF INR DURATION EVIDENCE COMMENTS


VTE EVENT

DVT/PE with 2 3 3 months 1A Initiate warfarin together


reversible risk with LMWH (preferred),
factors UFH or fondaparinux and
continue for at>5 days &
until INR > 2 for 24 hr

First idiopathic 2 3 At least 3 1A After 1st 3 months, INR


proximal months, then goal for long-term
DVT/PE long-term if therapy can be 1.5-1.9 if
low bleeding less frequent monitoring
risk is strongly preferred

Patient Case 16
J.J. is a 30 y/o woman receiving warfarin for a
proximal DVT. She was taking oral
contraceptives at the time her DVT was
diagnosed; they have since been discontinued.
Which of the following is correct with regards to
recommended duration of warfarin?
A. 3 months
B. 6 months
C. 1 year
D. Indefinite
Page 225

25
Patient Case 17

B.D. is an 89 y/o man taking warfarin 5 mg daily


for a. fib. H/O depression, gastritis, and subdural
hematoma (1 year ago). Meds: fluoxetine (started 1
mo ago) &omeprazole (started 6 mo.
mo. mo ago).
ago) Has
warfarin 5, 2 and 1 mg. Having mild nosebleeds; 5
in past 2 days (5 min each) and unexpected
bruising. Last INR 6 wk ago (in range)
INR: 8

Page 213

Patient Case 17
Which of the following is the best way to deal
with B.D.s high INR?
A. Hold warfarinx 1 day then restart at lower dose (do
not check INR)
B. Hold warfarinx 2 days then restart at a lower dose (do
not check INR)
C. Hold warfarin, give po vitamin K 10 mg x 1 then
restart at lower dose when INR approaches 3
D. Hold warfarin, give po vitamin K 2.5 mg x 1 then
restart at lower dose when INR approaches 3
Page 213

Warfarin Drug Interactions

Warfarin is a racemic mixture of R- and S-


isomers
Sisomer is more potent vitamin K antagonist
S isomer is metabolized primarily by CYP 2C9
S-isomer
R-isomer is metabolized primarily by CYP 3A4
Most common interactions are through
inhibition of CYP 2C9 and 3A4, resulting in
increased warfarin effects
Pages 212

26
Warfarin Drug Interactions
Pg 212
S - warfarin* (CYP 2C9) - inhibitors
e.g., Metronidazole, TMP/SMX, fluconazole,
INH, cimetidine, fluoxetine, sertraline, zafirlukast,
amiodarone, clopidogrel, lovastatin
R - warfarin (CYP 3A3/4/5) - inhibitors
e.g., Cimetidine, omeprazole, clarithromycin,
erythromycin, azole antifungals, nefazodone,
zafirlukast, fluoxetine, amiodarone, CYA, sertraline,
GF juice, ciprofloxacin, norfloxacin, protease
inhibitors, cyclosporine, diltiazem, verapamil, INH,
metronidazole, zafirlukast

Page 214
Warfarin Reversal Guidelines

Patient Case 17
Which of the following is the best way to deal
with B.D.s high INR?
A. Hold warfarinx 1 day then restart at lower dose (do
not check INR)
B. Hold warfarinx 2 days then restart at a lower dose (do
not check INR)
C. Hold warfarin, give po vitamin K 10 mg x 1 then
restart at lower dose when INR approaches 3
D. Hold warfarin, give po vitamin K 2.5 mg x 1 then
restart at lower dose when INR approaches 3
Page 225

27
Patient Case 18

When warfarin is reinitiated in B.D., which of


the following is the best dose to start (he was
taking 5 mg daily)?

A. 5 mg 2 days/wk & 2.5 mg 5 days/wk


B. 2.5 mg/day
C. 4 mg/day
D. 4.5 mg 2 days/wk & 5 mg 5 days/wk

Page 213

Adjusting Warfarin Dose

For out-of-range INR, increase or decrease


cumulative weekly warfarin dose by 5%20%
depending on INR
If INR is high,
high may hold 11-22 doses and resume
at a lower dose
Usually do not need to adjust dose if INR is
within 0.1 of goal (but monitor more closely)

Page 210

Patient Case 18

When warfarin is reinitiated in B.D., which of


the following is the best dose to start (he was
taking 5 mg daily)?

A. 5 mg 2 days/wk & 2.5 mg 5 days/wk


B. 2.5 mg/day
C. 4 mg/day
D. 4.5 mg 2 days/wk & 5 mg 5 days/wk

Page 225

28
Patient Case 19
M.H. is a 63 y/o woman with mechanical mitral
valve replacement, HTN, dyslipidemia. Meds:
warfarin 8 mg/d, lisinopril 20 mg/d, atorvastatin
10 mg/d. What is M.H.s goal INR?

A. 1.5 2.5
B. 1.8 2.6
C. 23
D. 2.5 3.5
Page 213

VALVE TYPE GOAL DURATION EVI- COMMENTS


INR DENCE Page 209

Bioprosthetic heart 2 3 3 months, 1B For aortic valve and NSR : ASA


valve replacement then ASA 81mg/d (1B)
(mitral) and normal 81mg/day If RF present (AF, low EF,
sinus rhythm (NSR) hypercoag): VKA
If LA thrombus at surgery or h/o
systemic embolism, continue for
3-12 mo.
Mechanical valve 23 Long-term 1B If normal LA size and in sinus
replacement rhythm. Valves: St. Jude bileaflet,
(MVR): AORTIC Carbomedicsbileaflet, Medtronic
Carbomedicsbileaflet
tilting disk. 2.53.5 if AF or LA
enlargement.
Mechanical valve 2.5 Long-term 1B
replacement 3.5
(MVR): MITRAL
Any MVR + risk 2.5 Long-term 1B ADD ASA 81mg/d
factors OR any 3.5 Risk factors: AF, hypercoagulable
MVR with systemic state, low EF, atherosclerotic
embolism with vascular disease ; also if caged-
therapeutic INR ball or caged-disk valves

Patient Case 19
M.H. is a 63 y/o woman with mechanical mitral
valve replacement, HTN, dyslipidemia. Meds:
warfarin 8 mg/d, lisinopril 20 mg/d, atorvastatin
10 mg/d. What is M.H.s goal INR?

A. 1.5 2.5
B. 1.8 2.6
C. 23
D. 2.5 3.5
Page 225

29
Patient Case 20

M.H. (63 y/o woman with mitral MVR, HTN,


dyslipidemia, on warfarin, lisinopril, atorvastatin) has
now developed atrial fibrillation. Which of the
following is most appropriate?
A. Warfarin with goal INR 2.0-3.0 plus aspirin 81 mg daily
B. Warfarin with goal INR 2.0-3.0 plus aspirin 325 mg daily
C. Warfarin with goal INR 2.5-3.5 plus aspirin 81 mg daily
D. Warfarin with goal INR 2.5-3.5 plus aspirin 325 mg daily

Page 213

VALVE TYPE GOAL DURATION EVI- COMMENTS P


INR DENCE a
Bioprosthetic heart 2 3 3 months, 1B g
For aortic valve and NSR: ASA
valve replacement then ASA 81mg/d (1B) e
(mitral) and normal 81mg/day If RF present (AF, low EF,
sinus rhythm (NSR) hypercoag): VKA 2
0
If LA thrombus at surgery or h/o
9
systemic embolism, continue for
3-12 mo.
Mechanical valve 23 Long-term 1B If normal LA size and in sinus
replacement rhythm. Valves: St. Jude
(MVR): AORTIC bileaflet, Carbomedicsbileaflet,
bileaflet Carbomedicsbileaflet
Medtronic tilting disk. 2.53.5 if
AF or LA enlargement.
Mechanical valve 2.5 Long-term 1B
replacement 3.5
(MVR): MITRAL
Any MVR + risk 2.5 Long-term 1B ADD ASA 81mg/d
factors OR any 3.5 Risk factors: AF,
MVR with systemic hypercoagulable state, low EF,
embolism with atherosclerotic vascular disease
therapeutic INR Also if caged-ball or caged-disk
valves

Patient Case 20

M.H. (63 y/o woman with mitral MVR, HTN,


dyslipidemia, on warfarin, lisinopril, atorvastatin)
has now developed atrial fibrillation. Which of the
followingg is most appropriate?
pp p
A. Warfarin with goal INR 2.0-3.0 plus aspirin 81 mg daily
B. Warfarin with goal INR 2.0-3.0 plus aspirin 325 mg daily
C. Warfarin with goal INR 2.5-3.5 plus aspirin 81 mg daily
D. Warfarin with goal INR 2.5-3.5 plus aspirin 325 mg daily

Page 225

30
Patient Case 21
A 77 y/o man with atrial fibrillation, HTN,
diabetes, and h/o TIA 3 years ago. Having major
abdominal surgery in 1 week and will need to hold
his warfarin. Which of the following is the most
appropriate LMWH bridge therapy for him?
A. No bridge LMWH is needed; just hold warfarin
B. Enoxaparin 30 mg BID
C. Enoxaparin 1mg/kg BID
D. Either enoxaparin 30 mg BID or 1 mg/kg BID are
options
Page 213

Interruption of Warfarin for Procedures


First:
Determine bleeding risk during procedure (often
determined by the surgeon)
Next:
Determine thromboembolic risk of patients underlying
condition
Minor dental or dermatologic procedures or
cataract removal do not require holding warfarin

Page 215-216

CHADS2 Score
Categorizes thromboembolic risk in atrial
fibrillation; assigns points for risk factors
CHF (any history) 1 point
HTN 1 point
Age > 75 1 point
Diabetes - 1 point
S2troke, TIA, systemic embolism - 2 points each

Pages 215-216

31
High Risk of Thromboembolism

Mechanical heart valve:


Any mechanical mitral valve, older aortic valve (caged ball,
tilting disk), recent stroke/TIA (past 6 mo.)
Atrialfibrillation:
CHADS2score of 5 - 6, recent stroke/TIA (past 3 mo.),
presence of rheumatic valvular heart disease
VTE:
Recent VTE (past 3 mo.), severe thrombophilia

Page 216

Page 216
High Risk of Thromboembolism
Stop warfarin 5 days before surgery
In 2 days, start therapeutic dose LMWH
Last dose the AM prior to surgery: half dose
Check INR day before surgery;
g give
g 1-2mgg vitamin
K if INR > 1.5
Post-op, commence LMWH (24 hr after surgery)
and warfarin (day of or day after surgery)
Continue LMWH until warfarin therapeutic

Therapeutic dose subcutaneous LMWH:


Enoxaparin 1 mg/kg BID
Enoxaparin 1.5 mg/kg once daily
Dalteparin 200 IU/kg once daily
Dalteparin 100 IU/kg BID
Tinzaparin 175 IU/kg one daily
Low-dose subcutaneous LMWH:
Enoxaparin 30 mg/kg BID
Dalteparin 5,000 IU once daily

Page 216

32
Patient Case 21
A 77 y/o man with atrial fibrillation, HTN,
diabetes, and h/o TIA 3 years ago. Having
major abdominal surgery in 1 week and will need
to hold his warfarin. Which of the following is
the most appropriate LMWH bridge therapy for
him?
A. No bridge LMWH is needed; just hold warfarin
B. Enoxaparin 30 mg BID
C. Enoxaparin 1mg/kg BID
D. Either enoxaparin 30 mg BID or 1 mg/kg BID are
options Page 225

Moderate or Low Risk of


Thromboembolism
Moderate Risk:
Bridge with therapeutic OR low dose LMWH

Low Risk:
No bridge OR bridge with low dose LMWH

Page 216

Home INR Monitoring/Management


Recent meta-analysis; 22 trials; 8413 patients
PURPOSE:
To determine outcomes of patient self-testing (PST) alone or
together with self-dose-adjustment (patient self-management
[[PSM])
]) compared
p to standard care
RESULTS:
PST or PSM compared to usual care:
Lower mortality (OR 0.74; 95% CI 0.63-0.87)
Lower risk for major thromboembolism (OR 0.58; 95% CI 0.45-
0.75)
No increased risk for major bleeding
Bloomfield HE, et al. Ann Intern Med 2011 (April 5);154:472-482.

33
Home INR Monitoring/Management
NNT to prevent 1 thromboembolic event: 67
NNT to prevent one death: 36
LIMITATIONS:
If half of the trials, < 50% of the patients successfully
completed training and agreed to participate
Highly selected group of very motivated adults
Strength of evidence for mortality was low
Appears that benefit is mostly from PSM rather than PST
Withdrawal rates up to 25% despite improved QOL
Cost may be higher than usual care

Bloomfield HE, et al. Ann Intern Med 2011 (April 5);154:472-482.

New Anticoagulants
Dabigatran (Pradaxa)
Oral direct thrombin inhibitor
Indicated for the prevention of stroke/systemic
embolism in nonvalvularatrial fibrillation
Desirudin (Iprivask)
Specific inhibitor of human thrombin
Indicated for prophylaxis of DVT in patients
undergoing elective hip replacement surgery

Page 217

New Anticoagulants

Desirudin (Iprivask); cont:


Dose:
15 mg subcutaneously every 12 hours; initial dose
515 minutes before surgery.
g y Duration of upp to 12
days has been well tolerated.
Caution/decreased dose in renal impairment
(CrCl< 60); daily monitoring required

Page 217

34
ADULT
IMMUNIZATIONS

Page 218

Patient Case 22

E.V. is a 71 y/o woman with COPD. Her only


med is tiotropium inhaled 1 capsule/day. She
received influenza and H1N1 vaccines last
October her last Td vaccine was at age 65,
October, 65 and
her pneumococcal vaccine was at age 60. She
does not have close contact with infants or
young children. Which one of the following
vaccines should she receive at her October
internal medicine clinic appointment?
Page 222

Patient Case 22

A. Only the influenza vaccine should be given.


B. Influenza and pneumococcal polysaccharide
vaccines should be given.
given
C. Influenza, pneumococcal polysaccharide, and
zoster vaccines should be given.
D. Influenza, pneumococcal polysaccharide, and
Tdap vaccines should be given.

Page 222

35
Early pneumococcal vaccination
Pneumococcal vaccine is indicated prior to age 65 in:
Chronic lung disease (eg. COPD, asthma)
Chronic CV disease
Diabetes
Chronic liver disease,, cirrhosis
Chronic alcoholism
Functional or anatomic asplenia
Immunocompromising conditions
Smokers (age 19 64)
Cochlear implants, CSF leaks
Nursing home/LTCF patients Page 219

Revaccination with Pneumococcal


Vaccine
One time re-vaccination with pneumococcal
vaccine is indicated 5 years after 1st vaccine in:
Chronic renal failure or nephrotic syndrome
Functional
F i l or anatomic i asplenia
l i
Immunocompromising conditions
For persons > 65 y/o, one-time revaccination if they
were vaccinated > 5 years ago and were < age 65 at
time of first vaccination

Page 219

Zoster Vaccine

Zoster vaccine (Zostavax) is indicated in:


All adults age 60 and older
Should receive, whether or not they have had a prior
episode of zoster

Page 219

36
Recommended Adult Immunization Schedule
2011

Page 218

Patient Case 22

A. Only the influenza vaccine should be given.


B. Influenza and pneumococcal polysaccharide
vaccines should be given.
C. Influenza, pneumococcal polysaccharide, and
zoster vaccines should be given.
D. Influenza, pneumococcal polysaccharide, and
Tdap vaccines should be given.

Page 225

Patient Case 23
S.C.: 20 y/o female going away to college; living in the
dorm. Smokes ppd; no other medical conditions.
She is up to date with all her routine childhood vaccines,
but no vaccines in the past 11 years. Not sexually active.
What vaccines should she receive today?
A. Td and HPV vaccines.
B. Tdap, meningococcal and HPV vaccines.
C. Meningococcal, pneumococcal polysaccharide, and
Td vaccines.
D. Meningococcal, pneumococcal polysaccharide, Tdap
and HPV vaccines Page 222

37
Meningococcal vaccine
First-year college students living in dormatories should
receive meningococcal vaccine
No revaccination after 5 years even if still living in on-
campus housing (other indications may require
revaccination)
Two types: MCV4 (Menactra)- now called quadrivalent- and
MPSV4 (Menomune)
Age < 55 should receive MCV4

Page 219

Pneumococcal vaccine:
Smoker age 19-64
HPV vaccine
For girls/women age 11-26
Ideally prior to sexual activity, but still administer to
sexually active girls/women
Still administer to women with a h/o HPV, genital warts,
abnormal pap
Two different HPV vaccines now available (HPV2-
Cervarix & HPV4-Gardasil); either can be used
May be administered to boys/men age 9-26 to reduce risk
of genital warts
Page 219

New Tdap recommendations (2011):


Everyone age1164 not previously been vaccinated with Tdap
(or unknown status) should be vaccinated with Tdap as soon as
feasible.
Adults > 65 y/o years with close contact with infants younger
than 1 y/o not previously vaccinated with Tdap (including
th
those with
ith unknown
k p t i status)
pertussis t t ) should
h ld receive
i a single
i l
dose of Tdap (off-label use)
Other adults > 65 y/o may receive a single dose of Tdap if not
previously vaccinated, in place of usual Td booster
Tdap can be administered regardless of the interval since the
last Td vaccine.

Page 221

38
Recommended Adult Immunization Schedule
2011

Page 218

Patient Case 23

A. Td and HPV vaccines.


B. Tdap, meningococcal and HPV vaccines.
C. Meningococcal, pneumococcal polysaccharide,
and
d Td vaccines.
i
D. Meningococcal, pneumococcal polysaccharide,
Tdap and HPV vaccines

Page 226

2011 Updates in Therapeutics:


The Pharmacotherapy Preparatory Review &
Recertification Course

39