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Duloxetine in the Treatment of

Diabetic Peripheral
Neuropathic Pain (DPNP)
SUMMARY SLIDE SET
Contents

♦ Introduction

♦ Mechanism of Action

♦ Efficacy in DPNP

♦ Pharmacokinetics, Safety and Tolerability

♦ Conclusion
Contents

♦ Introduction

♦ Mechanism of Action

♦ Efficacy in DPNP

♦ Pharmacokinetics, Safety and Tolerability

♦ Conclusion
Neuropathic Pain is a Frequent
Complication of Diabetes

♦ 30–60% of patients with diabetes develop long-term


complications of diabetic peripheral neuropathy and
up to 10–20% of these experience pain1–3
• Increased risk with longer duration of diabetes and with poor
glucose control4

♦ Diabetic peripheral neuropathic pain (DPNP)


interferes with patients’ functioning and quality of life4
♦ Patients’ quality of life and level of daily function
decrease further with increasing disease severity 4,5

1. Clark CM, et al. N Engl J Med. 1995;332:1210–1217; 2. Boulton AJM, et al. Diabetes Care. 2004;27:1458–1486; 3. Eastman RC.
Neuropathy in Diabetes. In: Diabetes Data Group, eds. Diabetes in America, 2nd ed. NIH Publication: Washington, DC;1995:339–348.
4. Argoff CE, et al. Mayo Clin Proc. 2006; 81(4):S3–11; 5. Sullivan SD, et al. Pharmacoeconomics. 2002;20:1079–1089.
DPNP Can Negatively Impact Patients’
Quality of Life1,2
“Pain is an unpleasant
sensory and emotional
experience associated
with actual or potential
tissue damage, or
The majority described in terms of
of patients such damage3”
experience pain
on a constant, mood
daily basis1
sleep
energy
mobility
work
social activities
enjoyment of life

1. Galer BS, et al. Diabetes Res Clin Pract. 2000;47:123–128; 2. Benbow SJ, et al. QJM.
1998;91:733–737;3. IASP website (http://www.iasp-pain.org/terms-p.html#Pain). Accessed October 05, 2006.
Multiple Mechanisms of Neuropathic Pain

♦ Multiple mechanisms play a role in neuropathic


pain:
• Peripheral nervous system input:
 Peripheral sensitization
 Ectopic excitability

• Central nervous system processing:


 Central sensitization
 Structural reorganization
 Disinhibition

1. Woolf CJ. Ann Intern Med. 2004;140:441–451.


Distinguishing Nociceptive and
Neuropathic Pain

Nociceptive pain Neuropathic pain


♦ Adaptive ♦ Maladaptive
♦ Identifiable stimuli that ♦ Often spontaneous (occurring
normally produce tissue without identifiable stimuli)
damage ♦ Often chronic
♦ Usually self-limiting ♦ May involve structural and
♦ Transmitted by structurally functional changes in pain
and functionally intact pain pathways
pathways ♦ Examples: Polyneuropathy
♦ Examples: post-operative (eg, diabetic, HIV), trigeminal
pain, burns, ischemic pain neuralgia, central post-stroke
pain
♦ Clinical pain syndromes occur along a spectrum from nociceptive
to neuropathic
♦ Nociceptive and neuropathic pain may coexist in the same patient
1. Portenoy RK and Kanner RM. Definition and assessment of pain. In: Portenoy RK and Kanner RM, eds. Pain Management:
Theory and Practice;1996:4; 2. Galer BS and Dworkin RH. A Clinical Guide to Neuropathic Pain. Minneapolis: McGraw-Hill; 2000:8–9.
Goals of Neuropathic Pain Treatment

♦ Primary goal = reduction in pain


♦ Secondary goals
• Improvement in physical function
• Reduction in affective distress
• Improvement in quality of life
♦ Achieving these goals is predicated upon
• Accurate diagnosis of any underlying etiology
• Preventive treatment of underlying etiology
(eg diabetes, joint inflammation, etc.), if possible

1. Turk DC. Clin J Pain. 2000;16:279–280; 2. Belgrade MJ. Postgrad Med. 1999;106:127–140.
Management of DPNP

♦ Off-Label Agents:1
• Tricyclic antidepressants – i.e., amitriptyline
• Anticonvulsants – i.e., gabapentin
• Opioid analgesics
• Tramadol
• Other antidepressants – i.e., venlafaxine
♦ FDA-Approved Agents in US:
• Cymbalta2
• Lyrica3
1. Argoff CE, et al. Mayo Clin Proc. 2006;81(4):S12–25; 2. Cymbalta US Prescribing Information; 3. Lyrica US Prescribing Information.
Contents

♦ Introduction

♦ Mechanism of Action

♦ Efficacy in DPNP

♦ Pharmacokinetics, Safety and Tolerability

♦ Conclusion
Serotonin & Norepinephrine
Play a Major Role in Pain

♦ Neuropathic pain is
associated with increased
excitation and decreased
inhibition of ascending
pain pathways
♦ Descending pathways
modulate ascending signals 5-HT
♦ NE and 5-HT are key
neurotransmitters in
descending inhibitory NE
pain pathways
♦ Increasing the availability of
NE and 5-HT may promote pain
inhibition centrally

1. Figure adapted from: Fields HL and Basbaum AI. Central nervous system mechanisms of pain modulation. In: Wall PD and Melzack R,
eds. Textbook of Pain, 4th ed. Churchill Livingstone: London, UK;1999,310.
The Combination of an NRI and an SSRI is
More Effective than Either Alone

Total paw-licking time (late phase)


120
Paroxetine
Less Pain Behavior

Vehicle control
100
% of Vehicle Control

Thionisoxetine
80
Paroxetine
60 * * 1 mg/kg +
Thionisoxetine

40 N=5–12
* P < .05
20 vs thionisoxetine alone

0
0.1 1 10
Drug (mg/kg)
Higher Dose

1. Iyengar S, et al. J Pharmacol Exp Ther. 2004;311:576–584.


Duloxetine is a Potent Inhibitor of
Persistent Pain in the Formalin Model

Total paw-licking time (late phase)


% of Vehicle Control

Vehicle Vehicle
Less Pain Behavior

100 control
100
control

75 * * 75
*
*
* *
50 50
* * *
#
25 * 25
* *
0 0
1 10 100 1 10 100
Drug (mg/kg i.p. 30 min) Drug (mg/kg i.p. 30 min)
Higher Dose Duloxetine Higher Dose
N=6–9 Venlafaxine
* P < .05 vs vehicle Milnacipran
# Rotorod effects Amitriptyline

1. Iyengar S, et al. J Pharmacol Exp Ther. 2004;311:576–584.


Duloxetine Reverses Mechanical Allodynia in the Spinal L5/L6
Nerve Ligation Model of Neuropathic Pain

Withdrawal Threshold Response (g)

14
* Vehicle control
Less Pain Behavior

12
Duloxetine
10 30 mg/kg p.o.
8 once daily

6 N=4–5

4
* P < .05
2
vs vehicle
0
pre base Day 1
3 hrs

Time
pre = pre-surgery baseline, base = post-surgery baseline

1. Iyengar S, et al. J Pharmacol Exp Ther. 2004;311:576–584.


Contents

♦ Introduction

♦ Mechanism of Action

♦ Efficacy in DPNP

♦ Pharmacokinetics, Safety and Tolerability

♦ Conclusion
Completed Duloxetine Clinical Trials in DPNP

Treatment
Study Treatment Groups duration
(weeks) N

Goldstein et al1 20, 60, 120 mg/day


vs placebo 12 457

Wernicke et al2
60 and 120 mg/day
vs placebo 12 334

Raskin et al3 60 and 120 mg/day


vs placebo 12 348

Maintenance Study4 60 mg/day 8 + 26 115

1-year, open-label safety 120 mg vs


52 867
extension of above studies5 routine care

6-month, open-label 60 mg BID vs


safety study6 28 449
120 mg QD

dstein DJ, et al. Pain. 2005;116:109–118; 2. Wernicke JF, et al. Neurology. 2006;67:1411–1420; 3. Raskin J, et al. Pain Med. 2005;6:346–356;
a on file, Eli Lilly; 5. Poster: Raskin J, et al. 25th American Pain Society (APS) Annual Scientific Meeting; San Antonio, TX; May 3–6, 2006;
6. Raskin J, et al. Pain Med. 2006;7:373–385.
Duloxetine Reduces 24-Hour Average
Pain Severity in DPNP
Pooled data from 3 studies
0.0
Average Pain Severity Score

Placebo
Mean Change in 24-hour

-0.5 (n=330)
Duloxetine
-1.0 * 20 mg QD
Improvement

(n=111)
-1.5
* * Duloxetine
-2.0 * 60 mg QD
* * (n=334)
* * * * *
-2.5 * * *
* * Duloxetine
-3.0
* * * 60 mg BID
* * * (n=333)
* *
-3.5 * P ≤ .05
0 1 2 3 4 5 6 7 8 9 10 11 12 13 vs placebo
Weeks MMRM
♦ A reduction of approximately 2 points or 30% represents a clinically
important difference (mean baseline score was 5.83)

Poster: Raskin J, et al. 25th American Pain Society (APS) Annual Scientific Meeting; San Antonio, TX; May 3–6, 2006.
Duloxetine Improves Response Rates in
DPNP After 12 Weeks†

30% Reduction 50% Reduction


in 24-hour Average Pain in 24-hour Average Pain
80 80
** ** *** *** **
**
60 60 *** *** ***
Patients (%)

* **
40 40
*

20 20

0 0
Study 11 Study 23 Study 31 Study 12 Study 23 Study 34

Placebo
Duloxetine 20 mg QD * P < .05 vs placebo
Duloxetine 60 mg QD ** P < .01 vs placebo
Duloxetine 60 mg BID

Completer analysis *** P < .001 vs placebo
1. Presentation: Raskin J, et al. 41st European Association for the Study of Diabetes (EASD) Annual Meeting; Athens, Greece;
September 12–15, 2005; 2. Goldstein DJ, et al. Pain. 2005;116:109–118; 3. Wernicke JF, et al. Neurology. 2006;67:1411–1420;
4. Raskin J, et al. Pain Med. 2005;6:346–356
60 mg QD Duloxetine Improves Worst
Pain Severity in DPNP
24-hour Worst Pain after 12 Weeks Data from three 12-week efficacy and safety studies

Goldstein1 Wernicke2 Raskin3


Mean Change From Baseline in

0
n=111 n=112 n=106 n=110 n=103 n=114
Placebo
Duloxetine
-1 60 mg QD

-2

-3

** **
*
-4

* P ≤ .05, ** P < .001 MMRM


1. Goldstein DJ, et al. Pain. 2005;116:109–118; 2. Wernicke JF, et al. Neurology. 2006;67:1411–1420; 3. Raskin J, et al. J Pain Med.
2005;6:346–356.
60 mg QD Duloxetine Reduces Pain at
Night in DPNP

Data from three 12-week efficacy and safety studies

Goldstein1 Wernicke2 Raskin3


Mean Change From Baseline in

0
Night Pain After 12 Weeks

n=111 n=112 n=106 n=109 n=103 n=114


Placebo
Duloxetine
-1 60 mg QD

-2

-3
* ** **
-4

* P ≤ .05, ** P < .05


1. Goldstein DJ, et al. Pain. 2005;116:109–118; 2. Wernicke JF, et al. Neurology. 2006;67:1411–1420; 3. Raskin J, et al. J Pain Med.
2005;6:346–356.
Do Improvements in Pain Ratings Correspond
to Patients Actually Feeling Better?

♦ In clinical trials, efficacy is often measured with numerical or categorical


pain scales
♦ Scales used in the Cymbalta DPNP clinical trials include
• 24-hour Average Pain Likert Scores
• Brief Pain Inventory (BPI) Average Pain Score 1
Please rate your pain by circling the one number Pain as bad
No that best describes your pain on average
as you can
Pain
imagine
0 1 2 3 4 5 6 7 8 9 10
♦ Global assessment of improvement assessed in Cymbalta DPNP Clinical
Trials: Patient Global Impression of Improvement (PGI-I) Scale2
Check one box that best describes how you have felt overall since you began taking this medication

1 Very much better 3 A little better 5 A little worse


2 Much better 4 No change 6 Much worse
7 Very much worse

1. Cleeland CS and Ryan KM. Ann Acad Med Singapore. 1994;23:129–138;


2. Guy W. ECDEU Assessment Manual for Psychopharmacology. 1976;217–222:313–331.
Duloxetine DPNP Data – Relationship Between
Change in BPI Pain Score and PGI Category

Patient Global Inventory (PGI) Score Categories

Very
Much Worse/ A Little No A Little Much Very Much
30 Much Worse Worse Change Better Better Better
% Change in BPI Average
Pain Score at Endpoint

10
Improvement

-10
-30
-50
-70
-90
Study 1: Duloxetine 20, 60, 120 mg; placebo (N=457)
Study 2: Duloxetine 60 and 120 mg; placebo (N=334)
Study 3: Duloxetine 60 and 120 mg; placebo (N=348)

Poster: Farrar J, et al. Presented at: 25th American Pain Society (APS) Annual Meeting; San Antonio, TX; May 3–6, 2006.
Duloxetine Decreased the Impact of Pain on Daily
Activity, Function, and Enjoyment of Life (BPI-I)
Pooled data from 3 studies
BPI Avg General Walking Normal Relationship Enjoyment
Score Activity Mood Ability Work With Others Sleep of Life
0
Decreased Impact / Improvement

-0.5
LS Mean Change from
Baseline BPI-I Score

-1

-1.5
*
-2
***

-2.5 ***
*** *** **
*** ***
-3 *** *** *** ***
*** ***
-3.5 ** ***
Placebo * P < .05 vs placebo
Duloxetine 60 mg QD
Duloxetine 60 mg BID ** P < .01 vs placebo
*** P < .001 vs placebo
Armstrong DG, et al. Pain Med. 2007;8(5):410-418.
Maintenance Study Design
Study Study Study Study
Period I Period II Period III Period IV

Screening Acute Therapy Maintenance and Rescue


Taper Phase
Phase Phase Therapy Phase
2 Weeks
5-9 Days 8 Weeks 26 Weeks

120 mg once daily


(nonresponders)*

60 mg once daily

60 mg once daily

60 mg once daily 30 mg once


(responders)* daily
30 mg once daily

Visit 1 2 3 4 5 6 7 8 8 or ED 301

Week -1 0 1 8 12 16 24 34 34 or ED 36

* Responders are defined as patients with a ≥30% reduction from Visit 2 on the BPI 24-hour
average pain item at Visit 4. All other patients are considered nonresponders. Patients who
have been taking duloxetine 60 mg once daily for at least 7 days entered the taper phase
Data on File
Patient Disposition
Enrolled Patients
N = 216

Discontinuations Acute Phase


32 (14.8%)
Reasons for discontinuations
Adverse events 20 (9.3%)
Lack of efficacy 1 (0.5%)
Other 11 (5.1%)

Enter Maintenance Phase Enter Rescue Phase


115 (53.2%) 69 (31.9%)

Stay on DLX60 QD Increase to 120 QD


Discontinuations Completed
N = 103 (89.6%) N = 12 (10.4%)
N = 36 (52.2%) N = 33 (47.8%)
Reasons for discontinuations
Adverse events 5 (7.2%)
Discontinuations Lack of efficacy 24 (34.8%)
N = 26 (25.2%) Other 7 (10.1%)
Reasons for discontinuations Discontinuations
Adverse events 14 (13.6%)
Lack of efficacy
Lack of efficacy 1 (1.0%) 3 (25.0%)
Other 11 (10.7%)

Completed
Completed
N = 9 (75.0%)
N = 77 (74.8%)

Data on File
BPI 24-hour Average Pain Score
BPI Average Pain Score

8
5.85 Acute Duloxetine
LOCF 30/60 mg
6

4 3.36

***
2

0
0 4 8
Weeks on Therapy
*** P ≤ .001
BPI = Brief Pain Inventory;
LOCF = Last observation carried forward

Data on File
BPI 24-hour Average Pain Score
2
MMRM

1.5 Duloxetine
*** 60 mg
1
LS Mean Change

Responders
Improvement

* Duloxetine
0.5
120 mg
0
8 12 16 20 24 28 32 36
-0.5
***
-1 *

-1.5 *** ***


Nonresponders
-2
Weeks on Therapy
Baseline scores at Week 8: Responders = 1.76,
Nonresponders = 5.48
* P ≤ .05 ** P ≤ .01 *** P ≤ .001
Data on File
PGI-Improvement at Endpoint of Maintenance Phase

3.5

2.5
Improvement

1.5

0.5

0
Responders Non-Responders
(60 mg) (120 mg)
Responders defined as ≥30% reduction on BPI average pain during acute phase.
PGI-Improvement = Patient’s Global Impression of Improvement

Data on File
BPI 24-Hour Average Pain Score - 50%
Response Rates at Endpoint

Duloxetine

N n (%)
Responders 114 76 (66.7)
Nonresponders 66 21 (31.8)

N = number of patients with a baseline and at least 1 nonmissing postbaseline;


n = number of patients with a ≥50% pain reduction from Visit 2

Data on File
Contents
♦ Introduction

♦ Mechanism of Action

♦ Efficacy in DPNP

♦ Pharmacokinetics, Safety and Tolerability

♦ Conclusion
Duloxetine Pharmacokinetic Data

♦ Clinical pharmacology1-7:
• t1/2 about 12 hours (in plasma)
• Protein binding >90%
♦ Observed duration of action with once-daily dosing
suggests:
• Therapeutic effects may persist after drug is cleared
• Brain concentration may differ from plasma concentration
♦ No need for dose adjustment based on
• Age, gender and/or smoking
• Excretion data

1. Sharma A, et al. J Clin Pharmacol. 2000;40:161–167; 2. Skinner MH, et al. Clin Pharmacol Ther. 2000;67:129; 3. Takahashi A, et al.
Neuropsychopharmacology. 1994;10 (Supp 3 Pt 1):S651; 4. Johnson JT, et al. Pharm Res. 2001;12 (Supp 9):S387; 5. Cymbalta SPC.
Hepatic Safety Profile of Duloxetine

♦ Metabolized by CYP2D6 and 1A21


• Moderate inhibitor of 2D6
• No clinically significant inhibition of 1A2, 3A, 2C9, or 2C19
• No induction of CYP isoenzymes

♦ In the overall duloxetine clinical trial database


(N=3,372), just three duloxetine-treated patients
met laboratory thresholds predictive of liver injury1

♦ No specific laboratory tests are recommended,


although duloxetine should ordinarily not be prescribed
to patients with substantial alcohol use nor patients
with any hepatic insufficiency1

1. Cymbalta US Prescribing Information.


Discontinuation Rates Due to
Adverse Events
Pooled data from 3 studies
20
*
16.4
Percent of Patients

*
10.8
10

5.3
4.3

0
Placebo Duloxetine Duloxetine Duloxetine
(n=339) 20 mg QD 60 mg QD 60 mg BID
(n=115) (n=344) (n=341)
*P ≤ .05 vs placebo

Poster: Robinson M, et al. Presented at: 8th International Conference on the Mechanisms and Treatment of Neuropathic Pain (ICMTNP);
San Francisco, CA; Nov 5, 2005.
Most Common Adverse Events
Associated with Duloxetine in DPNP
Pooled data from 3 studies
Cymbalta Adverse Events that Occurred 5% and Twice Placebo
50
Placebo (n=339)
Duloxetine 20 mg/day (n=115)
% Incidence of Adverse Events

Duloxetine 60 mg/day (n=334)


40 Duloxetine 120 mg/day (n=341)
Duration*
4 days
5 days
Duration*
30 6 days
23 days *Median duration data:
13 days Placebo
Duration*
15 days Duloxetine (60 mg)
5 days
20 Duloxetine (120 mg)
4 days
6 days

10

0
Nausea Somnolence Dizziness Constipation Sweating Dry Mouth Appetite

Poster: Robinson M, et al. Presented at: 8th International Conference on the Mechanisms and Treatment of Neuropathic Pain (ICMTNP);
San Francisco, CA; Nov 5, 2005.
Most Common Adverse Events as
Reason for Discontinuation
Pooled data from 3 studies
5
Placebo (n=339)
Duloxetine 20 mg/day (n=115)
4 Duloxetine 60 mg/day (n=334)
* *
Percent of Patients

Duloxetine 120 mg/day (n=341)


3.2 3.2
3
*
2.6

2
1.5 1.5
1.2 1.2
0.9 0.9 0.9 0.9
1 0.6
0.3 0.3
0 0 0 0 0 0
0
Nausea Somnolence Dizziness Fatigue Vomiting

*P ≤ .05 vs placebo

Poster: Robinson M, et al. Presented at: 8th International Conference on the Mechanisms and Treatment of Neuropathic Pain (ICMTNP);
San Francisco, CA; Nov 5, 2005.
Clinical Profile of the 3 Most Common
Adverse Events
Pooled data from 3 studies
Onset Median Duration Severity (60 mg/QD)
50 9% 2%
40 Nausea 13%
% Patients Reporting AE (New Cases)

30 Duloxetine 60 mg/day=5 days


20 76%
Duloxetine 120 mg/day=6 days
10 Placebo=4 days
0
1 2 3 4 5 6 7 8 9 10 11 12
50
2%
40 Somnolence 12% 3%
30
Duloxetine 60 mg/day=13 days 85%
20 Duloxetine 120 mg/day=15 days
10 Placebo=23 days
0
1 2 3 4 5 6 7 8 9 10 11 12
50
40 Dizziness 3% 1%
6%
30
20
Duloxetine 60 mg/day=4 days 90%
Duloxetine 120 mg/day=6 days
10 Placebo=5 days
0
1 2 3 4 5 6 7 8 9 10 11 12
Weeks Mild Severe
Placebo (n=339) Cymbalta 60 mg/day (n=334) Cymbalta 120 mg/day (n=341) Moderate None

Poster: Robinson M, et al. Presented at: 8th International Conference on the Mechanisms and Treatment of Neuropathic Pain (ICMTNP);
San Francisco, CA; Nov 5, 2005.
Nausea on Duloxetine is Common, but is
Short-Lived and Mostly Mild or Moderate
Pooled data from 3 studies

Severity of Treatment-emergent Nausea on Duloxetine 60 mg QD

Moderate 9% Severe 2%
Mild 13%

None 76%

♦ Of all the DPNP patients reporting nausea, 92% reported it as mild to moderate
♦ Nausea occurred primarily during the first week of treatment and resolved
rapidly with continued treatment (median duration 5 days)
Poster: Robinson M, et al. Presented at: 8th International Conference on the Mechanisms and Treatment of Neuropathic Pain (ICMTNP);
San Francisco, CA; Nov 5, 2005.
Duloxetine Causes Minimal Long-term
Weight Change in DPNP

Pooled data from three 52-week studies

Mean Weight Change (kg) 2

1.5

0.51
0.5
0.31

Routine Care (n=260) Duloxetine 60 mg BID (n=546)

Poster: Raskin J, et al. 25th American Pain Society (APS) Annual Scientific Meeting; San Antonio, TX; May 3–6, 2006.
Effects on Fasting Glucose Levels and
Hemoglobin A1c

Pooled data from three 52-week studies


1 0.006
*
0.67 **
0.005
Mean Change (mmol/L)

0.5

Mean Change
0.004

0
0.002
0.002
-0.5
-0.64
-1 0
Fasting Glucose Hemoglobin A1c
Routine Care (n=559) Routine Care (n=265)
Duloxetine 60 mg BID (n=269) Duloxetine 60 mg BID (n=548)

♦ Changes are not clinically relevant * P ≤ .001 vs routine care


** P < .001 vs routine care

Poster: Raskin J, et al. 25th American Pain Society (APS) Annual Scientific Meeting; San Antonio, TX; May 3–6, 2006.
No Clinically Significant Long-term
Blood Pressure Changes with Duloxetine
Pooled data from three 52-week studies
Supine Systolic BP Supine Diastolic BP
5
Blood Pressure (mm Hg)

4
Mean Change in

2
*
1.41
1.35 1.38 * P < .05 vs routine care
1

0
-0.15
-1
Routine Care (N=287) Duloxetine 60 mg BID (N=577)

♦ Although there was a statistically significant difference in supine diastolic blood


pressure between duloxetine 60 mg BID and routine care, none of the changes
were considered clinically relevant due to their small magnitude

Poster: Raskin J, et al. 25th American Pain Society (APS) Annual Scientific Meeting; San Antonio, TX; May 3–6, 2006.
No Evidence of an Increased Risk of
Suicidality with Duloxetine
♦ The data from studies of adult patients with MDD demonstrate that
duloxetine significantly reduces the risk of worsening suicidal
ideation and significantly increases the chances for improvement in
ideation for patients who had suicidal ideation at baseline.

♦ The data from studies of adult patients with nonpsychiatric


indications (including SUI, FM and DPNP) support the conclusion
that duloxetine is not associated with the development of suicidal
ideation in depressed or non-depressed adult patients receiving
duloxetine for any of the indications.

NOTE: The duloxetine FDA black box warning about suicidality in adults is derived from a meta-analysis
of all drugs in this class. Although primarily based on studies of MDD, the warning applies to all
indications.

Data on file.
Contents

♦ Introduction

♦ Mechanism of Action

♦ Efficacy in DPNP

♦ Pharmacokinetics, Safety and Tolerability

♦ Conclusion
Summary
♦ DPNP is a relatively widespread condition that significantly
impacts patients’ functioning and quality of life

♦ Duloxetine, a potent and balanced dual 5-HT and NE


reuptake inhibitor, has been shown to significantly
decrease pain in DPNP patients

♦ Following 8 weeks of acute therapy, duloxetine 60 mg once


daily maintained its efficacy in the management of diabetic
peripheral neuropathic pain for 26 weeks.

♦ Duloxetine is safe and well-tolerated

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