Lunesta Letter - Haymarket Media Group

PRESCRIBING ALERT
Dear Healthcare Professional,
At MPR, we strive to bring you important drug information in a concise and timely fashion.
In keeping with this goal, we are pleased to bring you this PRESCRIBING ALERT announcing
the FDA approval of a new indication for Cymbalta ® (duloxetine hydrochloride) from Eli Lilly
and Company. In addition to prior approvals for the acute and maintenance treatment of major
depressive disorder (MDD), the management of diabetic peripheral neuropathic pain, and the
acute treatment of generalized anxiety disorder, Cymbalta is now approved for the management
of fibromyalgia.
Fibromyalgia is a disorder characterized by chronic widespread pain and tenderness. Fibromyalgia
is estimated to affect 2%-4% of the population of the United States, the majority being women. 1
Two studies were conducted to evaluate the efficacy of Cymbalta in patients with fibromyalgia.
Efficacy was assessed at week 12 in one study, and at week 15 in a second study. Compared with
placebo, Cymbalta (60 mg/day) significantly reduced Brief Pain Inventory (BPI) 24-hr average pain
from baseline to endpoint in individual and pooled data for the 2 studies. 2a Some patients taking
Cymbalta also experienced significant improvement beginning at week 1 in BPI 24-hr average pain
score. 2b
The most commonly reported adverse events for fibromyalgia (≥5% and at least twice placebo) for
Cymbalta vs placebo in controlled clinical trials for the management of fibromyalgia were: nausea
(29% vs 11%), dry mouth (18% vs 5%), constipation (15% vs 4%), somnolence ‡ (11% vs 3%),
decreased appetite § (11% vs 2%), increased sweating (7% vs 1%), and agitation ›› (6% vs 2%). 3
In the placebo-controlled clinical trials, the overall discontinuation rates due to adverse events for
Cymbalta vs placebo were: 19.5% vs 11.8%. The common adverse events reported as a reason for
discontinuation (≥1%) and considered to be drug related were: nausea (1.9% vs 0.7%), somnolence ‡
(1.5% vs 0%), and fatigue (1.3% vs 0.2%). 3
‡ Somnolence also contains: sedation and hypersomnia
§ Decreased appetite also contains: anorexia
›› Agitation also contains: feeling jittery, nervousness, restlessness, tension, and psychomotor agitation
More information about the use of Cymbalta is available in the current edition of MPR.
Please see Important Safety Information, including Boxed Warning, for Cymbalta on the reverse
side and enclosed full Prescribing Information.
Sincerely,
Tammy Chernin, RPh
Director,
MPR Custom Programs
References:
www.PrescribingReference.com
1. American College of Rheumatology. Fibromyalgia. Available at: http://www.rheumatology.org/public/factsheets/
fibromya_new.asp. Accessed April 1, 2008.
2. Data on file, Lilly Research Laboratories: a: CYM20080508C; b: CYM20080508F.
3. Cymbalta full Prescribing Information.
DD-50803-0

Important Safety Information
Cymbalta is indicated in adults for:
• The acute and maintenance treatment of major depressive disorder (MDD)
• The acute treatment of generalized anxiety disorder (GAD)
• The management of diabetic peripheral neuropathic pain (DPNP)
• The management of fibromyalgia (FM)
Suicidality and Antidepressant Drugs—Antidepressants increased the risk compared to placebo of suicidal thinking and
behavior (suicidality) in children, adolescents, and young adults in short-term studies of major depressive disorder (MDD)
and other psychiatric disorders. Anyone considering the use of Cymbalta or any other antidepressant in a child, adolescent,
or young adult must balance this risk with the clinical need. Short-term studies did not show an increase in the risk
of suicidality with antidepressants compared to placebo in adults beyond age 24; there was a reduction in risk with antidepressants
compared to placebo in adults aged 65 and older. Depression and certain other psychiatric disorders are themselves
associated with increases in the risk of suicide. Patients of all ages who are started on antidepressant therapy should
be monitored appropriately and observed closely for clinical worsening, suicidality, or unusual changes in behavior.
Families and caregivers should be advised of the need for close observation and communication with the prescriber.
Cymbalta is not approved for use in pediatric patients.
Contraindications
• Cymbalta should not be used in combination with MAOIs and is contraindicated for at least 14 days after discontinuation of an
MAOI. After stopping therapy on Cymbalta, at least 5 days should be allowed before starting an MAOI.
• Cymbalta was associated with an increased risk of mydriasis; therefore, it should not be used in patients with uncontrolled
narrow-angle glaucoma and used cautiously in patients with controlled narrow-angle glaucoma.
• Clinical Worsening and Suicide Risk
All patients being treated with antidepressants for any indication should be monitored appropriately and observed closely for
clinical worsening, suicidality, and unusual changes in behavior, especially within the first few months of treatment and when
changing the dose. Consider changing the therapeutic regimen, including possibly discontinuing the medication in patients whose
depression is persistently worse or includes symptoms of anxiety, agitation, panic attacks, insomnia, irritability, hostility, aggressiveness,
impulsivity, akathisia (psychomotor restlessness), hypomania, mania, or suicidality that are severe, abrupt in onset, or
were not part of the patient’s presenting symptoms. If discontinuing treatment, the medication should be tapered. Families and
caregivers of patients being treated with antidepressants for any indication should be alerted about the need to monitor patients.
• Hepatic failure, sometimes fatal, has been reported in patients treated with Cymbalta. Cymbalta should be discontinued in
patients who develop jaundice or other evidence of clinically significant liver dysfunction and should not be resumed unless
another cause can be established.
• Because it is possible that Cymbalta and alcohol may interact to cause liver injury or that Cymbalta may aggravate preexisting
liver disease, Cymbalta should ordinarily not be prescribed to patients with substantial alcohol use or evidence of
chronic liver disease.
• Orthostatic hypotension and syncope have been reported with therapeutic doses of Cymbalta. Consideration should be given to
discontinuing Cymbalta in patients who experience symptomatic orthostatic hypotension and/or syncope.
• Development of a potentially life-threatening serotonin syndrome may occur with SNRIs and SSRIs, including Cymbalta treatment,
particularly with concomitant use of serotonergic drugs, including triptans. Concomitant use is not recommended.
• SSRIs and SNRIs, including Cymbalta, may increase the risk of bleeding events. Patients should be cautioned about the risk of
bleeding associated with concomitant use of Cymbalta and NSAIDs, aspirin, warfarin, or other drugs that affect coagulation.
• On abrupt or tapered discontinuation, spontaneous reports of adverse events, some of which may be serious, have been
reported during the marketing of SSRIs and SNRIs. A gradual reduction in dose rather than abrupt cessation is recommended
when possible.
• As with many antidepressants, Cymbalta should be used cautiously in patients with a history of mania or with a history of a
seizure disorder.
• In clinical trials across indications relative to placebo, treatment with Cymbalta was associated with mean increases of up to
2.3 mm Hg systolic and diastolic blood pressure. There was no significant difference in the frequency of sustained (3 consecutive
visits) elevated blood pressure. Blood pressure should be measured prior to initiating treatment and periodically measured
throughout treatment.
• Coadministration of Cymbalta with potent CYP1A2 inhibitors or thioridazine should be avoided.
• SSRIs and SNRIs, including Cymbalta, have been associated with cases of clinically significant hyponatremia that appeared to
be reversible when Cymbalta was discontinued. Elderly patients may be at greater risk of developing hyponatremia with SSRIs
and SNRIs.
• The effect that alterations in gastric motility may have on the stability of the enteric coating of Cymbalta is unknown. As duloxetine
is rapidly hydrolyzed in acidic media to naphthol, caution is advised in using Cymbalta in patients with conditions that may
slow gastric emptying (eg, some diabetics).
• Cymbalta should ordinarily not be administered to patients with any hepatic insufficiency or patients with end-stage renal disease
(requiring dialysis) or severe renal impairment (creatinine clearance

Cymbalta ® PRESCRIBING ALERT
Delayed-Release Capsules
(duloxetine HCI)
Company: Eli Lilly and Company
Pharmacologic class: Serotonin and
norepinephrine reuptake inhibitor
Indications: Management of fibromyalgia.
Management of diabetic peripheral
neuropathic pain (DPNP).Acute and
maintenance treatment of major depressive
disorder (MDD).Acute treatment of
generalized anxiety disorder (GAD).
Dosing: Fibromyalgia: 30-60 mg.*
DPNP: 60 mg/day (once daily).
MDD Acute: 40 mg/day (20 mg twice daily)
to 60 mg/day (once daily or as 30 mg twice
daily).
MDD Maintenance: 60 mg/day.
GAD Acute: 60 mg/day (once daily).
Now approved for the
management of fibromyalgia
How supplied: Caps (20 mg,30 mg,
60 mg)—100
*Treatment should begin at 30 mg once daily for
1 week, to allow patients to adjust to the medication
before increasing to 60 mg once daily.
In fibromyalgia, Cymbalta demonstrated significant and potent
pain relief
Cymbalta has demonstrated efficacy for patients with fibromyalgia
CYMBALTA 60 MG/DAY IN FIBROMYALGIA CLINICAL TRIALS:
1a †
BPI 24-HOUR AVERAGE PAIN AT ENDPOINT
Improvement
% Change in Mean BPI 24-hour Average Pain
Score Baseline to Endpoint
100
60
50
40
30
20
10
0
*
Cymbalta 60 mg/day (N=260)
Placebo (N=257)
2 pooled studies (LOCF)
* P

Cymbalta provides rapid relief of fibromyalgia pain
• Cymbalta provided rapid pain relief in patients with pain from fibromyalgia 1c
• A statistically significant reduction in pain over placebo was seen as early as
week 1 in fibromyalgia trials 1c
Safety and tolerability
Nausea
Dry mouth
Constipation
Somnolence *
Decreased appetite †
Increased sweating
Agitation ‡
PRESCRIBING ALERT
CYMBALTA 60 MG/DAY IN FIBROMYALGIA CLINICAL TRIALS:
EFFECT ON BPI 24-HOUR AVERAGE PAIN SCORE 1c†
Improvement
% Change in Mean BPI 24-hour Average Pain Score
0
-5
-10
-15
-20
-25
-30
-35
-40
-45
Weeks on Study Drug
0 2 4 6 8 10 12
*
*
*
MOST COMMON ADVERSE EVENTS IN FIBROMYALGIA STUDIES 1d,2
Cymbalta
20-120 mg/day
(N=876)
(%)
29
18
15
11
11
7
6
*
Placebo
(N=535)
(%)
*
Somnolence also contains: sedation and hypersomnia
†
Decreased appetite also contains: anorexia
‡
Agitation also contains: feeling jittery, nervousness, restlessness, tension, and psychomotor agitation
Adverse events reported at a rate of ≥5% and at least twice the rate of placebo
Data are from two 3-month and two 6-month placebo-controlled studies
Overall discontinuation rate due to adverse events: Cymbalta (20-120 mg/day): 20% vs placebo: 12% 2
Please see Important Safety Information, including Boxed Warning,
for Cymbalta and enclosed full Prescribing Information.
*
*
11
5
4
3
2
1
2
*
Cymbalta 60 mg/day (N=116)
Placebo (N=118)
One outpatient study (MMRM)
* P≤.05, Cymbalta vs placebo
In a separate study, % change in
mean BPI 24-hour average pain
score improvement was measured
at weeks 1, 2, 4, 7, 11, and 151c – Cymbalta 60 mg/day was not
significantly different vs placebo
at weeks 7, 11, and 15
† As measured by an 11-point
Likert Scale
Mean baseline score 6.41b BPI= Brief Pain Inventory
MMRM=Mixed-effects Models
Repeated Measures analysis
% of patients on Cymbalta
who discontinued due
to treatment-emergent
adverse events 1d
1.9
0.1
0.3
2.1
0.1
0.5
0.7
(continued on next page)

Important Safety Information
PRESCRIBING ALERT
Cymbalta is indicated in adults for:
• The acute and maintenance treatment of major depressive disorder (MDD)
• The acute treatment of generalized anxiety disorder (GAD)
• The management of diabetic peripheral neuropathic pain (DPNP)
• The management of fibromyalgia (FM)
Suicidality and Antidepressant Drugs—Antidepressants increased the risk compared to
placebo of suicidal thinking and behavior (suicidality) in children, adolescents, and young
adults in short-term studies of major depressive disorder (MDD) and other psychiatric disorders.
Anyone considering the use of Cymbalta or any other antidepressant in a child, adolescent,
or young adult must balance this risk with the clinical need. Short-term studies did
not show an increase in the risk of suicidality with antidepressants compared to placebo in
adults beyond age 24; there was a reduction in risk with antidepressants compared to placebo
in adults aged 65 and older. Depression and certain other psychiatric disorders are themselves
associated with increases in the risk of suicide. Patients of all ages who are started on
antidepressant therapy should be monitored appropriately and observed closely for clinical
worsening, suicidality, or unusual changes in behavior. Families and caregivers should be
advised of the need for close observation and communication with the prescriber. Cymbalta
is not approved for use in pediatric patients.
Contraindications
• Cymbalta should not be used in combination with MAOIs and is contraindicated for at
least 14 days after discontinuation of an MAOI. After stopping therapy on Cymbalta, at
least 5 days should be allowed before starting an MAOI.
• Cymbalta was associated with an increased risk of mydriasis; therefore, it should not be
used in patients with uncontrolled narrow-angle glaucoma and used cautiously in
patients with controlled narrow-angle glaucoma.
• Clinical Worsening and Suicide Risk
All patients being treated with antidepressants for any indication should be monitored
appropriately and observed closely for clinical worsening, suicidality, and unusual
changes in behavior, especially within the first few months of treatment and when changing
the dose. Consider changing the therapeutic regimen, including possibly discontinuing
the medication in patients whose depression is persistently worse or includes symptoms
of anxiety, agitation, panic attacks, insomnia, irritability, hostility, aggressiveness,
impulsivity, akathisia (psychomotor restlessness), hypomania, mania, or suicidality that
are severe, abrupt in onset, or were not part of the patient’s presenting symptoms. If discontinuing
treatment, the medication should be tapered. Families and caregivers of
patients being treated with antidepressants for any indication should be alerted about
the need to monitor patients.
• Hepatic failure, sometimes fatal, has been reported in patients treated with Cymbalta.
Cymbalta should be discontinued in patients who develop jaundice or other evidence of
clinically significant liver dysfunction and should not be resumed unless another cause
can be established.
• Because it is possible that Cymbalta and alcohol may interact to cause liver injury or that
Cymbalta may aggravate pre-existing liver disease, Cymbalta should ordinarily not be
prescribed to patients with substantial alcohol use or evidence of chronic liver disease.
• Orthostatic hypotension and syncope have been reported with therapeutic doses of
Cymbalta. Consideration should be given to discontinuing Cymbalta in patients who
experience symptomatic orthostatic hypotension and/or syncope.
• Development of a potentially life-threatening serotonin syndrome may occur with
SNRIs and SSRIs, including Cymbalta treatment, particularly with concomitant use of
serotonergic drugs, including triptans. Concomitant use is not recommended.
(continued on back)

PRESCRIBING ALERT
• SSRIs and SNRIs, including Cymbalta, may increase the risk of bleeding events. Patients
should be cautioned about the risk of bleeding associated with concomitant use of
Cymbalta and NSAIDs, aspirin, warfarin, or other drugs that affect coagulation.
• On abrupt or tapered discontinuation, spontaneous reports of adverse events, some of
which may be serious, have been reported during the marketing of SSRIs and SNRIs. A
gradual reduction in dose rather than abrupt cessation is recommended when possible.
• As with many antidepressants, Cymbalta should be used cautiously in patients with a
history of mania or with a history of a seizure disorder.
• In clinical trials across indications relative to placebo, treatment with Cymbalta was associated
with mean increases of up to 2.3 mm Hg systolic and diastolic blood pressure.
There was no significant difference in the frequency of sustained (3 consecutive visits)
elevated blood pressure. Blood pressure should be measured prior to initiating treatment
and periodically measured throughout treatment.
• Coadministration of Cymbalta with potent CYP1A2 inhibitors or thioridazine should be
avoided.
• SSRIs and SNRIs, including Cymbalta, have been associated with cases of clinically significant
hyponatremia that appeared to be reversible when Cymbalta was discontinued.
Elderly patients may be at greater risk of developing hyponatremia with SSRIs and SNRIs.
• The effect that alterations in gastric motility may have on the stability of the enteric coating of
Cymbalta is unknown.As duloxetine is rapidly hydrolyzed in acidic media to naphthol, caution
is advised in using Cymbalta in patients with conditions that may slow gastric emptying
(eg, some diabetics).
• Cymbalta should ordinarily not be administered to patients with any hepatic insufficiency
or patients with end-stage renal disease (requiring dialysis) or severe renal impairment
(creatinine clearance