A1,
A2,
B,
C1,
C2,
D,
E,
F,
G-H,
I-K,
L,
M,
N,
O,
P1,
P2,
Q-R,
S,
T,
U-V,
W-Z
Cymbalta Side Effects, and Drug Interactions - Duloxetine Hcl
Cymbalta Side Effects, and Drug Interactions - Duloxetine Hcl
SIDE EFFECTS
Cymbalta has been evaluated for safety in 2418 patients diagnosed
with major depressive disorder who participated in multiple-dose premarketing
trials, representing 1099 patient-years of exposure. Among these 2418 Cymbalta-treated
patients, 1139 patients participated in eight 8- or 9-week, placebo-controlled
trials at doses ranging from 40 to 120 mg/day, while the remaining 1279 patients
were followed for up to 1 year in an open-label safety study using flexible
doses from 80 to 120 mg/day. Two placebo-controlled studies with doses of 80
and 120 mg/day had 6-month maintenance extensions. Of these 2418 patients, 993
Cymbalta-treated patients were exposed for at least 180 days and 445 Cymbalta-treated
patients were exposed for at least 1 year.
Cymbalta has also been evaluated for safety in 1074 patients
with diabetic peripheral neuropathy representing 472 patient-years of exposure.
Among these 1074 Cymbalta-treated patients, 568 patients participated in two
12- to 13-week, placebo-controlled trials at doses ranging from 20 to 120 mg/day.
An additional 449 patients were enrolled in an open-label safety study using
120 mg/day for a duration of 6 months. Another 57 patients, originally treated
with placebo, were exposed to Cymbalta for up to 12 months at 60 mg twice daily
in an extension phase. Among these 1074 patients, 484 had 6 months of exposure
to Cymbalta, and 220 had 12 months of exposure.
For both MDD and DPN clinical trials, adverse reactions were
assessed by collecting adverse events, results of physical examinations, vital
signs, weights, laboratory analyses, and ECGs.
Clinical investigators recorded adverse events using descriptive
terminology of their own choosing. To provide a meaningful estimate of the proportion
of individuals experiencing adverse events, grouping similar types of events
into a smaller number of standardized event categories is necessary. In the
tables and tabulations that follow, MedDRA terminology has been used to classify
reported adverse events.
The stated frequencies of adverse events represent the proportion
of individuals who experienced, at least once, a treatment-emergent adverse
event of the type listed. An event was considered treatment-emergent if it occurred
for the first time or worsened while receiving therapy following baseline evaluation.
Events reported during the studies were not necessarily caused by the therapy,
and the frequencies do not reflect investigator impression (assessment) of causality.
The cited figures provide the prescriber with some basis for
estimating the relative contribution of drug and non-drug factors to the adverse
event incidence rate in the population studied. The prescriber should be aware
that the figures in the tables and tabulations cannot be used to predict the
incidence of adverse events in the course of usual medical practice where patient
characteristics and other factors differ from those that prevailed in the clinical
trials. Similarly, the cited frequencies cannot be compared with figures obtained
from other clinical investigations involving different treatments, uses, and
investigators.
Adverse Events Reported as Reasons for Discontinuation of Treatment
in Placebo-Controlled Trials
Major Depressive Disorder
Approximately 10% of the 1139 patients who received Cymbalta
in the MDD placebo-controlled trials discontinued treatment due to an adverse
event, compared with 4% of the 777 patients receiving placebo. Nausea (Cymbalta
1.4%, placebo 0.1%) was the only common adverse event reported as reason for
discontinuation and considered to be drug-related (i.e., discontinuation occurring
in at least 1% of the Cymbalta-treated patients and at a rate of at least twice
that of placebo).
Diabetic Peripheral Neuropathic Pain
Approximately 14% of the 568 patients who received Cymbalta
in the DPN placebo-controlled trials discontinued treatment due to an adverse
event, compared with 7% of the 223 patients receiving placebo. Nausea (Cymbalta
3.5%, placebo 0.4%), dizziness (Cymbalta 1.6%, placebo 0.4%), somnolence (Cymbalta
1.6%, placebo 0%) and fatigue (Cymbalta 1.1%, placebo 0%) were the common adverse
events reported as reasons for discontinuation and considered to be drug-related
(i.e., discontinuation occurring in at least 1% of the Cymbalta-treated patients
and at a rate of at least twice that of placebo).
Adverse Events Occurring at an Incidence of 2% or More Among
Cymbalta-Treated Patients in Placebo-Controlled Trials
Major Depressive Disorder
Table 1 gives the incidence of treatment-emergent adverse events
that occurred in 2% or more of patients treated with Cymbalta in the acute phase
of MDD placebo-controlled trials and with an incidence greater than placebo.
The most commonly observed adverse events in Cymbalta-treated MDD patients (incidence
of 5% or greater and at least twice the incidence in placebo patients) were:
nausea; dry mouth; constipation; decreased appetite; fatigue; somnolence; and
increased sweating (see Table 1).
|
Table 1: Treatment-Emergent Adverse Events Incidence in
MDD Placebo-Controlled Trials1
|
|
System Organ Class / Adverse Event
|
Percentage of Patients Reporting Event
|
|
Cymbalta (N=1139)
|
Placebo (N=777)
|
|
Gastrointestinal Disorders
|
|
Nausea
|
20
|
7
|
|
Dry mouth
|
15
|
6
|
|
Constipation
|
11
|
4
|
|
Diarrhea
|
8
|
6
|
|
Vomiting
|
5
|
3
|
|
Metabolism and Nutrition Disorders
|
|
Appetite decreased2
|
8
|
2
|
|
Investigations
|
|
Weight decreased
|
2
|
1
|
|
General Disorders and Administration Site Conditions
|
|
Fatigue
|
8
|
4
|
|
Nervous System Disorders
|
|
Dizziness
|
9
|
5
|
|
Somnolence
|
7
|
3
|
|
Tremor
|
3
|
1
|
|
Skin and Subcutaneous Tissue Disorders
|
|
Sweating increased
|
6
|
2
|
|
Vascular Disorders
|
|
Hot flushes
|
2
|
1
|
|
Eye Disorders
|
|
Vision blurred
|
4
|
1
|
|
Psychiatric Disorders
|
|
Insomnia3
|
11
|
6
|
|
Anxiety
|
3
|
2
|
|
Libido decreased
|
3
|
1
|
|
Orgasm abnormal4
|
3
|
1
|
|
Reproductive System and Breast Disorders
|
|
Erectile dysfunction5
|
4
|
1
|
|
Ejaculation delayed5
|
3
|
1
|
|
Ejaculatory dysfunction5, 6
|
3
|
1
|
|
1 Events reported by at least 2% of patients
treated with Cymbalta and more often with placebo. The following events
were reported by at least 2% of patients treated with Cymbalta for MDD
and had an incidence equal to or less than placebo: upper abdominal pain,
palpitations, dyspepsia, back pain, arthralgia, headache, pharyngitis,
cough, nasopharyngitis, and upper respiratory tract infection.
|
|
2 Term includes anorexia.
|
|
3 Term includes middle insomnia.
|
|
4 Term includes anorgasmia.
|
|
5 Male patients only.
|
|
6 Term includes ejaculation disorder and ejaculation
failure.
|
Diabetic Peripheral Neuropathic Pain
Table 2 gives the incidence of treatment-emergent adverse events
that occurred in 2% or more of patients treated with Cymbalta in the acute phase
of DPN placebo-controlled trials (doses of 20 to 120 mg/day) and with an incidence
greater than placebo. The most commonly observed adverse events in Cymbalta-treated
DPN patients (incidence of 5% or greater and at least twice the incidence in
placebo patients) were: nausea; somnolence; dizziness; constipation; dry mouth;
hyperhidrosis; decreased appetite; and asthenia (see Table 2).
|
Table 2: Treatment-Emergent Adverse Events Incidence
in DPN Placebo-Controlled Trials1
|
|
System Organ Class /
Adverse Event
|
Percentage of Patients Reporting Event
|
|
Cymbalta 60 mg BID (N=225)
|
Cymbalta 60 mg QD (N=228)
|
Cymbalta 20 mg QD (N=115)
|
Placebo (N=223)
|
|
Gastrointestinal Disorders
|
|
Nausea
|
30
|
22
|
14
|
9
|
|
Constipation
|
15
|
11
|
5
|
3
|
|
Diarrhea
|
7
|
11
|
13
|
6
|
|
Dry mouth
|
12
|
7
|
5
|
4
|
|
Vomiting
|
5
|
5
|
6
|
4
|
|
Dyspepsia
|
4
|
4
|
4
|
3
|
|
Loose stools
|
2
|
3
|
2
|
1
|
|
General Disorders and Administration Site Conditions
|
|
Fatigue
|
12
|
10
|
2
|
5
|
|
Asthenia
|
8
|
4
|
2
|
1
|
|
Pyrexia
|
3
|
1
|
2
|
1
|
|
Infections and Infestations
|
|
Nasopharyngitis
|
9
|
7
|
9
|
5
|
|
Metabolism and Nutrition Disorders
|
|
Decreased appetite
|
11
|
4
|
3
|
<1
|
|
Anorexia
|
5
|
3
|
3
|
<1
|
|
Musculoskeletal and Connective Tissue Disorders
|
|
Muscle cramp
|
4
|
4
|
5
|
3
|
|
Myalgia
|
4
|
1
|
3
|
<1
|
|
Nervous System Disorders
|
|
Somnolence
|
21
|
15
|
7
|
5
|
|
Headache
|
15
|
13
|
13
|
10
|
|
Dizziness
|
17
|
14
|
6
|
6
|
|
Tremor
|
5
|
1
|
0
|
0
|
|
Psychiatric Disorders
|
|
Insomnia
|
13
|
8
|
9
|
7
|
|
Renal and Urinary Disorders
|
|
Pollakiuria
|
5
|
1
|
3
|
2
|
|
Reproductive System and Breast Disorders
|
|
Erectile dysfunction2
|
4
|
1
|
0
|
0
|
|
Respiratory, Thoracic and Mediastinal Disorders
|
|
Cough
|
5
|
3
|
6
|
4
|
|
Pharyngolaryngeal pain
|
6
|
1
|
3
|
1
|
|
Skin and Subcutaneous Tissue Disorders
|
|
Hyperhidrosis
|
8
|
6
|
6
|
2
|
|
1 Events reported by at least 2% of patients
treated with Cymbalta and more often than placebo. The following events
were reported by at least 2% of patients treated with Cymbalta for DPN
and had an incidence equal to or less than placebo: edema peripheral,
influenza, upper respiratory tract infection, back pain, arthralgia, pain
in extremity, and pruritus.
|
|
2 Male patients only.
|
Adverse events seen in men and women were generally similar
except for effects on sexual function (described below). Clinical studies of
Cymbalta did not suggest a difference in adverse event rates in people over
or under 65 years of age. There were too few non-Caucasian patients studied
to determine if these patients responded differently from Caucasian patients.
Effects on Male and Female Sexual Function
Although changes in sexual desire, sexual performance and sexual
satisfaction often occur as manifestations of a psychiatric disorder, they may
also be a consequence of pharmacologic treatment. Reliable estimates of the
incidence and severity of untoward experiences involving sexual desire, performance
and satisfaction are difficult to obtain, however, in part because patients
and physicians may be reluctant to discuss them. Accordingly, estimates of the
incidence of untoward sexual experience and performance cited in product labeling
are likely to underestimate their actual incidence. Table 3 displays the incidence
of sexual side effects spontaneously reported by at least 2% of either male
or female patients taking Cymbalta in MDD placebo-controlled trials.
|
Table 3: Treatment-Emergent Sexual Dysfunction-Related
Adverse Events Incidence in MDD Placebo-Controlled Trials1
|
|
Adverse Event
|
Percentage of Patients Reporting Event
|
|
% Male Patients
|
% Female Patients
|
|
Cymbalta (N=378)
|
Placebo (N=247)
|
Cymbalta (N=761)
|
Placebo (N=530)
|
|
|
Orgasm abnormal2
|
4
|
1
|
2
|
0
|
|
Ejaculatory dysfunction3
|
3
|
1
|
NA
|
NA
|
|
Libido decreased
|
6
|
2
|
1
|
0
|
|
Erectile dysfunction
|
4
|
1
|
NA
|
NA
|
|
Ejaculation delayed
|
3
|
1
|
NA
|
NA
|
|
1 Events reported by at least 2% of patients
treated with Cymbalta and more often than with placebo.
|
|
2 Term includes anorgasmia.
|
|
3 Term includes ejaculation disorder and ejaculation
failure.
|
|
NA=Not applicable.
|
Because adverse sexual events are presumed to be voluntarily
underreported, the Arizona Sexual Experience Scale (ASEX), a validated measure
designed to identify sexual side effects, was used prospectively in 4 MDD placebo-controlled
trials. In these trials, as shown in Table 4 below, patients treated with Cymbalta
experienced significantly more sexual dysfunction, as measured by the total
score on the ASEX, than did patients treated with placebo. Gender analysis showed
that this difference occurred only in males. Males treated with Cymbalta experienced
more difficulty with ability to reach orgasm (ASEX Item 4) than males treated
with placebo. Females did not experience more sexual dysfunction on Cymbalta
than on placebo as measured by ASEX total score. These studies did not, however,
include an active control drug with known effects on female sexual dysfunction,
so that there is no evidence that its effects differ from other antidepressants.
Negative numbers signify an improvement from a baseline level of dysfunction,
which is commonly seen in depressed patients. Physicians should routinely inquire
about possible sexual side effects.
|
Table 4: Mean Change in ASEX Scores by Gender in MDD Placebo-Controlled
Trials
|
| |
Male Patients
|
Female Patients
|
|
Cymbalta (n=175)
|
Placebo (n=83)
|
Cymbalta (n=241)
|
Placebo (n=126)
|
|
ASEX Total (Items 1-5)
|
0.56*
|
-1.07
|
-1.15
|
-1.07
|
|
Item 1 — Sex drive
|
-0.07
|
-0.12
|
-0.32
|
-0.24
|
|
Item 2 — Arousal
|
0.01
|
-0.26
|
-0.21
|
-0.18
|
|
Item 3 — Ability to achieve erection (men); Lubrication(women)
|
0.03
|
-0.25
|
-0.17
|
-0.18
|
|
Item 4 — Ease of reaching orgasm
|
0.40**
|
-0.24
|
-0.09
|
-0.13
|
|
Item 5 — Orgasm satisfaction
|
0.09
|
-0.13
|
-0.11
|
-0.17
|
|
n=Number of patients with non-missing change score for
ASEX total.
|
|
*p=0.013 versus placebo.
|
|
**p<0.001 versus placebo.
|
Urinary Hesitation
Cymbalta is in a class of drugs known to affect urethral resistance.
If symptoms of urinary hesitation develop during treatment with Cymbalta, consideration
should be given to the possibility that they might be drug-related.
Laboratory Changes
Cymbalta treatment, for up to 9-weeks in MDD or 13-weeks in
DPN placebo-controlled clinical trials, was associated with small mean increases
from baseline to endpoint in ALT, AST, CPK, and alkaline phosphatase; infrequent,
modest, transient, abnormal values were observed for these analytes in Cymbalta-treated
patients when compared with placebo-treated patients (see PRECAUTIONS).
Vital Sign Changes
Cymbalta treatment, for up to 9-weeks in MDD placebo-controlled
clinical trials of 40 to 120 mg daily doses caused increases in blood pressure,
averaging 2 mm Hg systolic and 0.5 mm Hg diastolic compared to placebo and an
increase in the incidence of at least one measurement of systolic blood pressure
over 140 mm Hg (see PRECAUTIONS).
Cymbalta treatment, for up to 9-weeks in MDD placebo-controlled clinical trials
and for up to 13-weeks in DPN placebo-controlled trials caused a small increase
in heart rate compared to placebo of about 2 beats per minute.
Weight Changes
In MDD placebo-controlled clinical trials, patients treated
with Cymbalta for up to 9-weeks experienced a mean weight loss of approximately
0.5 kg, compared with a mean weight gain of approximately 0.2 kg in placebo-treated
patients. In DPN placebo-controlled clinical trials, patients treated with Cymbalta
for up to 13-weeks experienced a mean weight loss of approximately 1.1 kg, compared
with a mean weight gain of approximately 0.2 kg in placebo-treated patients.
Electrocardiogram Changes
Electrocardiograms were obtained from 321 Cymbalta-treated
patients with major depressive disorder and 169 placebo-treated patients in
clinical trials lasting up to 8-weeks. The rate-corrected QT (QTc) interval
in Cymbalta-treated patients did not differ from that seen in placebo-treated
patients. No clinically significant differences were observed for QT, PR, and
QRS intervals between Cymbalta-treated and placebo-treated patients.
Electrocardiograms were obtained from 528 Cymbalta-treated
patients with DPN and 205 placebo-treated patients in clinical trials lasting
up to 13-weeks. The rate-corrected QT (QTc) interval in Cymbalta-treated patients
did not differ from that seen in placebo-treated patients. No clinically significant
differences were observed for QT, PR, QRS, or QTc measurements between Cymbalta-treated
and placebo-treated patients.
Other Adverse Events Observed During the Premarketing Evaluation
of Cymbalta for MDD and the Pain of DPN
Following is a list of modified MedDRA terms that reflect treatment-emergent
adverse events as defined in the introduction to the ADVERSE
REACTIONS section reported by patients treated with Cymbalta at multiple
doses throughout the dose range studied during any phase of a trial within the
premarketing database. The events included are those not already listed elsewhere
in ADVERSE REACTIONS and not considered in
the WARNINGS and PRECAUTIONS
sections, that were reported with an incidence of greater than or equal to 0.05%
and by more than one patient, are not common as background events and were considered
possibly drug related (e.g., because of the drug’s pharmacology) or potentially
important.
It is important to emphasize that, although the events reported
occurred during treatment with Cymbalta, they were not necessarily caused by
it. Events are further categorized by body system and listed in order of decreasing
frequency according to the following definitions: frequent adverse events are
those occurring in at least 1/100 patients (only those not already listed in
the tabulated results from placebo-controlled trials appear in this listing);
infrequent adverse events are those occurring in 1/100 to 1/1000 patients; rare
events are those occurring in fewer than 1/1000 patients.
Blood and Lymphatic System Disorders
Infrequent: anemia, leukopenia, increased white blood
cell count, lymphadenopathy, and thrombocytopenia.
Cardiac Disorders
Infrequent: atrial fibrillation, bundle branch block
right, cardiac failure, cardiac failure congestive, coronary artery disease,
and myocardial infarction.
Eye Disorders
Infrequent: diplopia, glaucoma, keroconjunctivitis sicca,
macular degeneration, maculopathy, photopsia, and retinal detachment.
Gastrointestinal Disorders
Frequent: gastritis; Infrequent: apthous stomatitis,
blood in stool, colitis, diverticulitis, dysphagia, esophageal stenosis acquired,
gastric irritation, gastric ulcer, gingivitis, impaired gastric emptying, irritable
bowel syndrome, lower abdominal pain, and melena.
General Disorders and Administration Site Conditions
Frequent: rigors;
Infrequent: edema, feeling jittery, influenza-like illness,
and thirst.
Hepato-biliary Disorders
Infrequent: hepatic steatosis.
Investigations
Frequent: weight increased; Infrequent: blood
cholesterol increased, blood creatinine increased, and urine output decreased.
Metabolism and Nutrition Disorders
Frequent: hypoglycemia and increased appetite; Infrequent:
dehydration, dyslipidemia, hypercholesterolemia, hyperlipidemia, and hypertriglyceridemia.
Musculoskeletal and Connective Tissue Disorders
Infrequent: muscular weakness.
Nervous System Disorders
Frequent: hypoesthesia; Infrequent: ataxia and
dysarthria.
Psychiatric Disorders
Frequent: initial insomnia, irritability, lethargy,
nervousness, nightmare, restlessness, and sleep disorder; Infrequent:
completed suicide, mania, mood swings, pressure of speech, sluggishness, and
suicide attempt.
Renal and Urinary Disorders
Frequent: dysuria; Infrequent: micturition urgency,
nephropathy, urinary hesitation, urinary incontinence, urinary retention, and
urine flow decreased.
Respiratory, Thoracic and Mediastinal Disorders
Infrequent: oropharyngeal swelling.
Skin and Subcutaneous Tissue Disorders
Frequent: night sweats, pruritus, rash, and skin ulcer;
Infrequent: acne, alopecia, cold sweat, ecchymosis, eczema, erythema,
erythematous rash, exfoliative dermatitis, face edema, hyperkeratosis, increased
tendency to bruise, photosensitivity reaction, and pruritic rash.
Vascular Disorders
Infrequent: hypertensive crisis, peripheral edema, and
phlebitis.
DRUG ABUSE AND DEPENDENCE
Controlled Substance Class
Duloxetine is not a controlled substance.
Physical and Psychological Dependence
In animal studies, duloxetine did not demonstrate barbiturate-like
(depressant) abuse potential. In drug dependence studies, duloxetine did not
demonstrate dependence-producing potential in rats.
While Cymbalta has not been systematically studied in humans
for its potential for abuse, there was no indication of drug-seeking behavior
in the clinical trials. However, it is not possible to predict on the basis
of premarketing experience the extent to which a CNS active drug will be misused,
diverted, and/or abused once marketed. Consequently, physicians should carefully
evaluate patients for a history of drug abuse and follow such patients closely,
observing them for signs of misuse or abuse of Cymbalta (e.g., development of
tolerance, incrementation of dose, drug-seeking behavior).
DRUG INTERACTIONS
(also see CLINICAL PHARMACOLOGY,
Drug-Drug Interactions)
Potential for Other Drugs to Affect Cymbalta
Both CYP1A2 and CYP2D6 are responsible for duloxetine metabolism.
Inhibitors of CYP1A2
Concomitant use of duloxetine with fluvoxamine, an inhibitor
of CYP1A2, results in approximately a 6-fold increase in AUC and about a 2.5-fold
increase in Cmax of duloxetine. Some quinolone antibiotics would
be expected to have similar effects and these combinations should be avoided.
Inhibitors of CYP2D6
Because CYP2D6 is involved in duloxetine metabolism, concomitant
use of duloxetine with potent inhibitors of CYP2D6 may result in higher concentrations
of duloxetine. Paroxetine (20 mg QD) increased the concentration of duloxetine
(40 mg QD) by about 60%, and greater degrees of inhibition are expected with
higher doses of paroxetine. Similar effects would be expected with other potent
CYP2D6 inhibitors (e.g., fluoxetine, quinidine).
Potential for Duloxetine to Affect Other Drugs
Drugs Metabolized by CYP1A2
In vitro drug interaction studies demonstrate that duloxetine
does not induce CYP1A2 activity, and it is unlikely to have a clinically significant
effect on the metabolism of CYP1A2 substrates (see CLINICAL
PHARMACOLOGY, Drug Interactions).
Drugs Metabolized by CYP2D6
Duloxetine is a moderate inhibitor of CYP2D6. When duloxetine
was administered (at a dose of 60 mg BID) in conjunction with a single 50-mg
dose of desipramine, a CYP2D6 substrate, the AUC of desipramine increased 3-fold.
Therefore, co-administration of Cymbalta with other drugs that are extensively
metabolized by this isozyme and which have a narrow therapeutic index, including
certain antidepressants (tricyclic antidepressants [TCAs], such as nortriptyline,
amitriptyline, and imipramine), phenothiazines and Type 1C antiarrhythmics (e.g.,
propafenone, flecainide), should be approached with caution. Plasma TCA concentrations
may need to be monitored and the dose of the TCA may need to be reduced if a
TCA is co-administered with Cymbalta. Because of the risk of serious ventricular
arrhythmias and sudden death potentially associated with elevated plasma levels
of thioridazine, Cymbalta and thioridazine should not be co-administered.
Drugs Metabolized by CYP3A
Results of in vitro studies demonstrate that duloxetine
does not inhibit or induce CYP3A activity (see CLINICAL
PHARMACOLOGY, Drug Interactions).
Cymbalta May Have a Clinically Important Interaction with the
Following Other Drugs:
Alcohol
When Cymbalta and ethanol were administered several hours apart
so that peak concentrations of each would coincide, Cymbalta did not increase
the impairment of mental and motor skills caused by alcohol.
In the Cymbalta clinical trials database, three Cymbalta-treated
patients had liver injury as manifested by ALT and total bilirubin elevations,
with evidence of obstruction. Substantial intercurrent ethanol use was present
in each of these cases, and this may have contributed to the abnormalities seen
(see PRECAUTIONS, Hepatotoxicity).
CNS Acting Drugs
Given the primary CNS effects of Cymbalta, it should be used
with caution when it is taken in combination with or substituted for other centrally
acting drugs, including those with a similar mechanism of action.
Potential for Interaction with Drugs that Affect Gastric Acidity
Cymbalta has an enteric coating that resists dissolution until
reaching a segment of the gastrointestinal tract where the pH exceeds 5.5. In
extremely acidic conditions, Cymbalta, unprotected by the enteric coating, may
undergo hydrolysis to form naphthol. Caution is advised in using Cymbalta in
patients with conditions that may slow gastric emptying (e.g., some diabetics).
Drugs that raise the gastrointestinal pH may lead to an earlier release of duloxetine.
However, co-administration of Cymbalta with aluminum- and magnesium-containing
antacids (51 mEq) or Cymbalta with famotidine, had no significant effect on
the rate or extent of duloxetine absorption after administration of a 40-mg
oral dose. It is unknown whether the concomitant administration of proton pump
inhibitors affects duloxetine absorption.
Monoamine Oxidase Inhibitors
See CONTRAINDICATIONS
and WARNINGS.
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