should be used with caution in patients with a history of mania or a
diagnosis of bipolar disorder, and/or seizures.
has been reported in association with duloxetine, therefore, caution
should be used when prescribing Cymbalta to patients with increased
intraocular pressure, or those at risk of acute narrow-angle
pressure and heart rate
has been associated with an increase in blood pressure and clinically
significant hypertension in some patients. This may be due to the
noradrenergic effect of duloxetine. Cases of hypertensive crisis have
been reported with duloxetine, especially in patients with
pre-existing hypertension. Therefore, in patients with known
hypertension and/or other cardiac disease, blood pressure monitoring
is recommended, especially during the first month of treatment.
Duloxetine should be used with caution in patients whose conditions
could be compromised by an increased heart rate or by an increase in
blood pressure. Caution should also be exercised when duloxetine is
used with medicinal products that may impair its metabolism. For
patients who experience a sustained increase in blood pressure while
receiving duloxetine either dose reduction or gradual discontinuation
should be considered. In patients with uncontrolled hypertension
duloxetine should not be initiated.
plasma concentrations of duloxetine occur in patients with severe
renal impairment on haemodialysis (creatinine clearance <30
ml/min). For patients with severe renal impairment, see section 4.3.
See section 4.2 for information on patients with mild or moderate
with other serotonergic agents, serotonin syndrome, a potentially
life-threatening condition, may occur with duloxetine treatment,
particularly with concomitant use of other serotonergic agents
(including SSRIs, SNRIs tricyclic antidepressants or triptans), with
agents that impair metabolism of serotonin such as MAOIs, or with
antipsychotics or other dopamine antagonists that may affect the
serotonergic neurotransmitter systems.
syndrome symptoms may include mental status changes (e.g., agitation,
hallucinations, coma), autonomic instability (e.g., tachycardia,
labile blood pressure, hyperthermia), neuromuscular aberrations (e.g.
hyperreflexia, incoordination) and/or gastrointestinal symptoms
(e.g., nausea, vomiting, diarrhoea).
concomitant treatment with duloxetine and other serotonergic agents
that may affect the serotonergic and/or dopaminergic neurotransmitter
systems is clinically warranted, careful observation of the patient
is advised, particularly during treatment initiation and dose
reactions may be more common during concomitant use of Cymbalta and
herbal preparations containing St John’s wort (Hypericum
Depressive Disorder and Generalised Anxiety Disorder: Depression is
associated with an increased risk of suicidal thoughts, self harm and
suicide (suicide-related events). This risk persists until
significant remission occurs. As improvement may not occur during the
first few weeks or more of treatment, patients should be closely
monitored until such improvement occurs. It is general clinical
experience that the risk of suicide may increase in the early stages
psychiatric conditions for which Cymbalta is prescribed can also be
associated with an increased risk of suicide-related events. In
addition, these conditions may be co-morbid with major depressive
disorder. The same precautions observed when treating patients with
major depressive disorder should therefore be observed when treating
patients with other psychiatric disorders.
with a history of suicide-related events or those exhibiting a
significant degree of suicidal thoughts prior to commencement of
treatment are known to be at greater risk of suicidal thoughts or
suicidal behaviour, and should receive careful monitoring during
treatment. A meta-analysis of placebo-controlled clinical trials of
antidepressant medicinal products in psychiatric disorders showed an
increased risk of suicidal behaviour with antidepressants compared to
placebo in patients less than 25 years old.
of suicidal thoughts and suicidal behaviours have been reported
during duloxetine therapy or early after treatment discontinuation.
supervision of patients and in particular those at high risk should
accompany medicinal product therapy especially in early treatment and
following dose changes. Patients (and caregivers of patients) should
be alerted about the need to monitor for any clinical worsening,
suicidal behaviour or thoughts and unusual changes in behaviour and
to seek medical advice immediately if these symptoms present.
Peripheral Neuropathic Pain:
As with other medicinal products with similar pharmacological action
(antidepressants), isolated cases of suicidal ideation and suicidal
behaviours have been reported during duloxetine therapy or early
after treatment discontinuation. Concerning risk factors for
suicidality in depression, see above. Physicians should encourage
patients to report any distressing thoughts or feelings at any time.
in children and adolescents under 18 years of age
should not be used in the treatment of children and adolescents under
the age of 18 years. Suicide-related behaviours (suicide attempts and
suicidal thoughts), and hostility (predominantly aggression,
oppositional behaviour and anger), were more frequently observed in
clinical trials among children and adolescents treated with
antidepressants compared to those treated with placebo. If, based on
clinical need, a decision to treat is nevertheless taken, the patient
should be carefully monitored for the appearance of suicidal
symptoms. In addition, long-term safety data in children and
adolescents concerning growth, maturation and cognitive and
behavioural development are lacking.
have been reports of bleeding abnormalities, such as ecchymoses,
purpura and gastrointestinal haemorrhage with selective serotonin
reuptake inhibitors (SSRIs) and serotonin/noradrenaline reuptake
inhibitors (SNRIs), including duloxetine. Duloxetine may increase the
risk of postpartum haemorrhage. Caution is advised in patients taking
anticoagulants and/or medicinal products known to affect platelet
function (e.g. NSAIDs or acetylsalicylic acid (ASA)), and in patients
with known bleeding tendencies.
has been reported when administering Cymbalta, including cases with
serum sodium lower than 110 mmol/l. Hyponatraemia may be due to a
syndrome of inappropriate anti-diuretic hormone secretion (SIADH).
The majority of cases of hyponatraemia were reported in the elderly,
especially when coupled with a recent history of, or condition
pre-disposing to, altered fluid balance. Caution is required in
patients at increased risk for hyponatraemia, such as elderly,
cirrhotic, or dehydrated patients or patients treated with diuretics.
symptoms when treatment is discontinued are common, particularly if
discontinuation is abrupt. In clinical trials adverse events seen on
abrupt treatment discontinuation occurred in approximately 45% of
patients treated with Cymbalta and 23% of patients taking placebo.
The risk of withdrawal symptoms seen with SSRI’s and SNRI’s
may be dependent on several factors including the duration and dose
of therapy and the rate of dose reduction. The most commonly reported
reactions are listed in section 4.8. Generally these symptoms are
mild to moderate, however, in some patients they may be severe in
intensity. They usually occur within the first few days of
discontinuing treatment, but there have been very rare reports of
such symptoms in patients who have inadvertently missed a dose.
Generally these symptoms are self-limiting and usually resolve within
2 weeks, though in some individuals they may be prolonged (2-3 months
or more). It is therefore advised that duloxetine should be gradually
tapered when discontinuing treatment over a period of no less than 2
weeks, according to the patient’s needs.
on the use of Cymbalta 120 mg in elderly patients with major
depressive disorder and generalised anxiety disorder are limited.
Therefore, caution should be exercised when treating the elderly with
the maximum dosage.
use of duloxetine has been associated with the development of
akathisia, characterised by a subjectively unpleasant or distressing
restlessness and need to move often accompanied by an inability to
sit or stand still. This is most likely to occur within the first few
weeks of treatment. In patients who develop these symptoms,
increasing the dose may be detrimental.
products containing duloxetine
is used under different trademarks in several indications (treatment
of diabetic neuropathic pain, major depressive disorder, generalised
anxiety disorder and stress urinary incontinence). The use of more
than one of these products concomitantly should be avoided.
of liver injury, including severe elevations of liver enzymes (>10
times upper limit of normal), hepatitis and jaundice have been
reported with duloxetine. Most of them occurred during the first
months of treatment. The pattern of liver damage was predominantly
hepatocellular. Duloxetine should be used with caution in patients
treated with other medicinal products associated with hepatic injury.
serotonin reuptake inhibitors (SSRIs)/serotonin norepinephrine
reuptake inhibitors (SNRIs) may cause symptoms of sexual dysfunction.
There have been reports of long-lasting sexual dysfunction where the
symptoms have continued despite discontinuation of SSRIs/SNRI.
hard gastro-resistant capsules contain sucrose. Patients with rare
hereditary problems of fructose intolerance, glucose-galactose
malabsorption or sucrase-isomaltase insufficiency should not take
medicine contains less than 1 mmol sodium (23 mg) per capsule, that
is to say essentially ‘sodium-free’.
Summary of Product Characteristics [SPC])
[Summary of Product Characteristics]. Utrecht, The Netherlands: Eli
Lilly Nederland B.V.