Xeristar

1 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX I 
 

SUMMARY OF PRODUCT CHARACTERISTICS 
 



 

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1. NAME OF THE MEDICINAL PRODUCT 
 
Xeristar 30 mg hard gastro-resistant capsules 
Xeristar 60 mg hard gastro-resistant capsules 
 
 
2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 
Xeristar 30 mg 
Each capsule contains 30 mg of duloxetine (as hydrochloride).  
 
Excipient(s) with known effect 
Each capsule may contain up to 56 mg sucrose. 
 
Xeristar 60 mg 
Each capsule contains 60 mg of duloxetine (as hydrochloride). 
 
Excipient(s) with known effect 
Each capsule may contain up to 111 mg sucrose. 
 
For the full list of excipients, see section 6.1. 
 
 
3. PHARMACEUTICAL FORM 
 
Hard gastro-resistant capsule. 
 
Xeristar 30 mg 
Opaque white body, imprinted with ‘30 mg’ and an opaque blue cap, imprinted with ‘9543’. 
 
Xeristar 60 mg 
Opaque green body, imprinted with ‘60 mg’ and an opaque blue cap, imprinted with ‘9542’. 
 
 
4. CLINICAL PARTICULARS 
 
4.1 Therapeutic indications 
 
Treatment of major depressive disorder. 
Treatment of diabetic peripheral neuropathic pain. 
Treatment of generalised anxiety disorder. 
 
Xeristar is indicated in adults. 
For further information see section 5.1. 
 
4.2 Posology and method of administration 
 
Posology 
 
Major depressive disorder 
The starting and recommended maintenance dose is 60 mg once daily with or without food. Dosages 
above 60 mg once daily, up to a maximum dose of 120 mg per day have been evaluated from a safety 
perspective in clinical trials. However, there is no clinical evidence suggesting that patients not 
responding to the initial recommended dose may benefit from dose up-titrations. 
 
Therapeutic response is usually seen after 2-4 weeks of treatment. 
 



 

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After consolidation of the antidepressive response, it is recommended to continue treatment for several 
months, in order to avoid relapse. In patients responding to duloxetine, and with a history of repeated 
episodes of major depression, further long-term treatment at a dose of 60 to 120 mg/day could be 
considered. 
 
Generalised anxiety disorder 
The recommended starting dose in patients with generalised anxiety disorder is 30 mg once daily with 
or without food. In patients with insufficient response the dose should be increased to 60 mg, which is 
the usual maintenance dose in most patients.  
 
In patients with co-morbid major depressive disorder, the starting and maintenance dose is 60 mg once 
daily (please see also dosing recommendation above). 
 
Doses up to 120 mg per day have been shown to be efficacious and have been evaluated from a safety 
perspective in clinical trials. In patients with insufficient response to 60 mg, escalation up to 90 mg or 
120 mg may therefore be considered. Dose escalation should be based upon clinical response and 
tolerability. 
 
After consolidation of the response, it is recommended to continue treatment for several months, in 
order to avoid relapse. 
 
Diabetic peripheral neuropathic pain 
The starting and recommended maintenance dose is 60 mg daily with or without food. Dosages above 
60 mg once daily, up to a maximum dose of 120 mg per day administered in evenly divided doses, 
have been evaluated from a safety perspective in clinical trials. The plasma concentration of 
duloxetine displays large inter-individual variability (see section 5.2). Hence, some patients that 
respond insufficiently to 60 mg may benefit from a higher dose. 
 
Response to treatment should be evaluated after 2 months. In patients with inadequate initial response, 
additional response after this time is unlikely. 
 
The therapeutic benefit should be reassessed regularly (at least every three months) (see section 5.1). 
 
Special populations 
 
Elderly 
No dosage adjustment is recommended for elderly patients solely on the basis of age. However, as 
with any medicine, caution should be exercised when treating the elderly, especially with Xeristar 
120 mg per day for major depressive disorder or generalised anxiety disorder, for which data are 
limited (see sections 4.4 and 5.2). 
 
Hepatic impairment 
Xeristar must not be used in patients with liver disease resulting in hepatic impairment (see 
sections 4.3 and 5.2). 
 
Renal impairment  
No dosage adjustment is necessary for patients with mild or moderate renal dysfunction (creatinine 
clearance 30 to 80 ml/min). Xeristar must not be used in patients with severe renal impairment 
(creatinine clearance <30 ml/min; see section 4.3). 
 
Paediatric population 
Duloxetine should not be used in children and adolescents under the age of 18 years for the treatment 
of major depressive disorder because of safety and efficacy concerns (see sections 4.4, 4.8 and 5.1).  
 
The safety and efficacy of duloxetine for the treatment of generalised anxiety disorder in paediatric 
patients aged 7-17 years have not been established. Current available data are described in 
sections 4.8, 5.1 and 5.2. 



 

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The safety and efficacy of duloxetine for the treatment of diabetic peripheral neuropathic pain has not 
been studied. No data are available. 
 
Discontinuation of treatment 
Abrupt discontinuation should be avoided. When stopping treatment with Xeristar the dose should be 
gradually reduced over a period of at least one to two weeks in order to reduce the risk of withdrawal 
reactions (see sections 4.4 and 4.8). If intolerable symptoms occur following a decrease in the dose or 
upon discontinuation of treatment, then resuming the previously prescribed dose may be considered. 
Subsequently, the physician may continue decreasing the dose, but at a more gradual rate. 
 
Method of administration 
For oral use. 
 
4.3 Contraindications 
 
Hypersensitivity to the active substance or to any of the excipients listed in section 6.1. 
 
Concomitant use of Xeristar with nonselective, irreversible monoamine oxidase inhibitors (MAOIs) is 
contraindicated (see section 4.5). 
 
Liver disease resulting in hepatic impairment (see section 5.2). 
 
Xeristar should not be used in combination with fluvoxamine, ciprofloxacin or enoxacin (i.e. potent 
CYP1A2 inhibitors) since the combination results in elevated plasma concentrations of duloxetine (see 
section 4.5). 
 
Severe renal impairment (creatinine clearance <30 ml/min) (see section 4.4). 
 
The initiation of treatment with Xeristar is contraindicated in patients with uncontrolled hypertension 
that could expose patients to a potential risk of hypertensive crisis (see sections 4.4 and 4.8). 
 
4.4 Special warnings and precautions for use 
 
Mania and seizures 
Xeristar should be used with caution in patients with a history of mania or a diagnosis of bipolar 
disorder, and/or seizures. 
 
Mydriasis 
Mydriasis has been reported in association with duloxetine, therefore, caution should be used when 
prescribing Xeristar to patients with increased intraocular pressure, or those at risk of acute narrow-
angle glaucoma. 
 
Blood pressure and heart rate 
Duloxetine 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 (see section 4.5). For patients who experience 
a sustained increase in blood pressure while receiving duloxetine either dose reduction or gradual 
discontinuation should be considered (see section 4.8). In patients with uncontrolled hypertension 
duloxetine should not be initiated (see section 4.3). 
 



 

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Renal impairment 
Increased 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 renal dysfunction. 
 
Serotonin syndrome 
As 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 (see sections 4.3 and 4.5). 
 
Serotonin 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). 
 
If 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 increases. 
 
St John’s wort 
Adverse reactions may be more common during concomitant use of Xeristar and herbal preparations 
containing St John’s wort (Hypericum perforatum). 
 
Suicide 
Major 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 of recovery.  
 
Other psychiatric conditions for which Xeristar 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. 
 
Patients 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.  
 
Cases of suicidal thoughts and suicidal behaviours have been reported during duloxetine therapy or 
early after treatment discontinuation (see section 4.8). 
 
Close 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. 
 



 

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Diabetic 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. 
 
Use in children and adolescents under 18 years of age 
Xeristar 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 (see section 5.1). In addition, long-term safety data in children 
and adolescents concerning growth, maturation and cognitive and behavioural development are 
lacking (see section 4.8). 
 
Haemorrhage  
There 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 (see section 4.6). 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. 
 
Hyponatraemia 
Hyponatraemia has been reported when administering Xeristar, 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.  
 
Discontinuation of treatment 
Withdrawal symptoms when treatment is discontinued are common, particularly if discontinuation is 
abrupt (see section 4.8). In clinical trials adverse events seen on abrupt treatment discontinuation 
occurred in approximately 45% of patients treated with Xeristar 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 (see section 4.2). 
 
Elderly 
Data on the use of Xeristar 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 (see sections 4.2 and 5.2).  
 
Akathisia/psychomotor restlessness 
The 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. 
 



 

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Medicinal products containing duloxetine 
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. 
 
Hepatitis/increased liver enzymes  
Cases of liver injury, including severe elevations of liver enzymes (>10 times upper limit of normal), 
hepatitis and jaundice have been reported with duloxetine (see section 4.8). 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. 
 
Sexual dysfunction 
Selective serotonin reuptake inhibitors (SSRIs)/serotonin norepinephrine reuptake inhibitors (SNRIs) 
may cause symptoms of sexual dysfunction (see section 4.8). There have been reports of long-lasting 
sexual dysfunction where the symptoms have continued despite discontinuation of SSRIs/SNRIs. 
 
Sucrose 
Xeristar hard gastro-resistant capsules contain sucrose. Patients with rare hereditary problems of 
fructose intolerance, glucose-galactose malabsorption or sucrase-isomaltase insufficiency should not 
take this medicine. 
 
4.5 Interaction with other medicinal products and other forms of interaction 
 
Monoamine oxidase inhibitors (MAOIs): Due to the risk of serotonin syndrome, duloxetine should not 
be used in combination with non-selective irreversible monoamine oxidase inhibitors (MAOIs), or 
within at least 14 days of discontinuing treatment with an MAOI. Based on the half-life of duloxetine, 
at least 5 days should be allowed after stopping Xeristar before starting an MAOI (see section 4.3). 
 
The concomitant use of Xeristar with selective, reversible MAOIs, like moclobemide, is not 
recommended (see section 4.4). The antibiotic linezolid is a reversible non-selective MAOI and should 
not be given to patients treated with Xeristar (see section 4.4). 
 
Inhibitors of CYP1A2: Because CYP1A2 is involved in duloxetine metabolism, concomitant use of 
duloxetine with potent inhibitors of CYP1A2 is likely to result in higher concentrations of duloxetine. 
Fluvoxamine (100 mg once daily), a potent inhibitor of CYP1A2, decreased the apparent plasma 
clearance of duloxetine by about 77% and increased AUCo-t 6-fold. Therefore Xeristar should not be 
administered in combination with potent inhibitors of CYP1A2 like fluvoxamine (see section 4.3). 
 
CNS medicinal products: The risk of using duloxetine in combination with other CNS-active 
medicinal products has not been systematically evaluated, except in the cases described in this section. 
Consequently, caution is advised when Xeristar is taken in combination with other centrally acting 
medicinal products or substances, including alcohol and sedative medicinal products (e.g. 
benzodiazepines, morphinomimetics, antipsychotics, phenobarbital, sedative antihistamines). 
 
Serotonergic agents: In rare cases, serotonin syndrome has been reported in patients using 
SSRIs/SNRIs concomitantly with serotonergic agents. Caution is advisable if Xeristar is used 
concomitantly with serotonergic agents like SSRIs, SNRIs, tricyclic antidepressants like clomipramine 
or amitriptyline, MAOIs like moclobemide or linezolid, St John’s wort (Hypericum perforatum) or 
triptans, tramadol, pethidine and tryptophan (see section 4.4). 
 
Effect of duloxetine on other medicinal products 
Medicinal products metabolised by CYP1A2: The pharmacokinetics of theophylline, a CYP1A2 
substrate, were not significantly affected by co-administration with duloxetine (60 mg twice daily).  
 
Medicinal products metabolised by CYP2D6: Duloxetine is a moderate inhibitor of CYP2D6. When 
duloxetine was administered at a dose of 60 mg twice daily with a single dose of desipramine, a 



 

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CYP2D6 substrate, the AUC of desipramine increased 3-fold. The co-administration of duloxetine (40 
mg twice daily) increases steady state AUC of tolterodine (2 mg twice daily) by 71 %, but does not 
affect the pharmacokinetics of its active 5-hydroxyl metabolite and no dosage adjustment is 
recommended. Caution is advised if Xeristar is co-administered with medicinal products that are 
predominantly metabolised by CYP2D6 (risperidone, tricyclic antidepressants [TCAs] such as 
nortriptyline, amitriptyline, and imipramine) particularly if they have a narrow therapeutic index (such 
as flecainide, propafenone and metoprolol). 
 
Oral contraceptives and other steroidal agents: Results of in vitro studies demonstrate that duloxetine 
does not induce the catalytic activity of CYP3A. Specific in vivo drug interaction studies have not 
been performed. 
 
Anticoagulants and antiplatelet agents: Caution should be exercised when duloxetine is combined 
with oral anticoagulants or antiplatelet agents due to a potential increased risk of bleeding attributable 
to a pharmacodynamic interaction. Furthermore, increases in INR values have been reported when 
duloxetine was co-administered to patients treated with warfarin. However, concomitant 
administration of duloxetine with warfarin under steady state conditions, in healthy volunteers, as part 
of a clinical pharmacology study, did not result in a clinically significant change in INR from baseline 
or in the pharmacokinetics of R- or S-warfarin. 
 
Effects of other medicinal products on duloxetine 
Antacids and H2 antagonists: Co-administration of duloxetine with aluminium- and magnesium-
containing antacids or duloxetine with famotidine had no significant effect on the rate or extent of 
duloxetine absorption after administration of a 40 mg oral dose. 
 
Inducers of CYP1A2: Population pharmacokinetic analyses have shown that smokers have almost 50% 
lower plasma concentrations of duloxetine compared with non-smokers. 
 
4.6 Fertility, pregnancy and lactation 
 
Fertility 
Duloxetine had no effect on male fertility, and effects in females were only evident at doses that 
caused maternal toxicity. 
 
Pregnancy  
There are no adequate data on the use of duloxetine in pregnant women.  
 
Studies in animals have shown reproductive toxicity at systemic exposure levels (AUC) of duloxetine 
lower than the maximum clinical exposure (see section 5.3).  
 
The potential risk for humans is unknown.  
 
Epidemiological data have suggested that the use of SSRIs in pregnancy, particularly in late 
pregnancy, may increase the risk of persistent pulmonary hypertension in the newborn (PPHN). 
Although no studies have investigated the association of PPHN to SNRI treatment, this potential risk 
cannot be ruled out with duloxetine taking into account the related mechanism of action (inhibition of 
the re-uptake of serotonin).  
 
As with other serotonergic medicinal products, discontinuation symptoms may occur in the neonate 
after maternal duloxetine use near term. Discontinuation symptoms seen with duloxetine may include 
hypotonia, tremor, jitteriness, feeding difficulty, respiratory distress and seizures. The majority of 
cases have occurred either at birth or within a few days of birth. 
 
Observational data have provided evidence of an increased risk (less than 2-fold) of postpartum 
haemorrhage following duloxetine exposure within the month prior to birth. 
 



 

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Xeristar should be used in pregnancy only if the potential benefit justifies the potential risk to the 
foetus. Women should be advised to notify their physician if they become pregnant, or intend to 
become pregnant, during therapy.  
 
Breast feeding 
Duloxetine is very weakly excreted into human milk based on a study of 6 lactating patients, who did 
not breast feed their children. The estimated daily infant dose on a mg/kg basis is approximately 
0.14% of the maternal dose (see section 5.2). As the safety of duloxetine in infants is not known, the 
use of Xeristar while breast-feeding is not recommended. 
 
4.7 Effects on ability to drive and use machines 
 
No studies on the effects on the ability to drive and use machines have been performed. Xeristar may 
be associated with sedation and dizziness. Patients should be instructed that if they experience 
sedation or dizziness they should avoid potentially hazardous tasks such as driving or operating 
machinery. 
 
4.8 Undesirable effects 
 
a. Summary of the safety profile 
The most commonly reported adverse reactions in patients treated with Xeristar were nausea, 
headache, dry mouth, somnolence, and dizziness. However, the majority of common adverse reactions 
were mild to moderate, they usually started early in therapy, and most tended to subside even as 
therapy was continued.  
 
b. Tabulated summary of adverse reactions 
Table 1 gives the adverse reactions observed from spontaneous reporting and in placebo-controlled 
clinical trials. 
 
Table 1: Adverse reactions 
Frequency estimate: Very common (≥1/10), common (≥1/100 to <1/10), uncommon (≥1/1,000 to 
<1/100), rare (≥1/10,000 to <1/1,000), very rare (<1/10,000). 
 
Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness. 
 

Very common Common Uncommon Rare Very Rare 
Infections and infestations 
  Laryngitis   
Immune system disorders 
   Anaphylactic 

reaction  
Hyper-sensitivity 
disorder 

 

Endocrine disorders 
   Hypo-thyroidism  
Metabolism and nutrition disorders 
 Decreased 

Appetite  
Hyperglycaemia 
(reported 
especially in 
diabetic patients) 

Dehydration 
Hyponatraemia 
SIADH6 

 



 

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Very common Common Uncommon Rare Very Rare 
Psychiatric disorders 
 Insomnia 

Agitation 
Libido decreased 
Anxiety 
Orgasm abnormal 
Abnormal dreams 

Suicidal 
ideation5,7 
Sleep disorder 
Bruxism 
Disorientation 
Apathy 

Suicidal 
behaviour5,7 
Mania 
Hallucinations 
Aggression and 
anger4 

 

Nervous system disorders 
Headache 
Somnolence  

Dizziness 
Lethargy 
Tremor 
Paraesthesia 
 

Myoclonus 
Akathisia7 
Nervousness 
Disturbance in 
attention 
Dysgeusia 
Dyskinesia 
Restless legs 
syndrome 
Poor quality sleep 

Serotonin 
syndrome6 
Convulsion1 
Psychomotor 
restlessness6 
Extra-pyramidal 
symptoms6 

 

Eye disorders 
 Blurred vision Mydriasis  

Visual impairment 
Glaucoma  

Ear and labyrinth disorders 
 Tinnitus1  Vertigo 

Ear pain 
  

Cardiac disorders 
 Palpitations Tachycardia 

Supra-ventricular 
arrhythmia, 
mainly atrial 
fibrillation 

  

Vascular disorders 
 Blood pressure 

increase3 
Flushing 

Syncope2 
Hypertension3,7 
Orthostatic 
hypotension2 
Peripheral 
coldness 

Hypertensive 
crisis3,6 
 

 

Respiratory, thoracic and mediastinal disorders 
 Yawning Throat tightness 

Epistaxis 
Interstitial lung 
disease10 
Eosinophilic 
pneumonia6 

 

Gastrointestinal disorders  
Nausea 
Dry mouth 

Constipation 
Diarrhoea 
Abdominal pain 
Vomiting  
Dyspepsia 
Flatulence 

Gastrointestinal 
haemorrhage7 
Gastroenteritis 
Eructation 
Gastritis 
Dysphagia 

Stomatitis 
Haematochezia 
Breath odour 
Microscopic 
colitis9 
 

 

Hepato-biliary disorders 
  Hepatitis3 

Elevated liver 
enzymes (ALT, 
AST, alkaline 
phosphatase) 

Hepatic failure6 
Jaundice6 

 



 

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Very common Common Uncommon Rare Very Rare 
Acute liver injury 

Skin and subcutaneous tissue disorders 
 Sweating 

increased 
Rash 

Night sweats 
Urticaria 
Dermatitis contact 
Cold sweat 
Photo-sensitivity 
reactions 
Increased 
tendency to bruise 

Stevens-Johnson 
Syndrome6 
Angio-neurotic 
oedema6 

Cutaneous 
vasculitis 

Musculoskeletal and connective tissue disorders 
 Musculo-skeletal 

pain 
Muscle spasm 

Muscle tightness 
Muscle twitching 

Trismus  

Renal and urinary disorders 
 Dysuria 

Pollakiuria 
Urinary retention 
Urinary hesitation 
Nocturia 
Polyuria 
Urine flow 
decreased 

Urine odour 
abnormal 

 

Reproductive system and breast disorders 
 Erectile 

dysfunction 
Ejaculation 
disorder  
Ejaculation 
delayed 

Gynaecological 
haemorrhage 
Menstrual 
disorder 
Sexual 
dysfunction  
Testicular pain  

Menopausal 
symptoms 
Galactorrhoea 
Hyperprolactinae
mia  
Postpartum 
haemorrhage6 

 

General disorders and administration site conditions 
 Falls8 

Fatigue  
Chest pain7  
Feeling abnormal 
Feeling cold 
Thirst 
Chills 
Malaise 
Feeling hot 
Gait disturbance 

  

Investigations 
 Weight decrease  Weight increase 

Blood creatine 
phosphokinase 
increased 
Blood potassium 
increased 

Blood cholesterol 
increased 

 

 
1 Cases of convulsion and cases of tinnitus have also been reported after treatment discontinuation. 
2 Cases of orthostatic hypotension and syncope have been reported especially at the initiation of 

treatment. 
3 See section 4.4. 
4 Cases of aggression and anger have been reported particularly early in treatment or after treatment 

discontinuation. 
5 Cases of suicidal ideation and suicidal behaviours have been reported during duloxetine therapy or 

early after treatment discontinuation (see section 4.4). 



 

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6 Estimated frequency of post-marketing surveillance reported adverse reactions; not observed in 
placebo-controlled clinical trials. 

7 Not statistically significantly different from placebo. 
8 Falls were more common in the elderly (≥65 years old). 
9 Estimated frequency based on all clinical trial data. 
10Estimated frequency based on placebo-controlled clinical trials. 
 
c. Description of selected adverse reactions 
Discontinuation of duloxetine (particularly when abrupt) commonly leads to withdrawal symptoms. 
Dizziness, sensory disturbances (including paraesthesia or electric shock-like sensations, particularly 
in the head), sleep disturbances (including insomnia and intense dreams), fatigue, somnolence, 
agitation or anxiety, nausea and/or vomiting, tremor, headache, myalgia, irritability, diarrhoea, 
hyperhydrosis and vertigo are the most commonly reported reactions. 
 
Generally, for SSRIs and SNRIs, these events are mild to moderate and self-limiting, however, in 
some patients they may be severe and/or prolonged. It is therefore advised that when duloxetine 
treatment is no longer required, gradual discontinuation by dose tapering should be carried out (see 
sections 4.2 and 4.4). 
 
In the 12 week acute phase of three clinical trials of duloxetine in patients with diabetic neuropathic 
pain, small but statistically significant increases in fasting blood glucose were observed in duloxetine-
treated patients. HbA1c was stable in both duloxetine-treated and placebo-treated patients. In the 
extension phase of these studies, which lasted up to 52 weeks, there was an increase in HbA1c in both 
the duloxetine and routine care groups, but the mean increase was 0.3% greater in the duloxetine-
treated group. There was also a small increase in fasting blood glucose and in total cholesterol in 
duloxetine-treated patients while those laboratory tests showed a slight decrease in the routine care 
group.  
 
The heart rate-corrected QT interval in duloxetine-treated patients did not differ from that seen in 
placebo-treated patients. No clinically significant differences were observed for QT, PR, QRS, or 
QTcB measurements between duloxetine-treated and placebo-treated patients. 
 
d. Paediatric population 
A total of 509 paediatric patients aged 7 to 17 years with major depressive disorder and 241 paediatric 
patients aged 7 to 17 years with generalised anxiety disorder were treated with duloxetine in clinical 
trials. In general, the adverse reaction profile of duloxetine in children and adolescents was similar to 
that seen for adults. 
 
A total of 467 paediatric patients initially randomized to duloxetine in clinical trials experienced a 0.1 
kg mean decrease in weight at 10-weeks compared with a 0.9 kg mean increase in 353 placebo-treated 
patients. Subsequently, over the four- to six-month extension period, patients on average trended 
toward recovery to their expected baseline weight percentile based on population data from age- and 
gender-matched peers. 
 
In studies of up to 9 months an overall mean decrease of 1% in height percentile (decrease of 2% in 
children (7-11 years) and increase of 0.3% in adolescents (12-17 years)) was observed in duloxetine-
treated paediatric patients (see section 4.4).  
 
Reporting of suspected adverse reactions 
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It 
allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare 
professionals are asked to report any suspected adverse reactions via the national reporting system 
listed in Appendix V. 
 
4.9 Overdose 
 
Cases of overdoses, alone or in combination with other medicinal products, with duloxetine doses of 



 

 13 

5400 mg were reported. Some fatalities have occurred, primarily with mixed overdoses, but also with 
duloxetine alone at a dose of approximately 1000 mg. Signs and symptoms of overdose (duloxetine 
alone or in combination with other medicinal products) included somnolence, coma, serotonin 
syndrome, seizures, vomiting and tachycardia.   
 
No specific antidote is known for duloxetine but if serotonin syndrome ensues, specific treatment 
(such as with cyproheptadine and/or temperature control) may be considered. A free airway should be 
established. Monitoring of cardiac and vital signs is recommended, along with appropriate 
symptomatic and supportive measures. Gastric lavage may be indicated if performed soon after 
ingestion or in symptomatic patients. Activated charcoal may be useful in limiting absorption. 
Duloxetine has a large volume of distribution and forced diuresis, haemoperfusion, and exchange 
perfusion are unlikely to be beneficial. 
 
 
5. PHARMACOLOGICAL PROPERTIES 
 
5.1  Pharmacodynamic properties 
 
Pharmacotherapeutic group: Other antidepressants. ATC code: N06AX21. 
 
Mechanism of action 
Duloxetine is a combined serotonin (5-HT) and noradrenaline (NA) reuptake inhibitor. It weakly 
inhibits dopamine reuptake with no significant affinity for histaminergic, dopaminergic, cholinergic 
and adrenergic receptors. Duloxetine dose-dependently increases extracellular levels of serotonin and 
noradrenaline in various brain areas of animals. 
 
Pharmacodynamic effects 
Duloxetine normalised pain thresholds in several preclinical models of neuropathic and inflammatory 
pain and attenuated pain behaviour in a model of persistent pain. The pain inhibitory action of 
duloxetine is believed to be a result of potentiation of descending inhibitory pain pathways within the 
central nervous system. 
 
Clinical efficacy and safety 
Major Depressive Disorder: Xeristar was studied in a clinical programme involving 3,158 patients 
(1,285 patient-years of exposure) meeting DSM-IV criteria for major depression. The efficacy of 
Xeristar at the recommended dose of 60 mg once a day was demonstrated in three out of three 
randomised, double-blind, placebo-controlled, fixed dose acute studies in adult outpatients with major 
depressive disorder. Overall, Xeristar’s efficacy has been demonstrated at daily doses between 60 and 
120 mg in a total of five out of seven randomised, double-blind, placebo-controlled, fixed dose acute 
studies in adult outpatients with major depressive disorder. 
 
Xeristar demonstrated statistical superiority over placebo as measured by improvement in the 17-item 
Hamilton Depression Rating Scale (HAM-D) total score (including both the emotional and somatic 
symptoms of depression). Response and remission rates were also statistically significantly higher 
with Xeristar compared with placebo. Only a small proportion of patients included in pivotal clinical 
trials had severe depression (baseline HAM-D>25). 
 
In a relapse prevention study, patients responding to 12-weeks of acute treatment with open-label 
Xeristar 60 mg once daily were randomised to either Xeristar 60 mg once daily or placebo for a further 
6-months. Xeristar 60 mg once daily demonstrated a statistically significant superiority compared to 
placebo (p=0.004) on the primary outcome measure, the prevention of depressive relapse, as measured 
by time to relapse. The incidence of relapse during the 6-months double-blind follow-up period was 
17% and 29% for duloxetine and placebo, respectively. 
 
During 52 weeks of placebo-controlled double blind treatment, duloxetine-treated patients with 
recurrent MDD had a significantly longer symptom free period (p<0.001) compared with patients 
randomised to placebo. All patients had previously responded to duloxetine during open-label 



 

 14 

duloxetine treatment (28 to 34 weeks) at a dose of 60 to 120 mg/day. During the 52-week placebo-
controlled double blind treatment phase 14.4% of the duloxetine-treated patients and 33.1% of the 
placebo-treated patients experience a return of their depressive symptoms (p<0.001). 
 
The effect of Xeristar 60 mg once a day in elderly depressed patients (≥65 years) was specifically 
examined in a study that showed a statistically significant difference in the reduction of the HAMD17 
score for duloxetine-treated patients compared to placebo. Tolerability of Xeristar 60 mg once daily in 
elderly patients was comparable to that seen in the younger adults. However, data on elderly patients 
exposed to the maximum dose (120mg per day) are limited and thus, caution is recommended when 
treating this population. 
 
Generalised Anxiety Disorder: Xeristar demonstrated statistically significant superiority over placebo 
in five out of five studies including four randomised, double-blind, placebo-controlled acute studies 
and a relapse prevention study in adult patients with generalised anxiety disorder.  
 
Xeristar demonstrated statistically significant superiority over placebo as measured by improvement in 
the Hamilton Anxiety Scale (HAM-A) total score and by the Sheehan Disability Scale (SDS) global 
functional impairment score. Response and remission rates were also higher with Xeristar compared to 
placebo. Xeristar showed comparable efficacy results to venlafaxine in terms of improvements on the 
HAM-A total score.  
 
In a relapse prevention study, patients responding to 6 months of acute treatment with open-label 
Xeristar were randomised to either Xeristar or placebo for a further 6-months. Xeristar 60 mg to 
120 mg once daily demonstrated statistically significant superiority compared to placebo (p<0.001) on 
the prevention of relapse, as measured by time to relapse. The incidence of relapse during the 6-
months double-blind follow-up period was 14% for Xeristar and 42% for placebo. 
The efficacy of Xeristar 30-120 mg (flexible dosing) once a day in elderly patients (>65 years) with 
generalised anxiety disorder was evaluated in a study that demonstrated statistically significant 
improvement in the HAM-A total score for duloxetine treated patients compared to placebo treated 
patients.  The efficacy and safety of Xeristar 30-120 mg once daily in elderly patients with generalised 
anxiety disorder was similar to that seen in studies of younger adult patients.  However, data on 
elderly patients exposed to the maximum dose (120 mg per day) are limited and, thus, caution is 
recommended when using this dose with the elderly population. 
 
Diabetic Peripheral Neuropathic Pain: The efficacy of Xeristar as a treatment for diabetic neuropathic 
pain was established in 2 randomised, 12-week, double-blind, placebo-controlled, fixed dose studies in 
adults (22 to 88 years) having diabetic neuropathic pain for at least 6 months. Patients meeting 
diagnostic criteria for major depressive disorder were excluded from these trials. The primary outcome 
measure was the weekly mean of 24-hour average pain, which was collected in a daily diary by 
patients on an 11-point Likert scale. 
 
In both studies, Xeristar 60 mg once daily and 60 mg twice daily significantly reduced pain compared 
with placebo. The effect in some patients was apparent in the first week of treatment. The difference in 
mean improvement between the two active treatment arms was not significant. At least 30% reported 
pain reduction was recorded in approximately 65% of duloxetine treated patients versus 40% for 
placebo. The corresponding figures for at least 50% pain reduction were 50% and 26% respectively. 
Clinical response rates (50% or greater improvement in pain) were analysed according to whether or 
not the patient experienced somnolence during treatment. For patients not experiencing somnolence, 
clinical response was observed in 47% of patients receiving duloxetine and 27% of patients on 
placebo. Clinical response rates in patients experiencing somnolence were 60% on duloxetine and 
30% on placebo. Patients not demonstrating a pain reduction of 30% within 60 days of treatment were 
unlikely to reach this level during further treatment. 
 
In an open label long-term uncontrolled study, the pain reduction in patients responding to 8-weeks of 
acute treatment of Xeristar 60 mg once daily was maintained for a further 6-months as measured by 
change on the Brief Pain Inventory (BPI) 24-hour average pain item. 
 



 

 15 

Paediatric population 
Duloxetine has not been studied in patients under the age of 7.   
 
Two randomized, double-blind, parallel clinical trials were performed in 800 paediatric patients aged 7 
to 17 years with major depressive disorder (see section 4.2). These two studies included a 10 week 
placebo and active (fluoxetine) controlled acute phase followed by six months period of active 
controlled extension treatment. Neither duloxetine (30-120 mg) nor the active control arm (fluoxetine 
20-40 mg) statistically separated from placebo on change from baseline to endpoint in the Children´s 
Depression Rating Scale-Revised (CDRS-R) total score. Discontinuation due to adverse events was 
higher in patients taking duloxetine compared with those treated with fluoxetine, mostly due to nausea. 
During the 10-week acute treatment period, suicidal behaviours were reported (duloxetine 0/333 [0%], 
fluoxetine 2/225 [0.9%], placebo 1/220 [0.5%]). Over the entire 36-week course of the study, 6 out of 
333 patients initially randomized to duloxetine and 3 out of 225 patients initially randomized to 
fluoxetine experienced suicidal behaviour (exposure adjusted incidence 0.039 events per patient year 
for duloxetine and 0.026 for fluoxetine). In addition, one patient who transitioned from placebo to 
duloxetine experienced a suicidal behaviour while taking duloxetine. 
 
A randomised, double-blind, placebo-controlled study was performed in 272 patients aged 7-17 years 
with generalised anxiety disorder.  The study included a 10 week placebo-controlled acute phase, 
followed by an 18 week extension treatment period.  A flexible dose regimen was used in this study, to 
allow for slow dose escalation from 30 mg once daily to higher doses (maximum 120 mg once daily).  
Treatment with duloxetine showed a statistically significantly greater improvement in GAD 
symptoms, as measured by PARS severity score for GAD (mean difference between duloxetine and 
placebo of 2.7 points [95% CI 1.3-4.0]), after 10 weeks of treatment. The maintenance of the effect has 
not been evaluated. There was no statistically significant difference in discontinuation due to adverse 
events between duloxetine and placebo groups during the 10 week acute treatment phase. Two patients 
who transitioned from placebo to duloxetine after the acute phase experienced suicidal behaviours 
while taking duloxetine during the extension phase. A conclusion on the overall benefit/risk in this age 
group has not been established (see also sections 4.2 and 4.8). 
 
A single study has been performed in paediatric patients with juvenile primary fibromyalgia syndrome 
(JPFS) in which the duloxetine-treated group did not separate from placebo group for the primary 
efficacy measure. Therefore, there is no evidence of efficacy in this paediatric patient population. The 
randomised, double-blind, placebo-controlled, parallel study of duloxetine was conducted in 
184 adolescents aged 13 to 18 years (mean age 15.53 years) with JPFS. The study included a 13-week 
double-blind period where patients were randomised to duloxetine 30 mg/60 mg, or placebo daily. 
Duloxetine did not show efficacy in reducing pain as measured by primary outcome measure of Brief 
Pain Inventory (BPI) average pain score endpoint: least squares (LS) mean change from baseline in 
BPI average pain score at 13 weeks was -0.97 in the placebo group, compared with -1.62 in the 
duloxetine 30/60 mg group (p = 0.052). The safety results from this study were consistent with the 
known safety profile of duloxetine. 
 
The European Medicines Agency has waived the obligation to submit the results of studies with 
Xeristar in all subsets of the paediatric population in the treatment of major depressive disorder, 
diabetic neuropathic pain and generalised anxiety disorder. See section 4.2 for information on 
paediatric use. 
 
5.2 Pharmacokinetic properties 
 
Duloxetine is administered as a single enantiomer. Duloxetine is extensively metabolised by oxidative 
enzymes (CYP1A2 and the polymorphic CYP2D6), followed by conjugation. The pharmacokinetics 
of duloxetine demonstrate large intersubject variability (generally 50-60%), partly due to gender, age, 
smoking status and CYP2D6 metaboliser status.  
 
Absorption: Duloxetine is well absorbed after oral administration with a Cmax occurring 6 hours post 
dose. The absolute oral bioavailability of duloxetine ranged from 32% to 80% (mean of 50%). Food 
delays the time to reach the peak concentration from 6 to 10 hours and it marginally decreases the 



 

 16 

extent of absorption (approximately 11 %). These changes do not have any clinical significance.  
 
Distribution: Duloxetine is approximately 96% bound to human plasma proteins. Duloxetine binds to 
both albumin and alpha-l acid glycoprotein. Protein binding is not affected by renal or hepatic 
impairment. 
 
Biotransformation: Duloxetine is extensively metabolised and the metabolites are excreted principally 
in urine. Both cytochromes P450-2D6 and 1A2 catalyse the formation of the two major metabolites 
glucuronide conjugate of 4-hydroxy duloxetine and sulfate conjugate of 5-hydroxy 6-methoxy 
duloxetine. Based upon in vitro studies, the circulating metabolites of duloxetine are considered 
pharmacologically inactive. The pharmacokinetics of duloxetine in patients who are poor metabolisers 
with respect to CYP2D6 has not been specifically investigated. Limited data suggest that the plasma 
levels of duloxetine are higher in these patients. 
 
Elimination: The elimination half-life of duloxetine ranges from 8 to 17 hours (mean of 12 hours). 
After an intravenous dose the plasma clearance of duloxetine ranges from 22 l/hr to 46 l/hr (mean of 
36 l/hr). After an oral dose the apparent plasma clearance of duloxetine ranges from 33 to 261 l/hr 
(mean 101 l/hr). 
 
Special populations 
Gender: Pharmacokinetic differences have been identified between males and females (apparent 
plasma clearance is approximately 50% lower in females). Based upon the overlap in the range of 
clearance, gender-based pharmacokinetic differences do not justify the recommendation for using a 
lower dose for female patients.  
 
Age: Pharmacokinetic differences have been identified between younger and elderly females (≥65 
years) (AUC increases by about 25% and half-life is about 25% longer in the elderly), although the 
magnitude of these changes is not sufficient to justify adjustments to the dose. As a general 
recommendation, caution should be exercised when treating the elderly (see sections 4.2 and 4.4). 
 
Renal impairment: End stage renal disease (ESRD) patients receiving dialysis had 2-fold higher 
duloxetine Cmax and AUC values compared with healthy subjects. Pharmacokinetic data on duloxetine 
is limited in patients with mild or moderate renal impairment. 
 
Hepatic impairment: Moderate liver disease (Child Pugh Class B) affected the pharmacokinetics of 
duloxetine. Compared with healthy subjects, the apparent plasma clearance of duloxetine was 79% 
lower, the apparent terminal half-life was 2.3 times longer, and the AUC was 3.7 times higher in 
patients with moderate liver disease. The pharmacokinetics of duloxetine and its metabolites have not 
been studied in patients with mild or severe hepatic insufficiency. 
 
Breast-feeding mothers: The disposition of duloxetine was studied in 6 lactating women who were at 
least 12-weeks postpartum. Duloxetine is detected in breast milk, and steady-state concentrations in 
breast milk are about one-fourth those in plasma. The amount of duloxetine in breast milk is 
approximately 7 µg/day while on 40 mg twice daily dosing. Lactation did not influence duloxetine 
pharmacokinetics.  
 
Paediatric population: Pharmacokinetics of duloxetine in paediatric patients aged 7 to 17 years with 
major depressive disorder following oral administration of 20 to 120 mg once daily dosing regimen 
was characterized using population modelling analyses based on data from 3 studies. The model-
predicted duloxetine steady state plasma concentrations in paediatric patients were mostly within the 
concentration range observed in adult patients. 
 
5.3 Preclinical safety data 
 
Duloxetine was not genotoxic in a standard battery of tests and was not carcinogenic in rats. 
Multinucleated cells were seen in the liver in the absence of other histopathological changes in the rat 
carcinogenicity study. The underlying mechanism and the clinical relevance are unknown. Female 



 

 17 

mice receiving duloxetine for 2 years had an increased incidence of hepatocellular adenomas and 
carcinomas at the high dose only (144 mg/kg/day), but these were considered to be secondary to 
hepatic microsomal enzyme induction. The relevance of this mouse data to humans is unknown. 
Female rats receiving duloxetine (45 mg/kg/day) before and during mating and early pregnancy had a 
decrease in maternal food consumption and body weight, oestrous cycle disruption, decreased live 
birth indices and progeny survival, and progeny growth retardation at systemic exposure levels 
estimated to be at the most at maximum clinical exposure (AUC). In an embryotoxicity study in the 
rabbit, a higher incidence of cardiovascular and skeletal malformations was observed at systemic 
exposure levels below the maximum clinical exposure (AUC). No malformations were observed in 
another study testing a higher dose of a different salt of duloxetine. In prenatal/postnatal toxicity 
studies in the rat, duloxetine induced adverse behavioural effects in the offspring at exposures below 
maximum clinical exposure (AUC). 
 
Studies in juvenile rats reveal transient effects on neurobehaviour, as well as significantly decreased 
body weight and food consumption; hepatic enzyme induction; and hepatocellular vacuolation at 45 
mg/kg/day. The general toxicity profile of duloxetine in juvenile rats was similar to that in adult rats. 
The no-adverse effect level was determined to be 20 mg/kg/day.  
 
 
6. PHARMACEUTICAL PARTICULARS 
 
6.1 List of excipients 
 
Capsule content 
Hypromellose 
Hypromellose acetate succinate 
Sucrose 
Sugar spheres 
Talc 
Titanium dioxide (E171) 
Triethyl citrate 
 
Capsule shell 
 
Xeristar 30 mg 
Gelatin 
Sodium lauryl sulfate 
Titanium dioxide (E171) 
Indigo carmine (E132) 
Edible green ink  
 
Edible green ink contains: 
Black iron oxide - synthetic (E172) 
Yellow iron oxide - synthetic (E172) 
Propylene glycol 
Shellac 
 
Xeristar 60 mg 
Gelatin 
Sodium lauryl sulfate 
Titanium dioxide (E171) 
Indigo carmine (E132) 
Yellow iron oxide (E172) 
Edible white ink  
 
Edible white ink contains: 
Titanium dioxide (E171) 



 

 18 

Propylene glycol 
Shellac 
Povidone 
 
6.2 Incompatibilities 
 
Not applicable. 
 
6.3 Shelf life 
 
3 years. 
 
6.4 Special precautions for storage 
 
Store in the original package in order to protect from moisture. Do not store above 30º C. 
 
6.5 Nature and contents of container 
 
Polyvinylchloride (PVC), polyethylene (PE), and polychlorotrifluoroethylene (PCTFE) blister sealed 
with an aluminium foil. 
 
Xeristar 30 mg 
Xeristar 30 mg is available in packs of 7 and 28 hard gastro-resistant capsules.  
 
Xeristar 60 mg 
Xeristar 60 mg is available in packs of 28, 56, 84, and 98 hard gastro-resistant capsules and in 
multipacks containing 100 (5 packs of 20) and 500 (25 packs of 20) hard gastro-resistant capsules. 
 
Not all pack sizes may be marketed. 
 
6.6 Special precautions for disposal  
 
No special requirements. 
 
 
7. MARKETING AUTHORISATION HOLDER 
 
Esteve Pharmaceuticals, S.A., Passeig de la Zona Franca, 109, 08038 Barcelona, Spain. 
 
 
8. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/04/297/001 
EU/1/04/297/002 
EU/1/04/297/003 
EU/1/04/297/004 
EU/1/04/297/005 
EU/1/04/297/006 
EU/1/04/297/007 
EU/1/04/297/008 
 
 
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 
Date of first authorisation: 17 December 2004 
Date of latest renewal: 24 June 2009 
 



 

 19 

 
10. DATE OF REVISION OF THE TEXT 
 
Detailed information on this medicine is available on the European Medicines Agency (EMA) web 
site: http://www.ema.europa.eu 



 

 20 

 
 
 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX II 
 
A. MANUFACTURER(S) RESPONSIBLE FOR BATCH 

RELEASE 
 
B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY 

AND USE 
 

C. OTHER CONDITIONS AND REQUIREMENTS OF THE 
MARKETING AUTHORISATION 

 
D. CONDITIONS OR RESTRICTIONS WITH REGARD TO 

THE SAFE AND EFFECTIVE USE OF THE MEDICINAL 
PRODUCT 



 

 21 

A. MANUFACTURER(S) RESPONSIBLE FOR BATCH RELEASE 
 
Name and address of the manufacturer(s) responsible for batch release 
 
Lilly S.A.  
Avda. de la Industria Nº 30,  
28108 Alcobendas  
Madrid 
Spain 
 
 
B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE 
 
Medicinal product subject to medical prescription 
 
 
C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING 

AUTHORISATION 
 
• Periodic Safety Update Reports 
 
The requirements for submission of periodic safety update reports for this medicinal product are set 
out in the list of Union reference dates (EURD list) provided for under Article 107c(7) of Directive 
2001/83/EC and any subsequent updates published on the European medicines web-portal.  
 
 
D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND 

EFFECTIVE USE OF THE MEDICINAL PRODUCT 
 
• Risk Management Plan (RMP)  
 
The MAH shall perform the  required pharmacovigilance activities and interventions detailed in the 
agreed RMP presented in Module 1.8.2. of the Marketing Authorisation and any agreed subsequent 
updates of the RMP.  
 
An updated RMP should be submitted: 
• At the request of the European Medicines Agency; 
• Whenever the risk management system is modified, especially as the result of new information 

being received that may  lead to a significant change to the benefit risk profile or as the result of 
an important (pharmacovililance or risk minimisation) milestone being reached. 

 
. 
 
 
 



 

 22 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX III 
 

LABELLING AND PACKAGE LEAFLET 



 

 23 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

A. LABELLING 



 

 24 

 
PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
CARTONS FOR 30 MG HARD GASTRO-RESISTANT CAPSULES 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Xeristar 30 mg hard gastro-resistant capsules. 
Duloxetine  
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each capsule contains 30 mg of duloxetine (as hydrochloride) 
 
 
3. LIST OF EXCIPIENTS 
 
Contains sucrose 
See leaflet for further information 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
28 hard gastro-resistant capsules 
7 hard gastro-resistant capsules 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Oral use. 
Read the package leaflet before use. 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 
 
Keep out of the sight and reach of children. 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
 
8. EXPIRY DATE 
 
EXP 
 
 
9. SPECIAL STORAGE CONDITIONS 
 
Store in the original package in order to protect from moisture. Do not store above 30°C 
 
 
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 



 

 25 

APPROPRIATE 
 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
Esteve Pharmaceuticals, S.A. 
Passeig de la Zona Franca, 109  
08038 Barcelona 
Spain 
 
 
12. MARKETING AUTHORISATION NUMBER(S) 
 
EU/1/04/297/001 (28 hard gastro-resistant capsules) 
EU/1/04/297/006 (7 hard gastro-resistant capsules) 
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
Medicinal product subject to medical prescription. 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Xeristar 30 mg 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 
PC:  
SN:  
NN: 
 



 

 26 

 
MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS 
30 mg hard gastro-resistant capsules 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Xeristar 30 mg hard gastro-resistant capsules 
Duloxetine 
 
 
2. NAME OF THE MARKETING AUTHORISATION HOLDER 
 
Esteve 
 
 
3. EXPIRY DATE 
 
EXP  
 
 
4. BATCH NUMBER 
 
Lot 
 
 
5. OTHER 
 



 

 27 

 
PARTICULARS TO APPEAR ON THE OUTER PACKAGING  
 
CARTONS FOR 60 MG HARD GASTRO-RESISTANT CAPSULES 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Xeristar 60 mg hard gastro-resistant capsules. 
Duloxetine  
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each capsule contains 60 mg of duloxetine (as hydrochloride) 
 
 
3. LIST OF EXCIPIENTS 
 
Contains sucrose 
See leaflet for further information 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
28 hard gastro-resistant capsules 
84 hard gastro-resistant capsules 
98 hard gastro-resistant capsules  
56 hard gastro-resistant capsules 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Oral use. 
Read the leaflet before use. 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 
 
Keep out of the sight and reach of children. 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
 
8. EXPIRY DATE 
 
EXP 
 
 
9. SPECIAL STORAGE CONDITIONS 
 
Store in the original package in order to protect from moisture. Do not store above 30°C 
 
 



 

 28 

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 
OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 

 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
Esteve Pharmaceuticals, S.A. 
Passeig de la Zona Franca, 109  
08038 Barcelona 
Spain 
 
 
12. MARKETING AUTHORISATION NUMBER(S) 
 
EU/1/04/297/002 (28 hard gastro-resistant capsules) 
EU/1/04/297/003 (84 hard gastro-resistant capsules) 
EU/1/04/297/004 (98 hard gastro-resistant capsules) 
EU/1/04/297/005 (56 hard gastro-resistant capsules) 
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
Medicinal product subject to medical prescription. 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Xeristar 60 mg  
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 
PC:  
SN:  
NN: 
 



 

 29 

 
 
PARTICULARS TO APPEAR ON THE OUTER PACKAGING  
 
MULTIPACK- INNER CARTON FOR 60 MG HARD GASTRO-RESISTANT CAPSULES 
(without blue box) 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Xeristar 60 mg hard gastro-resistant capsules. 
Duloxetine  
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each capsule contains 60 mg of duloxetine (as hydrochloride) 
 
 
3. LIST OF EXCIPIENTS 
 
Contains sucrose 
See leaflet for further information 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
20 hard gastro-resistant capsules. Component of a multipack, can’t be sold separately. 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Oral use. 
Read the leaflet before use. 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 
 
Keep out of the sight and reach of children. 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
 
8. EXPIRY DATE 
 
EXP 
 
 
9. SPECIAL STORAGE CONDITIONS 
 
Store in the original package in order to protect from moisture. Do not store above 30°C 
 
 
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 



 

 30 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 

 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
Esteve Pharmaceuticals, S.A. 
Passeig de la Zona Franca, 109  
08038 Barcelona 
Spain 
 
 
12. MARKETING AUTHORISATION NUMBER(S) 
 
EU/1/04/297/007 (500 hard gastro-resistant capsules) (25 packs of 20) 
EU/1/04/297/008 (100 hard gastro-resistant capsules) (5 packs of 20) 
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
Medicinal product subject to medical prescription. 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Xeristar 60 mg  
 
 



 

 31 

 
PARTICULARS TO APPEAR ON THE OUTER PACKAGING  
 
MULTIPACK-OUTER CARTON FOR 60 MG HARD GASTRO-RESISTANT CAPSULES 
(with blue box) 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Xeristar 60 mg hard gastro-resistant capsules. 
Duloxetine  
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each capsule contains 60 mg of duloxetine (as hydrochloride) 
 
 
3. LIST OF EXCIPIENTS 
 
Contains sucrose 
See leaflet for further information 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Multipack: 500 (25 packs of 20) hard gastro-resistant capsules 
Multipack: 100 (5 packs of 20) hard gastro-resistant capsules 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Oral use. 
Read the leaflet before use. 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 
 
Keep out of the sight and reach of children. 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
 
8. EXPIRY DATE 
 
EXP 
 
 
9. SPECIAL STORAGE CONDITIONS 
 
Store in the original package in order to protect from moisture. Do not store above 30°C 
 
 
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 



 

 32 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 

 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
Esteve Pharmaceuticals, S.A. 
Passeig de la Zona Franca, 109  
08038 Barcelona 
Spain 
 
 
12. MARKETING AUTHORISATION NUMBER(S) 
 
EU/1/04/297/007 (500 hard gastro-resistant capsules) (25 packs of 20) 
EU/1/04/297/008 (100 hard gastro-resistant capsules) (5 packs of 20) 
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
Medicinal product subject to medical prescription. 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Xeristar 60 mg  
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 
PC:  
SN: 
NN:  
 



 

 33 

 
MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS 
60 mg hard gastro-resistant capsules 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Xeristar 60 mg hard gastro-resistant capsules 
Duloxetine 
 
 
2. NAME OF THE MARKETING AUTHORISATION HOLDER 
 
Esteve  
 
 
3. EXPIRY DATE 
 
EXP  
 
 
4. BATCH NUMBER 
 
Lot 
 
 
5. OTHER 
 



 

 34 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

B. PACKAGE LEAFLET 



 

 35 

Package leaflet: information for the user 
 

Xeristar 30 mg hard gastro-resistant capsules 
Xeristar 60 mg hard gastro-resistant capsules 

Duloxetine (as hydrochloride) 
 
 

Read all of this leaflet carefully before you start taking this medicine because it contains 
important information for you. 
- Keep this leaflet. You may need to read it again. 
- If you have any further questions, ask your doctor or pharmacist. 
- This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, 

even if their signs of illness are the same as yours. 
- If you get any of the side effects talk to your doctor or pharmacist. This includes any possible 

side effects not listed in this leaflet. See section 4.. 
 
What is in this leaflet:  
1. What Xeristar is and what it is used for 
2. What you need to know before you take Xeristar 
3. How to take Xeristar 
4. Possible side effects 
5. How to store Xeristar 
6. Contents of the pack and other information 
 
 
1. What Xeristar is and what it is used for 
 
Xeristar contains the active substance duloxetine. Xeristar increases the levels of serotonin and 
noradrenaline in the nervous system. 
 
Xeristar is used in adults to treat: 
• depression 
• generalised anxiety disorder (chronic feeling of anxiety or nervousness) 
• diabetic neuropathic pain (often described as burning, stabbing, stinging, shooting or aching or 

like an electric shock. There may be loss of feeling in the affected area, or sensations such as 
touch, heat, cold or pressure may cause pain) 

 
Xeristar starts to work in most people with depression or anxiety within two weeks of starting 
treatment, but it may take 2-4 weeks before you feel better. Tell your doctor if you do not start to feel 
better after this time. Your doctor may continue to give you Xeristar when you are feeling better to 
prevent your depression or anxiety from returning. 
 
In people with diabetic neuropathic pain it can take some weeks before you feel better. Talk to your 
doctor if you do not feel better after 2 months. 
 
 
2. What you need to know before you take Xeristar 
 
DO NOT take Xeristar if you: 
− are allergic to duloxetine or any of the other ingredients of this medicine (listed in section 6) 
− have liver disease 
− have severe kidney disease 
− are taking or have taken within the last 14 days, another medicine known as a monoamine 

oxidase inhibitor (MAOI) (see ‘Other medicines and Xeristar’) 
− are taking fluvoxamine which is usually used to treat depression, ciprofloxacin or enoxacin 

which are used to treat some infections 



 

 36 

− are taking other medicines containing duloxetine (see ‘Other medicines and Xeristar’)  
Talk to your doctor if you have high blood pressure or heart disease. Your doctor will tell you if you 
should be taking Xeristar. 
 
Warnings and precautions 
The following are reasons why Xeristar may not be suitable for you. Talk to your doctor before you 
take Xeristar if you: 
- are taking other medicines to treat depression (see ‘Other medicines and Xeristar’) 
- are taking St. John’s Wort, a herbal treatment (Hypericum perforatum) 
- have kidney disease 
- have had seizures (fits) 
- have had mania 
- suffer from bipolar disorder 
- have eye problems, such as certain kinds of glaucoma (increased pressure in the eye) 
- have a history of bleeding disorders (tendency to develop bruises), especially if you are 

pregnant (see ‘Pregnancy and breast-feeding‘) 
- are at risk of low sodium levels (for example if you are taking diuretics, especially if you are 

elderly) 
- are currently being treated with another medicine which may cause liver damage 
- are taking other medicines containing duloxetine (see ‘Other medicines and Xeristar’) 
 
Xeristar may cause a sensation of restlessness or an inability to sit or stand still. You should tell your 
doctor if this happens to you. 
 
Medicines like Xeristar (so called SSRIs/SNRIs) may cause symptoms of sexual dysfunction (see 
section 4). In some cases, these symptoms have continued after stopping treatment. 
 
Thoughts of suicide and worsening of your depression or anxiety disorder 
If you are depressed and/or have anxiety disorders you can sometimes have thoughts of harming or 
killing yourself. These may be increased when first starting antidepressants, since these medicines all 
take time to work, usually about two weeks but sometimes longer. 
You may be more likely to think like this if you:  
- have previously had thoughts about killing or harming yourself 
- are a young adult. Information from clinical trials has shown an increased risk of suicidal 

behaviour in adults aged less than 25 years with psychiatric conditions who were treated with an 
antidepressant 

 
If you have thoughts of harming or killing yourself at any time, contact your doctor or go to a 
hospital straight away. 
You may find it helpful to tell a relative or close friend that you are depressed or have an anxiety 
disorder, and ask them to read this leaflet. You might ask them to tell you if they think your depression 
or anxiety is getting worse, or if they are worried about changes in your behaviour. 
 
Children and adolescents under 18 years of age 
Xeristar should normally not be used for children and adolescents under 18 years. Also, you should 
know that patients under 18 have an increased risk of side-effects such as suicide attempt, suicidal 
thoughts and hostility (predominantly aggression, oppositional behaviour and anger) when they take 
this class of medicines. Despite this, your doctor may prescribe Xeristar for patients under 18 because 
he/she decides that this is in their best interests. If your doctor has prescribed Xeristar for a patient 
under 18 and you want to discuss this, please go back to your doctor. You should inform your doctor 
if any of the symptoms listed above develop or worsen when patients under 18 are taking Xeristar. 
Also, the long-term safety effects concerning growth, maturation, and cognitive and behavioural 
development of Xeristar in this age group have not yet been demonstrated. 
 
Other medicines and Xeristar 
Tell your doctor or pharmacist if you are taking, have recently taken or might take any other 
medicines, including medicines obtained without a prescription.  



 

 37 

 
The main ingredient of Xeristar, duloxetine, is used in other medicines for other conditions:  

• diabetic neuropathic pain, depression, anxiety and urinary incontinence  
Using more than one of these medicines at the same time should be avoided. Check with your doctor if 
you are already taking other medicines containing duloxetine.  
 
Your doctor should decide whether you can take Xeristar with other medicines. Do not start or stop 
taking any medicines, including those bought without a prescription and herbal remedies, before 
checking with your doctor.   
 
You should also tell your doctor if you are taking any of the following: 
 
Monoamine oxidase inhibitors (MAOIs): You should not take Xeristar if you are taking, or have 
recently taken (within the last 14 days) another antidepressant medicine called a monoamine oxidase 
inhibitor (MAOI). Examples of MAOIs include moclobemide (an antidepressant) and linezolid (an 
antibiotic). Taking a MAOI together with many prescription medicines, including Xeristar, can cause 
serious or even life-threatening side effects. You must wait at least 14 days after you have stopped 
taking an MAOI before you can take Xeristar. Also, you need to wait at least 5 days after you stop 
taking Xeristar before you take a MAOI. 
 
Medicines that cause sleepiness: These include medicines prescribed by your doctor including 
benzodiazepines, strong painkillers, antipsychotics, phenobarbital and antihistamines.  
 
Medicines that increase the level of serotonin: Triptans, tramadol, tryptophan, SSRIs (such as 
paroxetine and fluoxetine), SNRIs (such as venlafaxine), tricyclic antidepressants (such as 
clomipramine, amitriptyline), pethidine, St John’s Wort and MAOIs (such as moclobemide and 
linezolid). These medicines increase the risk of side effects; if you get any unusual symptom taking 
any of these medicines together with Xeristar, you should see your doctor. 
 
Oral anticoagulants or antiplatelet agents: Medicines which thin the blood or prevent the blood from 
clotting. These medicines might increase the risk of bleeding. 
 
Xeristar with food, drink and alcohol 
Xeristar may be taken with or without food. Care should be taken if you drink alcohol while you are 
being treated with Xeristar. 
 
Pregnancy and breast-feeding 
If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask 
your doctor or pharmacist for advice before taking this medicine. 
• Tell your doctor if you become pregnant, or you are trying to become pregnant, while you are 

taking Xeristar. You should use Xeristar only after discussing the potential benefits and any 
potential risks to your unborn child with your doctor. 

 
• Make sure your midwife and/or doctor knows you are on Xeristar. When taken during 

pregnancy, similar drugs (SSRIs) may increase the risk of a serious condition in babies, called 
persistent pulmonary hypertension of the newborn (PPHN), making the baby breathe faster and 
appear bluish. These symptoms usually begin during the first 24 hours after the baby is born. If 
this happens to your baby you should contact your midwife and/or doctor immediately. 
 

• If you take Xeristar near the end of your pregnancy, your baby might have some symptoms 
when it is born. These usually begin at birth or within a few days of your baby being born. 
These symptoms may include floppy muscles, trembling, jitteriness, not feeding properly, 
trouble with breathing and fits. If your baby has any of these symptoms when it is born, or you 
are concerned about your baby’s health, contact your doctor or midwife who will be able to 
advise you. 
 



 

 38 

• If you take Xeristar near the end of your pregnancy there is an increased risk of excessive 
vaginal bleeding shortly after birth, especially if you have a history of bleeding disorders. Your 
doctor or midwife should be aware that you are taking duloxetine so they can advise you. 

 
• Tell your doctor if you are breast-feeding. The use of Xeristar while breastfeeding is not 

recommended. You should ask your doctor or pharmacist for advice. 
 
Driving and using machines 
Xeristar may make you feel sleepy or dizzy. Do not drive or use any tools or machines until you know 
how Xeristar affects you. 
 
Xeristar contains sucrose 
Xeristar contains sucrose. If you have been told by your doctor that you have an intolerance to some 
sugars, contact your doctor before taking this medicinal product. 
 
 
3. How to take Xeristar 
 
Always take this medicine exactly as your doctor or pharmacist has told you. Check with your doctor 
or pharmacist if you are not sure. 
 
Xeristar is for oral use. You should swallow your capsule whole with a drink of water. 
 
For depression and diabetic neuropathic pain:  
The usual dose of Xeristar is 60 mg once a day, but your doctor will prescribe the dose that is right for 
you.  
 
For generalised anxiety disorder: 
The usual starting dose of Xeristar is 30 mg once a day after which most patients will receive 60 mg 
once a day, but your doctor will prescribe the dose that is right for you. The dose may be adjusted up 
to 120 mg a day based on your response to Xeristar. 
 
To help you remember to take Xeristar, you may find it easier to take it at the same times every day. 
 
Talk with your doctor about how long you should keep taking Xeristar. Do not stop taking Xeristar, or 
change your dose, without talking to your doctor. Treating your disorder properly is important to help 
you get better.  If it is not treated, your condition may not go away and may become more serious and 
difficult to treat. 
 
If you take more Xeristar than you should 
Call your doctor or pharmacist immediately if you take more than the amount of Xeristar prescribed 
by your doctor. Symptoms of overdose include sleepiness, coma, serotonin syndrome (a rare reaction 
which may cause feelings of great happiness, drowsiness, clumsiness, restlessness, feeling of being 
drunk, fever, sweating or rigid muscles), fits, vomiting and fast heart rate. 
 
If you forget to take Xeristar 
If you miss a dose, take it as soon as you remember. However, if it is time for your next dose, skip the 
missed dose and take only a single dose as usual. Do not take a double dose to make up for a forgotten 
dose. Do not take more than the daily amount of Xeristar that has been prescribed for you in one day. 
 
If you stop taking Xeristar 
DO NOT stop taking your capsules without the advice of your doctor even if you feel better. If your 
doctor thinks that you no longer need Xeristar he or she will ask you to reduce your dose over at least 
2 weeks before stopping treatment altogether.  
 



 

 39 

Some patients who stop taking Xeristar suddenly have had symptoms such as: 
• dizziness, tingling feelings like pins and needles or electric shock-like feelings (particularly in 

the head), sleep disturbances (vivid dreams, nightmares, inability to sleep), fatigue, sleepiness, 
feeling restless or agitated, feeling anxious, feeling sick (nausea) or being sick (vomiting), 
shaking (tremor), headaches, muscle pain, feeling irritable, diarrhoea, excessive sweating or 
vertigo. 

These symptoms are usually not serious and disappear within a few days, but if you have symptoms 
that are troublesome you should ask your doctor for advice. 
 
If you have any further questions on the use of this medicine, ask your doctor or pharmacist. 
 
 
4. Possible side effects 
 
Like all medicines, this medicine can cause side effects, although not everybody gets them. These 
effects are normally mild to moderate and often disappear after a few weeks. 
 
Very common side effects (may affect more than 1 in 10 people) 
• headache, feeling sleepy 
• feeling sick (nausea), dry mouth 
 
Common side effects (may affect up to 1 in 10 people) 
• lack of appetite 
• trouble sleeping, feeling agitated, less sex drive, anxiety, difficulty or failure to experience 

orgasm, unusual dreams 
• dizziness, feeling sluggish, tremor, numbness, including numbness, pricking or tingling of the 

skin 
• blurred eyesight 
• tinnitus (hearing sound in the ear when there is no external sound) 
• feeling the heart pumping in the chest,  
• increased blood pressure, flushing 
• increased yawning 
• constipation, diarrhoea, stomach pain, being sick (vomiting), heartburn or indigestion, breaking 

wind 
• increased sweating, (itchy) rash  
• muscle pain, muscle spasm 
• painful urination, frequent urination 
• problems getting an erection, changes in ejaculation 
• falls (mostly in elderly people), fatigue 
• weight loss 

 
Children and adolescents under 18 years of age with depression treated with this medicine had some 
weight loss when they first start taking this medicine. Weight increased to match other children and 
adolescents of their age and sex after 6 months of treatment. 
 
Uncommon side effects (may affect up to 1 in 100 people) 
• throat inflammation that causes a hoarse voice 
• suicidal thoughts, difficulty sleeping, grinding or clenching the teeth, feeling disorientated, lack 

of motivation 
• sudden involuntary jerks or twitches of the muscles, sensation of restlessness or an inability to 

sit or stand still, feeling nervous, difficulty concentrating, changes in sense of taste, difficulty 
controlling movement e.g. lack of coordination or involuntary movements of the muscles, 
restless legs syndrome, poor sleep quality  

• large pupils (the dark centre of the eye), problems with eyesight 
• feeling of dizziness or “spinning” (vertigo), ear pain 



 

 40 

• fast and/or irregular heart beat 
• fainting, dizziness, lightheadedness or fainting on standing up, cold fingers and/or toes 
• throat tightness, nose bleeds 
• vomiting blood, or black tarry stools (faeces), gastroenteritis, burping, difficulty swallowing 
• inflammation of the liver that may cause abdominal pain and yellowing of the skin or whites of 

the eyes 
• night sweats, hives, cold sweats, sensitivity to sunlight, increased tendency to bruise   
• muscle tightness, muscle twitching  
• difficulty or inability to pass urine, difficulty to start urinating, needing to pass urine during the 

night, needing to pass more urine than normal, having a decreased urine flow 
• abnormal vaginal bleeding, abnormal periods, including heavy, painful, irregular or prolonged 

periods, unusually light or missed periods, pain in the testicles or scrotum 
• chest pain, feeling cold, thirst, shivering, feeling hot, abnormal gait 
• weight gain 
• Xeristar may cause effects that you may not be aware of, such as increases in liver enzymes or 

blood levels of potassium, creatine phosphokinase, sugar, or cholesterol 
 

Rare side effects (may affect up to 1 in 1000 people) 
• serious allergic reaction which causes difficulty in breathing or dizziness with swollen tongue or 

lips, allergic reactions  
• decreased thyroid gland activity which can cause tiredness or weight gain  
• dehydration, low levels of sodium in the blood (mostly in elderly people; the symptoms may 

include feeling dizzy, weak, confused, sleepy or very tired, or feeling or being sick, more 
serious symptoms are fainting, fits or falls), syndrome of inappropriate secretion of anti-diuretic 
hormone (SIADH)   

• suicidal behaviour, mania (over activity, racing thoughts and decreased need for sleep), 
hallucinations, aggression and anger 

•  “Serotonin syndrome” (a rare reaction which may cause feelings of great happiness, 
drowsiness, clumsiness, restlessness, feeling of being drunk, fever, sweating or rigid muscles), 
fits 

• increased pressure in the eye (glaucoma) 
• coughing, wheezing and shortness of breath which may be accompanied by a high temperature 
• inflammation of the mouth, passing bright red blood in your stools, bad breath, inflammation of 

the large intestine (leading to diarrhoea) 
• liver failure, yellowing of the skin or whites of the eyes (jaundice) 
• Stevens-Johnson syndrome (serious illness with blistering of the skin, mouth, eyes and genitals), 

serious allergic reaction which causes swelling of the face or throat (angioedema) 
• contraction of the jaw muscle 
• abnormal urine odour  
• menopausal symptoms, abnormal production of breast milk in men or women 
• excessive vaginal bleeding shortly after birth (postpartum haemorrhage) 
 
Very rare side effects (may affect up to 1 in 10,000 people) 
• inflammation of the blood vessels in the skin (cutaneous vasculitis) 
 
Reporting of side effects 
If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects 
not listed in this leaflet. You can also report side effects directly via the national reporting system 
listed in Appendix V. By reporting side effects you can help provide more information on the safety of 
this medicine. 
 
 



 

 41 

5. How to store Xeristar 
 
Keep this medicine out of the sight and reach of children. 
 
Do not use this medicine after the expiry date which is stated on the carton. 
 
Store in the original package to protect from moisture. Do not store above 30°C. 
 
Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to 
throw away medicines you no longer use. These measures will help to protect the environment. 
 
 
6. Contents of the pack and other information 
 
What Xeristar contains 
The active substance is duloxetine.  
Each capsule contains 30 or 60 mg of duloxetine (as hydrochloride). 
 
The other ingredients are: 
Capsule content: hypromellose, hypromellose acetate succinate, sucrose, sugar spheres, talc, titanium 
dioxide (E171), triethyl citrate (See end of section 2 for further information on sucrose). 
Capsule shell: gelatin, sodium lauryl sulfate, titanium dioxide (E171), indigo carmine (E132), yellow 
iron oxide (E172) (60 mg only) and edible green ink (30 mg) or edible white ink (60 mg). 
Edible green ink: synthetic black iron oxide (E172), synthetic yellow iron oxide (E172), propylene 
glycol, shellac. 
Edible white ink: titanium dioxide (E171), propylene glycol, shellac, povidone. 
 
What Xeristar looks like and contents of the pack 
Xeristar is a hard gastro-resistant capsule. Each capsule of Xeristar contains pellets of duloxetine 
hydrochloride with a covering to protect them from stomach acid.   
 
Xeristar is available in 2 strengths: 30 mg and 60 mg. 
The 30 mg capsules are blue and white and are printed with ‘30 mg’ and the code ‘9543’. 
The 60 mg capsules are blue and green and are printed with ‘60 mg’ and the code ‘9542’. 
 
Xeristar 30 mg is available in packs of 7 and 28 capsules.  
Xeristar 60 mg is available in packs of 28, 56, 84, 98, 100 and 500 capsules. 
 
Not all pack sizes may be marketed. 
 
Marketing Authorisation Holder and Manufacturer 
Marketing Authorisation Holder: Esteve Pharmaceuticals, S.A. Passeig de la Zona Franca, 109, 08038 
Barcelona, Spain. 
Manufacturer: Lilly S.A., Avda. De la Industria, 30, 28108 Alcobendas, Madrid, Spain. 
 
 
This leaflet was last revised in 
 
Detailed information on this medicine is available on the European Medicines Agency web site: 
http://www.ema.europa.eu. 
 


	SUMMARY OF PRODUCT CHARACTERISTICS
	A. MANUFACTURER(S) RESPONSIBLE FOR BATCH RELEASE
	B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE
	C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING AUTHORISATION
	D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND EFFECTIVE USE OF THE MEDICINAL PRODUCT
	A. LABELLING
	B. PACKAGE LEAFLET