Duloxetine Zentiva

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ANNEX I 
 

SUMMARY OF PRODUCT CHARACTERISTICS 



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1. NAME OF THE MEDICINAL PRODUCT 
 
Duloxetine Zentiva 30 mg gastro-resistant hard capsules 
Duloxetine Zentiva 60 mg gastro-resistant hard capsules 
 
 
2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 
Duloxetine Zentiva 30 mg gastro-resistant hard capsules 
 
Each capsule contains duloxetine hydrochloride equivalent to 30 mg duloxetine. 
 
Excipient(s) with known effect 
 
Each capsule contains 42.26 – 46.57 mg of sucrose. 
 
Duloxetine Zentiva 60 mg gastro-resistant hard capsules 
 
Each capsule contains duloxetine hydrochloride equivalent to 60 mg duloxetine. 
 
Excipient(s) with known effect 
 
Each capsule contains 84.51 - 93.14 mg of sucrose. 
 
For the full list of excipients, see section 6.1. 
 
 
3. PHARMACEUTICAL FORM 
 
Gastro-resistant hard capsule 
 
Duloxetine Zentiva 30 mg gastro-resistant hard capsules 
 
Hard opaque gelatin capsules of length approx. 15.9 mm with white opaque body and light-blue 
opaque cap which contain off-white to light-brown-yellow spherical pellets. 
 
Duloxetine Zentiva 60 mg gastro-resistant hard capsules 
 
Hard opaque gelatin capsules of length approx. 19.4 mm with ivory opaque body and light-blue 
opaque cap which contain off-white to light-brown-yellow spherical pellets. 
 
 
4. CLINICAL PARTICULARS 
 
4.1 Therapeutic indications 
 
Treatment of major depressive disorder. 
Treatment of diabetic peripheral neuropathic pain. 
Treatment of generalised anxiety disorder. 
 
Duloxetine Zentiva is indicated in adults. 
For further information see section 5.1. 



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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. 
 
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 duloxetine 
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 

Duloxetine Zentiva must not be used in patients with liver disease resulting in hepatic impairment (see 
sections 4.3 and 5.2). 



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Renal impairment 

No dosage adjustment is necessary for patients with mild or moderate renal dysfunction (creatinine 
clearance 30 to 80 ml/min). Duloxetine Zentiva 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. 
 
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 Duloxetine Zentiva 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 Duloxetine Zentiva with nonselective, irreversible monoamine oxidase inhibitors 
(MAOIs) is contraindicated (see section 4.5). 
 
Liver disease resulting in hepatic impairment (see section 5.2). 
 
Duloxetine Zentiva 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 Duloxetine Zentiva 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 
 
Duloxetine should be used with caution in patients with a history of mania or a diagnosis of bipolar 
disorder, and/or seizures. 
 



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Mydriasis 
 
Mydriasis has been reported in association with duloxetine, therefore, caution should be used when 
prescribing Duloxetine Zentiva 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). 
 
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 Duloxetine Zentiva 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. 
 



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Other psychiatric conditions for which duloxetine 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. 
 
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 
 
Duloxetine 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 duloxetine, 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. 
 



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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 duloxetine 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 duloxetine 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. 
 
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 
 
Duloxetine Zentiva gastro-resistant hard capsules contain sucrose. Patients with rare hereditary 
problems of fructose intolerance, glucose-galactose malabsorption or sucrase-isomaltase insufficiency 
should not take this medicine. 
 



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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 Duloxetine Zentiva before starting an MAOI (see section 4.3). 
 
The concomitant use of Duloxetine Zentiva 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 duloxetine (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 Duloxetine Zentiva 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 duloxetine 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 duloxetine 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 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 duloxetine 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. 
 



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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 
 

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. 
 
Duloxetine 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 duloxetine while breast-feeding is not recommended. 
 



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Fertility 
 
In animal studies, duloxetine had no effect on male fertility, and effects in females were only evident 
at doses that caused maternal toxicity. 
 
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. Duloxetine 
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 
 
Summary of the safety profile 
 
The most commonly reported adverse reactions in patients treated with duloxetine 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. 
 
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 

 

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 

Serotonin syndrome6 
Convulsion1 
Psychomotor 
restlessness6 
Extra-pyramidal 

 



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Very common  Common  Uncommon  Rare  Very Rare 
Dysgeusia 
Dyskinesia 
Restless legs 
syndrome 
Poor quality sleep 

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) 
Acute liver injury 

Hepatic failure6 
Jaundice6 

 

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 Urinary retention Urine odour abnormal  



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Very common  Common  Uncommon  Rare  Very Rare 
Pollakiuria Urinary hesitation 

Nocturia 
Polyuria 
Urine flow decreased 

Reproductive system and breast disorders 
 Erectile 

dysfunction 
Ejaculation 
disorder 
Ejaculation 
delayed 

Gynaecological 
haemorrhage 
Menstrual disorder 
Sexual dysfunction 
Testicular pain 

Menopausal 
symptoms 
Galactorrhoea 
Hyperprolactinaemia 
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). 
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. 
 
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 



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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. 
 
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 
5400 mg were reported. Some fatalities have occurred, primarily with mixed overdoses, but also with 
duloxetine alone at a dose of approximately 1,000 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. 
 
 

http://www.ema.europa.eu/docs/en_GB/document_library/Template_or_form/2013/03/WC500139752.doc


14 

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 

Duloxetine 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 duloxetine 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, duloxetine’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. 
 
Duloxetine 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 duloxetine 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 
duloxetine 60 mg once daily were randomised to either duloxetine 60 mg once daily or placebo for a 
further 6-months. Duloxetine 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 
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 duloxetine 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 duloxetine 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 (120 mg per day) are limited and thus, caution is recommended 
when treating this population. 



15 

 

Generalised Anxiety Disorder 
Duloxetine 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. 
 
Duloxetine 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 
duloxetine compared to placebo. Duloxetine 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 
duloxetine were randomised to either duloxetine or placebo for a further 6-months. Duloxetine 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 duloxetine and 42% for placebo. 
 
The efficacy of duloxetine 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 duloxetine 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 duloxetine 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, duloxetine 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 duloxetine 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. 
 
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 



16 

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 the 
reference medicinal product containing duloxetine 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 extent of 
absorption (approximately 11 %). These changes do not have any clinical significance. 
 



17 

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 sulphate 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 h). After an intravenous 
dose the plasma clearance of duloxetine ranges from 22 l/h to 46 l/h (mean of 36 l/h). After an oral 
dose the apparent plasma clearance of duloxetine ranges from 33 to 261 l/h (mean 101 l/h). 
 
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 



18 

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 
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 
 
Sucrose 
Maize starch 
Hypromellose 
Talc 
Hypromellose acetate succinate 
Triethyl citrate 
 
Capsule shell 
 
Duloxetine Zentiva 30 mg gastro-resistant hard capsules 
Capsule cap 
− Indigo carmine (E132) 
− Titanium dioxide (E171) 
− Gelatin 
Capsule body 
− Titanium dioxide (E171) 
− Gelatin 
 
Duloxetine Zentiva 60 mg gastro-resistant hard capsules 
Capsule cap 

− Indigo carmine (E132) 
− Titanium dioxide (E171) 
− Gelatin 



19 

Capsule body 

− Yellow iron oxide (E172) 
− Titanium dioxide (E171) 
− Gelatin 
 
6.2 Incompatibilities 
 
Not applicable. 
 
6.3 Shelf life 
 
2 years 
 
6.4 Special precautions for storage 
 

This medicinal product does not require any special temperature storage conditions. Store in the 
original package in order to protect from moisture. 
 
6.5 Nature and contents of container 
 
Opaque PVC/PCTFE/Alu blisters. 
 
Pack size: 
Duloxetine Zentiva 30 mg gastro-resistant hard capsules 
7, 28, 56, 84 and 98 capsules 
 
Duloxetine Zentiva 60 mg gastro-resistant hard capsules 
28, 56, 84 and 98 capsules 
 
Not all pack sizes may be marketed. 
 
6.6 Special precautions for disposal  
 
No special requirements. 
 
 
7. MARKETING AUTHORISATION HOLDER 
 
Zentiva, k.s. 
U Kabelovny 130 
102 37 Prague 10 
Czech Republic 
 
 
8. MARKETING AUTHORISATION NUMBER(S)  
 
Duloxetine Zentiva 30 mg gastro-resistant hard capsules 
 
EU/1/15/1028/001 
EU/1/15/1028/002 
EU/1/15/1028/003 
EU/1/15/1028/008 
EU/1/15/1028/009 
 
Duloxetine Zentiva 60 mg gastro-resistant hard capsules 
 
EU/1/15/1028/004 



20 

EU/1/15/1028/005 
EU/1/15/1028/006 
EU/1/15/1028/007 
 
 
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 
Date of first authorisation: 20/08/2015 
Date of latest renewal:  
 
 
10. DATE OF REVISION OF THE TEXT 
 
 
Detailed information on this medicinal product is available on the website of the European Medicines 
Agency http://www.ema.europa.eu. 

http://www.ema.europa.eu/


21 

 
 
 
 
 
 
 
 
 
 
 
 
 
 

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 



22 

 
A. MANUFACTURER(S) RESPONSIBLE FOR BATCH RELEASE 
 
Name and address of the manufacturer(s) responsible for batch release 
 
S.C. Zentiva S.A 
Theodor Pallady Nr 50 
032266 Bucharest 
Romania 
 
 
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 (pharmacovigilance or risk minimisation) milestone being reached. 

 



23 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX III 
 

LABELLING AND PACKAGE LEAFLET 



24 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

A. LABELLING 



25 

 
PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
PAPER FOLDING BOX 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Duloxetine Zentiva 30 mg gastro-resistant hard capsules 
duloxetine 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each capsule contains duloxetine hydrochloride equivalent to 30 mg duloxetine. 
 
 
3. LIST OF EXCIPIENTS 
 
Contains sucrose. 
See leaflet for further information. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Gastro-resistant hard capsule 
 

7 gastro-resistant hard capsules 
28 gastro-resistant hard capsules 
56 gastro-resistant hard capsules 
84 gastro-resistant hard capsules 
98 gastro-resistant hard capsules 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Read the package leaflet before use. 
Oral 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 
 
 



26 

9. SPECIAL STORAGE CONDITIONS 
 
Store in the original package in order to protect from moisture. 
 
 
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 
 
Zentiva, k.s. 
U Kabelovny 130 
102 37 Prague 10 
Czech Republic 
 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/15/1028/001 
EU/1/15/1028/002 
EU/1/15/1028/003 
EU/1/15/1028/008 
EU/1/15/1028/009 
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 

 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Duloxetine Zentiva 30 mg 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
 
18. UNIQUE IDENTIFIER – HUMAN READABLE DATA 
 
PC: 
SN: 
NN: 



27 

 
MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS 
 
BLISTER 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 

Duloxetine Zentiva 30 mg gastro-resistant hard capsules 
duloxetine 
 
 
2. NAME OF THE MARKETING AUTHORISATION HOLDER 
 
Zentiva logo 
 
 
3. EXPIRY DATE 
 
EXP 
 
 
4. BATCH NUMBER 
 
Lot 
 
 
5. OTHER 
 



28 

 
PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
PAPER FOLDING BOX 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Duloxetine Zentiva 60 mg gastro-resistant hard capsules 
duloxetine 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each capsule contains duloxetine hydrochloride equivalent to 60 mg duloxetine. 
 
 
3. LIST OF EXCIPIENTS 
 
Contains sucrose. 
See leaflet for further information. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Gastro-resistant hard capsule 
 

28 gastro-resistant hard capsules 
56 gastro-resistant hard capsules 
84 gastro-resistant hard capsules 
98 gastro-resistant hard capsules 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Read the package leaflet before use. 
Oral 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 
 
 



29 

9. SPECIAL STORAGE CONDITIONS 
 
Store in the original package in order to protect from moisture. 
 
 
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 
 
Zentiva, k.s. 
U Kabelovny 130 
102 37 Prague 10 
Czech Republic 
 
 
12. MARKETING AUTHORISATION NUMBER(S) 
 
EU/1/15/1028/004 
EU/1/15/1028/005 
EU/1/15/1028/006 
EU/1/15/1028/007 
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Duloxetine Zentiva 60 mg 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 
PC: 
SN: 
NN: 



30 

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



31 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

B. PACKAGE LEAFLET 



32 

Package leaflet: Information for the user 
 

Duloxetine Zentiva 30 mg gastro-resistant hard capsules 
Duloxetine Zentiva 60 mg gastro-resistant hard capsules 

 
duloxetine 

 
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 Duloxetine Zentiva is and what it is used for 
2. What you need to know before you take Duloxetine Zentiva 
3. How to take Duloxetine Zentiva 
4. Possible side effects 
5. How to store Duloxetine Zentiva 
6. Contents of the pack and other information 
 
 
1. What Duloxetine Zentiva is and what it is used for 
 
Duloxetine Zentiva contains the active substance duloxetine. Duloxetine Zentiva increases the levels 
of serotonin and noradrenaline in the nervous system. 
 
Duloxetine Zentiva 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). 

 
Duloxetine Zentiva 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 Duloxetine Zentiva 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 Duloxetine Zentiva 
 

Do not take Duloxetine Zentiva 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 Duloxetine Zentiva’); 
• are taking fluvoxamine which is usually used to treat depression, ciprofloxacin or enoxacin 

which are used to treat some infections. 



33 

• are taking other medicines containing duloxetine (see ‘Other medicines and Duloxetine 
Zentiva’)  

 
Talk to your doctor if you have high blood pressure or heart disease. Your doctor will tell you if you 
should be taking Duloxetine Zentiva. 
 
Warnings and precautions 
The following are reasons why Duloxetine Zentiva may not be suitable for you. Talk to your doctor 
before taking Duloxetine Zentiva if you: 
• are taking other medicines to treat depression (see ‘Other medicines and Duloxetine Zentiva’); 
• 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 Duloxetine 

Zentiva’). 
 
Duloxetine Zentiva 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 Duloxetine Zentiva (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 
Duloxetine Zentiva 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 Duloxetine Zentiva for 
patients under 18 because he/she decides that this is in their best interests. If your doctor has 
prescribed Duloxetine Zentiva 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 Duloxetine Zentiva. Also, the long-term safety effects concerning 



34 

growth, maturation, and cognitive and behavioural development of duloxetine in this age group have 
not yet been demonstrated. 
 
Other medicines and Duloxetine Zentiva 
Tell your doctor or pharmacist if you are taking, have recently taken or might take any other 
medicines. 
 
The main ingredient of Duloxetine Zentiva, 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 Duloxetine Zentiva 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 Duloxetine Zentiva 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 Duloxetine Zentiva, 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 
Duloxetine Zentiva. Also, you need to wait at least 5 days after you stop taking Duloxetine 
Zentiva 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 Duloxetine Zentiva, 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. 

 
Duloxetine Zentiva with food, drink and alcohol 
Duloxetine Zentiva may be taken with or without food. Care should be taken if you drink alcohol 
while you are being treated with Duloxetine Zentiva. 
 
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 Duloxetine Zentiva. You should use Duloxetine Zentiva 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 Duloxetine Zentiva. 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 Duloxetine Zentiva 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 



35 

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. 

 
• If you take Duloxetine Zentiva 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 Duloxetine Zentiva while breast-feeding is 

not recommended. You should ask your doctor or pharmacist for advice. 
 
Driving and using machines 
Duloxetine Zentiva may make you feel sleepy or dizzy. Do not drive or use any tools or machines 
until you know how Duloxetine Zentiva affects you. 
 
Duloxetine Zentiva 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 Duloxetine Zentiva 
 
Always take this medicine exactly as your doctor or pharmacist has told you. Check with your doctor 
or pharmacist if you are not sure. 
 
Duloxetine Zentiva 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 Duloxetine Zentiva 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 Duloxetine Zentiva 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 Duloxetine Zentiva. 
 
To help you remember to take Duloxetine Zentiva, 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 Duloxetine Zentiva. Do not stop taking 
Duloxetine Zentiva, 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 Duloxetine Zentiva than you should 
Call your doctor or pharmacist immediately if you take more than the amount of Duloxetine Zentiva 
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 Duloxetine Zentiva 
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 Duloxetine Zentiva that has been prescribed for you 
in one day. 



36 

 
If you stop taking Duloxetine Zentiva 
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 Duloxetine Zentiva he or she will ask you to reduce your dose 
over at least 2 weeks before stopping treatment altogether. 
 
Some patients who stop taking Duloxetine Zentiva 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; 



37 

• 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; 
• fast and/or irregular heart beat; 
• fainting, dizziness, light-headedness 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; 
• Duloxetine Zentiva 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 1,000 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. 

http://www.ema.europa.eu/docs/en_GB/document_library/Template_or_form/2013/03/WC500139752.doc


38 

 
 
5. How to store Duloxetine Zentiva 
 
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/blister after EXP. The 
expiry date refers to the last day of that month. 
 
This medicine does not require any special temperature storage conditions. Store in the original 
package in order to protect from moisture. 
 
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 protect the environment. 
 
 
6. Contents of the pack and other information 
 
What Duloxetine Zentiva contains 
The active substance is duloxetine. Each capsule contains duloxetine hydrochloride equivalent to 30 or 
60 mg duloxetine. 
 
The other ingredients are: 
Capsule content: sucrose, maize starch, hypromellose, talc, hypromellose acetate succinate, triethyl 
citrate. 
Capsule shell: 
Duloxetine Zentiva 30 mg: 

Capsule cap: Indigo carmine (E132), titanium dioxide (E171), gelatin 
Capsule body: titanium dioxide (E171), gelatin 
Duloxetine Zentiva 60 mg: 

Capsule cap: Indigo carmine (E132), titanium dioxide (E171), gelatin 
Capsule body: yellow iron oxide (E172), titanium dioxide (E171), gelatin 
 
What Duloxetine Zentiva looks like and contents of the pack 
Duloxetine Zentiva is a gastro-resistant hard capsule. Each capsule of Duloxetine Zentiva contains 
pellets of duloxetine hydrochloride with a covering to protect them from stomach acid. 
 
Duloxetine Zentiva is available in 2 strengths: 30 mg and 60 mg. 
 
The 30 mg capsules are hard opaque gelatin capsules of length approx. 15.9 mm with white opaque 
body and light-blue opaque cap which contain off-white to light-brown-yellow spherical pellets. 
 
The 60 mg capsules are hard opaque gelatin capsules of length approx. 19.4 mm with ivory opaque 
body and light-blue opaque cap which contain off-white to light-brown-yellow spherical pellets. 
 
Duloxetine Zentiva 30 mg is available in packs of 7, 28, 56, 84 and 98 capsules. 
Duloxetine Zentiva 60 mg is available in packs of 28, 56, 84 and 98 capsules. 
Not all pack sizes may be marketed. 
 
Marketing Authorisation Holder 
Zentiva, k.s. 
U Kabelovny 130 
102 37 Prague 10 
Czech Republic 
 
Manufacturer 
S.C. Zentiva S.A 



39 

Theodor Pallady Nr 50 
032266 Bucharest 
Romania 
 
For any information about this medicine, please contact the local representative of the Marketing 
Authorisation Holder: 
 
België/Belgique/Belgien 
Zentiva, k.s. 
Tél/Tel: +32 280 86 420 
PV-Belgium@zentiva.com 

Lietuva 
Zentiva, k.s. 
Tel: +370 52152025 
PV-Lithuania@zentiva.com 

България 
Zentiva, k.s. 
Тел: + 359 2 805 72 08 
PV-Bulgaria@zentiva.com 

Luxembourg/Luxemburg 
Zentiva, k.s. 
Tél/Tel: +352 208 82330 
PV-Luxembourg@zentiva.com 

Česká republika 
Zentiva, k.s. 
Tel: +420 267 241 111 
PV-Czech-Republic@zentiva.com 

Magyarország 
Zentiva, k.s. 
Tel.: +36 165 55 722 
PV-Hungary@zentiva.com 

Danmark 
Zentiva, k.s. 
Tlf: +45 787 68 400 
PV-Denmark@zentiva.com 

Malta 
Zentiva, k.s. 
Tel: +356 277 82 052 
PV-Malta@zentiva.com 

Deutschland 
Zentiva Pharma GmbH  
Tel: +49 (0) 800 53 53 010 
PV-Germany@zentiva.com 

Nederland 
Zentiva, k.s. 
Tel: +31 202 253 638 
PV-Netherlands@zentiva.com 

Eesti 
Zentiva, k.s. 
Tel: +372 52 70308 
PV-Estonia@zentiva.com 

Norge 
Zentiva, k.s. 
Tlf: +47 219 66 203 
PV-Norway@zentiva.com 

Ελλάδα 
Zentiva, k.s. 
Τηλ: +30 211 198 7510 
PV-Greece@zentiva.com 

Österreich 
Zentiva, k.s. 
Tel: +43 720 778 877 
PV-Austria@zentiva.com 

España 
Zentiva, k.s. 
Tel: +34 931 815 250 
PV-Spain@zentiva.com 

Polska 
Zentiva Polska Sp. z o.o. 
Tel: + 48 22 375 92 00 
PV-Poland@zentiva.com 

France 
Zentiva France 
Tél: +33 (0) 800 089 219  
PV-France@zentiva.com 

Portugal 
Zentiva Portugal, Lda 
Tel: +351210601360 
PV-Portugal@zentiva.com 

Hrvatska 
Zentiva, k.s. 
Tel: +385 155 17 772 
PV-Croatia@zentiva.com 

România 
ZENTIVA S.A. 
Tel: +40 021.304.7597 
zentivaRO@zentiva.com 

Ireland 
Zentiva, k.s. 
Tel: +353 766 803 944 
PV-Ireland@zentiva.com 

Slovenija 
Zentiva, k.s. 
Tel: +386 360 00 408 
PV-Slovenia@zentiva.com 



40 

Ísland 
Zentiva, k.s. 
Sími: +354 539 0650 
PV-Iceland@zentiva.com 

Slovenská republika 
Zentiva, a.s. 
Tel: +421 2 3918 3010 
PV-Slovakia@zentiva.com 

Italia 
Zentiva Italia S.r.l. 
Tel: +39-02-38598801 
PV-Italy@zentiva.com 

Suomi/Finland 
Zentiva, k.s. 
Puh/Tel: +358 942 598 648 
PV-Finland@zentiva.com 

Κύπρος 
Zentiva, k.s. 
Τηλ: +357 240 30 144 
PV-Cyprus@zentiva.com 

Sverige 
Zentiva, k.s. 
Tel: +46 840 838 822 
PV-Sweden@zentiva.com 

Latvija 
Zentiva, k.s. 
Tel: +371 67893939 
PV-Latvia@zentiva.com 

United Kingdom 
Zentiva Pharma UK Limited 
Tel: +44 (0) 845 372 7101 
PV-United-Kingdom@zentiva.com 

 
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. 
 

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