Brintellix

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ANNEX I 

SUMMARY OF PRODUCT CHARACTERISTICS 

 

 

 

 

 

 

 

 

 

 

 

 



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1. NAME OF THE MEDICINAL PRODUCT 

 

Brintellix 5 mg film-coated tablets 

Brintellix 10 mg film-coated tablets 

Brintellix 15 mg film-coated tablets 

Brintellix 20 mg film-coated tablets 

 

 

2. QUALITATIVE AND QUANTITATIVE COMPOSITION 

 

Brintellix 5 mg film-coated tablets 

 

Each film-coated tablet contains vortioxetine hydrobromide equivalent to 5 mg vortioxetine. 

 

Brintellix 10 mg film-coated tablets 

 

Each film-coated tablet contains vortioxetine hydrobromide equivalent to 10 mg vortioxetine. 

 

Brintellix 15 mg film-coated tablets 

 

Each film-coated tablet contains vortioxetine hydrobromide equivalent to 15 mg vortioxetine. 

 

Brintellix 20 mg film-coated tablets 

 

Each film-coated tablet contains vortioxetine hydrobromide equivalent to 20 mg vortioxetine. 

 

For the full list of excipients, see section 6.1. 

 

 

3. PHARMACEUTICAL FORM 

 

Film-coated tablet (tablet) 

 

Brintellix 5 mg film-coated tablets 

 

Pink, almond-shaped (5 x 8.4 mm) film-coated tablet engraved with “TL” on one side and “5” on the 

other side. 

 

Brintellix 10 mg film-coated tablets 

 

Yellow, almond-shaped (5 x 8.4 mm) film-coated tablet engraved with “TL” on one side and “10” on 

the other side. 

 

Brintellix 15 mg film-coated tablets 

 

Orange, almond-shaped (5 x 8.4 mm) film-coated tablet engraved with “TL” on one side and “15” on 

the other side. 

 

Brintellix 20 mg film-coated tablets 

 

Red, almond-shaped (5 x 8.4 mm) film-coated tablet engraved with “TL” on one side and “20” on the 

other side. 

 

 

 

 



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4. CLINICAL PARTICULARS 

 

4.1 Therapeutic indications 

 

Brintellix is indicated for the treatment of major depressive episodes in adults. 

 

4.2 Posology and method of administration 

 

Posology 

 

The starting and recommended dose of Brintellix is 10 mg vortioxetine once daily in adults less than 

65 years of age. 

 

Depending on individual patient response, the dose may be increased to a maximum of 20 mg 

vortioxetine once daily or decreased to a minimum of 5 mg vortioxetine once daily. 

 

After the depressive symptoms resolve, treatment for at least 6 months is recommended for 

consolidation of the antidepressive response. 

 

Treatment discontinuation 

 

Patients treated with vortioxetine can abruptly stop taking the medicinal product without the need for a 

gradual reduction in dose (see section 5.1). 

 

Special populations 

 

Elderly patients 

The lowest effective dose of 5 mg vortioxetine once daily should always be used as the starting dose in 

patients ≥ 65 years of age. Caution is advised when treating patients ≥ 65 years of age with doses 

higher than 10 mg vortioxetine once daily for which data are limited (see section 4.4). 

 

Cytochrome P450 inhibitors 

Depending on individual patient response, a lower dose of vortioxetine may be considered if a strong 

CYP2D6 inhibitor (e.g. bupropion, quinidine, fluoxetine, paroxetine) is added to vortioxetine 

treatment (see section 4.5). 

 

Cytochrome P450 inducers 

Depending on individual patient response, a dose adjustment of vortioxetine may be considered if a 

broad cytochrome P450 inducer (e.g., rifampicin, carbamazepine, phenytoin) is added to vortioxetine 

treatment (see section 4.5). 

 

Paediatric population 

The safety and efficacy of Brintellix in children aged 7 to 11 years have not been established. No data 

are available (see section 4.4). Brintellix should not be used in adolescents aged 12 to 17 years with 

major depressive disorder (MDD) because efficacy has not been demonstrated (see section 5.1). The 

safety of Brintellix in adolescents aged 12 to 17 years is described in section 4.4, 4.8 and 5.1. 

 

Renal or hepatic impairment 

No dose adjustment is needed based on renal or hepatic function (see section 4.4 and 5.2). 

 

Method of administration  

 

Brintellix is for oral use. 

The film-coated tablets can be taken with or without food. 

 

 



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4.3 Contraindications 

 

Hypersensitivity to the active substance or to any of the excipients listed in section 6.1. 

 

Concomitant use with nonselective monoamine oxidase inhibitors (MAOIs) or selective MAO-A 

inhibitors (see section 4.5). 

 

4.4 Special warnings and precautions for use 

 

Use in paediatric population 

 

Brintellix is not recommended for the treatment of depression in children aged 7 to 11 years since the 

safety and efficacy of vortioxetine have not been established in this age group. Brintellix should not be 

used in adolescents aged 12 to 17 years with major depressive disorder (MDD) because efficacy has 

not been demonstrated (see section 5.1). In general , the adverse reaction profile of vortioxetine in 

adolescents was similar to that seen for adults except for higher incidences reported in adolescents 

than in adults for abdominal pain-related events and suicidal ideation (see section 4.8 and 5.1). In 

clinical studies in children and adolescents treated with antidepressants, suicide-related behaviour 

(suicide attempt and suicidal thoughts) and hostility (predominantly aggression, oppositional 

behaviour, anger) were more frequently observed than in those treated with placebo. 

 

Suicide/suicidal thoughts or clinical worsening 

 

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. 

 

Patients with a history of suicide-related events or those exhibiting a significant degree of suicidal 

ideation prior to commencement of treatment are known to be at greater risk of suicidal thoughts or 

suicide attempts, and should receive careful monitoring during treatment. A meta-analysis of 

placebo-controlled clinical studies of antidepressants in adult patients with psychiatric disorders 

showed an increased risk of suicidal behaviour with antidepressants compared to placebo, in patients 

less than 25 years old. 

 

Close supervision of patients and in particular those at high risk should accompany treatment 

especially in early treatment and following dose changes. Patients (and caregivers of patients) should 

be alerted to 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. 

 

Seizures 

 

Seizures are a potential risk with antidepressants. Therefore, vortioxetine should be introduced 

cautiously in patients who have a history of seizures or in patients with unstable epilepsy (see section 

4.5). Treatment should be discontinued in any patient who develops seizures or for whom there is an 

increase in seizure frequency. 

 

Serotonin Syndrome (SS) or Neuroleptic Malignant Syndrome (NMS) 

 

Serotonin Syndrome (SS) or Neuroleptic Malignant Syndrome (NMS), potentially life-threatening 

conditions, may occur with vortioxetine. The risk of SS or NMS is increased with concomitant use of 

serotonergic-active substances (including triptans), medicinal products that impair the metabolism of 

serotonin (including MAOIs), antipsychotics, and other dopamine antagonists. Patients should be 

monitored for the emergence of signs and symptoms of SS or NMS (see sections 4.3 and 4.5). 

 



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Serotonin Syndrome symptoms include mental status changes (e.g., agitation, hallucinations, coma), 

autonomic instability (e.g., tachycardia, labile blood pressure, hyperthermia), neuromuscular 

aberrations (e.g., hyperreflexia, uncoordination) and/or gastrointestinal symptoms (e.g., nausea, 

vomiting, diarrhoea). If this occurs, treatment with vortioxetine should be discontinued immediately 

and symptomatic treatment should be initiated. 

 

Mania/hypomania 

 

Vortioxetine should be used with caution in patients with a history of mania/hypomania and should be 

discontinued in any patient entering a manic phase. 

 

Aggression/agitation 

Patients treated with antidepressants, including vortioxetine, may also experience feelings of 

aggression, anger, agitation and irritability. Patient’s condition and disease status should be closely 

monitored. Patients (and caregivers of patients) should be alerted to seek medical advice, if 

aggressive/agitated behaviour emerges or aggravates. 

 

Haemorrhage 

 

Bleeding abnormalities, such as ecchymoses, purpura and other haemorrhagic events, such as 

gastrointestinal or gynaecological bleeding, have been reported rarely with the use of antidepressants 

with serotonergic effect, including vortioxetine. SSRIs/SNRIs may increase the risk of postpartum 

haemorrhage, and this risk could potentially apply also to vortioxetine (see section 4.6). Caution is 

advised in patients taking anticoagulants and/or medicinal products known to affect platelet function 

[e.g., atypical antipsychotics and phenothiazines, most tricyclic antidepressants, non-steroidal anti-

inflammatory drugs (NSAIDs), acetylsalicylic acid (ASA)] (see section 4.5) and in patients with 

known bleeding tendencies/disorders. 

 

Hyponatraemia 

 

Hyponatraemia, probably due to inappropriate antidiuretic hormone secretion (SIADH), has been 

reported rarely with the use of antidepressants with serotonergic effect (SSRIs, SNRIs). Caution 

should be exercised in patients at risk, such as the elderly, patients with cirrhosis of the liver or 

patients concomitantly treated with medicinal products known to cause hyponatraemia. 

Discontinuation of vortioxetine should be considered in patients with symptomatic hyponatraemia and 

appropriate medical intervention should be instituted. 

 

Glaucoma 

 

Mydriasis has been reported in association with use of antidepressants, including vortioxetine. This 

mydriatic effect has the potential to narrow the eye angle resulting in increased intraocular pressure 

and angle-closure glaucoma. Caution is advised when prescribing vortioxetine to patients with 

increased intraocular pressure, or those at risk of acute narrow-angle glaucoma. 

 

Elderly 

 

Data on the use of Brintellix in elderly patients with major depressive episodes are limited. Therefore, 

caution should be exercised when treating patients ≥ 65 years of age with doses higher than 10 mg 

vortioxetine once daily (see sections 4.2, 4.8 and 5.2). 

 

Renal or hepatic impairment 

 

Given that subjects with renal or hepatic impairment are vulnerable and given that the data on the use 

of Brintellix in these subpopulations are limited, caution should be exercised when treating these 

patients. (see section 4.2 and 5.2). 



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Brintellix contains Sodium 

 

This medicinal product contains less than 1 mmol sodium (23 mg) per tablet, that is to say essentially 

‘sodium-free’. 

 

4.5 Interaction with other medicinal products and other forms of interaction 

 

Vortioxetine is extensively metabolised in the liver, primarily through oxidation catalysed by CYP2D6 

and to a minor extent CYP3A4/5 and CYP2C9 (see section 5.2). 

 

Potential for other medicinal products to affect vortioxetine 

 

Irreversible non-selective MAOIs 

Due to the risk of serotonin syndrome, vortioxetine is contraindicated in any combination with 

irreversible non-selective MAOIs. Vortioxetine must not be initiated for at least 14 days after 

discontinuation of treatment with an irreversible non-selective MAOI. Vortioxetine must be 

discontinued for at least 14 days before starting treatment with an irreversible non-selective MAOI 

(see section 4.3). 

 

Reversible, selective MAO-A inhibitor (moclobemide) 

The combination of vortioxetine with a reversible and selective MAO-A inhibitor, such as 

moclobemide, is contraindicated (see section 4.3). If the combination proves necessary, the added 

medicinal product should be given with minimum dosage and under close clinical monitoring for 

serotonin sSyndrome (see section 4.4). 

 

Reversible, non-selective MAOI (linezolid) 

The combination of vortioxetine with a weak reversible and non-selective MAOI, such as the 

antibiotic linezolid, is contraindicated (see section 4.3). If the combination proves necessary, the added 

medicinal product should be given with minimum dosage and under close clinical monitoring for 

serotonin syndrome (see section 4.4). 

 

Irreversible, selective MAO-B inhibitor (selegiline, rasagiline) 

Although a lower risk of serotonin syndrome is expected with selective MAO-B inhibitors than with 

MAO-A inhibitors, the combination of vortioxetine with irreversible MAO-B inhibitors, such as 

selegiline or rasagiline should be administered with caution. Close monitoring for serotonin syndrome 

is necessary if used concomitantly (see section 4.4). 

 

Serotonergic medicinal products 

Co-administration of medicinal products with serotonergic effect (e.g., tramadol, sumatriptan and 

other triptans) may lead to serotonin syndrome (see section 4.4). 

 

St. John’s wort 

Concomitant use of antidepressants with serotonergic effect and herbal remedies containing St. John’s 

wort (Hypericum perforatum) may result in a higher incidence of adverse reactions including 

Serotonin Syndrome (see section 4.4). 

 

Medicinal products lowering the seizure threshold 

Antidepressants with serotonergic effect can lower the seizure threshold. Caution is advised when 

concomitantly using other medicinal products capable of lowering the seizure threshold [e.g., 

antidepressants (tricyclics, SSRIs, SNRIs), neuroleptics (phenothiazines, thioxanthenes and 

butyrophenones), mefloquine, bupropion, tramadol] (see section 4.4). 

 

 

 



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ECT (electroconvulsive therapy) 

There is no clinical experience with concurrent administration of vortioxetine and ECT, therefore 

caution is advisable. 

 

CYP2D6 inhibitors 

The exposure to vortioxetine increased 2.3-fold for area under the curve (AUC) when vortioxetine 

10 mg/day was co-administered with bupropion (a strong CYP2D6 inhibitor 150 mg twice daily) for 

14 days in healthy subjects. Co-administration resulted in a higher incidence of adverse reactions 

when bupropion was added to vortioxetine than when vortioxetine was added to bupropion. 

Depending on individual patient response, a lower dose of vortioxetine may be considered if strong 

CYP2D6 inhibitor (e.g., bupropion, quinidine, fluoxetine, paroxetine) is added to vortioxetine 

treatment (see section 4.2). 

 

CYP3A4 inhibitors and CYP2C9, and CYP2C19 inhibitors 

When vortioxetine was co-administered following 6 days of ketoconazole 400 mg/day (a CYP3A4/5 

and P-glycoprotein inhibitor) or following 6 days of fluconazole 200 mg/day (a CYP2C9, CYP2C19, 

and CYP3A4/5 inhibitor) in healthy subjects, a 1.3-fold and 1.5-fold increase, respectively, in 

vortioxetine AUC was observed. No dose adjustment is needed. 

 

No inhibitory effect of 40 mg single-dose omeprazole (CYP2C19 inhibitor) was observed on the 

multiple-dose pharmacokinetics of vortioxetine in healthy subjects. 

 

Interactions in CYP2D6 poor metabolisers 

Co-administration of strong inhibitors of CYP3A4 (such as itraconazol, voriconazole, clarithromycin, 

telithromycin, nefazodone, conivaptan and many of the HIV protease inhibitors) and inhibitors of 

CYP2C9 (such as fluconazole and amiodarone) to CYP2D6 poor metabolisers (see section 5.2) has 

not been investigated specifically, but it is anticipated that it will lead to a more marked increased 

exposure of vortioxetine in these patients as compared to the moderate effect described above. 

Depending on individual patient response, a lower dose of vortioxetine may be considered if a strong 

inhibitor of CYP3A4 or CYP2C9 is co-administered in CYP2D6 poor metabolisers. 

 

Cytochrome P450 inducers 

When a single dose of 20 mg vortioxetine was co-administered following 10 days of rifampicin 

600 mg/day (a broad inducer of CYP isozymes) in healthy subjects, a 72% decrease in AUC of 

vortioxetine was observed. Depending on individual patient response, a dose adjustment may be 

considered if a broad cytochrome P450 inducer (e.g., rifampicin, carbamazepine, phenytoin) is added 

to vortioxetine treatment (see section 4.2). 

 

Alcohol 

No effect on the pharmacokinetics of vortioxetine or ethanol and no significant impairment, relative to 

placebo, in cognitive function were observed when vortioxetine in a single dose of 20 mg or 40 mg 

was co-administered with a single dose of ethanol (0.6 g/kg) in healthy subjects. However, alcohol 

intake is not advisable during antidepressant treatment. 

 

Acetylsalicylic acid 

No effect of multiple doses of acetylsalicylic acid 150 mg/day on the multiple-dose pharmacokinetics 

of vortioxetine was observed in healthy subjects. 

 

Potential for vortioxetine to affect other medicinal products 

 

Anticoagulants and antiplatelet medicinal products 

No significant effects, relative to placebo, were observed in INR, prothrombin or plasma 

R-/S-warfarin values following co-administration of multiple doses of vortioxetine with stable doses 

of warfarin in healthy subjects. Also, no significant inhibitory effect, relative to placebo, on platelet 

aggregation or pharmacokinetics of acetylsalicylic acid or salicylic acid was observed when 

acetylsalicylic acid 150 mg/day was co-administered following multiple doses of vortioxetine 



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administration in healthy subjects. However, caution should be exercised when vortioxetine is 

combined with oral anticoagulants or antiplatelet medicinal products due to a potential increased risk 

of bleeding attributable to a pharmacodynamic interaction (see section 4.4). 

 

Cytochrome P450 substrates 

In vitro, vortioxetine did not show any relevant potential for inhibition or induction of 

cytochrome P450 isozymes (see section 5.2). 

 

Following multiple doses of vortioxetine, no inhibitory effect was observed in healthy subjects for the 

cytochrome P450 isozymes CYP2C19 (omeprazole, diazepam), CYP3A4/5 (ethinyl estradiol, 

midazolam), CYP2B6 (bupropion), CYP2C9 (tolbutamide, S-warfarin), CYP1A2 (caffeine) or 

CYP2D6 (dextromethorphan). 

 

No pharmacodynamic interactions were observed. No significant impairment, relative to placebo, in 

cognitive function was observed for vortioxetine following co-administration with a single 10 mg dose 

of diazepam. No significant effects, relative to placebo, were observed in the levels of sex hormones 

following co-administration of vortioxetine with a combined oral contraceptive (ethinyl estradiol 

30 µg/ levonorgestrel 150 µg). 

 

Lithium, tryptophan 

No clinically relevant effect was observed during steady-state lithium exposure following co-

administration with multiple doses of vortioxetine in healthy subjects. However, there have been 

reports of enhanced effects when antidepressants with serotonergic effect have been given together 

with lithium or tryptophan; therefore, concomitant use of vortioxetine with these medicinal products 

should be undertaken with caution. 

 

Interference with urine drug screens 

There have been reports of false positive results in urine enzyme immunoassays for methadone in 

patients who have taken vortioxetine. Caution should be exercised in the interpretation of positive 

urine drug screen results, and confirmation by an alternative analytical technique (e.g., 

chromatographic methods) should be considered. 

 

4.6 Fertility, pregnancy and lactation 

 

Pregnancy 

 

There are limited data from the use of vortioxetine in pregnant women. 

Studies in animals have shown reproductive toxicity (see section 5.3). 

 

The following symptoms may occur in the newborn after maternal use of a serotonergic medicinal 

product in the later stages of pregnancy: respiratory distress, cyanosis, apnoea, seizures, temperature 

instability, feeding difficulty, vomiting, hypoglycaemia, hypertonia, hypotonia, hyperreflexia, tremor, 

jitteriness, irritability, lethargy, constant crying, somnolence and difficulty sleeping. These symptoms 

could be due to either discontinuation effects or excess serotonergic activity. In the majority of 

instances, such complications began immediately or soon (<24 hours) after delivery. 

 

Epidemiological data suggest 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 with vortioxetine treatment, this potential risk cannot be 

ruled out taking into account the related mechanism of action (increase in serotonin concentrations). 

 

Brintellix should only be administered to pregnant women if the expected benefits outweigh the 

potential risk to the foetus. 

 

Observational data have provided evidence of an increased risk (less than 2-fold) of postpartum 

haemorrhage following exposure to an SSRI or SNRI within the month prior to birth. Although no 



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studies have investigated an association between vortioxetine treatment and postpartum haemorrhage, 

there is a potential risk, taking into account the related mechanism of action (See section 4.4) 

 

Breast-feeding 

 

Available data in animals have shown excretion of vortioxetine/ vortioxetine metabolites in milk. It is 

expected that vortioxetine will be excreted into human milk (see section 5.3). 

 

A risk to the breastfeeding child cannot be excluded. 

 

A decision must be made whether to discontinue breast-feeding or to discontinue/abstain from 

Brintellix treatment taking into account the benefit of breast-feeding for the child and the benefit of 

therapy for the woman. 

 

Fertility 

 

Fertility studies in male and female rats showed no effect of vortioxetine on fertility, sperm quality or 

mating performance (see section 5.3). 

Human case reports with medicinal products from the related pharmacological class of antidepressants 

(SSRIs) have shown an effect on sperm quality that is reversible. Impact on human fertility has not 

been observed so far. 

 

4.7 Effects on ability to drive and use machines 

 

Brintellix has no or negligible influence on the ability to drive and use machines. However, as adverse 

reactions such as dizziness have been reported, patients should exercise caution when driving or 

operating hazardous machinery, especially when starting treatment with vortioxetine or when 

changing the dose. 

 

4.8 Undesirable effects 

 

Summary of the safety profile 

 

The most common adverse reaction was nausea.  

 

Tabulated list of adverse reactions  

 

Adverse reactions are listed below using the following convention: 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), not known (cannot be estimated from the available data).  The list is based on 

information from clinical trials and post-marketing experience. 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 



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SYSTEM ORGAN CLASS FREQUENCY ADVERSE REACTION 

Immune system disorders  Not known* Anaphylactic reaction 

Metabolism and nutrition disorders Not known * Hyponatraemia 

Psychiatric disorders Common Abnormal dreams 

Not known * Insomnia 

Not known * Agitation, aggression (see section 4.4) 

Nervous system disorders Common Dizziness 

Not known * Serotonin Syndrome  

Eye disorders Rare  Mydriasis (which may lead to acute 

narrow angle glaucoma - see section 

4.4) 

Vascular disorders Uncommon Flushing 

Not known* Haemorrhage (including contusion, 

ecchymosis, epistaxis, gastrointestinal 

or vaginal bleeding) 

Gastrointestinal disorders Very common Nausea 

Common Diarrhoea, 

Constipation, 

Vomiting 

Skin and subcutaneous tissue disorders Common Pruritus, including pruritus 

generalised 

Uncommon Night sweats 

Not known* Angioedema, 

Urticaria 

Rash 

* Based on post-marketing cases 

 

Description of selected adverse reactions 

 

Nausea 

Nausea was usually mild or moderate and occurred within the first two weeks of treatment. The 

reactions were usually transient and did not generally lead to cessation of therapy. Gastrointestinal 

adverse reactions, such as nausea, occurred more frequently in women than men. 

 

Elderly patients 

For doses ≥10 mg vortioxetine once daily, the withdrawal rate from the studies was higher in patients 

aged ≥65 years. 

For doses of 20 mg vortioxetine once daily, the incidences of nausea and constipation were higher in 

patients aged ≥65 years (42% and 15%, respectively) than in patients aged <65 years (27% and 4%, 

respectively)(see section 4.4). 

 

Sexual dysfunction 

In clinical studies, sexual dysfunction was assessed using the Arizona Sexual Experience Scale 

(ASEX). Doses of 5 to 15 mg showed no difference to placebo. However, the 20 mg dose of 

vortioxetine was associated with an increase in sexual dysfunction (TESD)(see section 5.1) . 

 

Class effect 

Epidemiological studies, mainly conducted in patients 50 years of age and older, show an increased 

risk of bone fractures in patients receiving a medicinal product from related pharmacological classes 

of antidepressants (SSRIs or TCAs). The mechanism behind this risk is unknown, and it is not known 

if this risk is also relevant for vortioxetine. 

 

 

 



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Paediatric population  

A total of 308 adolescent patients aged 12 to 17 years with major depressive disorder (MDD) were 

treated with vortioxetine in a double-blind, placebo-controlled study. In general, the adverse reaction 

profile of vortioxetine in adolescents was similar to that seen for adults except for higher incidences 

reported in adolescents than in adults for abdominal pain-related events and suicidal ideation. 

 

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 

 

Ingestion of vortioxetine in clinical trials in the dose range of 40 mg to 75 mg has caused an 

aggravation of the following adverse reactions: nausea, postural dizziness, diarrhoea, abdominal 

discomfort, generalised pruritus, somnolence and flushing. 

 

Post-marketing experience mainly concerns vortioxetine overdoses of up to 80 mg. In the majority of 

cases, no symptoms or mild symptoms were reported. The most frequently reported symptoms were 

nausea and vomiting.  

 

There is limited experience with vortioxetine overdoses above 80 mg. Following dosages several fold 

higher than the therapeutic dose range, events of seizure and serotonin syndrome have been reported. 

 

Management of overdose should consist of treating clinical symptoms and relevant monitoring. 

Medical follow-up in a specialised environment is recommended. 

 

 

5. PHARMACOLOGICAL PROPERTIES 

 

5.1  Pharmacodynamic properties 

 

Pharmacotherapeutic group: Psychoanaleptics; Other antidepressants, ATC code: N06AX26 

 

Mechanism of action 

 

The mechanism of action of vortioxetine is thought to be related to its direct modulation of 

serotonergic receptor activity and inhibition of the serotonin (5-HT) transporter. Nonclinical data 

indicate that vortioxetine is a 5-HT3, 5-HT7, and 5-HT1D receptor antagonist, 5-HT1B receptor partial 

agonist, 5-HT1A receptor agonist and inhibitor of the 5-HT transporter, leading to modulation of 

neurotransmission in several systems, including predominantly the serotonin but probably also the 

norepinephrine, dopamine, histamine, acetylcholine, GABA and glutamate systems. This multimodal 

activity is considered responsible for the antidepressant and anxiolytic-like effects and the 

improvement of cognitive function, learning and memory observed with vortioxetine in animal 

studies. However, the precise contribution of the individual targets to the observed pharmacodynamic 

profile remains unclear and caution should be applied when extrapolating animal data directly to man.  

 

In humans, two positron emission tomography (PET) studies have been conducted using 5-HT 

transporter ligands (11C-MADAM or 11C-DASB) to quantify the 5-HT transporter occupancy in the 

brain across different dose levels. The mean 5-HT transporter occupancy in the raphe nuclei was 

approximately 50% at 5 mg/day, 65% at 10 mg/day and increased to above 80% at 20 mg/day.  

 

 

 

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


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Clinical efficacy and safety 

 

The efficacy and safety of vortioxetine have been studied in a clinical programme that included more 

than 6,700 patients, of whom more than 3,700 were treated with vortioxetine in short-term 

(≤12 weeks) studies of major depressive disorder (MDD). Twelve double-blind, placebo controlled, 

6/8-week, fixed-dose studies have been conducted to investigate the short-term efficacy of 

vortioxetine in MDD in adults (including the elderly). The efficacy of vortioxetine was demonstrated 

with at least one dosage group across 9 of the 12 studies, showing at least a 2-point difference to 

placebo in the Montgomery and Åsberg Depression Rating Scale (MADRS) or Hamilton Depression 

Rating Scale 24-item (HAM-D24) total score. This was supported by clinical relevance as 

demonstrated by the proportions of responders and remitters and the improvement in the Clinical 

Global Impression – Global Improvement (CGI-I) score. The efficacy of vortioxetine increased with 

increasing dose.  

 

The effect in the individual studies was supported by the meta-analysis (MMRM) of the mean change 

from baseline in MADRS total score at Week 6/8 in the short-term, placebo-controlled studies in 

adults. In the meta-analysis, the overall mean difference to placebo across the studies was statistically 

significant: -2.3 points (p = 0.007), -3.6 points (p <0.001), and -4.6 points (p <0.001) for the 5, 10, and 

20 mg/day doses, respectively; the 15 mg/day dose did not separate from placebo in the meta-analysis, 

but the mean difference to placebo was -2.6 points. The efficacy of vortioxetine is supported by the 

pooled responder analysis, in which the proportion of responders ranged from 46% to 49% for 

vortioxetine versus 34% for placebo (p <0.01; NRI analysis). 

 

Furthermore, vortioxetine, in the dose range of 5-20 mg/day, demonstrated efficacy on the broad range 

of depressive symptoms (assessed by improvement in all MADRS single–item scores).  

 

The efficacy of vortioxetine 10 or 20 mg/day was further demonstrated in a 12-week, double-blind, 

flexible-dose comparative study versus agomelatine 25 or 50 mg/day in patients with MDD. 

Vortioxetine was statistically significantly better than agomelatine as measured by improvement in the 

MADRS total score and supported by the clinical relevance as demonstrated by the proportions of 

responders and remitters and improvement in the CGI-I. 

 

Maintenance 

The maintenance of antidepressant efficacy was demonstrated in a relapse-prevention study. Patients 

in remission after an initial 12-week open-label treatment period with vortioxetine were randomised to 

vortioxetine 5 or 10 mg/day or placebo and observed for relapse during a double-blind period of at 

least 24 weeks (24 to 64 weeks). Vortioxetine was superior (p=0.004) to placebo on the primary 

outcome measure, the time to relapse of MDD, with a hazard ratio of 2.0; that is, the risk of relapse 

was two times higher in the placebo group than in the vortioxetine group. 

 

Elderly 

In the 8-week, double-blind, placebo-controlled, fixed-dose study in elderly depressed patients (aged 

≥65 years, n=452, 156 of whom were on vortioxetine), vortioxetine 5 mg/day was superior to placebo 

as measured by improvement in the MADRS and HAM-D24 total scores. The effect seen with 

vortioxetine was a 4.7 point difference to placebo in MADRS total score at Week 8 (MMRM 

analysis). 

 

Patients with severe depression or with depression and high levels of anxiety symptoms 

In severely depressed patients (baseline MADRS total score ≥30) and in depressed patients with a high 

level of anxiety symptoms (baseline HAM-A total score ≥20) vortioxetine also demonstrated efficacy 

in the short-term studies in adults (the overall mean difference to placebo in MADRS total score at 

Week 6/8 ranged from 2.8 to 7.3 points and from 3.6 to 7.3 points, respectively,(MMRM analysis)). In 

the dedicated study in elderly, vortioxetine was also effective in these patients. 

The maintenance of antidepressant efficacy was also demonstrated in this patient population in the 

long-term relapse prevention study. 

 



13 

Effects of vortioxetine on the Digit Symbol Substitution Test (DSST), the University of California San 

Diego Performance-Based Skills Assessment (UPSA) (objective measures) and Perceived Deficits 

Questionnaire (PDQ) and Cognitive and Physical Functioning Questionnaire CPFQ (subjective 

measures) scores 

The efficacy of vortioxetine (5-20 mg/day) in patients with MDD has been investigated in 2 adult and 

1 elderly short-term, placebo-controlled studies. 

 

Vortioxetine had a statistically significant effect versus placebo on the Digit Symbol Substitution Test 

(DSST), ranging from Δ = 1.75 (p = 0.019) to 4.26 (p <0.0001) in the 2 studies in adults and Δ = 2.79 

(p = 0.023) in the study in the elderly. In the meta-analyses (ANCOVA, LOCF) of the mean change 

from baseline in DSST number of correct symbols in all 3 studies, vortioxetine separated from placebo 

(p<0.05) with a standardised effect size of 0.35. When adjusting for the change in MADRS the total 

score in the meta-analysis of the same studies showed that vortioxetine separated from placebo 

(p<0.05) with a standardised effect size of 0.24.  

 

One study assessed the effect of vortioxetine on functional capacity using the University of California 

San Diego Performance-Based Skills Assessment (UPSA). Vortioxetine separated from placebo 

statistically with results of 8.0 for vortioxetine versus 5.1 points for placebo (p=0.0003). 

 

In one study, vortioxetine was superior to placebo on subjective measures, evaluated using the 

Perceived Deficits Questionnaire with results of -14.6 for vortioxetine and -10.5 for placebo 

(p=0.002). Vortioxetine did not separate from placebo on subjective measures when evaluated using 

the Cognitive and Physical Functioning Questionnaire with results of -8.1 for vortioxetine versus -6.9 

for placebo (p=0.086). 

 

Tolerability and safety 

The safety and tolerability of vortioxetine have been established in short- and long-term studies across 

the dose range of 5 to 20 mg/day. For information on undesirable effects, see section 4.8. 

Vortioxetine did not increase the incidence of insomnia or somnolence relative to placebo. 

 

In clinical short- and long-term placebo-controlled studies, potential discontinuation symptoms were 

systematically evaluated after abrupt treatment cessation of vortioxetine. There was no clinically 

relevant difference to placebo in the incidence or nature of the discontinuation symptoms after either 

short-term (6-12 weeks) or long-term (24-64 weeks) treatment with vortioxetine. 

 

The incidence of self-reported adverse sexual reactions was low and similar to placebo in clinical 

short- and long-term studies with vortioxetine. In studies using the Arizona Sexual Experience Scale 

(ASEX), the incidence of treatment-emergent sexual dysfunction (TESD) and the ASEX total score 

showed no clinically relevant difference to placebo in symptoms of sexual dysfunction at the 5 to 

15 mg/day doses of vortioxetine. For the 20 mg/day dose, an increase in TESD was seen compared to 

placebo (an incidence difference of 14.2%, 95% CI [1.4, 27.0]). 

 

The effect of vortioxetine on sexual function was further evaluated in an 8-week, double-blind, 

flexible-dose, comparative study (n=424) versus escitalopram in patients treated for at least 6 weeks 

with an SSRI (citalopram, paroxetine, or sertraline), with a low level of depressive symptoms 

(baseline CGI-S ≤ 3) and TESD induced by the prior SSRI treatment. Vortioxetine 10-20 mg/day had 

statistically significantly less TESD than escitalopram 10-20 mg/day as measured by change in the 

CSFQ-14 total score (2.2 points, p=0.013) at week 8. The proportion of responders  was not 

significantly different in the vortioxetine group (162 (74.7%)) compared with the escitalopram group 

(137 (66.2%)) at week 8  (OR 1.5 p=0.057). The antidepressant effect was maintained in both 

treatment groups. 

 

Vortioxetine had no effect relative to placebo on body weight, heart rate, or blood pressure in clinical 

short- and long-term studies. 

 

No clinically significant changes were observed in hepatic or renal assessments in clinical studies.  



14 

Vortioxetine has not shown any clinically significant effect on ECG parameters, including the QT, 

QTc, PR and QRS intervals, in patients with MDD. In a thorough QTc study in healthy subjects at 

doses up to 40 mg daily, no potential for the prolongation of the QTc interval was observed. 

Paediatric population 

One randomised, double-blind, placebo-controlled, active-referenced, fixed dose, 8-week study was 

conducted in adolescent patients with MDD aged 12 to 17 years. The study included a 4-week single-

blind placebo lead-in period with standardized psychosocial intervention (N=777); only non-

responders from the lead-in period were randomised (N=615). Neither vortioxetine 10 mg/day nor 20 

mg/day was statistically significantly superior to placebo based on the Children´s Depression Rating 

Scale-Revised (CDRS-R) total score. The active reference (fluoxetine 20 mg/day) separated 

statistically from placebo on the CDRS-R total score. In general, the adverse reaction profile of 

vortioxetine in adolescents was similar to that seen for adults except for higher incidences reported in 

adolescent than in adults for abdominal pain-related event and suicidal ideation. Discontinuation due 

to adverse events (mostly due to suicidal ideation, nausea and vomiting) was highest in patients treated 

with vortioxetine 20 mg/day (5.6%) as compared to vortioxetine 10 mg/day (2.7%), fluoxetine (3.3%), 

and placebo (1.3%). The most commonly reported adverse events in the vortioxetine treatment groups 

were nausea, vomiting and headache. Suicidal ideation and behaviour were reported as adverse events 

both during the 4-week single-blind lead-in period (placebo 13/777 [1.7%]), and during the 8-week 

treatment period (vortioxetine 10 mg/day 2/147 [1.4%], vortioxetine 20 mg/day 6/161 [3.7%], 

fluoxetine 6/153 [3.9%], placebo 0/154 [0%]). Suicidal ideation and behaviour as measured by 

Columbia-Suicide Severity Rating Scale (C-SSRS) was similar across treatment groups. 

 

The European Medicines Agency has waived the obligation to submit the results of studies in major 

depressive disorder with vortioxetine in children aged less than 7 years (see section 4.2 for information 

on paediatric use). 

 

The European Medicines Agency has deferred the obligation to submit the results of studies with 

vortioxetine in one or more subsets of the paediatric population in treatment of major depressive 

disorder (see section 4.2 for information on paediatric use). 

 

5.2 Pharmacokinetic properties 

 

Absorption 

Vortioxetine is slowly, but well absorbed after oral administration and the peak plasma concentration 

is reached within 7 to 11 hours. Following multiple dosing of 5, 10, or 20 mg/day, mean Cmax values of 

9 to 33 ng/mL were observed. The absolute bioavailability is 75%. No effect of food on the 

pharmacokinetics was observed (see section 4.2). 

 

Distribution 

The mean volume of distribution (Vss) is 2,600 L, indicating extensive extravascular distribution. 

Vortioxetine is highly bound to plasma proteins (98 to 99%) and the binding appears to be 

independent of vortioxetine plasma concentrations. 

 

Biotransformation 

Vortioxetine is extensively metabolised in the liver, primarily through oxidation catalysed by CYP2D6 

and to a minor extent CYP3A4/5 and CYP2C9, and subsequent glucuronic acid conjugation. 

 

No inhibitory or inducing effect of vortioxetine was observed in the drug-drug interaction studies for 

the CYP isozymes CYP1A2, CYP2A6, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP2E1, 

or CYP3A4/5 (see section 4.5). Vortioxetine is a poor P-gp substrate and inhibitor. 

 

The major metabolite of vortioxetine is pharmacologically inactive. 

 

 



15 

Elimination 

The mean elimination half-life and oral clearance are 66 hours and 33 L/h, respectively. 

Approximately 2/3 of the inactive vortioxetine metabolites are excreted in the urine and approximately 

1/3 in the faeces. Only negligible amounts of vortioxetine are excreted in the faeces. Steady-state 

plasma concentrations are achieved in approximately 2 weeks. 

 

Linearity/non-linearity 

The pharmacokinetics are linear and time independent in the dose range studied (2.5 to 60 mg/day). 

 

In accordance with the half-life, the accumulation index is 5 to 6 based on AUC0-24h following multiple 

doses of 5 to 20 mg/day. 

 

Special populations 

Elderly 

In elderly healthy subjects (aged ≥65 years; n=20), the exposure to vortioxetine increased up to 27% 

(Cmax and AUC) compared to young healthy control subjects (aged ≤45 years) after multiple doses of 

10 mg/day. The lowest effective dose of 5 mg vortioxetine once daily should always be used as the 

starting dose in patients ≥ 65 years (see section 4.2). However, caution should be exercised when 

prescribing to elderly patients at doses higher than 10 mg vortioxetine once daily (see section 4.4). 

 

Renal impairment 

Following a single dose of 10 mg vortioxetine, renal impairment estimated using the Cockcroft-Gault 

formula (mild, moderate, or severe; n=8 per group) caused modest exposure increases (up to 30%), 

compared to healthy matched controls. In patients with end-stage renal disease, only a small fraction 

of vortioxetine was lost during dialysis (AUC and Cmax were 13% and 27% lower, respectively; n=8) 

following a single 10 mg dose of vortioxetine. No dose adjustment is needed based on renal function 

(see section 4.2 and 4.4). 

 

Hepatic impairment 

The pharmacokinetics in subjects (N = 6-8) with mild, moderate, or severe hepatic impairment (Child-

Pugh Criteria A, B, or C, respectively) were compared to healthy volunteers. The changes in AUC 

were less than 10% lower in subjects with mild or moderate hepatic impairment, and 10% higher in 

those with severe hepatic impairment. The changes in Cmax were less than 25% lower in all groups. No 

dose adjustment is needed based on hepatic function (see section 4.2 and 4.4). 

 

CYP2D6 gene types 

The plasma concentration of vortioxetine was approximately two times higher in CYP2D6 poor 

metabolisers than in extensive metabolisers. Co-administration of strong CYP3A4/2C9 inhibitors to 

CYP2D6 poor metabolisers could potentially result in higher exposure (see section 4.5). 

 

In CYP2D6 ultra-rapid metabolisers, the plasma concentration of vortioxetine 10 mg/day were 

between those obtained in extensive metabolisers at 5 mg/day and 10 mg/day. 

Depending on individual patient response, a dose adjustment may be considered (see section 4.2). 

 

Paediatric population 

Pharmacokinetics of vortioxetine in paediatric patients with major depressive disorder following oral 

administration of 5 to 20 mg once daily was characterized using population modeling analyses based 

on data from a pharmacokinetic study (7-17 years) and an efficacy and safety study (12-17 years). The 

pharmacokinetics of vortioxetine in paediatric patients was similar to that observed in adult patients. 

 

5.3 Preclinical safety data 

 

Administration of vortioxetine in the general toxicity studies in mice, rats and dogs was mainly 

associated with CNS-related clinical signs. These included salivation (rat and dog), pupil dilatation 



16 

(dog), and two incidences of convulsions in dogs in the general toxicity study programme. A no-effect 

level for convulsions was established with a corresponding safety margin of 5 considering the 

maximum recommended therapeutic dose of 20 mg/day. Target organ toxicity was restricted to 

kidneys (rats) and liver (mice and rats). The changes in the kidney in rats (glomerulonephritis, renal 

tubular obstruction, crystalline material in renal tubule) and in the liver of mice and rats 

(hepatocellular hypertrophy, hepatocyte necrosis, bile duct hyperplasia, crystalline material in bile 

ducts) were seen at exposures more than 10-fold (mice) and 2-fold (rats) the human exposure at the 

maximum recommended therapeutic dose of 20 mg/day. These findings were mainly attributed to 

rodent-specific vortioxetine-related crystalline material obstruction of the renal tubules and the bile 

ducts, respectively, and considered of low risk to humans. 

 

Vortioxetine was not genotoxic in a standard battery of in vitro and in vivo tests. 

 

Based on results from conventional 2-year carcinogenicity studies in mice or rats, vortioxetine is not 

considered to pose a risk of carcinogenicity in humans. 

 

Vortioxetine had no effect on rat fertility, mating performance, reproductive organs, or sperm 

morphology and motility. Vortioxetine was not teratogenic in rats or rabbits, but reproductive toxicity 

in terms of effects on foetal weight and delayed ossification were seen in the rat at exposures more 

than 10-fold the human exposure at the maximum recommended therapeutic dose of 20 mg/day. 

Similar effects were seen in the rabbit at sub-therapeutic exposure. 

 

In a pre- and post-natal study in rats, vortioxetine was associated with increased pup mortality, 

reduced bodyweight gain, and delayed pup development at doses that did not result in maternal 

toxicity and with associated exposures similar to those achieved in humans following administration 

of vortioxetine 20 mg/day (see section 4.6). 

 

Vortioxetine-related material was distributed to the milk of lactating rats (see section 4.6). 

In juvenile toxicity studies in rats, all vortioxetine treatment-related findings were consistent with 

those noted in adult animals. 

 

Environmental risk assessment studies have shown that vortioxetine has the potential to be persistent, 

bioaccumulative and toxic to the environment (risk to fish). However, by recommended patient usage 

vortioxetine is considered to pose negligible risk to the aquatic and terrestrial environment (see section 

6.6). 

 

 

6. PHARMACEUTICAL PARTICULARS 

 

6.1 List of excipients 

 

Brintellix 5 mg film-coated tablets 

 

Tablet core 

Mannitol 

Microcrystalline cellulose 

Hydroxypropylcellulose 

Sodium starch glycolate (type A) 

Magnesium stearate 

 

Tablet coating 

Hypromellose 

Macrogol 400  

Titanium dioxide (E171)  



17 

Iron oxide red (E172) 

 

Brintellix 10 mg film-coated tablets 

 

Tablet core 

Mannitol 

Microcrystalline cellulose 

Hydroxypropylcellulose 

Sodium starch glycolate (type A) 

Magnesium stearate 

 

Tablet coating 

Hypromellose 

Macrogol 400  

Titanium dioxide (E171)  

Iron oxide yellow (E172) 

 

Brintellix 15 mg film-coated tablets 

 

Tablet core 

Mannitol 

Microcrystalline cellulose 

Hydroxypropylcellulose 

Sodium starch glycolate (type A) 

Magnesium stearate 

 

Tablet coating 

Hypromellose 

Macrogol 400  

Titanium dioxide (E171)  

Iron oxide red (E172) 

Iron oxide yellow (E172) 

 

Brintellix 20 mg film-coated tablets 

 

Tablet core 

Mannitol 

Microcrystalline cellulose 

Hydroxypropylcellulose 

Sodium starch glycolate (type A) 

Magnesium stearate 

 

Tablet coating 

Hypromellose 

Macrogol 400  

Titanium dioxide (E171)  

Iron oxide red (E172) 

 

6.2 Incompatibilities 

 

Not applicable. 



18 

6.3 Shelf life 

 

4 years. 

 

6.4 Special precautions for storage 

 

This medicinal product does not require any special storage conditions. 

 

6.5 Nature and contents of container  

 

Brintellix 5 mg film-coated tablets 

 

Blister: Transparent; PVC/PVdC/aluminium blister. 

Pack sizes of 14, 28 and 98 film-coated tablets. 

 

Perforated unit dose blisters: PVC/PVdC/aluminium. 

Pack sizes of 56 x 1 and 98 x 1 film-coated tablets. 

Multipack containing 126 (9 x 14) and 490 (5 x (98x1)) film-coated tablets. 

 

High-density polyethylene (HDPE) tablet container. 

Pack sizes of 100 and 200 film-coated tablets. 

 

Brintellix 10 mg film-coated tablets 

Blister: Transparent; PVC/PVdC/aluminium blister. 

Pack sizes of 7, 14, 28, 56 and 98 film-coated tablets. 

 

Perforated unit dose blisters: PVC/PVdC/aluminium. 

Pack sizes of 56 x 1 and 98 x 1 film-coated tablets. 

Multipack containing 126 (9 x 14) and 490 (5 x (98x1)) film-coated tablets. 

 

High-density polyethylene (HDPE) tablet container. 

Pack sizes of 100 and 200 film-coated tablets. 

 

Brintellix 15 mg film-coated tablets 

Blister: Transparent; PVC/PVdC/aluminium blister. 

Pack sizes of 14, 28, 56 and 98 film-coated tablets. 

 

Perforated unit dose blisters: PVC/PVdC/aluminium. 

Pack sizes of 56 x 1 and 98 x 1 film-coated tablets. 

Multipack containing 490 (5 x (98x1)) film-coated tablets. 

 

High-density polyethylene (HDPE) tablet container. 

Pack sizes of 100 and 200 film-coated tablets. 

 

Brintellix 20 mg film-coated tablets  

Blister: Transparent; PVC/PVdC/aluminium blister. 

Pack sizes of 14, 28, 56 and 98 film-coated tablets. 

 

Perforated unit dose blisters: PVC/PVdC/aluminium. 

Pack sizes of 56 x 1 and 98 x 1 film-coated tablets. 

Multipack containing 126 (9 x 14) and 490 (5 x (98x1)) film-coated tablets. 

 

High-density polyethylene (HDPE) tablet container. 

Pack sizes of 100 and 200 film-coated tablets. 

 

Not all pack sizes may be marketed. 



19 

6.6 Special precautions for disposal  

 

This medicinal product may pose a risk to the environment (see section 5.3). 

Any unused medicinal product or waste material should be disposed of in accordance with local 

requirements. 

 

 

7. MARKETING AUTHORISATION HOLDER 

 

H. Lundbeck A/S 

Ottiliavej 9 

2500 Valby 

Denmark 

 

 

8. MARKETING AUTHORISATION NUMBER(S)  

 

Brintellix 5 mg film-coated tablets  

 

EU/1/13/891/001-007 

EU/1/13/891/037-038 

 

Brintellix 10 mg film-coated tablets  

 

EU/1/13/891/008-017 

EU/1/13/891/039 

 

Brintellix 15 mg film-coated tablets  

 

EU/1/13/891/018-026 

 

Brintellix 20 mg film-coated tablets  

 

EU/1/13/891/027-035 

EU/1/13/891/040 

 

 

9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 

 

Date of first authorisation: 18 December 2013 

Date of latest renewal: 20 November 2018 

 

 

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/


20 

1. NAME OF THE MEDICINAL PRODUCT 

 

Brintellix 20 mg/ml oral drops, solution 

 

 

2. QUALITATIVE AND QUANTITATIVE COMPOSITION 

 

Each ml of solution contains vortioxetine (D,L)-lactate equivalent to 20 mg vortioxetine. 

 

Each drop contains vortioxetine (D,L)-lactate equivalent to 1 mg vortioxetine. 

 

Excipients with known effect 

 

Each drop contains 4.25 mg of ethanol. 

 

For the full list of excipients, see section 6.1. 

 

 

3. PHARMACEUTICAL FORM 

 

Oral drops, solution. 

 

Clear, nearly colourless to yellowish solution. 

 

 

4. CLINICAL PARTICULARS 

 

4.1 Therapeutic indications 

 

Brintellix is indicated for the treatment of major depressive episodes in adults. 

 

4.2 Posology and method of administration 

 

Posology 

 

The starting and recommended dose of Brintellix is 10 mg vortioxetine once daily in adults less than 

65 years of age. 

 

Depending on individual patient response, the dose may be increased to a maximum of 20 mg 

vortioxetine once daily or decreased to a minimum of 5 mg vortioxetine once daily. 

 

5 mg corresponding to 5 drops. 

10 mg corresponding to 10 drops. 

15 mg corresponding to 15 drops. 

20 mg corresponding to 20 drops. 

 

After the depressive symptoms resolve, treatment for at least 6 months is recommended for 

consolidation of the antidepressive response. 

 

Treatment discontinuation 

 

Patients treated with vortioxetine can abruptly stop taking the medicinal product without the need for a 

gradual reduction in dose (see section 5.1). 

 

 

 



21 

Special populations 

 

Elderly patients 

The lowest effective dose of 5 mg vortioxetine once daily should always be used as the starting dose in 

patients ≥ 65 years of age. Caution is advised when treating patients ≥ 65 years of age with doses 

higher than 10 mg vortioxetine once daily for which data are limited (see section 4.4). 

 

Cytochrome P450 inhibitors 

Depending on individual patient response, a lower dose of vortioxetine may be considered if a strong 

CYP2D6 inhibitor (e.g., bupropion, quinidine, fluoxetine, paroxetine) is added to vortioxetine 

treatment (see section 4.5). 

 

Cytochrome P450 inducers 

Depending on individual patient response, a dose adjustment of vortioxetine may be considered if a 

broad cytochrome P450 inducer (e.g., rifampicin, carbamazepine, phenytoin) is added to vortioxetine 

treatment (see section 4.5). 

 

Paediatric population 

The safety and efficacy of Brintellix in children aged 7 to 11 years have not been established. No data 

are available (see section 4.4). Brintellix should not be used in adolescents aged 12 to 17 years with 

major depressive disorder (MDD) because efficacy has not been demonstrated (see section 5.1). The 

safety of Brintellix in adolescents aged 12 to 17 years is described in section 4.4, 4.8 and 5.1. 

 

Renal or hepatic impairment 

No dose adjustment is needed based on renal or hepatic function (see section 4.4 and 5.2). 

 

Method of administration  

 

Brintellix is for oral use. 

The oral drops can be taken with or without food.  

The drops can be mixed with water, juice or other non-alcoholic drinks. 

 

The bottle must be turned completely upside down. If no drops come out, the bottle can be tapped lightly 

to start the flow. 

 

 
 

4.3 Contraindications 

 

Hypersensitivity to the active substance or to any of the excipients listed in section 6.1. 

 

Concomitant use with nonselective monoamine oxidase inhibitors (MAOIs) or selective MAO-A 

inhibitors (see section 4.5). 

 

4.4 Special warnings and precautions for use 

 

Use in paediatric population 

 

Brintellix is not recommended for the treatment of depression in children aged 7 to 11 years, since the 

safety and efficacy of vortioxetine have not been established in this age group. Brintellix should not be 

used in adolescents aged 12 to 17 years with major depressive disorder (MDD) because efficacy has 



22 

not been demonstrated (see section 5.1). In general , the adverse reaction profile of vortioxetine in 

adolescents was similar to that seen for adults except for higher incidences reported in adolescents 

than in adults for abdominal pain-related events and suicidal ideation (see section 4.8 and 5.1). In 

clinical studies in children and adolescents treated with antidepressants, suicide-related behaviour 

(suicide attempt and suicidal thoughts) and hostility (predominantly aggression, oppositional 

behaviour, anger) were more frequently observed than in those treated with placebo. 

 

Suicide/suicidal thoughts or clinical worsening 

 

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. 

 

Patients with a history of suicide-related events or those exhibiting a significant degree of suicidal 

ideation prior to commencement of treatment are known to be at greater risk of suicidal thoughts or 

suicide attempts, and should receive careful monitoring during treatment. A meta-analysis of 

placebo-controlled clinical studies of antidepressants in adult patients with psychiatric disorders 

showed an increased risk of suicidal behaviour with antidepressants compared to placebo, in patients 

less than 25 years old. 

 

Close supervision of patients and in particular those at high risk should accompany treatment 

especially in early treatment and following dose changes. Patients (and caregivers of patients) should 

be alerted to 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. 

 

Seizures 

 

Seizures are a potential risk with antidepressants. Therefore, vortioxetine should be introduced 

cautiously in patients who have a history of seizures or in patients with unstable epilepsy (see section 

4.5). Treatment should be discontinued in any patient who develops seizures or for whom there is an 

increase in seizure frequency. 

 

Serotonin Syndrome (SS) or Neuroleptic Malignant Syndrome (NMS) 

 

Serotonin Syndrome (SS) or Neuroleptic Malignant Syndrome (NMS), potentially life-threatening 

conditions, may occur with vortioxetine. The risk of SS or NMS is increased with concomitant use of 

serotonergic-active substances (including triptans), medicinal products that impair the metabolism of 

serotonin (including MAOIs), antipsychotics, and other dopamine antagonists. Patients should be 

monitored for the emergence of signs and symptoms of SS or NMS (see sections 4.3 and 4.5). 

 

Serotonin Syndrome symptoms include mental status changes (e.g., agitation, hallucinations, coma), 

autonomic instability (e.g., tachycardia, labile blood pressure, hyperthermia), neuromuscular 

aberrations (e.g., hyperreflexia, uncoordination) and/or gastrointestinal symptoms (e.g., nausea, 

vomiting, diarrhoea). If this occurs, treatment with vortioxetine should be discontinued immediately 

and symptomatic treatment should be initiated. 

 

Mania/hypomania 

 

Vortioxetine should be used with caution in patients with a history of mania/hypomania and should be 

discontinued in any patient entering a manic phase. 

 

 

 



23 

Aggression/agitation 

Patients treated with antidepressants, including vortioxetine, may also experience feelings of 

aggression, anger, agitation and irritability. Patient’s condition and disease status should be closely 

monitored. Patients (and caregivers of patients) should be alerted to seek medical advice, if 

aggressive/agitated behaviour emerges or aggravates. 

 

Haemorrhage 

 

Bleeding abnormalities, such as ecchymoses, purpura and other haemorrhagic events, such as 

gastrointestinal or gynaecological bleeding, have been reported rarely with the use of antidepressants 

with serotonergic effect, including vortioxetine. SSRIs/SNRIs may increase the risk of postpartum 

haemorrhage, and this risk could potentially apply also to vortioxetine (see section 4.6). Caution is 

advised in patients taking anticoagulants and/or medicinal products known to affect platelet function 

[e.g. atypical antipsychotics and phenothiazines, most tricyclic antidepressants, non-steroidal anti-

inflammatory drugs (NSAIDs), acetylsalicylic acid (ASA)] (see section 4.5) and in patients with 

known bleeding tendencies/disorders. 

 

Hyponatraemia 

 

Hyponatraemia, probably due to inappropriate antidiuretic hormone secretion (SIADH), has been 

reported rarely with the use of antidepressants with serotonergic effect (SSRIs, SNRIs). Caution 

should be exercised in patients at risk, such as the elderly, patients with cirrhosis of the liver or 

patients concomitantly treated with medicinal products known to cause hyponatraemia. 

Discontinuation of vortioxetine should be considered in patients with symptomatic hyponatraemia and 

appropriate medical intervention should be instituted. 

 

Glaucoma 

 

Mydriasis has been reported in association with use of antidepressants, including vortioxetine. This 

mydriatic effect has the potential to narrow the eye angle resulting in increased intraocular pressure 

and angle-closure glaucoma. Caution is advised when prescribing vortioxetine to patients with 

increased intraocular pressure, or those at risk of acute narrow-angle glaucoma. 

 

Elderly 

 

Data on the use of Brintellix in elderly patients with major depressive episodes are limited. Therefore,  

caution should be exercised when treating patients ≥ 65 years of age with doses higher than 10 mg 

vortioxetine once daily (see sections 4.2, 4.8 and 5.2). 

 

Renal or hepatic impairment 

 

Given that subjects with renal or hepatic impairment are vulnerable and given that the data on the use 

of Brintellix in these subpopulations are limited, caution should be exercised when treating these 

patients. (see section 4.2 and 5.2). 

 

 Excipient contents 

 

This medicinal product contains 85 mg of alcohol (ethanol 96%) in each ml which is equivalent to 

10.1 % v/v.  

 

4.5 Interaction with other medicinal products and other forms of interaction 

 

Vortioxetine is extensively metabolised in the liver, primarily through oxidation catalysed by CYP2D6 

and to a minor extent CYP3A4/5 and CYP2C9 (see section 5.2). 

 



24 

 

 

Potential for other medicinal products to affect vortioxetine 

 

Irreversible non-selective MAOIs 

Due to the risk of Serotonin Syndrome, vortioxetine is contraindicated in any combination with 

irreversible non-selective MAOIs. Vortioxetine must not be initiated for at least 14 days after 

discontinuation of treatment with an irreversible non-selective MAOI. Vortioxetine must be 

discontinued for at least 14 days before starting treatment with an irreversible non-selective MAOI 

(see section 4.3). 

 

Reversible, selective MAO-A inhibitor (moclobemide) 

The combination of vortioxetine with a reversible and selective MAO-A inhibitor, such as 

moclobemide, is contraindicated (see section 4.3). If the combination proves necessary, the added 

medicinal product should be given with minimum dosage and under close clinical monitoring for 

Serotonin Syndrome (see section 4.4). 

 

Reversible, non-selective MAOI (linezolid) 

The combination of vortioxetine with a weak reversible and non-selective MAOI, such as the 

antibiotic linezolid, is contraindicated (see section 4.3). If the combination proves necessary, the added 

medicinal product should be given with minimum dosage and under close clinical monitoring for 

Serotonin Syndrome (see section 4.4). 

 

Irreversible, selective MAO-B inhibitor (selegiline, rasagiline) 

Although a lower risk of Serotonin Syndrome is expected with selective MAO-B inhibitors than with 

MAO-A inhibitors, the combination of vortioxetine with irreversible MAO-B inhibitors, such as 

selegiline or rasagiline should be administered with caution. Close monitoring for Serotonin Syndrome 

is necessary if used concomitantly (see section 4.4). 

 

Serotonergic medicinal products 

Co-administration of medicinal products with serotonergic effect (e.g., tramadol, sumatriptan and 

other triptans) may lead to Serotonin Syndrome (see section 4.4). 

 

St. John’s wort 

Concomitant use of antidepressants with serotonergic effect and herbal remedies containing St. John’s 

wort (Hypericum perforatum) may result in a higher incidence of adverse reactions including 

Serotonin Syndrome (see section 4.4). 

 

Medicinal products lowering the seizure threshold 

Antidepressants with serotonergic effect can lower the seizure threshold. Caution is advised when 

concomitantly using other medicinal products capable of lowering the seizure threshold [e.g. 

antidepressants (tricyclics, SSRIs, SNRIs), neuroleptics (phenothiazines, thioxanthenes and 

butyrophenones), mefloquine, bupropion, tramadol] (see section 4.4). 

 

ECT (electroconvulsive therapy) 

There is no clinical experience with concurrent administration of vortioxetine and ECT, therefore 

caution is advisable. 

 

CYP2D6 inhibitors 

The exposure to vortioxetine increased 2.3-fold for area under the curve (AUC) when vortioxetine 

10 mg/day was co-administered with bupropion (a strong CYP2D6 inhibitor 150 mg twice daily) for 

14 days in healthy subjects. Co-administration resulted in a higher incidence of adverse reactions 

when bupropion was added to vortioxetine than when vortioxetine was added to bupropion. 

Depending on individual patient response, a lower dose of vortioxetine may be considered if a strong 

CYP2D6 inhibitor (e.g., bupropion, quinidine, fluoxetine, paroxetine) is added to vortioxetine 

treatment (see section 4.2). 



25 

 

 

CYP3A4 inhibitors and CYP2C9, and CYP2C19 inhibitors 

When vortioxetine was co-administered following 6 days of ketoconazole 400 mg/day (a CYP3A4/5 

and P-glycoprotein inhibitor) or following 6 days of fluconazole 200 mg/day (a CYP2C9, CYP2C19, 

and CYP3A4/5 inhibitor) in healthy subjects, a 1.3-fold and 1.5-fold increase, respectively, in 

vortioxetine AUC was observed. No dose adjustment is needed. 

 

No inhibitory effect of 40 mg single-dose omeprazole (CYP2C19 inhibitor) was observed on the 

multiple-dose pharmacokinetics of vortioxetine in healthy subjects. 

 

Interactions in CYP2D6 poor metabolisers 

Co-administration of strong inhibitors of CYP3A4 (such as itraconazol, voriconazole, clarithromycin, 

telithromycin, nefazodone, conivaptan and many of the HIV protease inhibitors) and inhibitors of 

CYP2C9 (such as fluconazole and amiodarone) to CYP2D6 poor metabolisers (see section 5.2) has 

not been investigated specifically, but it is anticipated that it will lead to a more marked increased 

exposure of vortioxetine in these patients as compared to the moderate effect described above. 

Depending on individual patient response, a lower dose of vortioxetine may be considered if a strong 

inhibitor of CYP3A4 or CYP2C9 is co-administered in CYP2D6 poor metabolisers. 

 

Cytochrome P450 inducers 

When a single dose of 20 mg vortioxetine was co-administered following 10 days of rifampicin 

600 mg/day (a broad inducer of CYP isozymes) in healthy subjects, a 72% decrease in AUC of 

vortioxetine was observed. Depending on individual patient response, a dose adjustment may be 

considered if a broad cytochrome P450 inducer (e.g., rifampicin, carbamazepine, phenytoin) is added 

to vortioxetine treatment (see section 4.2). 

 

Alcohol 

No effect on the pharmacokinetics of vortioxetine or ethanol and no significant impairment, relative to 

placebo, in cognitive function were observed when vortioxetine in a single dose of 20 mg or 40 mg 

was co-administered with a single dose of ethanol (0.6 g/kg) in healthy subjects. However, alcohol 

intake is not advisable during antidepressant treatment. 

 

Acetylsalicylic acid 

No effect of multiple doses of acetylsalicylic acid 150 mg/day on the multiple-dose pharmacokinetics 

of vortioxetine was observed in healthy subjects. 

 

Potential for vortioxetine to affect other medicinal products 

 

Anticoagulants and antiplatelet medicinal products 

No significant effects, relative to placebo, were observed in INR, prothrombin or plasma 

R-/S-warfarin values following co-administration of multiple doses of vortioxetine with stable doses 

of warfarin in healthy subjects. Also, no significant inhibitory effect, relative to placebo, on platelet 

aggregation or pharmacokinetics of acetylsalicylic acid or salicylic acid was observed when 

acetylsalicylic acid 150 mg/day was co-administered following multiple doses of vortioxetine 

administration in healthy subjects. However, caution should be exercised when vortioxetine is 

combined with oral anticoagulants or antiplatelet medicinal products due to a potential increased risk 

of bleeding attributable to a pharmacodynamic interaction (see section 4.4). 

 

Cytochrome P450 substrates 

In vitro, vortioxetine did not show any relevant potential for inhibition or induction of cytochrome 

P450 isozymes (see section 5.2). 

 

Following multiple doses of vortioxetine, no inhibitory effect was observed in healthy subjects for the 

cytochrome P450 isozymes CYP2C19 (omeprazole, diazepam), CYP3A4/5 (ethinyl estradiol, 



26 

midazolam), CYP2B6 (bupropion), CYP2C9 (tolbutamide, S-warfarin), CYP1A2 (caffeine) or 

CYP2D6 (dextromethorphan). 

 

No pharmacodynamic interactions were observed. No significant impairment, relative to placebo, in 

cognitive function was observed for vortioxetine following co-administration with a single 10 mg dose 

of diazepam. No significant effects, relative to placebo, were observed in the levels of sex hormones 

following co-administration of vortioxetine with a combined oral contraceptive (ethinyl estradiol 

30 µg/ levonorgestrel 150 µg). 

 

Lithium, tryptophan 

No clinically relevant effect was observed during steady-state lithium exposure following co-

administration with multiple doses of vortioxetine in healthy subjects. However, there have been 

reports of enhanced effects when antidepressants with serotonergic effect have been given together 

with lithium or tryptophan; therefore, concomitant use of vortioxetine with these medicinal products 

should be undertaken with caution. 

 

Interference with urine drug screens 

There have been reports of false positive results in urine enzyme immunoassays for methadone in 

patients who have taken vortioxetine. Caution should be exercised in the interpretation of positive 

urine drug screen results, and confirmation by an alternative analytical technique (e.g., 

chromatographic methods) should be considered. 

 

4.6 Fertility, pregnancy and lactation 

 

Pregnancy 

 

There are limited data from the use of vortioxetine in pregnant women. 

 

Studies in animals have shown reproductive toxicity (see section 5.3). 

 

The following symptoms may occur in the newborn after maternal use of a serotonergic medicinal 

product in the later stages of pregnancy: respiratory distress, cyanosis, apnoea, seizures, temperature 

instability, feeding difficulty, vomiting, hypoglycaemia, hypertonia, hypotonia, hyperreflexia, tremor, 

jitteriness, irritability, lethargy, constant crying, somnolence and difficulty sleeping. These symptoms 

could be due to either discontinuation effects or excess serotonergic activity. In the majority of 

instances, such complications began immediately or soon (<24 hours) after delivery. 

 

Epidemiological data suggest 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 with vortioxetine treatment, this potential risk cannot be 

ruled out taking into account the related mechanism of action (increase in serotonin concentrations). 

 

Brintellix should only be administered to pregnant women if the expected benefits outweigh the 

potential risk to the foetus. 

 

Observational data have provided evidence of an increased risk (less than 2-fold) of postpartum 

haemorrhage following exposure to an SSRI or SNRI within the month prior to birth. Although no 

studies have investigated an association between vortioxetine treatment and postpartum haemorrhage, 

there is a potential risk, taking into account the related mechanism of action (See section 4.4) 

 

Breast-feeding 

 

Available data in animals have shown excretion of vortioxetine/ vortioxetine metabolites in milk. It is 

expected that vortioxetine will be excreted into human milk (see section 5.3). 

 

A risk to the breastfeeding child cannot be excluded. 



27 

 

A decision must be made whether to discontinue breast-feeding or to discontinue/abstain from 

Brintellix treatment taking into account the benefit of breast-feeding for the child and the benefit of 

therapy for the woman. 

 

Fertility 

 

Fertility studies in male and female rats showed no effect of vortioxetine on fertility, sperm quality or 

mating performance (see section 5.3). 

Human case reports with medicinal products from the related pharmacological class of antidepressants 

(SSRIs) have shown an effect on sperm quality that is reversible. Impact on human fertility has not 

been observed so far. 

 

4.7 Effects on ability to drive and use machines 

 

Brintellix has no or negligible influence on the ability to drive and use machines. However, as adverse 

reactions such as diziness have been reported, patients should exercise caution when driving or 

operating hazardous machinery, especially when starting treatment with vortioxetine or when 

changing the dose. 

 

4.8 Undesirable effects 

 

Summary of the safety profile 

 

The most common adverse reaction was nausea.  

 

Tabulated list of adverse reactions  

 

Adverse reactions are listed below using the following convention: 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), not known (cannot be estimated from the available data). The list is based on information 

from clinical trials and post-marketing experience. 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 



28 

SYSTEM ORGAN CLASS FREQUENCY ADVERSE REACTION 

Immune system disorders  Not known * Anaphylactic reaction 

Metabolism and nutrition disorders Not known * Hyponatraemia 

Psychiatric disorders Common Abnormal dreams 

Not known * Insomnia 

Not known * Agitation, aggression (see section 4.4) 

Nervous system disorders Common Dizziness 

Not known * Serotonin Syndrome  

Eye disorders Rare  Mydriasis (which may lead to acute 

narrow angle glaucoma - see section 

4.4) 

Vascular disorders Uncommon Flushing 

Not known * Haemorrhage (including contusion, 

ecchymosis, epistaxis, gastrointestinal 

or vaginal bleeding) 

Gastrointestinal disorders Very common Nausea 

Common Diarrhoea, 

Constipation, 

Vomiting 

Skin and subcutaneous tissue disorders Common Pruritus, including  pruritus generalised 

Uncommon Night sweats 

Not known* Angioedema, 

Urticaria 

Rash 

* Based on post-marketing cases 

 

 

Description of selected adverse reactions 

 

Nausea 

Nausea was usually mild or moderate and occurred within the first two weeks of treatment. The 

reactions were usually transient and did not generally lead to cessation of therapy. Gastrointestinal 

adverse reactions, such as nausea, occurred more frequently in women than men. 

 

Elderly patients 

For doses ≥10 mg vortioxetine once daily, the withdrawal rate from the studies was higher in patients 

aged ≥65 years. 

For doses of 20 mg vortioxetine once daily, the incidences of nausea and constipation were higher in 

patients aged ≥65 years (42% and 15%, respectively) than in patients aged <65 years (27% and 4%, 

respectively)(see section 4.4). 

 

Sexual dysfunction 

In clinical studies, sexual dysfunction was assessed using the Arizona Sexual Experience Scale 

(ASEX). Doses of 5 to 15 mg showed no difference to placebo. However, the 20 mg dose of 

vortioxetine was associated with an increase in  sexual dysfunction (TESD)(see section 5.1) . 

 

Class effect 

Epidemiological studies, mainly conducted in patients 50 years of age and older, show an increased 

risk of bone fractures in patients receiving a medicinal product from related pharmacological classes 

of antidepressants (SSRIs or TCAs). The mechanism behind this risk is unknown, and it is not known 

if this risk is also relevant for vortioxetine. 

 

Paediatric population  

A total of 308 adolescent patients aged 12 to 17 years with major depressive disorder (MDD) were 

treated with vortioxetine in a double-blind, placebo-controlled study. In general, the adverse reaction 



29 

profile of vortioxetine in adolescents was similar to that seen for adults except for higher incidences 

reported in adolescents than in adults for abdominal pain-related events and suicidal ideation. 

 

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 

 

Ingestion of vortioxetine in clinical trials in the dose range of 40 mg to 75 mg has caused an 

aggravation of the following adverse reactions: nausea, postural dizziness, diarrhoea, abdominal 

discomfort, generalised pruritus, somnolence and flushing. 

 

Post-marketing experience mainly concerns vortioxetine overdoses of up to 80 mg. In the majority of 

cases, no symptoms or mild symptoms were reported. The most frequently reported symptoms were 

nausea and vomiting.  

 

There is limited experience with vortioxetine overdoses above 80 mg. Following dosages several fold 

higher than the therapeutic dose range, events of seizure and serotonin syndrome have been reported. 

 

Management of overdose should consist of treating clinical symptoms and relevant monitoring. 

Medical follow-up in a specialised environment is recommended. 

 

 

5. PHARMACOLOGICAL PROPERTIES 

 

5.1  Pharmacodynamic properties 

 

Pharmacotherapeutic group: Psychoanaleptics; Other antidepressants, ATC-code: N06AX26 

 

Mechanism of action 

 

The mechanism of action of vortioxetine is thought to be related to its direct modulation of 

serotonergic receptor activity and inhibition of the serotonin (5-HT) transporter. Nonclinical data 

indicate that vortioxetine is a 5-HT3, 5-HT7, and 5-HT1D receptor antagonist, 5-HT1B receptor partial 

agonist, 5-HT1A receptor agonist and inhibitor of the 5-HT transporter, leading to modulation of 

neurotransmission in several systems, including predominantly the serotonin but probably also the 

norepinephrine, dopamine, histamine, acetylcholine, GABA and glutamate systems. This multimodal 

activity is considered responsible for the antidepressant and anxiolytic-like effects and the 

improvement of cognitive function, learning and memory observed with vortioxetine in animal 

studies. However, the precise contribution of the individual targets to the observed pharmacodynamic 

profile remains unclear and caution should be applied when extrapolating animal data directly to man.  

 

In humans, two positron emission tomography (PET) studies have been conducted using 5-HT 

transporter ligands (11C-MADAM or 11C-DASB) to quantify the 5-HT transporter occupancy in the 

brain across different dose levels. The mean 5-HT transporter occupancy in the raphe nuclei was 

approximately 50% at 5 mg/day, 65% at 10 mg/day and increased to above 80% at 20 mg/day.  

 

Clinical efficacy and safety 

 

The efficacy and safety of vortioxetine have been studied in a clinical programme that included more 

than 6,700 patients, of whom more than 3,700 were treated with vortioxetine in short-term 

(≤12 weeks) studies of major depressive disorder (MDD). Twelve double-blind, placebo-controlled, 

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


30 

6/8-week, fixed-dose studies have been conducted to investigate the short-term efficacy of 

vortioxetine in MDD in adults (including the elderly). The efficacy of vortioxetine was demonstrated 

with at least one dosage group across 9 of the 12 studies, showing at least a 2-point difference to 

placebo in the Montgomery and Åsberg Depression Rating Scale (MADRS) or Hamilton Depression 

Rating Scale 24-item (HAM-D24) total score. This was supported by clinical relevance as 

demonstrated by the proportions of responders and remitters and the improvement in the Clinical 

Global Impression – Global Improvement (CGI-I) score. The efficacy of vortioxetine increased with 

increasing dose.  

 

The effect in the individual studies was supported by the meta-analysis (MMRM) of the mean change 

from baseline in MADRS total score at Week 6/8 in the short-term, placebo-controlled studies in 

adults. In the meta-analysis, the overall mean difference to placebo across the studies was statistically 

significant: -2.3 points (p = 0.007), -3.6 points (p <0.001), and -4.6 points (p <0.001) for the 5, 10, and 

20 mg/day doses, respectively; the 15mg/day dose did not separate from placebo in the meta-analysis, 

but the mean difference to placebo was -2.6 points. The efficacy of vortioxetine is supported by the 

pooled responder analysis, in which the proportion of responders ranged from 46% to 49% for 

vortioxetine versus 34% for placebo (p <0.01; NRI analysis). 

 

Furthermore, vortioxetine, in the dose range of 5-20 mg/day, demonstrated efficacy on the broad range 

of depressive symptoms (assessed by improvement in all MADRS single–item scores).  

 

The efficacy of vortioxetine 10 or 20 mg/day was further demonstrated in a 12-week, 

double-blind, flexible-dose comparative study versus agomelatine 25 or 50 mg/day in patients with 

MDD. Vortioxetine was statistically significantly better than agomelatine as measured by 

improvement in the MADRS total score and supported by the clinical relevance as demonstrated by 

the proportions of responders and remitters and improvement in the CGI-I. 

 

Maintenance 

The maintenance of antidepressant efficacy was demonstrated in a relapse-prevention study. Patients 

in remission after an initial 12-week open-label treatment period with vortioxetine were randomised to 

vortioxetine 5 or 10 mg/day or placebo and observed for relapse during a double-blind period of at 

least 24 weeks (24 to 64 weeks). Vortioxetine was superior (p=0.004) to placebo on the primary 

outcome measure, the time to relapse of MDD, with a hazard ratio of 2.0; that is, the risk of relapse 

was two times higher in the placebo group than in the vortioxetine group. 

 

Elderly 

In the 8-week double-blind, placebo-controlled, fixed-dose study in elderly depressed patients (aged 

≥65 years, n=452, 156 of whom were on vortioxetine), vortioxetine 5 mg/day was superior to placebo 

as measured by improvement in the MADRS and HAM-D24 total scores. The effect seen with 

vortioxetine was a 4.7 point difference to placebo in MADRS total score at Week 8 (MMRM 

analysis). 

 

Patients with severe depression or with depression and high levels of anxiety symptoms 

In severely depressed patients (baseline MADRS total score ≥30) and in depressed patients with a high 

level of anxiety symptoms (baseline HAM-A total score ≥20) vortioxetine also demonstrated efficacy 

in the short-term studies in adults (the overall mean difference to placebo in MADRS total score at 

Week 6/8 ranged from 2.8 to 7.3 points and from 3.6 to 7.3 points, respectively, (MMRM analysis)). 

In the dedicated study in elderly, vortioxetine was also effective in these patients. 

The maintenance of antidepressant efficacy was also demonstrated in this patient population in the 

long-term relapse prevention study. 

 

Effects of vortioxetine on the Digit Symbol Substitution Test (DSST), the University of California San 

Diego Performance-Based Skills Assessment (UPSA) (objective measures) and Perceived Deficits 

Questionnaire (PDQ) and Cognitive and Physical Functioning Questionnaire CPFQ (subjective 

measures) scores 



31 

The efficacy of vortioxetine (5-20 mg/day) in patients with MDD has been investigated in 2 adult and 

1 elderly short-term, placebo-controlled studies. 

 

Vortioxetine had a statistically significant effect versus placebo on the Digit Symbol Substitution Test 

(DSST), ranging from Δ = 1.75 (p = 0.019) to 4.26 (p <0.0001) in the 2 studies in adults and Δ = 2.79 

(p = 0.023) in the study in the elderly. In the meta-analyses (ANCOVA, LOCF) of the mean change 

from baseline in DSST number of correct symbols in all 3 studies, vortioxetine separated from placebo 

(p<0.05) with a standardised effect size of 0.35. When adjusting for the change in MADRS the total 

score in the meta-analysis of the same studies showed that vortioxetine separated from placebo 

(p<0.05) with a standardised effect size of 0.24.  

One study assessed the effect of vortioxetine on functional capacity using the University of California 

San Diego Performance-Based Skills Assessment (UPSA). Vortioxetine separated from placebo 

statistically with results of 8.0 for vortioxetine versus 5.1 points for placebo (p=0.0003). 

 

In one study, vortioxetine was superior to placebo on subjective measures, evaluated using the 

Perceived Deficits Questionnaire with results of -14.6 for vortioxetine and -10.5 for placebo 

(p=0.002). Vortioxetine did not separate from placebo on subjective measures when evaluated using 

the Cognitive and Physical Functioning Questionnaire with results of -8.1 for vortioxetine versus -6.9 

for placebo (p=0.086). 

 

Tolerability and safety 

The safety and tolerability of vortioxetine have been established in short- and long-term studies across 

the dose range of 5 to 20 mg/day. For information on undesirable effects, see section 4.8. 

 

Vortioxetine did not increase the incidence of insomnia or somnolence relative to placebo. 

In clinical short- and long-term placebo-controlled studies, potential discontinuation symptoms were 

systematically evaluated after abrupt treatment cessation of vortioxetine. There was no clinically 

relevant difference to placebo in the incidence or nature of the discontinuation symptoms after either 

short-term (6-12 weeks) or long-term (24-64 weeks) treatment with vortioxetine. 

 

The incidence of self-reported adverse sexual reactions was low and similar to placebo in clinical 

short- and long-term studies with vortioxetine. In studies using the Arizona Sexual Experience Scale 

(ASEX), the incidence of treatment-emergent sexual dysfunction (TESD) and the ASEX total score 

showed no clinically relevant difference to placebo in symptoms of sexual dysfunction at the 5 to 

15 mg/day doses of vortioxetine. For the 20 mg/day dose, an increase in TESD was seen compared to 

placebo (an incidence difference of 14.2%, 95% CI [1.4, 27.0]). 

 

The effect of vortioxetine on sexual function was further evaluated in an 8-week, double-blind, 

flexible-dose, comparative study (n=424) versus escitalopram in patients treated for at least 6 weeks 

with an SSRI (citalopram, paroxetine, or sertraline), with a low level of depressive symptoms 

(baseline CGI-S ≤ 3) and TESD induced by the prior SSRI treatment. Vortioxetine 10-20 mg/day had 

statistically significantly less TESD than escitalopram 10-20 mg/day as measured by change in the 

CSFQ-14 total score (2.2 points, p=0.013) at week 8. The proportion of responders was not 

significantly different in the vortioxetine group (162 (74.7%)) compared with the escitalopram group 

(137 (66.2%)) at week 8 (OR 1.5 p=0.057). The antidepressant effect was maintained in both 

treatment groups. 

 

Vortioxetine had no effect relative to placebo on body weight, heart rate, or blood pressure in clinical 

short- and long-term studies. 

 

No clinically significant changes were observed in hepatic or renal assessments in clinical studies.  

 

Vortioxetine has not shown any clinically significant effect on ECG parameters, including the QT, 

QTc, PR and QRS intervals, in patients with MDD. In a thorough QTc study in healthy subjects at 

doses up to 40 mg daily, no potential for the prolongation of the QTc interval was observed. 

 



32 

Paediatric population 

One randomised, double-blind, placebo-controlled, active-referenced, fixed dose, 8-week study was 

conducted in adolescent patients with MDD aged 12 to 17 years. The study included a 4-week single-

blind placebo lead-in period with standardized psychosocial intervention (N=777); only non-

responders from the lead-in period were randomised (N=615). Neither vortioxetine 10 mg/day nor 20 

mg/day was statistically significantly superior to placebo based on the Children´s Depression Rating 

Scale-Revised (CDRS-R) total score. The active reference (fluoxetine 20 mg/day) separated 

statistically from placebo on the CDRS-R total score. In general, the adverse reaction profile of 

vortioxetine in adolescents was similar to that seen for adults except for higher incidences reported in 

adolescent than in adults for abdominal pain-related event and suicidal ideation. Discontinuation due 

to adverse events (mostly due to suicidal ideation, nausea and vomiting) was highest in patients treated 

with vortioxetine 20 mg/day (5.6%) as compared to vortioxetine 10 mg/day (2.7%), fluoxetine (3.3%), 

and placebo (1.3%). The most commonly reported adverse events in the vortioxetine treatment groups 

were nausea, vomiting and headache. Suicidal ideation and behaviour were reported as adverse events 

both during the 4-week single-blind lead-in period (placebo 13/777 [1.7%]), and during the 8-week 

treatment period (vortioxetine 10 mg/day 2/147 [1.4%], vortioxetine 20 mg/day 6/161 [3.7%], 

fluoxetine 6/153 [3.9%], placebo 0/154 [0%]). Suicidal ideation and behaviour as measured by 

Columbia-Suicide Severity Rating Scale (C-SSRS) was similar across treatment groups. 

 

The European Medicines Agency has waived the obligation to submit the results of studies in major 

depressive disorder with vortioxetine in children aged less than 7 years (see section 4.2 for information 

on paediatric use). 

 

The European Medicines Agency has deferred the obligation to submit the results of studies with 

vortioxetine in one or more subsets of the paediatric population in treatment of major depressive 

disorder (see section 4.2 for information on paediatric use). 

 

5.2 Pharmacokinetic properties 

 

Absorption 

Vortioxetine is slowly, but well absorbed after oral administration and the peak plasma concentration 

is reached within 7 to 11 hours. Following multiple dosing of 5, 10, or 20 mg/day, mean Cmax values of 

9 to 33 ng/mL were observed. The absolute bioavailability is 75%. No effect of food on the 

pharmacokinetics was observed (see section 4.2). 

 

Distribution 

The mean volume of distribution (Vss) is 2,600 L, indicating extensive extravascular distribution. 

Vortioxetine is highly bound to plasma proteins (98 to 99%) and the binding appears to be 

independent of vortioxetine plasma concentrations. 

 

Biotransformation 

Vortioxetine is extensively metabolised in the liver, primarily through oxidation catalysed by CYP2D6 

and to a minor extent CYP3A4/5 and CYP2C9and subsequent glucuronic acid conjugation. 

 

No inhibitory or inducing effect of vortioxetine was observed in the drug-drug interaction studies for 

the CYP isozymes CYP1A2, CYP2A6, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP2E1, 

or CYP3A4/5 (see section 4.5). Vortioxetine is a poor P-gp substrate and inhibitor. 

 

The major metabolite of vortioxetine is pharmacologically inactive. 

 

Elimination 

The mean elimination half-life and oral clearance are 66 hours and 33 L/h, respectively. 

Approximately 2/3 of the inactive vortioxetine metabolites are excreted in the urine and approximately 



33 

1/3 in the faeces. Only negligible amounts of vortioxetine are excreted in the faeces. Steady-state 

plasma concentrations are achieved in approximately 2 weeks. 

 

Linearity/non-linearity 

The pharmacokinetics are linear and time independent in the dose range studied (2.5 to 60 mg/day). 

 

In accordance with the half-life, the accumulation index is 5 to 6 based on AUC0-24h following multiple 

doses of 5 to 20 mg/day. 

 

Special populations 

Elderly 

In elderly healthy subjects (aged ≥65 years; n=20), the exposure to vortioxetine increased up to 27% 

(Cmax and AUC) compared to young healthy control subjects (aged ≤45 years) after multiple doses of 

10 mg/day. The lowest effective dose of 5 mg vortioxetine once daily should always be used as the 

starting dose in patients ≥ 65 years of age (see section 4.2). However, caution should be exercised 

when prescribing to elderly patients at doses higher than 10 mg vortioxetine once daily (see section 

4.4). 

 

Renal impairment 

Following a single dose of 10 mg vortioxetine, renal impairment estimated using the Cockcroft-Gault 

formula (mild, moderate, or severe; n=8 per group) caused modest exposure increases (up to 30%), 

compared to healthy matched controls. In patients with end-stage renal disease, only a small fraction 

of vortioxetine was lost during dialysis (AUC and Cmax were 13% and 27% lower, respectively; n=8) 

following a single 10 mg dose of vortioxetine. No dose adjustment is needed based on renal function 

(see section 4.2 and 4.4). 

 

Hepatic impairment 

The pharmacokinetics in subjects (N = 6-8) with mild, moderate, or severe hepatic impairment (Child-

Pugh Criteria A, B, or C, respectively) were compared to healthy volunteers. The changes in AUC 

were less than 10% lower in subjects with mild or moderate hepatic impairment, and 10% higher in 

those with severe hepatic impairment. The changes in Cmax were less than 25% lower in all groups. No 

dose adjustment is needed based on hepatic function (see section 4.2 and 4.4). 

 

CYP2D6 gene types 

The plasma concentration of vortioxetine was approximately two times higher in CYP2D6 poor 

metabolisers than in extensive metabolisers. Co-administration of strong CYP3A4/2C9-inhibitors to 

CYP2D6 poor metabolisers could potentially result in higher exposure (see section 4.5). 

 

In CYP2D6 ultra-rapid metabolisers, the plasma concentration of vortioxetine 10 mg/day were 

between those obtained in extensive metabolisers at 5 mg/day and 10 mg/day. 

Depending on individual patient response, a dose adjustment may be considered (see section 4.2). 

 

Paediatric population 

Pharmacokinetics of vortioxetine in paediatric patients with major depressive disorder following oral 

administration of 5 to 20 mg once daily was characterized using population modeling analyses based 

on data from a pharmacokinetic study (7-17 years) and an efficacy and safety study (12-17 years). The 

pharmacokinetics of vortioxetine in paediatric patients was similar to that observed in adult patients. 

 

5.3 Preclinical safety data 

 

Administration of vortioxetine in the general toxicity studies in mice, rats and dogs was mainly 

associated with CNS-related clinical signs. These included salivation (rat and dog), pupil dilatation 

(dog), and two incidences of convulsions in dogs in the general toxicity study programme.. A no-effect 

level for convulsions was established with a corresponding safety margin of 5 considering the 

maximum recommended therapeutic dose of 20 mg/day. Target organ toxicity was restricted to 



34 

kidneys (rats) and liver (mice and rats). The changes in the kidney in rats (glomerulonephritis, renal 

tubular obstruction, crystalline material in renal tubule) and in the liver of mice and rats 

(hepatocellular hypertrophy, hepatocyte necrosis, bile duct hyperplasia, crystalline material in bile 

ducts) were seen at exposures more than 10-fold (mice) and 2-fold (rats) the human exposure at the 

maximum recommended therapeutic dose of 20 mg/day. These findings were mainly attributed to 

rodent-specific vortioxetine-related crystalline material obstruction of the renal tubules and the bile 

ducts, respectively, and considered of low risk to humans. 

 

Vortioxetine was not genotoxic in a standard battery of in vitro and in vivo tests. 

 

Based on results from conventional 2-year carcinogenicity studies in mice or rats, vortioxetine is not 

considered to pose a risk of carcinogenicity in humans. 

 

Vortioxetine had no effect on rat fertility, mating performance, reproductive organs, or sperm 

morphology and motility. Vortioxetine was not teratogenic in rats or rabbits, but reproductive toxicity 

in terms of effects on foetal weight and delayed ossification were seen in the rat at exposures more 

than 10-fold the human exposure at the maximum recommended therapeutic dose of 20 mg/day. 

Similar effects were seen in the rabbit at sub-therapeutic exposure. 

 

In a pre- and post-natal study in rats, vortioxetine was associated with increased pup mortality, 

reduced bodyweight gain, and delayed pup development at doses that did not result in maternal 

toxicity and with associated exposures similar to those achieved in humans following administration 

of vortioxetine 20 mg/day (see section 4.6). 

 

Vortioxetine-related material was distributed to the milk of lactating rats (see section 4.6). 

 

In juvenile toxicity studies in rats, all vortioxetine treatment-related findings were consistent with 

those noted in adult animals. 

 

Environmental risk assessment studies have shown that vortioxetine has the potential to be pesistent, 

bioaccumulative and toxic to the environment (risk to fish). However, by recommended patient usage 

vortioxetine is considered to pose negligible risk to the aquatic and terrestrial environment (see section 

6.6). 

 

 

6. PHARMACEUTICAL PARTICULARS 

 

6.1 List of excipients 

 

Hydroxypropylbetadex 

Ethanol (96 per cent)  

Purified water 

 

6.2 Incompatibilities 

 

In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal 

products. 

 

6.3 Shelf life 

 

3 years 

 

After opening the drops should be used within 8 weeks. 

 

 

 



35 

6.4 Special precautions for storage 

 

This medicinal product does not require any special storage conditions. 

 

6.5 Nature and contents of container  

 

15 ml in an amber glass bottle (type III) and screw cap (polypropylene) with dropper (LD-

polyethylene), (child-resistant closure). 

Pack of 1 glass bottle. 

 

6.6 Special precautions for disposal  

 

Any unused medicinal product or waste material should be disposed of in accordance with local 

requirements. 

 

 

7. MARKETING AUTHORISATION HOLDER 

 

H. Lundbeck A/S 

Ottiliavej 9 

2500 Valby 

Denmark 

 

 

8. MARKETING AUTHORISATION NUMBER(S)  

 

EU/1/13/891/036 

 

 

9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 

 

Date of first authorisation: 18 December 2013 

Date of latest renewal: 20 November 2018 

 

 

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/


36 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

ANNEX II 

A. MANUFACTURER 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 

 

 



37 

A. MANUFACTURER RESPONSIBLE FOR BATCH RELEASE 

H. Lundbeck A/S 

Ottiliavej 9 

2500 Valby 

DENMARK 

B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE 

 

Medicinal products subject to medical prescription.  

C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING 

AUTHORISATION  

• Periodic safety update reports  

The requirements for submission of periodic safety 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 agreeed 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.  

 

 



38 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

ANNEX III 

 

LABELLING AND PACKAGE LEAFLET 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 



39 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

A. LABELLING 

 



40 

 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING AND THE IMMEDIATE 

PACKAGING 

 

CARTON AND LABEL FOR THE TABLET CONTAINER 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Brintellix 5 mg film-coated tablets  

vortioxetine  

 

2. STATEMENT OF ACTIVE SUBSTANCE(S) 

 

Each film-coated tablet contains 5 mg vortioxetine (as hydrobromide) 

 

3. LIST OF EXCIPIENTS 

 

 

4. PHARMACEUTICAL FORM AND CONTENTS 

 

14 film-coated tablets 

28 film-coated tablets 

98 film-coated tablets 

56x1 film-coated tablets 

98x1 film-coated tablets 

100 film-coated tablets 

200 film-coated tablets  

 

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 {MM-YYYY} 

 

9. SPECIAL STORAGE CONDITIONS 

 

 

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 

APPROPRIATE 

 



41 

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 

 

H. Lundbeck A/S 

Ottiliavej 9 

2500 Valby 

Denmark 

 

12. MARKETING AUTHORISATION NUMBER(S)  

 

EU/1/13/891/001 14 film-coated tablets 

EU/1/13/891/002 28 film-coated tablets 

EU/1/13/891/003 56 x 1 film-coated tablets  

EU/1/13/891/004 98 x 1 film-coated tablets 

EU/1/13/891/006 100 film-coated tablets 

EU/1/13/891/007 200 film-coated tablets 

EU/1/13/891/037 98 film-coated tablets 

 

13. BATCH NUMBER 

 

Lot 

 

14. GENERAL CLASSIFICATION FOR SUPPLY 

 

 

15. INSTRUCTIONS ON USE 

 

 

16. INFORMATION IN BRAILLE 

 

Brintellix 5 mg  

 

17. UNIQUE IDENTIFIER – 2D BARCODE 

 

2D barcode carrying the unique identifier included. 

 

18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 

 

PC: 

SN: 

NN:



42 

 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 

 

CARTON FOR INTERMEDIATE PACK / COMPONENT OF A MULTIPACK  

(WITHOUT BLUE BOX) 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Brintellix 5 mg film-coated tablets  

vortioxetine  

 

2. STATEMENT OF ACTIVE SUBSTANCE(S) 

 

Each film-coated tablet contains 5 mg vortioxetine (as hydrobromide) 

 

3. LIST OF EXCIPIENTS 

 

 

4. PHARMACEUTICAL FORM AND CONTENTS 

 

14 film-coated tablets. 

98 x 1 film-coated tablets. 

Component of a multipack, can’t be sold separately. 

 

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 {MM-YYYY} 

 

9. SPECIAL STORAGE CONDITIONS 

 

 

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 

APPROPRIATE 

 



43 

 

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 

 

H. Lundbeck A/S 

Ottiliavej 9 

2500 Valby 

Denmark 

 

12. MARKETING AUTHORISATION NUMBER(S)  

 

EU/1/13/891/038 126 film-coated tablets (9 packs of 14) 

EU/1/13/891/005 490 film-coated tablets (5 packs of 98x1) 

 

13. BATCH NUMBER 

 

Lot 

 

14. GENERAL CLASSIFICATION FOR SUPPLY 

 

 

15. INSTRUCTIONS ON USE 

 

 

16. INFORMATION IN BRAILLE 

 

Brintellix 5 mg  

 

17. UNIQUE IDENTIFIER – 2D BARCODE 

 

 

18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 

 



44 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 

 

OUTER WRAPPER LABEL ON MULTIPACKS WRAPPED IN FOIL  

(INCLUDING BLUE BOX) 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Brintellix 5 mg film-coated tablets  

Vortioxetine  

 

2. STATEMENT OF ACTIVE SUBSTANCE(S) 

 

Each film-coated tablet contains 5 mg vortioxetine (as hydrobromide) 

 

3. LIST OF EXCIPIENTS 

 

 

4. PHARMACEUTICAL FORM AND CONTENTS 

 

Multipack: 126 (9 packs of 14) film-coated tablets. 

Multipack: 490 (5 packs of 98 x 1) film-coated tablets. 

 

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 {MM-YYYY} 

 

9. SPECIAL STORAGE CONDITIONS 

 

 

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 

APPROPRIATE 

 

 

 

 

 

 

 



45 

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 

 

H. Lundbeck A/S 

Ottiliavej 9 

2500 Valby 

Denmark 

 

12. MARKETING AUTHORISATION NUMBER(S)  

 

EU/1/13/891/038 126 film-coated tablets (9 packs of 14) 

EU/1/13/891/005 490 film-coated tablets (5 packs of 98x1) 

 

13. BATCH NUMBER 

 

Lot 

 

14. GENERAL CLASSIFICATION FOR SUPPLY 

 

 

15. INSTRUCTIONS ON USE 

 

 

16. INFORMATION IN BRAILLE 

 

Brintellix 5 mg  

 

17. UNIQUE IDENTIFIER – 2D BARCODE 

 

2D barcode carrying the unique identifier included. 

 

18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 

 

PC: 

SN: 

NN: 

 

 



46 

MINIMUM PARTICULARS TO APPEAR ON BLISTERS  

 

BLISTER FOR TABLETS 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Brintellix 5 mg tablet  

vortioxetine 

 

2. NAME OF THE MARKETING AUTHORISATION HOLDER 

 

H. Lundbeck A/S 

 

3. EXPIRY DATE 

 

EXP (MM-YYYY) 

 

4. BATCH NUMBER 

 

Lot 

 

5. OTHER 

 

 

 



47 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING AND THE IMMEDIATE 

PACKAGING 

 

CARTON AND LABEL FOR THE TABLET CONTAINER 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Brintellix 10 mg film-coated tablets  

vortioxetine  

 

2. STATEMENT OF ACTIVE SUBSTANCE(S) 

 

Each film-coated tablet contains 10 mg vortioxetine (as hydrobromide) 

 

3. LIST OF EXCIPIENTS 

 

 

4. PHARMACEUTICAL FORM AND CONTENTS 

 

7 film-coated tablets 

14 film-coated tablets 

28 film-coated tablets 

56 film-coated tablets 

56 x 1 film-coated tablets 

98 film-coated tablets 

98 x 1 film-coated tablets 

100 film-coated tablets 

200 film-coated tablets 

 

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 {MM-YYYY} 

 

9. SPECIAL STORAGE CONDITIONS 

 

 

 



48 

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 

 

H. Lundbeck A/S 

Ottiliavej 9 

2500 Valby 

Denmark 

 

12. MARKETING AUTHORISATION NUMBER(S)  

 

EU/1/13/891/008 7 film-coated tablets 

EU/1/13/891/009 14 film-coated 

EU/1/13/891/010 28 film-coated tablets 

EU/1/13/891/011 56 film-coated tablets 

EU/1/13/891/012 98 film-coated tablets 

EU/1/13/891/013 56x1 film-coated tablets 

EU/1/13/891/014 98x1 film-coated tablets 

EU/1/13/891/016 100 film-coated tablets 

EU/1/13/891/017 200 film-coated tablets 

 

 

13. BATCH NUMBER 

 

Lot 

 

14. GENERAL CLASSIFICATION FOR SUPPLY 

 

 

15. INSTRUCTIONS ON USE 

 

 

16. INFORMATION IN BRAILLE 

 

Brintellix 10 mg  

 

17. UNIQUE IDENTIFIER – 2D BARCODE 

 

2D barcode carrying the unique identifier included. 

 

18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 

 

PC: 

SN: 

NN: 

 

 



49 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 

 

CARTON FOR INTERMEDIATE PACK / COMPONENT OF A MULTIPACK 

(WITHOUT BLUE BOX) 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Brintellix 10 mg film-coated tablets  

vortioxetine  

 

2. STATEMENT OF ACTIVE SUBSTANCE(S) 

 

Each film-coated tablet contains 10 mg vortioxetine (as hydrobromide) 

 

3. LIST OF EXCIPIENTS 

 

 

4. PHARMACEUTICAL FORM AND CONTENTS 

 

14 film-coated tablets 

98 x 1 film-coated tablets 

Component of a multipack, can’t be sold separately. 

 

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 {MM-YYYY} 

 

9. SPECIAL STORAGE CONDITIONS 

 

 

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 

APPROPRIATE 

 



50 

 

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 

 

H. Lundbeck A/S 

Ottiliavej 9 

2500 Valby 

Denmark 

 

12. MARKETING AUTHORISATION NUMBER(S)  

 

EU/1/13/891/039 126 film-coated tablets (9 packs of 14) 

EU/1/13/891/015 490 film-coated tablets (5 packs of 98x1) 

 

13. BATCH NUMBER 

 

Lot 

 

14. GENERAL CLASSIFICATION FOR SUPPLY 

 

 

15. INSTRUCTIONS ON USE 

 

 

16. INFORMATION IN BRAILLE 

 

Brintellix 10 mg  

 

17. UNIQUE IDENTIFIER – 2D BARCODE 

 

 

18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 

 

 

 

 

 



51 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 

 

OUTER WRAPPER LABEL ON MULTIPACKS WRAPPED IN FOIL  

(INCLUDING BLUE BOX) 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Brintellix 10 mg film-coated tablets  

vortioxetine  

 

2. STATEMENT OF ACTIVE SUBSTANCE(S) 

 

Each film-coated tablet contains 10 mg vortioxetine (as hydrobromide) 

 

3. LIST OF EXCIPIENTS 

 

 

4. PHARMACEUTICAL FORM AND CONTENTS 

 

Multipack: 126 (9 packs of 14) film-coated tablets. 

Multipacks: 490 (5 packs of 98 x 1) film-coated tablets. 

 

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 {MM-YYYY} 

 

9. SPECIAL STORAGE CONDITIONS 

 

 

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 

APPROPRIATE 

 



52 

 

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 

 

H. Lundbeck A/S 

Ottiliavej 9 

2500 Valby 

Denmark 

 

12. MARKETING AUTHORISATION NUMBER(S)  

 

EU/1/13/891/039   126 film-coated tablets (9 packs of 14) 

EU/1/13/891/015  490 film-coated tablets (5 packs of 98x1). 

 

13. BATCH NUMBER 

 

Lot 

 

14. GENERAL CLASSIFICATION FOR SUPPLY 

 

 

15. INSTRUCTIONS ON USE 

 

 

16. INFORMATION IN BRAILLE 

 

Brintellix 10 mg 

 

17. UNIQUE IDENTIFIER – 2D BARCODE 

 

2D barcode carrying the unique identifier included. 

 

18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 

 

PC: 

SN: 

NN: 

 

 

 

 

 



53 

MINIMUM PARTICULARS TO APPEAR ON BLISTERS  

 

BLISTER FOR TABLETS 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Brintellix 10 mg tablet 

vortioxetine 

 

2. NAME OF THE MARKETING AUTHORISATION HOLDER 

 

H. Lundbeck A/S 

 

3. EXPIRY DATE 

 

EXP (MM-YYYY) 

 

4. BATCH NUMBER 

 

Lot 

 

5. OTHER 

 

 



54 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING AND THE IMMEDIATE 

PACKAGING 

 

CARTON AND LABEL FOR THE TABLET CONTAINER 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Brintellix 15 mg film-coated tablets  

vortioxetine  

 

2. STATEMENT OF ACTIVE SUBSTANCE(S) 

 

Each film-coated tablet contains 15 mg vortioxetine (as hydrobromide) 

 

3. LIST OF EXCIPIENTS 

 

 

4. PHARMACEUTICAL FORM AND CONTENTS 

 

14 film-coated tablets 

28 film-coated tablets 

56 film-coated tablets 

56 x 1 film-coated tablets 

98 film-coated tablets 

98 x 1 film-coated tablets 

100 film-coated tablets  

200 film-coated tablets  

 

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 {MM-YYYY} 

 

9. SPECIAL STORAGE CONDITIONS 

 

 

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 

APPROPRIATE 

 



55 

 

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 

 

H. Lundbeck A/S 

Ottiliavej 9 

2500 Valby 

Denmark 

 

 

12. MARKETING AUTHORISATION NUMBER(S)  

 

EU/1/13/891/018 14 film-coated tablets 

EU/1/13/891/019 28 film-coated tablets 

EU/1/13/891/020 56 film-coated tablets 

EU/1/13/891/021 98 film-coated tablets 

EU/1/13/891/022 56x1 film-coated tablets 

EU/1/13/891/023 98x1 film-coated tablets 

EU/1/13/891/025 100 film-coated tablets 

EU/1/13/891/026 200 film-coated tablets 

 

 

13. BATCH NUMBER 

 

Lot 

 

14. GENERAL CLASSIFICATION FOR SUPPLY 

 

 

15. INSTRUCTIONS ON USE 

 

 

16. INFORMATION IN BRAILLE 

 

Brintellix 15 mg  

 

17. UNIQUE IDENTIFIER – 2D BARCODE 

 

2D barcode carrying the unique identifier included. 

 

18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 

 

PC: 

SN: 

NN: 

 

 

 



56 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 

 

CARTON FOR INTERMEDIATE PACK / COMPONENT OF A MULTIPACK  

(WITHOUT BLUE BOX) 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Brintellix 15 mg film-coated tablets  

vortioxetine  

 

2. STATEMENT OF ACTIVE SUBSTANCE(S) 

 

Each film-coated tablet contains 15 mg vortioxetine (as hydrobromide) 

 

3. LIST OF EXCIPIENTS 

 

 

4. PHARMACEUTICAL FORM AND CONTENTS 

 

98 x 1 film-coated tablets. 

Component of a multipack, can’t be sold seperatly. 

 

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 {MM-YYYY} 

 

9. SPECIAL STORAGE CONDITIONS 

 

 

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 

APPROPRIATE 

 



57 

 

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 

 

H. Lundbeck A/S 

Ottiliavej 9 

2500 Valby 

Denmark 

 

12. MARKETING AUTHORISATION NUMBER(S)  

 

EU/1/13/891/024 490 film-coated tablets (5 packs of 98x1) 

 

13. BATCH NUMBER 

 

Lot 

 

14. GENERAL CLASSIFICATION FOR SUPPLY 

 

 

15. INSTRUCTIONS ON USE 

 

 

16. INFORMATION IN BRAILLE 

 

Brintellix 15 mg  

 

17. UNIQUE IDENTIFIER – 2D BARCODE 

 

 

18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 



58 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 

 

OUTER WRAPPER LABEL ON MULTIPACKS WRAPPED IN FOIL  

(INCLUDING BLUE BOX) 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Brintellix 15 mg film-coated tablets  

vortioxetine  

 

2. STATEMENT OF ACTIVE SUBSTANCE(S) 

 

Each film-coated tablet contains 15 mg vortioxetine (as hydrobromide) 

 

3. LIST OF EXCIPIENTS 

 

 

4. PHARMACEUTICAL FORM AND CONTENTS 

 

Multipack: 490 (5 packs of 98x1) film-coated tablets. 

 

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 {MM-YYYY} 

 

9. SPECIAL STORAGE CONDITIONS 

 

 

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 

 

H. Lundbeck A/S 

Ottiliavej 9 

2500 Valby 

Denmark 



59 

 

12. MARKETING AUTHORISATION NUMBER(S)  

 

EU/1/13/891/024 490 film-coated tablets (5 packs of 98x1) 

 

13. BATCH NUMBER 

 

Lot 

 

14. GENERAL CLASSIFICATION FOR SUPPLY 

 

 

15. INSTRUCTIONS ON USE 

 

 

16. INFORMATION IN BRAILLE 

 

Brintellix 15 mg 

 

17. UNIQUE IDENTIFIER – 2D BARCODE 

 

2D barcode carrying the unique identifier included. 

 

18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 

 

PC: 

SN: 

NN: 

 

 

 

 

 

 



60 

MINIMUM PARTICULARS TO APPEAR ON BLISTERS  

 

BLISTER FOR TABLETS 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Brintellix 15 mg tablet  

vortioxetine 

 

2. NAME OF THE MARKETING AUTHORISATION HOLDER 

 

H. Lundbeck A/S 

 

3. EXPIRY DATE 

 

EXP (MM-YYYY) 

 

4. BATCH NUMBER 

 

Lot 

 

5. OTHER 

 

 



61 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING AND THE IMMEDIATE 

PACKAGING 

 

CARTON AND LABEL FOR THE TABLET CONTAINER 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Brintellix 20 mg film-coated tablets  

vortioxetine  

 

2. STATEMENT OF ACTIVE SUBSTANCE(S) 

 

Each film-coated tablet contains 20 mg vortioxetine (as hydrobromide) 

 

3. LIST OF EXCIPIENTS 

 

 

4. PHARMACEUTICAL FORM AND CONTENTS 

 

14 film-coated tablets 

28 film-coated tablets 

56 film-coated tablets 

56 x 1 film-coated tablets 

98 film-coated tablets 

98 x 1 film-coated tablets 

100 film-coated tablets  

200 film-coated tablets  

 

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 {MM-YYYY} 

 

9. SPECIAL STORAGE CONDITIONS 

 

 

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 

APPROPRIATE 

 



62 

 

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 

 

H. Lundbeck A/S 

Ottiliavej 9 

2500 Valby 

Denmark 

 

12. MARKETING AUTHORISATION NUMBER(S)  

 

EU/1/13/891/027 14 film-coated tablets 

EU/1/13/891/028 28 film-coated tablets 

EU/1/13/891/029 56 film-coated tablets 

EU/1/13/891/030 98 film-coated tablets 

EU/1/13/891/031 56x1 film-coated tablets 

EU/1/13/891/032 98x1 film-coated tablets 

EU/1/13/891/034 100 film-coated tablets 

EU/1/13/891/035 200 film-coated tablets 

 

13. BATCH NUMBER 

 

Lot 

 

14. GENERAL CLASSIFICATION FOR SUPPLY 

 

 

15. INSTRUCTIONS ON USE 

 

 

16. INFORMATION IN BRAILLE 

 

Brintellix 20 mg  

 

17. UNIQUE IDENTIFIER – 2D BARCODE 

 

2D barcode carrying the unique identifier included. 

 

18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 

 

PC: 

SN: 

NN: 

 

 

 

 

 



63 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 

 

CARTON FOR INTERMEDIATE PACK / COMPONENT OF A MULTIPACK  

(WITHOUT BLUE BOX) 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Brintellix 20 mg film-coated tablets  

vortioxetine  

 

2. STATEMENT OF ACTIVE SUBSTANCE(S) 

 

Each film-coated tablet contains 20 mg vortioxetine (as hydrobromide) 

 

3. LIST OF EXCIPIENTS 

 

 

4. PHARMACEUTICAL FORM AND CONTENTS 

 

14 film-coated tablets 

98 x 1 film-coated tablets 

Component of a multipack, can’t be sold separately. 

 

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 {MM-YYYY} 

 

9. SPECIAL STORAGE CONDITIONS 

 

 

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 

APPROPRIATE 

 



64 

 

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 

 

H. Lundbeck A/S 

Ottiliavej 9 

2500 Valby 

Denmark 

 

12. MARKETING AUTHORISATION NUMBER(S)  

 

EU/1/13/891/040 126 film-coated tablets (9 packs of 14) 

EU/1/13/891/033 490 film-coated tablets (5 packs of 98x1) 

 

13. BATCH NUMBER 

 

Lot 

 

14. GENERAL CLASSIFICATION FOR SUPPLY 

 

 

15. INSTRUCTIONS ON USE 

 

 

16. INFORMATION IN BRAILLE 

 

Brintellix 20 mg  

 

17. UNIQUE IDENTIFIER – 2D BARCODE 

 

 

18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 



65 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 

 

OUTER WRAPPER LABEL ON MULTIPACKS WRAPPED IN FOIL  

(INCLUDING BLUE BOX) 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Brintellix 20 mg film-coated tablets  

Vortioxetine  

 

2. STATEMENT OF ACTIVE SUBSTANCE(S) 

 

Each film-coated tablet contains 20 mg vortioxetine (as hydrobromide) 

 

3. LIST OF EXCIPIENTS 

 

 

4. PHARMACEUTICAL FORM AND CONTENTS 

 

Multipack: 126 (9 packs of 14) film-coated tablets. 

Multipack: 490 (5 packs of 98x1) film-coated tablets. 

 

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 {MM-YYYY} 

 

9. SPECIAL STORAGE CONDITIONS 

 

 

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 

APPROPRIATE 

 

 

 

 

 

 

 



66 

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 

 

H. Lundbeck A/S 

Ottiliavej 9 

2500 Valby 

Denmark 

 

 

12. MARKETING AUTHORISATION NUMBER(S)  

 

EU/1/13/891/040 126 film-coated tablets (9 packs of 14) 

EU/1/13/891/033 490 film-coated tablets (5 packs of 98x1) 

 

13. BATCH NUMBER 

 

Lot 

 

14. GENERAL CLASSIFICATION FOR SUPPLY 

 

 

15. INSTRUCTIONS ON USE 

 

 

16. INFORMATION IN BRAILLE 

 

Brintellix 20 mg 

 

17. UNIQUE IDENTIFIER – 2D BARCODE 

 

2D barcode carrying the unique identifier included. 

 

18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 

 

PC: 

SN: 

NN: 

 

 

 

 

 

 

 

 

 



67 

MINIMUM PARTICULARS TO APPEAR ON BLISTERS  

 

BLISTER FOR TABLETS 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Brintellix 20 mg tablet  

vortioxetine 

 

2. NAME OF THE MARKETING AUTHORISATION HOLDER 

 

H. Lundbeck A/S 

 

3. EXPIRY DATE 

 

EXP (MM-YYYY) 

 

4. BATCH NUMBER 

 

Lot 

 

 

5. OTHER 

 

 



68 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING AND THE IMMEDIATE 

PACKAGING 

 

CARTON AND LABEL FOR BOTTLE 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Brintellix 20 mg/ml oral drops, solution  

vortioxetine  

 

2. STATEMENT OF ACTIVE SUBSTANCE(S) 

 

Each drop contains 1 mg vortioxetine (as (D,L)- lactate) 

 

3. LIST OF EXCIPIENTS 

 

Contains ethanol 

 

4. PHARMACEUTICAL FORM AND CONTENTS 

 

oral drops, solution  

15 ml  

 

5. METHOD AND ROUTE(S) OF ADMINISTRATION 

 

Read the package leaflet before use 

Oral use 

 

[outer carton only]: 

Turn the bottle completely upside down. If no drops come out, tap the bottle lightly to start the flow. 

 

 

 

 

 

 

 

 

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 {MM-YYYY} 

When opened, use within 8 weeks  

 

 



69 

9. SPECIAL STORAGE CONDITIONS 

 

 

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 

 

H. Lundbeck A/S 

Ottiliavej 9 

2500 Valby 

Denmark 

 

12. MARKETING AUTHORISATION NUMBER(S)  

 

EU/1/13/891/036 15 ml 

 

13. BATCH NUMBER 

 

Lot 

 

14. GENERAL CLASSIFICATION FOR SUPPLY 

 

 

15. INSTRUCTIONS ON USE 

 

 

16. INFORMATION IN BRAILLE 

 

Brintellix 20 mg/ml [outer carton only] 

 

17. UNIQUE IDENTIFIER – 2D BARCODE 

 

2D barcode carrying the unique identifier included. [outer carton only] 

 

18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 

 

[outer carton only] 

PC: 

SN: 

NN:



70 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

B. PACKAGE LEAFLET 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 



71 

Package leaflet: Information for the patient 

 

Brintellix 5 mg film-coated tablets 

vortioxetine 

 

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 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 Brintellix is and what it is used for  

2. What you need to know before you take Brintellix  

3. How to take Brintellix  

4. Possible side effects  

5. How to store Brintellix  

6. Contents of the pack and other information 

 

 

1. What Brintellix is and what it is used for 

 

Brintellix contains the active substance vortioxetine. It belongs to a group of medicines called 

antidepressants. 

 

Brintellix is used to treat major depressive episodes in adults. 

 

Brintellix has been shown to reduce the broad range of depressive symptoms, including sadness, inner 

tension (feeling anxious), sleep disturbances (reduced sleep), reduced appetite, difficulty in 

concentrating, feelings of worthlessness, loss of interest in favourite activities, feeling of being slowed 

down. 

 

 

2. What you need to know before you take Brintellix 

 

Do not take Brintellix: 

 

- if you are allergic to vortioxetine or any of the other ingredients of this medicine (listed in 

section 6). 

- if you are taking other medicines for depression known as non-selective monoamine oxidase 

inhibitors or selective MAO-A inhibitors. Ask your doctor if you are uncertain.  

 

Warnings and precautions  

 

Talk to your doctor or pharmacist before taking Brintellix if you: 

 

- are taking medicines with a so-called serotonergic effect, such as: 

- tramadol (a strong painkiller).  

- sumatriptan and similar medicines with active substance names ending in “triptans” (used 

to treat migraine). 



72 

Taking these medicines together with Brintellix may increase the risk of serotonin syndrome. 

This syndrome may be associated with hallucinations, involuntary twitching, accelerated 

heartbeat, high blood pressure, fever, nausea and diarrhoea. 

 

- have had fits (seizures).  

Your doctor will treat you cautiously if you have a history of fits or have unstable fit 

disorders/epilepsy. Fits are a potential risk with medicines used to treat depression. Treatment 

should be discontinued in any patient who develops fits or where there is an increase in the 

frequency of fits. 

 

- have had mania 

- have a tendency to bleed or bruise easily, or if you are pregnant (See ‘Pregnancy, breast-feeding 

and fertility’). 

- have low sodium level in the blood. 

- are 65 years of age or older. 

- have a severe kidney disease. 

- have a severe liver disease or a liver disease called cirrhosis. 

- have or previously have had increased pressure in the eye or glaucoma. If your eyes become 

painful and you develop blurred vision during treatment, contact your doctor. 

 

When you are on antidepressant treatment, including vortioxetine, you may also experience feelings of 

aggression, agitation, anger and irritability. If this occurs, you should talk to your doctor.  

 

Thoughts of suicide and worsening of your depression 

 

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 

 

Brintellix is not recommended in children aged 7 to 11 years due to lack of information. Brintellix 

should not be used in adolescents aged 12 to 17 years because efficacy has not been demonstrated. The 

safety of Brintellix in adolescents aged 12 to 17 years is described in section 4.  

 

Other medicines and Brintellix 

 

Tell your doctor or pharmacist if you are taking, have recently taken or might take any other 

medicines. 

 

Tell your doctor if you are taking any of the following medicines: 

 

- phenelzine, iproniazid, isocarboxazid, nialamide, tranylcypromine (medicines to treat 

depression called non-selective monoamine oxidase inhibitors); you must not take any of these 



73 

medicines together with Brintellix. If you have taken any of these medicines, you will need to 

wait 14 days before you start taking Brintellix. After stopping Brintellix you must allow 14 days 

before taking any of these medicines. 

- moclobemide (a medicine to treat depression).  

- selegiline, rasagiline (medicines to treat Parkinson’s disease). 

- linezolid (a medicine to treat bacterial infections). 

- lithium (a medicine to treat depression and mental disorders) or tryptophan. 

- medicines known to cause low sodium level. 

- rifampicin (a medicine to treat tuberculosis and other infections). 

- carbamazepine, phenytoin (medicines to treat epilepsy or other illness). 

- warfarin, dipyridamole, phenprocoumon, low-dose acetylsalicylic acid (blood thinning 

medicines). 

 

Medicines that increase the risk of fits: 

- sumatriptan and similar medicines with active substance names ending in “triptans”. 

- tramadol (a strong painkiller).  

- mefloquine (a medicine to prevent and treat malaria). 

- bupropion (a medicine to treat depression also used to wean from smoking). 

- fluoxetine, paroxetine and other medicines to treat depression called SSRI/SNRIs, tricyclics.  

- St John’s wort (hypericum perforatum) (a medicine to treat depression). 

- quinidine (a medicine to treat heart rhythm disorders). 

- chlorpromazine, chlorprothixene, haloperidol (medicines to treat mental disorders belonging to 

the groups called phenothiazines, thioxanthenes, butyrophenones). 

 

Please tell your doctor if you are taking any of the medicines above, since your doctor needs to know 

if you already are at risk for seizures. 

 

If you are having a urine drug screen, taking Brintellix may cause positive results for methadone when 

some test methods are used, even though you may not be taking methadone. If this happens, a more 

specific test can be performed. 

 

Brintellix with alcohol 

 

Combining this medicine with alcohol is not advisable. 

 

Pregnancy, breast-feeding and fertility 

 

If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask 

your doctor for advice before taking this medicine. 

 

Pregnancy 

 

Brintellix should not be used during pregnancy unless the doctor says it is absolutely necessary. 

 

If you take medicines to treat depression, including Brintellix, during the last 3 months of your 

pregnancy, you should be aware that the following effects may be seen in your newborn baby: trouble 

with breathing, bluish skin, fits, body temperature changes, feeding difficulties, vomiting, low blood 

sugar, stiff or floppy muscles, vivid reflexes, tremor, jitteriness, irritability, lethargy, constant crying, 

sleepiness and sleeping difficulties. Contact your doctor immediately if your newborn baby has any of 

these symptoms.  

 

Make sure your midwife and/or doctor know you are on Brintellix. When taken during pregnancy, 

particularly in the last 3 months of pregnancy, medicines like Brintellix 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 



74 

after the baby is born. If this happens to your baby, you should contact your midwife and/or doctor 

immediately. 

 

If you take Brintellix near the end of your pregnancy there may be an increased risk of heavy 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 Brintellix so they can advise you. 

 

Breast-feeding 

 

It is expected that the ingredients of Brintellix will pass into breast milk. Brintellix is not to be used 

during breast-feeding. Your doctor will make a decision on whether you should stop breast-feeding, or 

stop using Brintellix taking into account the benefit of breast-feeding for your child, and the benefit of 

therapy for you. 

 

Driving and using machines 

 

Brintellix has no or negligible influence on the ability to drive and use machines. However, as adverse 

reactions such as diziness have been reported, caution is advised during such activities when 

beginning Brintellix treatment or changing the dose. 

 

Brintellix contains Sodium 

 

This medicine contains less than 1 mmol sodium (23 mg) per tablet, that is to say essentially ‘sodium-

free’. 

 

 

3. How to take Brintellix 

 

Always take this medicine exactly as your doctor has told you. Check with your doctor or pharmacist 

if you are not sure. 

 

The recommended dose of Brintellix is 10 mg vortioxetine taken as one daily dose in adults less than 

65 years of age. The dose may be increased by your doctor to a maximum of 20 mg vortioxetine per 

day or lowered to a minimum of 5 mg vortioxetine per day depending on your response to treatment. 

 

For elderly people 65 years of age or older, the starting dose is 5 mg vortioxetine taken once daily. 

 

Method of administration 

 

Take one tablet with a glass of water.  

The tablet can be taken with or without food. 

 

Duration of treatment 

 

Take Brintellix for as long as your doctor recommends. 

 

Continue to take Brintellix even if it takes some time before you feel any improvement in your 

condition.  

 

Treatment should be continued for at least 6 months after you feel well again. 

 

If you take more Brintellix than you should 

 

If you take more than the prescribed dose of Brintellix, contact your doctor or nearest hospital 

emergency department immediately. Have the container and any remaining tablets available. Do this 



75 

even if there are no signs of discomfort. Overdose signs could be dizziness, nausea, diarrhoea, 

stomach discomfort, itching of the whole body, sleepiness and flushing.  

 

Following intake of dosages several times higher than the prescribed dose, fits (seizures) and a rare 

condition called serotonin syndrome have been reported. 

 

If you forget to take Brintellix 

 

Take the next dose at the usual time. Do not take a double dose to make up for a forgotten dose. 

 

If you stop taking Brintellix 

 

Do not stop taking Brintellix without talking with your doctor.  

 

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. 

In general, the observed side effects were mild to moderate and occurred within the first two weeks of 

treatment. The reactions were usually temporary and did not lead to cessation of therapy. 

 

Side effects listed below have been reported in the following frequencies. 

 

Very common: may affect more than 1 in 10 people  

- nausea  

 

Common: may affect up to 1 in 10 people  

- diarrhoea, constipation, vomiting 

- dizziness 

- itching of the whole body  

- abnormal dreams 

 

Uncommon: may affect up to 1 in 100 people 

- flushing 

- night sweats 

 

Rare: may affect up to 1 in 1,000 people 

- enlarged pupils (mydriasis), which can increase the risk of glaucoma (see section 2) 

 

Not known: frequency cannot be estimated from available data 

- low levels of sodium in the blood (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) 

- serotonin syndrome (see section 2) 

- allergic reactions, that may be serious, causing swelling of the face, lips, tongue or throat, 

difficulties breathing or swallowing, and/or a sudden drop in blood pressure (making you feel 

dizzy or lightheaded) 

- hives 

- excessive or unexplained bleeding (including bruising, nose bleeding, gastrointestinal and 

vaginal bleeding) 

- rash 

- sleep disorders (insomnia) 

- agitation and aggression. If you experience these side effects, contact your doctor (see section 

2). 

 



76 

An increased risk of bone fractures has been observed in patients taking this type of medicines. 

 

Additional side effects in adolescents 

 

Side effects observed with vortioxetine in adolescents were similar to those seen for adults except for 

abdominal pain related events and suicidal thoughts that were observed more often in adolescents than 

in adults.  

 

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. 

 

How to store Brintellix 

 

Keep this medicine out of the sight and reach of children. 

 

Do not use this medicine after the expiry date that is stated on the packaging after EXP. The expiry 

date refers to the last day of that month.  

 

This medicine does not require any special storage conditions. 

 

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 Brintellix contains  

 

- The active substance is vortioxetine. Each film-coated tablet contains 5 mg vortioxetine (as 

hydrobromide). 

- The other ingredients are mannitol (E421), microcrystalline cellulose, hydroxypropylcellulose, 

sodium starch glycolate (type A), magnesium stearate, hypromellose, Macrogol 400, titanium 

dioxide (E171), iron oxide red (E172). 

 

What Brintellix looks like and contents of the pack 

 

Pink, almond-shaped 5 x 8.4 mm film-coated tablet (tablet) marked with “TL” on one side and “5” on 

the other side. 

 

Brintellix film-coated tablets 5 mg are available in blister packs of 14, 28, 98, 56x1, 98x1,  

126 (9x14) 490 (5x(98x1)) tablets and in tablet containers of 100 and 200 tablets. 

 

The pack sizes of 56 x 1, 98 x 1 and 490 film-coated tablets are presented in unit dose blister. 

Not all pack sizes may be marketed. 

 

Marketing Authorisation Holder and Manufacturer 

 

H. Lundbeck A/S 

Ottiliavej 9 

2500 Valby 

Denmark 

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


77 

 

For any information about this medicine, please contact the local representative of the Marketing 

Authorisation Holder: 

 

Belgique/België/Belgien 

Lundbeck S.A./N.V. 

Tél/Tel: +32 2 535 7979  

 

Lietuva 

H. Lundbeck A/S 

Tel: +45 36301311(Danija)  

lietuva@lundbeck.com 

 

България 

Lundbeck Export A/S Representative Office 

Tel: +359 2 962 4696 

 

Luxembourg/Luxemburg 

Lundbeck S.A. 

Tél: +32 2 535 7979 

 

Česká republika  

Lundbeck Česká republika s.r.o. 

Tel: +420 225 275 600 

Magyarország 

Lundbeck Hungaria Kft. 

Tel: +36 1 4369980 

Danmark 

Lundbeck Pharma A/S 

Tlf: +45 4371 4270 

Malta 

H. Lundbeck A/S 

Tel: + 45 36301311 

 

Deutschland 

Lundbeck GmbH 

Tel: +49 40 23649 0 

Nederland 

Lundbeck B.V. 

Tel: +31 20 697 1901 

 

Eesti 

Lundbeck Eesti AS 

Tel: + 372 605 9350 

 

Norge 

H. Lundbeck AS  

Tlf: +47 91 300 800 

 

Ελλάδα 

Lundbeck Hellas S.A. 

Τηλ: +30 210 610 5036 

 

Österreich 

Lundbeck Austria GmbH 

Tel: +43 1 253 621 6033  

 

España 

Lundbeck España S.A. 

Tel: +34 93 494 9620 

Polska 

Lundbeck Poland Sp. z o. o.  

Tel.: + 48 22 626 93 00 

 

France 

Lundbeck SAS 

Tél: + 33 1 79 41 29 00 

 

Portugal 

Lundbeck Portugal Lda 

Tel: +351 21 00 45 900 

 

Hrvatska 

Lundbeck Croatia d.o.o. 

Tel.: + 385 1 6448263 

 

România 

Lundbeck Romania SRL  

Tel: +40 21319 88 26 

 

Ireland 

Lundbeck (Ireland) Limited 

Tel: +353 468 9800 

 

Slovenija 

Lundbeck Pharma d.o.o. 

Tel.: +386 2 229 4500 

Ísland 

Vistor hf.  

Tel: +354 535 7000  

 

Slovenská republika 

Lundbeck Slovensko s.r.o. 

Tel: +421 2 5341 42 18 

 

Italia 

Lundbeck Italia S.p.A. 

Tel: +39 02 677 4171 

 

Suomi/Finland 

Oy H. Lundbeck Ab 

Puh/Tel: +358 2 276 5000 

 



78 

Κύπρος 

Lundbeck Hellas A.E 

Τηλ.: +357 22490305 

 

Sverige 

H. Lundbeck AB 

Tel: +46 40 699 8200  

 

Latvija 

H. Lundbeck A/S 

Tel: +45 36301311(Dānija) 

latvia@lundbeck.com 

 

United Kingdom 

Lundbeck Limited 

Tel: +44 1908 64 9966 

 

 

This leaflet was last revised in MM/YYYY 

 

 

Other sources of information 

 

Detailed information on this medicine is available on the European Medicines Agency web site: 

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

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


79 

Package leaflet: Information for the patient 

 

Brintellix 10 mg film-coated tablets 

vortioxetine 

 

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 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 Brintellix is and what it is used for  

2. What you need to know before you take Brintellix  

3. How to take Brintellix  

4. Possible side effects  

5. How to store Brintellix  

6. Contents of the pack and other information 

 

 

1. What Brintellix is and what it is used for 

 

Brintellix contains the active substance vortioxetine. It belongs to a group of medicines called 

antidepressants. 

 

Brintellix is used to treat major depressive episodes in adults. 

 

Brintellix has been shown to reduce the broad range of depressive symptoms, including sadness, inner 

tension (feeling anxious), sleep disturbances (reduced sleep), reduced appetite, difficulty in 

concentrating, feelings of worthlessness, loss of interest in favourite activities, feeling of being slowed 

down. 

 

 

2. What you need to know before you take Brintellix 

 

Do not take Brintellix: 

 

- if you are allergic to vortioxetine or any of the other ingredients of this medicine (listed in 

section 6). 

- if you are taking other medicines known for depression as non-selective monoamine oxidase 

inhibitors or selective MAO-A inhibitors. Ask your doctor if you are uncertain.  

 

Warnings and precautions  

 

Talk to your doctor or pharmacist before taking Brintellix if you: 

 

- are taking medicines with a so-called serotonergic effect, such as: 

- tramadol (a strong pain killer) 

- sumatriptan and similar medicines with active substance names ending in “triptans” (used 

to treat migraine).  



80 

Taking these medicines together with Brintellix may increase the risk of serotonin syndrome. 

This syndrome may be associated with hallucinations, involuntary twitching, accelerated 

heartbeat, high blood pressure, fever, nausea and diarrhoea. 

 

- have had fits (seizures).  

Your doctor will treat you cautiously if you have a history of fits or have unstable fit 

disorder/epilepsy. Fits are a potential risk with medicines used to treat depression. Treatment 

should be discontinued in any patient who develops fits or where there is an increase in the 

frequency of fits. 

 

- have had mania  

- have a tendency to bleed or bruise easily , or if you are pregnant (See ‘Pregnancy, breast-

feeding and fertility’). 

- have low sodium level in the blood. 

- are 65 years of age or older. 

- have a severe kidney disease. 

- have a severe liver disease or a liver disease called cirrhosis. 

- have or previously have had increased pressure in the eye or glaucoma. If your eyes become 

painful and you develop blurred vision during treatment, contact your doctor. 

 

When you are on antidepressant treatment, including vortioxetine, you may also experience feelings of 

aggression, agitation, anger and irritability. If this occurs, you should talk to your doctor.  

 

Thoughts of suicide and worsening of your depression 

 

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 

 

Brintellix is not recommended in children aged 7 to 11 years due to lack of information. Brintellix 

should not be used in adolescents aged 12 to 17 years because efficacy has not been demonstrated. The 

safety of Brintellix in adolescents aged 12 to 17 years is described in section 4.   

 

Other medicines and Brintellix 

 

Tell your doctor or pharmacist if you are taking, have recently taken or might take any other 

medicines. 

 

Tell your doctor if you are taking any of the following medicines: 

 

- phenelzine, iproniazid, isocarboxazid, nialamide, tranylcypromine (medicines to treat 

depression called non-selective monoamine oxidase inhibitors) you must not take any of these 



81 

medicines together with Brintellix. If you have taken any of these medicines, you will need to 

wait 14 days before you start taking Brintellix. After stopping Brintellix, you must allow 14 

days before taking any of these medicines. 

- moclobemide (a medicine to treat depression). 

- selegiline, rasagiline (medicines to treat Parkinson’s disease). 

- linezolid (a medicine to treat bacterial infections).  

- lithium (a medicine to treat depression and mental disorders) or tryptophan. 

- medicines known to cause low sodium level. 

- rifampicin (a medicine to treat tuberculosis and other infections)  

- carbamazepine, phenytoin (medicines to treat epilepsy or other illness) 

- Warfarin, dipyridamole, phenprocoumon, low-dose acetylsalicylic acid (blood thinning 

medicines). 

 

Medicines that increase the risk of fits: 

- sumatriptan and similar medicines with active substance names ending in “triptans”.  

- tramadol (a strong painkiller).  

- mefloquine (a medicine to prevent and treat malaria).  

- bupropion (a medicine to treat depression also used to wean from smoking). 

- fluoxetine, paroxetine and other medicines to treat depression called SSRI/SNRIs, tricyclics  

- St John’s wort (hypericum perforatum)(a medicine to treat depression). 

- quinidine (a medicine to treat heart rhythm disorders). 

- chlorpromazine, chlorprothixene, haloperidol (medicines to treat mental disorders belonging to 

the group called phenothiazines, thioxanthenes, butyrophenones). 

 

Please tell your doctor if you are taking any of the medicines above, since your doctor needs to know 

if you already are at risk for seizure. 

 

If you are having a urine drug screen, taking Brintellix may cause positive results for methadone when 

some test methods are used, even though you may not be taking methadone. If this happens, a more 

specific test can be performed. 

 

Brintellix with alcohol 

 

Combining this medicine with alcohol is not advisable. 

 

Pregnancy, breast-feeding and fertility 

 

If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask 

your doctor for advice before taking this medicine. 

 

Pregnancy 

 

Brintellix should not be used during pregnancy unless the doctor says it is absolutely necessary. 

 

If you take medicine to treat depression, including Brintellix, during the last 3 months of your 

pregnancy, you should be aware that the following effects may be seen in your newborn baby: trouble 

with breathing, bluish skin, fits, body temperature changes, feeding difficulties, vomiting, low blood 

sugar, stiff or floppy muscles, vivid reflexes, tremor, jitteriness, irritability, lethargy, constant crying, 

sleepiness and sleeping difficulties. Contact your doctor immediately if your newborn baby has any of 

these symptoms.  

 

Make sure your midwife and/or doctor know you are on Brintellix. When taken during pregnancy, 

particularly in the last 3 months of pregnancy, medicines like Brintellix 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 



82 

after the baby is born. If this happens to your baby, you should contact your midwife and/or doctor 

immediately. 

If you take Brintellix near the end of your pregnancy there may be an increased risk of heavy 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 Brintellix so they can advise you. 

 

Breast-feeding 

 

It is expected that the ingredients of Brintellix will pass into breast milk. Brintellix is not to be used 

during breast-feeding. Your doctor will make a decision on whether you should stop breast-feeding, or 

stop using Brintellix taking into account the benefit of breast-feeding for your child, and the benefit of 

therapy for you 

 

Driving and using machines 

 

Brintellix has no or negligible influence on the ability to drive and use machines. However, as adverse 

reactions such as diziness have been reported, caution is advised during such activities when 

beginning Brintellix treatment or changing the dose. 

 

Brintellix contains Sodium 

 

This medicine contains less than 1 mmol sodium (23 mg) per tablet, that is to say essentially ‘sodium-

free’. 

 

 

3. How to take Brintellix 

 

Always take this medicine exactly as your doctor has told you. Check with your doctor or pharmacist 

if you are not sure. 

 

The recommended dose of Brintellix is 10 mg vortioxetine taken as one daily dose in adults less than 

65 years of age. The dose may be increased by your doctor to a maximum of 20 mg vortioxetine per 

day or lowered to a minimum of 5 mg vortioxetine per day depending on your response to treatment. 

 

For elderly people 65 years of age or older the starting dose is 5 mg vortioxetine taken once daily. 

 

Method of administration 

 

Take one tablet with a glass of water.  

The tablet can be taken with or without food. 

 

Duration of treatment 

 

Take Brintellix for as long as your doctor recommends. 

 

Continue to take Brintellix even if it takes some time before you feel any improvement in your 

condition.  

 

Treatment should be continued for at least 6 months after you feel well again. 

 

If you take more Brintellix than you should 

 

If you take more than the prescribed dose of Brintellix, contact your doctor or nearest hospital 

emergency department immediately. Have the container and any remaining tablets available. Do this 

even if there are no signs of discomfort. Overdose signs could be dizziness, nausea, diarrhoea, 

stomach discomfort, itching of the whole body, sleepiness and flushing.  



83 

 

Following intake of dosages several times higher than the prescribed dose, fits (seizures) and a rare 

condition called serotonin syndrome have been reported. 

 

If you forget to take Brintellix 

 

Take the next dose at the usual time. Do not take a double dose to make up for a forgotten dose. 

 

If you stop taking Brintellix 

 

Do not stop taking Brintellix without talking with your doctor.  

 

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. 

In general, the observed side effects were mild to moderate and occurred within the first two weeks of 

treatment. The reactions were usually temporary and did not lead to cessation of therapy. 

 

Side effects listed below have been reported in the following frequencies. 

 

Very common: may affect more than 1 in 10 people 

- nausea  

 

Common: may affect up to 1 in 10 people 

- diarrhoea, constipation, vomiting 

- dizziness 

- itching of the whole body  

- abnormal dreams 

 

Uncommon: may affect up to 1 in 100 people 

- flushing 

- night sweats 

 

Rare: may affect up to 1 in 1,000 people 

- enlarged pupils (mydriasis), which can increase the risk of glaucoma (see section 2) 

 

Not known: frequency cannot be estimated from available data 

- low levels of sodium in the blood (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) 

- serotonin syndrome (see section 2) 

- allergic reactions, that may be serious, causing swelling of the face, lips, tongue or throat, 

difficulties breathing or swallowing, and/or a sudden drop in blood pressure (making you feel 

dizzy or lightheaded) 

- hives 

- excessive or unexplained bleeding (including bruising, nose bleeding, gastrointestinal and 

vaginal bleeding) 

- rash 

- sleep disorders (insomnia) 

- agitation and aggression. If you experience these side effects, contact your doctor (see section 

2). 

 

An increased risk of bone fractures has been observed in patients taking this type of medicines.  

 



84 

Additional side effects in adolescents 

 

Side effects observed with vortioxetine in adolescents were similar to those seen for adults except for 

abdominal pain related events and suicidal thoughts that were observed more often in adolescents than 

in adults.  

 

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. 

 

5. How to store Brintellix 

 

Keep this medicine out of the sight and reach of children. 

 

Do not use this medicine after the expiry date that is stated on the packaging after EXP. The expiry 

date refers to the last day of that month.  

 

This medicine does not require any special storage conditions. 

 

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 Brintellix contains  

 

- The active substance is vortioxetine. Each film-coated tablet contains 10 mg vortioxetine (as 

hydrobromide). 

- The other ingredients are mannitol (E421), microcrystalline cellulose, hydroxypropylcellulose, 

sodium starch glycolate (type A), magnesium stearate, hypromellose, Macrogol 400, titanium 

dioxide (E171), iron oxide yellow (E172). 

 

What Brintellix looks like and contents of the pack 

 

Yellow, almond-shaped 5 x 8.4 mm film-coated tablet (tablet) marked with “TL” on one side and “10” 

on the other side. 

 

Brintellix film-coated tablets 10 mg are available in blister packs of 7, 14, 28, 56, 56 x 1, 98, 98 x 1, 

126 (9x14), 490 (5 x (98x1)) tablets and in tablet containers of 100 and 200 tablets. 

 

The pack sizes of 56 x 1, 98 x 1 and 490 film-coated tablets are presented in unit dose blister. 

 

Not all pack sizes may be marketed. 

 

Marketing Authorisation Holder and Manufacturer 

 

H. Lundbeck A/S 

Ottiliavej 9 

2500 Valby 

Denmark 

 

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


85 

For any information about this medicine, please contact the local representative of the Marketing 

Authorisation Holder: 

 

Belgique/België/Belgien 

Lundbeck S.A./N.V. 

Tél/Tel: +32 2 535 797 9 

 

Lietuva 

H. Lundbeck A/S 

Tel: +45 36301311(Danija)  

lietuva@lundbeck.com 

 

България 

Lundbeck Export A/S Representative Office 

Tel: +359 2 962 4696 

 

Luxembourg/Luxemburg 

Lundbeck S.A. 

Tél: +32 2 535 7979 

 

Česká republika  

Lundbeck Česká republika s.r.o. 

Tel: +420 225 275 600 

 

Magyarország 

Lundbeck Hungaria Kft. 

Tel: +36 1 4369980 

Danmark 

Lundbeck Pharma A/S 

Tlf: +45 4371 4270 

Malta 

H. Lundbeck A/S 

Tel: + 45 36301311 

 

Deutschland 

Lundbeck GmbH 

Tel: +49 40 23649 0 

Nederland 

Lundbeck B.V. 

Tel: +31 20 697 1901 

 

Eesti 

Lundbeck Eesti AS 

Tel: + 372 605 9350 

 

 

Norge 

H. Lundbeck AS  

Tlf: +47 91 300 800 

Ελλάδα 

Lundbeck Hellas S.A. 

Τηλ: +30 210 610 5036 

 

Österreich 

Lundbeck Austria GmbH 

Tel: +43 1 253 621 6033  

 

España 

Lundbeck España S.A. 

Tel: +34 93 494 9620 

Polska 

Lundbeck Poland Sp. z o. o.  

Tel.: + 48 22 626 93 00 

 

France 

Lundbeck SAS 

Tél: + 33 1 79 41 29 00 

 

Portugal 

Lundbeck Portugal Lda 

Tel: +351 21 00 45 900 

 

Hrvatska 

Lundbeck Croatia d.o.o. 

Tel.: + 385 1 6448263 

 

România 

Lundbeck Romania SRL 

Tel: +40 21319 88 26 

 

Ireland 

Lundbeck (Ireland) Limited 

Tel: +353 468 9800 

Slovenija 

Lundbeck Pharma d.o.o. 

Tel.: +386 2 229 4500 

Ísland 

Vistor hf. 

Tel: +354 535 7000  

 

Slovenská republika 

Lundbeck Slovensko s.r.o. 

Tel: +421 2 5341 42 18 

 

Italia 

Lundbeck Italia S.p.A. 

Tel: +39 02 677 4171 

 

 

Suomi/Finland 

Oy H. Lundbeck Ab 

Puh/Tel: +358 2 276 5000 

 



86 

Κύπρος 

Lundbeck Hellas A.E 

Τηλ.: +357 22490305 

 

Sverige 

H. Lundbeck AB 

Tel: +46 40 699 8200  

 

Latvija 

H. Lundbeck A/S 

Tel: +45 36301311(Dānija) 

latvia@lundbeck.com 

 

United Kingdom 

Lundbeck Limited 

Tel: +44 1908 64 9966 

 

 

This leaflet was last revised in MM/YYYY 

 

Other sources of information 

 

Detailed information on this medicine is available on the European Medicines Agency web site: 

http://www.ema.europa.eu 

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


87 

 

Package leaflet: Information for the patient 

 

Brintellix 15 mg film-coated tablets 

vortioxetine 

 

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 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 Brintellix is and what it is used for  

2. What you need to know before you take Brintellix  

3. How to take Brintellix  

4. Possible side effects  

5. How to store Brintellix  

6. Contents of the pack and other information 

 

 

1. What Brintellix is and what it is used for 

 

Brintellix contains the active substance vortioxetine.It belongs to a group of medicines called 

antidepressants. 

 

Brintellix is used to treat major depressive episodes in adults. 

 

Brintellix has been shown to reduce the broad range of depressive symptoms, including sadness, inner 

tension (feeling anxious), sleep disturbances (reduced sleep), reduced appetite, difficulty in 

concentrating, feelings of worthlessness, loss of interest in favourite activities, feeling of being slowed 

down. 

 

 

2. What you need to know before you take Brintellix 

 

Do not take Brintellix: 

 

- if you are allergic to vortioxetine or any of the other ingredients of this medicine (listed in 

section 6). 

- if you are taking other medicines for depression known as non-selective monoamine oxidase 

inhibitors or selective MAO-A inhibitors. Ask your doctor if you are uncertain.  

 

Warnings and precautions  

 

Talk to your doctor or pharmacist before taking Brintellix if you: 

 

- are taking medicines with a so-called serotonergic effect, such as: 

- tramadol (a strong painkiller). 

- sumatriptan and similar medicines to Brintellix with active substance names ending in 

“triptans” (used to treatmigraine).  



88 

Taking these medicines together with Brintellix may increase the risk of serotonin syndrome. 

This syndrome may be associated with hallucinations, involuntary twitching, accelerated 

heartbeat, high blood pressure, fever, nausea and diarrhoea. 

 

- have had fits (seizures).  

Your doctor will treat you cautiously if you have a history of fits or have unstable fit 

disorders/elpilepsy. Fits are a potential risk with medicines used to treat depression. Treatment 

should be discontinued in any patient who develops fits or where there is an increase in the 

frequency of fits.  

 

- have had mania.  

- have a tendency bleed or bruise easily , or if you are pregnant (See ‘Pregnancy, breast-feeding 

and fertility’). 

- have low sodium level in the blood. 

- are 65 years of age or older. 

- have a severe kidney disease.. 

- have a severe liver disease or a liver disease called cirrhosis. 

- have or previously have had increased pressure in the eye or glaucoma. If your eyes become 

painful and you develop blurred vision during treatment, contact your doctor. 

When you are on antidepressant treatment, including vortioxetine, you may also experience feelings of 

aggression, agitation, anger and irritability. If this occurs, you should talk to your doctor.  

 

Thoughts of suicide and worsening of your depression 

 

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 

 

Brintellix is not recommended in children aged 7 to 11 years due to lack of information. Brintellix 

should not be used in adolescents aged 12 to 17 years because efficacy has not been demonstrated. The 

safety of Brintellix in adolescents aged 12 to 17 years is described in section 4.  

 

Other medicines and Brintellix 

 

Tell your doctor or pharmacist if you are taking, have recently taken or might take any other 

medicines. 

 

Tell your doctor if you are taking any of the following medicines: 

- phenelzine, iproniazid, isocarboxazid, nialamide, tranylcypromine (medicines to treat 

depression called non-selectve monoamine oxidase inhibitors) you must not take any of these 

medicines together with Brintellix. If you have taken any of these medicines, you will need to 



89 

wait 14 days before you start taking Brintellix. After stopping Brintellix, you must allow 14 

days before taking any of these medicines. 

- moclobemide (a medicine to treat depression).  

- selegiline, rasagiline (medicines to treat Parkinson’s disease).  

- linezolid (a medicine to treat bacterial infections) . 

- lithium (a medicine to treat depression and mental disorders) or tryptophan. 

- medicines known to cause low sodium level. 

- rifampicin (a medicine to treat tuberculosis and other infections).  

- carbamazepine, phenytoin (medicines to treat epilepsy or other illness). 

- warfarin, dipyridamole, phenprocoumon, low-dose acetylsalicylic acid (blood thinning 

medicines). 

 

Medicines that increase the risk of fits: 

- sumatriptan and similar medicines with active substance names ending in “triptans”.  

- tramadol (a strong painkiller).  

- mefloquine (a medicine to prevent and treat malaria).  

- bupropion (a medicine to treat depression also used to wean from smoking). 

- fluoxetine, paroxetine and other medicine to treat depression called SSRI/SNRIs, tricyclics.  

- St John’s wort (hypericum perforatum) (a medicine to treat depression). 

- quinidine (a medicine to treat heart rhythm disorders).  

- chlorpromazine, chlorprothixene, haloperidol (medicines to treat mental disorders belonging to 

the group called phenothiazines, thioxanthenes, butyrophenones). 

 

Please tell your doctor if you are taking any of the medicines above, since your doctor needs to know 

if you already are at risk for seizures. 

 

If you are having a urine drug screen, taking Brintellix may cause positive results for methadone when 

some test methods are used, even though you may not be taking methadone. If this happens, a more 

specific test can be performed. 

 

Brintellix with alcohol 

 

Combining this medicine with alcohol is not advisable. 

 

Pregnancy, breast-feeding and fertility 

 

If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask 

your doctor for advice before taking this medicine. 

 

Pregnancy 

 

Brintellix should not be used during pregnancy unless the doctor says it is absolutely necessary. 

 

If you take medicine to treat depression, including Brintellix, during the last 3 months of your 

pregnancy, you should be aware that the following effects may be seen in your newborn baby: trouble 

with breathing, bluish skin, fits, body temperature changes, feeding difficulties, vomiting, low blood 

sugar, stiff or floppy muscles, vivid reflexes, tremor, jitteriness, irritability, lethargy, constant crying, 

sleepiness and sleeping difficulties. Contact your doctor immediately if your newborn baby has any of 

these symptoms. 

 

Make sure your midwife and/or doctor know you are on Brintellix. When taken during pregnancy, 

particularly in the last 3 months of pregnancy, medicines like Brintellix 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. 



90 

 

 

If you take Brintellix near the end of your pregnancy there may be an increased risk of heavy 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 Brintellix so they can advise you. 

 

Breast-feeding 

 

It is expected that the ingredients of Brintellix will pass into breast milk. Brintellix is not to be used 

during breast-feeding. Your doctor will make a decision on whether you should stop breast-feeding, or 

stop using Brintellix taking into account the benefit of breast-feeding for your child, and the benefit of 

therapy for you 

 

Driving and using machines 

 

Brintellix has no or negligible influence on the ability to drive and use machines. However, as adverse 

reactions such as diziness have been reported, caution is advised during such activities when 

beginning Brintellix treatment or changing the dose. 

 

Brintellix contains Sodium 

 

This medicine contains less than 1 mmol sodium (23 mg) per tablet, that is to say essentially ‘sodium-

free’. 

 

 

3. How to take Brintellix 

 

Always take this medicine exactly as your doctor has told you. Check with your doctor or pharmacist 

if you are not sure. 

 

The recommended dose of Brintellix is 10 mg vortioxetine taken as one daily dose in adults less than 

65 years of age. The dose may be increased by your doctor to a maximum of 20 mg vortioxetine per 

day or lowered to a minimum of 5 mg vortioxetine per day depending on your response to treatment. 

 

For elderly people 65 years of age or older the starting dose is 5 mg vortioxetine taken once daily. 

 

Method of administration 

 

Take one tablet with a glass of water.  

The tablet can be taken with or without food. 

 

Duration of treatment 

 

Take Brintellix for as long as your doctor recommends. 

 

Continue to take Brintellix even if it takes some time before you feel any improvement in your 

condition.  

 

Treatment should be continued for at least 6 months after you feel well again. 

 

If you take more Brintellix than you should 

 

If you take more than the prescribed dose of Brintellix, contact your doctor or nearest hospital 

emergency department immediately. Have the container and any remaining tablets available. Do this 

even if there are no signs of discomfort. Overdose signs could be dizziness, nausea, diarrhoea, 

stomach discomfort, itching of the whole body, sleepiness and flushing.  



91 

 

Following intake of dosages several times higher than the prescribed dose, fits (seizures) and a rare 

condition called serotonin syndrome have been reported. 

 

If you forget to take Brintellix 

 

Take the next dose at the usual time. Do not take a double dose to make up for a forgotten dose. 

 

If you stop taking Brintellix 

 

Do not stop taking Brintellix without talking with your doctor.  

 

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. 

In general, the observed side effects were mild to moderate and occurred within the first two weeks of 

treatment. The reactions were usually temporary and did not lead to cessation of therapy. 

 

Side effects listed below have been reported in the following frequencies. 

 

Very common: may affect more than 1 in 10 people  

- nausea 

 

Common: may affect up to 1 in 10 people  

- diarrhoea, constipation, vomiting 

- dizziness 

- itching of the whole body  

- abnormal dreams 

 

Uncommon: may affect up to 1 in 100 people 

- flushing 

- night sweats 

 

Rare: may affect up to 1 in 1,000 people 

- enlarged pupils (mydriasis), which can increase the risk of glaucoma (see section 2) 

 

Not known: frequency cannot be estimated from available data 

- low levels of sodium in the blood (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) 

- serotonin syndrome (see section 2) 

- allergic reactions, that may be serious, causing swelling of the face, lips, tongue or throat, 

difficulties breathing or swallowing, and/or a sudden drop in blood pressure (making you feel 

dizzy or lightheaded) 

- hives 

- excessive or unexplained bleeding (including bruising, nose bleeding, gastrointestinal and 

vaginal bleeding) 

- rash 

- sleep disorders (insomnia) 

- agitation and aggression. If you experience these side effects, contact your doctor (see section 

2). 

 

An increased risk of bone fractures has been observed in patients taking this type of medicines. 

 



92 

Additional side effects in adolescents 

 

Side effects observed with vortioxetine in adolescents were similar to those seen for adults except for 

abdominal pain related events and suicidal thoughts that were observed more often in adolescents than 

in adults.  

 

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. 

 

 

5. How to store Brintellix 

 

Keep this medicine out of the sight and reach of children. 

 

Do not use this medicine after the expiry date that is stated on the packaging after EXP. The expiry 

date refers to the last day of that month.  

 

This medicine does not require any special storage conditions. 

 

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 Brintellix contains  

 

- The active substance is vortioxetine. Each film-coated tablet contains 15 mg vortioxetine (as 

hydrobromide). 

- The other ingredients are mannitol (E421), microcrystalline cellulose, hydroxypropylcellulose, 

sodium starch glycolate (type A), magnesium stearate, hypromellose, Macrogol 400, titanium 

dioxide (E171), iron oxide yellow (E172), iron oxide red (E172) 

 

What Brintellix looks like and contents of the pack 

 

Orange, almond-shaped 5 x 8.4 mm film-coated tablet (tablet) marked with “TL” on one side and “15” 

on the other side. 

 

Brintellix film-coated tablets 15 mg are available in blister packs of 14, 28, 56, 56 x 1, 98, 98 x 1, 490 

(5 x (98x1)) tablets and in tablet containers of 100 and 200 tablets. 

 

The pack sizes of 56 x 1, 98 x 1 and 490 film-coated tablets are presented in unit dose blister. 

 

Not all pack sizes may be marketed. 

 

Marketing Authorisation Holder and Manufacturer 

 

H. Lundbeck A/S 

Ottiliavej 9 

2500 Valby 

Denmark 

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


93 

 

For any information about this medicine, please contact the local representative of the Marketing 

Authorisation Holder: 

 

Belgique/België/Belgien 

Lundbeck S.A./N.V. 

Tél/Tel: +32 2 535 797 9 

 

 

Lietuva 

H. Lundbeck A/S 

Tel: +45 36301311(Danija)  

lietuva@lundbeck.com 

България 

Lundbeck Export A/S Representative Office 

Tel: +359 2 962 4696 

 

Luxembourg/Luxemburg 

Lundbeck S.A. 

Tél: +32 2 535 7979 

 

Česká republika  

Lundbeck Česká republika s.r.o. 

Tel: +420 225 275 600 

Magyarország 

Lundbeck Hungaria Kft. 

Tel: +36 1 4369980 

Danmark 

Lundbeck Pharma A/S 

Tlf: +45 4371 4270 

Malta 

H. Lundbeck A/S 

Tel: + 45 36301311 

 

Deutschland 

Lundbeck GmbH 

Tel: +49 40 23649 0 

Nederland 

Lundbeck B.V. 

Tel: +31 20 697 1901 

 

Eesti 

Lundbeck Eesti AS 

Tel: + 372 605 9350 

 

Norge 

H. Lundbeck AS  

Tlf: +47 91 300 800 

 

Ελλάδα 

Lundbeck Hellas S.A. 

Τηλ: +30 210 610 5036 

 

Österreich 

Lundbeck Austria GmbH 

Tel: +43 1 253 621 6033  

España 

Lundbeck España S.A. 

Tel: +34 93 494 9620 

Polska 

Lundbeck Poland Sp. z o. o.  

Tel.: + 48 22 626 93 00 

 

France 

Lundbeck SAS 

Tél: + 33 1 79 41 29 00 

 

Portugal 

Lundbeck Portugal Lda 

Tel: +351 21 00 45 900 

 

Hrvatska 

Lundbeck Croatia d.o.o. 

Tel.: + 385 1 6448263 

 

România 

Lundbeck Romania SRL 

Tel: +40 21319 88 26 

 

Ireland 

Lundbeck (Ireland) Limited 

Tel: +353 468 9800 

 

Slovenija 

Lundbeck Pharma d.o.o. 

Tel.: +386 2 229 4500 

Ísland 

Vistor hf. 

Tel: +354 535 7000  

 

Slovenská republika 

Lundbeck Slovensko s.r.o. 

Tel: +421 2 5341 42 18 

 

Italia 

Lundbeck Italia S.p.A. 

Tel: +39 02 677 4171 

 

Suomi/Finland 

Oy H. Lundbeck Ab 

Puh/Tel: +358 2 276 5000 

 



94 

Κύπρος 

Lundbeck Hellas A.E 

Τηλ.: +357 22490305 

 

Sverige 

H. Lundbeck AB 

Tel: +46 40 699 8200  

 

Latvija 

H. Lundbeck A/S 

Tel: +45 36301311(Dānija) 

latvia@lundbeck.com 

 

United Kingdom 

Lundbeck Limited 

Tel: +44 1908 64 9966 

 

This leaflet was last revised in MM/YYYY 

 

Other sources of information 

 

Detailed information on this medicine is available on the European Medicines Agency web site: 

http://www.ema.europa.eu 

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


95 

 

Package leaflet: Information for the patient 

 

Brintellix 20 mg film-coated tablets 

vortioxetine 

 

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 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 Brintellix is and what it is used for  

2. What you need to know before you take Brintellix  

3. How to take Brintellix  

4. Possible side effects  

5. How to store Brintellix  

6. Contents of the pack and other information 

 

 

1. What Brintellix is and what it is used for 

 

Brintellix contains the active substance vortioxetine. It belongs to a group of medicines called 

antidepressants. 

 

Brintellix is used to treat major depressive episodes in adults. 

 

Brintellix has been shown to reduce the broad range of depressive symptoms, including sadness, inner 

tension (feeling anxious), sleep disturbances (reduced sleep), reduced appetite, difficulty in 

concentrating, feelings of worthlessness, loss of interest in favourite activities, feeling of being slowed 

down. 

 

 

2. What you need to know before you take Brintellix 

 

Do not take Brintellix: 

 

- if you are allergic to vortioxetine or any of the other ingredients of this medicine (listed in 

section 6). 

- if you are taking other medicines for depression known as non-selective monoamine oxidase 

inhibitors or selective MAO-A inhibitors. Ask your doctor if you are uncertain.  

 

Warnings and precautions  

 

Talk to your doctor or pharmacist before taking Brintellix if you: 

 

- taking medicines with a so-called serotonergic effect, such as:  

- tramadol (a strong pain killer).  

- sumatriptan and similar medicines with active substance names ending in “triptans” (used 

to treat migraine).  



96 

Taking these medicines together with Brintellix may increase the risk of serotonin syndrome. 

This syndrome may be associated with hallucinations, involuntary twitching, accelerated 

heartbeat, high blood pressure, fever, nausea and diarrhoea. 

 

- have had fits (seizures).  

Your doctor will treat you cautiously if you have a history of fits or have unstable fit 

disorders/epilepsy. Fits are a potential risk with medicines used to treat depressionTreatment 

should be discontinued in any patient who develops fits or where there is an increase in the 

frequency of fits.  

 

- have had mania  

- have a tendency bleed or bruise easily , or if you are pregnant (See ‘Pregnancy, breast-feeding 

and fertility’). 

- have low sodium level in the blood. 

- are 65 years of age or older. 

- have a severe kidney disease. 

- have a severe liver disease or a liver disease called cirrhosis. 

- have or previously have had increased pressure in the eye or glaucoma. If your eyes become 

painful and you develop blurred vision during treatment, contact your doctor. 

 

When you are on antidepressant treatment, including vortioxetine, you may also experience feelings of 

aggression, agitation, anger and irritability. If this occurs, you should talk to your doctor.  

 

Thoughts of suicide and worsening of your depression 

 

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 

 

Brintellix is not recommended in children aged 7 to 11 years due to lack of information. Brintellix 

should not be used in adolescents aged 12 to 17 years because efficacy has not been demonstrated. The 

safety of Brintellix in adolescents aged 12 to 17 years is described in section 4.  

 

Other medicines and Brintellix 

 

Tell your doctor or pharmacist if you are taking, have recently taken or might take any other 

medicines. 

 

Tell your doctor if you are taking any of the following medicines: 

phenelzine, iproniazid, isocarboxazid, nialamide, tranylcypromine (medicines to treat 

depression called non-selective monoamine oxidase inhibitors) you must not take any of these 

medicines together with Brintellix. If you have taken any of these  medicines, you will need to 



97 

wait 14 days before you start taking Brintellix. After stopping Brintellix, you must allow 14 

days before taking any of these medicines. 

- moclobemide (a medicine to treat depression).  

- selegiline and rasagiline (medicines to treat Parkinson’s disease).  

- linezolid (a medicine to treat bacterial infections).  

- lithium (a medicine to treat depression and mental disorders) or tryptophan- 

- medicines known to cause low sodium level. 

- rifampicin (a medicine to treat tuberculosis and other infections).  

- carbamazepine, phenytoin (medicines to treat epilepsy or other illness). 

- warfarin, dipyridamole, phenprocoumon, low-dose acetylsalicylic acid (blood thinning 

medicines). 

 

Medicines that increase the risk of fits: 

- sumatriptan and similar medicines with active substance names ending in “triptans”  

- tramadol (a strong painkiller).  

- mefloquine (a medicine to prevent and treatmalaria).  

- bupropion (a medicine to treat depression also used to wean from smoking). 

- fluoxetine, paroxetine and other medicines to treat depression called SSRI/SNRIs, tricyclics.  

- St John’s wort (hypericum perforatum) (a medicine to treat depression). 

- quinidine (a medicine to treat heart rhythm disorders). 

- chlorpromazine, chlorprothixene, haloperidol (medicines to treat mental disorders belonging to 

the group called phenothiazines, thioxanthenes,butyrophenones).  

 

Please tell your doctor if you are taking any of the medicines above, since your doctor needs to know 

if you already are at risk for seizures. 

 

If you are having a urine drug screen, taking Brintellix may cause positive results for methadone when 

some test methods are used, even though you may not be taking methadone. If this happens, a more 

specific test can be performed. 

 

Brintellix with alcohol 

 

Combining this medicine with alcohol is not advisable. 

 

Pregnancy, breast-feeding and fertility 

 

If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask 

your doctor for advice before taking this medicine. 

 

Pregnancy 

 

Brintellix should not be used during pregnancy unless the doctor says it is absolutely necessary. 

If you take medicine to treat depression including Brintellix during the last 3 months of your 

pregnancy you should be aware that the following effects may be seen in your newborn baby: trouble 

with breathing, bluish skin, fits, body temperature changes, feeding difficulties, vomiting, low blood 

sugar, stiff or floppy muscles, vivid reflexes, tremor, jitteriness, irritability, lethargy, constant crying, 

sleepiness and sleeping difficulties. Contact your doctor immediately if your newborn baby has any of 

these symptoms. 

 

Make sure your midwife and/or doctor know you are on Brintellix. When taken during pregnancy, 

particularly in the last 3 months of pregnancy, medicines like Brintellix 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. 

 



98 

If you take Brintellix near the end of your pregnancy there may be an increased risk of heavy 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 Brintellix so they can advise you. 

 

Breast-feeding 

 

It is expected that the ingredients of Brintellix will pass into breast milk. Brintellix is not to be used 

during breast-feeding. Your doctor will make a decision on whether you should stop breast-feeding, or 

stop using Brintellix taking into account the benefit of breast-feeding for your child, and the benefit of 

therapy for you 

 

Driving and using machines 

 

Brintellix has no or negligible influence on the ability to drive and use machines. However, as adverse 

reactions such as diziness have been reported, caution is advised during such activities when 

beginning Brintellix treatment or changing the dose. 

 

Brintellix contains Sodium 

 

This medicine contains less than 1 mmol sodium (23 mg) per tablet, that is to say essentially ‘sodium-

free’. 

 

 

3. How to take Brintellix 

 

Always take this medicine exactly as your doctor has told you. Check with your doctor or pharmacist 

if you are not sure. 

 

The recommended dose of Brintellix is 10 mg vortioxetine taken as one daily dose in adults less than 

65 years of age. The dose may be increased by your doctor to a maximum of 20 mg vortioxetine per 

day or lowered to a minimum of 5 mg vortioxetine per day depending on your response to treatment. 

 

For elderly people 65 years of age or older the starting dose is 5 mg vortioxetine taken once daily. 

 

Method of administration 

 

Take one tablet with a glass of water.  

The tablet can be taken with or without food. 

 

Duration of treatment 

 

Take Brintellix for as long as your doctor recommends. 

 

Continue to take Brintellix even if it takes some time before you feel any improvement in your 

condition.  

 

Treatment should be continued for at least 6 months after you feel well again. 

 

If you take more Brintellix than you should 

 

If you take more than the prescribed dose of Brintellix, contact your doctor or nearest hospital 

emergency department immediately. Have the container and any remaining tablets available. Do this 

even if there are no signs of discomfort. Overdose signs could be dizziness, nausea, diarrhoea, 

stomach discomfort, itching of the whole body, sleepiness and flushing.  

 



99 

Following intake of dosages several times higher than the prescribed dose, fits (seizures) and a rare 

condition called serotonin syndrome have been reported. 

 

If you forget to take Brintellix 

 

Take the next dose at the usual time. Do not take a double dose to make up for a forgotten dose. 

 

If you stop taking Brintellix 

 

Do not stop taking Brintellix without talking with your doctor.  

 

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. 

 

In general, the observed side effects were mild to moderate and occurred within the first two weeks of 

treatment. The reactions were usually temporary and did not lead to cessation of therapy. 

 

Side effects listed below have been reported in the following frequencies. 

 

Very common: may affect more than 1 in 10 people  

- nausea  

 

Common: may affect up to 1 in 10 people  

- diarrhoea, constipation, vomiting 

- dizziness 

- itching of the whole body  

- abnormal dreams 

 

Uncommon: may affect up to 1 in 100 people 

- flushing 

- night sweats 

 

Rare: may affect up to 1 in 1,000 people 

- enlarged pupils (mydriasis), which can increase the risk of glaucoma (see section 2) 

 

Not known: frequency cannot be estimated from available data 

- low levels of sodium in the blood (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) 

- serotonin syndrome (see section 2) 

- allergic reactions, that may be serious, causing swelling of the face, lips, tongue or throat, 

difficulties breathing or swallowing, and/or a sudden drop in blood pressure (making you feel 

dizzy or lightheaded) 

- hives 

- excessive or unexplained bleeding (including bruising, nose bleeding, gastrointestinal and 

vaginal bleeding) 

- rash 

- sleep disorders (insomnia) 

- agitation and aggression. If you experience these side effects, contact your doctor (see section 

2). 

 

An increased risk of bone fractures has beenobserved in patients taking this type of medicines. 

 



100 

Additional side effects in adolescents 

 

Side effects observed with vortioxetine in adolescents were similar to those seen for adults except for 

abdominal pain related events and suicidal thoughts that were observed more often in adolescents than 

in adults.  

 

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. 

 

 

5. How to store Brintellix 

 

Keep this medicine out of the sight and reach of children. 

 

Do not use this medicine after the expiry date that is stated on the packaging after EXP. The expiry 

date refers to the last day of that month.  

 

This medicine does not require any special storage conditions. 

 

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 Brintellix contains  

 

- The active substance is vortioxetine. Each film-coated tablet contains 20 mg vortioxetine (as 

hydrobromide). 

- The other ingredients are mannitol (E421), microcrystalline cellulose, hydroxypropylcellulose, 

sodium starch glycolate (type A), magnesium stearate, hypromellose, Macrogol 400, titanium 

dioxide (E171), iron oxide red (E172). 

 

What Brintellix looks like and contents of the pack 

 

Red, almond-shaped 5 x 8.4 mm film-coated tablet (tablet) marked with “TL” on one side and “20” on 

the other side. 

 

Brintellix film-coated tablets 20 mg are available in blister packs of 14, 28, 56, 56x1, 98, 98x1, 126 

(9x14), 490 (5x(98x1)) tablets and in tablet containers of 100, 200 tablets. 

 

The pack sizes of 56 x1, 98 x1 and 490 film-coated tablets are presented in unit dose blister. 

 

Not all pack sizes may be marketed. 

 

Marketing Authorisation Holder and Manufacturer 

 

H. Lundbeck A/S 

Ottiliavej 9 

2500 Valby 

Denmark 

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


101 

 

For any information about this medicine, please contact the local representative of the Marketing 

Authorisation Holder: 

 

Belgique/België/Belgien 

Lundbeck S.A./N.V. 

Tél/Tel: +32 2 535 7979 

 

Lietuva 

H. Lundbeck A/S 

Tel: +45 36301311(Danija)  

lietuva@lundbeck.com 

 

България 

Lundbeck Export A/S Representative Office 

Tel: +359 2 962 4696 

 

Luxembourg/Luxemburg 

Lundbeck S.A. 

Tél: +32 2 535 7979 

 

Česká republika  

Lundbeck Česká republika s.r.o. 

Tel: +420 225 275 600 

Magyarország 

Lundbeck Hungaria Kft. 

Tel: +36 1 4369980 

Danmark 

Lundbeck Pharma A/S 

Tlf: +45 4371 4270 

 

Malta 

H. Lundbeck A/S 

Tel: + 45 36301311 

 

Deutschland 

Lundbeck GmbH 

Tel: +49 40 23649 0 

 

Nederland 

Lundbeck B.V. 

Tel: +31 20 697 1901 

 

Eesti 

Lundbeck Eesti AS 

Tel: + 372 605 9350 

 

Norge 

H. Lundbeck AS  

Tlf: +47 91 300 800 

 

Ελλάδα 

Lundbeck Hellas S.A. 

Τηλ: +30 210 610 5036 

 

Österreich 

Lundbeck Austria GmbH 

Tel: +43 1 253 621 6033  

España 

Lundbeck España S.A. 

Tel: +34 93 494 9620 

Polska 

Lundbeck Poland Sp. z o. o.  

Tel.: + 48 22 626 93 00 

 

France 

Lundbeck SAS 

Tél: + 33 1 79 41 29 00 

 

Portugal 

Lundbeck Portugal Lda 

Tel: +351 21 00 45 900 

 

Hrvatska 

Lundbeck Croatia d.o.o. 

Tel.: + 385 1 6448263 

 

România 

Lundbeck Romania SRL 

Tel: +40 21319 88 26 

 

Ireland 

Lundbeck (Ireland) Limited 

Tel: +353 468 9800 

 

Slovenija 

Lundbeck Pharma d.o.o. 

Tel.: +386 2 229 4500 

Ísland 

Vistor hf. 

Tel: +354 535 7000  

 

Slovenská republika 

Lundbeck Slovensko s.r.o. 

Tel: +421 2 5341 42 18 

Italia 

Lundbeck Italia S.p.A. 

Tel: +39 02 677 4171 

 

Suomi/Finland 

Oy H. Lundbeck Ab 

Puh/Tel: +358 2 276 5000 

 



102 

Κύπρος 

Lundbeck Hellas A.E 

Τηλ.: +357 22490305 

 

Sverige 

H. Lundbeck AB 

Tel: +46 40 699 8200  

 

Latvija 

H. Lundbeck A/S 

Tel: +45 36301311(Dānija) 

latvia@lundbeck.com 

 

United Kingdom 

Lundbeck Limited 

Tel: +44 1908 64 9966 

 

 

This leaflet was last revised in MM/YYYY 

 

 

Other sources of information 

 

Detailed information on this medicine is available on the European Medicines Agency web site: 

http://www.ema.europa.eu 

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


103 

 

Package leaflet: Information for the patient 

 

Brintellix 20 mg/ml oral drops, solution 

vortioxetine 

 

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 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 Brintellix is and what it is used for  

2. What you need to know before you take Brintellix  

3. How to take Brintellix  

4. Possible side effects  

5. How to store Brintellix  

6. Contents of the pack and other information 

 

 

1. What Brintellix is and what it is used for 

 

Brintellix contains the active substance vortioxetine.It belongs to a group of medicines called 

antidepressants. 

 

Brintellix is used to treat major depressive episodes in adults. 

 

Brintellix has been shown to reduce the broad range of depressive symptoms, including sadness, inner 

tension (feeling anxious), sleep disturbances (reduced sleep), reduced appetite, difficulty in 

concentrating, feelings of worthlessness, loss of interest in favourite activities, feeling of being slowed 

down. 

 

 

2. What you need to know before you take Brintellix 

 

Do not take Brintellix: 

 

- if you are allergic to vortioxetine or any of the other ingredients of this medicine (listed in 

section 6). 

- if you are taking other medicines for depression known as non-selective monoamine oxidase 

inhibitors or selective MAO-A inhibitors. Ask your doctor if you are uncertain.  

 

Warnings and precautions  

 

Talk to your doctor or pharmacist before taking Brintellix if you: 

 

- are taking medicines with a so-called serotonergic effect, such as: 

-  tramadol (a strong pain killer).  

- sumatriptan and similar medicines with active substance names ending in “triptans” (used 

to treat migraine).  



104 

Taking these medicines together with Brintellix may increase the risk of serotonin syndrome. 

This syndrome may be associated with hallucinations, involuntary twitching, accelerated 

heartbeat, high blood pressure, fever, nausea and diarrhoea. 

 

- have had fits (seizures).  

Your doctor will treat you cautiously if you have a history of fits or have unstable fit 

disorders/epilepsy. Fits are a potential risk with medicines used to treat depression.Treatment 

should be discontinued in any patient who develops fits or where there is an increase in the 

frequency of fits.  

 

- have had mania.  

- have a tendency to bleed or bruise easily , or if you are pregnant (See ‘Pregnancy, breast-

feeding and fertility’). 

- have low sodium level in the blood. 

- are 65 years of age or older. 

- have a severe kidney disease.  

- have a severe liver disease or a liver disease called cirrhosis. 

- have or previously have had increased pressure in the eye or glaucoma. If your eyes become 

painful and you develop blurred vision during treatment, contact your doctor. 

 

When you are on antidepressant treatment, including vortioxetine, you may also experience feelings of 

aggression, agitation, anger and irritability. If this occurs, you should talk to your doctor.  

 

Thoughts of suicide and worsening of your depression 

 

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 

 

Brintellix is not recommended in children aged 7 to 11 years due to lack of information. Brintellix 

should not be used in adolescents aged 12 to 17 years because efficacy has not been demonstrated. The 

safety of Brintellix in adolescents aged 12 to 17 years is described in section 4.   

 

Other medicines and Brintellix 

 

Tell your doctor or pharmacist if you are taking, have recently taken or might take any other 

medicines. 

 

Tell your doctor if you are taking any of the following medicines: 

- phenelzine, iproniazid, isocarboxazid, nialamide, tranylcypromine (medicines to treat 

depression called non-selective monoamine oxidase inhibitors) you must not take any of these 

medicines together with Brintellix. Iif you have taken any of these medicines, you will need to 



105 

wait 14 days before you start taking Brintellix. After stopping Brintellix, you must allow 14 

days before taking any of these medicines. 

- moclobemide (a medicine to treat depression).  

- selegiline and rasagiline (medicines to treat Parkinson’s disease).  

- linezolid (a medicine to treat bacterial infections).  

- lithium (a medicine to treat depression an d mental disorders) or tryptophan. 

- medicines known to cause low sodium level. 

- rifampicin (a medicine to treat tuberculosis and other infections).  

- carbamazepine, phenytoin (medicines to treat epilepsy or other illness). 

- warfarin, dipyridamole, phenprocoumon, low-dose acetylsalicylic acid (blood thinning 

medicines). 

 

Medicines that increase the risk of fits: 

- sumatriptan and similar medicines with active substance names ending in “triptans”.  

- tramadol (a strong painkiller). 

- mefloquine (a medicine to prevent and treat malaria).  

- bupropion (a medicine to treat depression also used to wean from smoking). 

- fluoxetine, paroxetine and other medicines to treat depression called SSRI/SNRIs, tricyclics.  

- St John’s wort (hypericum perforatum)(a medicine to treat depression). 

- quinidine (a medicine to treat heart rhythm disorders). 

- Chlorpromazine, chlorprothixene, haloperidol (medicines to treat mental disorders and belong to 

the group called phenothiazines, thioxanthenes, butyrophenones).  

 

Please tell your doctor if you are taking any of the medicines above, since your doctor needs to know 

if you already are at risk for seizure. 

 

If you are having a urine drug screen, taking Brintellix may cause positive results for methadone when 

some test methods are used, even though you may not be taking methadone. If this happens, a more 

specific test can be performed. 

 

Brintellix with alcohol 

 

Combining this medicine with alcohol is not advisable. 

 

Pregnancy, breast-feeding and fertility 

 

If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask 

your doctor for advice before taking this medicine. 

 

Pregnancy 

 

Brintellix should not be used during pregnancy unless the doctor says it is absolutely necessary. 

 

If you take medicine to treat depression, including Brintellix, during the last 3 months of your 

pregnancy, you should be aware that the following effects may be seen in your newborn baby: trouble 

with breathing, bluish skin, fits, body temperature changes, feeding difficulties, vomiting, low blood 

sugar, stiff or floppy muscles, vivid reflexes, tremor, jitteriness, irritability, lethargy, constant crying, 

sleepiness and sleeping difficulties. Contact your doctor immediately if your newborn baby has any of 

these symptoms. 

 

Make sure your midwife and/or doctor know you are on Brintellix. When taken during pregnancy, 

particularly in the last 3 months of pregnancy, medicines like Brintellix 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. 



106 

If you take Brintellix near the end of your pregnancy there may be an increased risk of heavy 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 Brintellix so they can advise you. 

 

Breast-feeding 

 

It is expected that the ingredients of Brintellix will pass into breast milk. Brintellix is not to be used 

during breast-feeding. Your doctor will make a decision on whether you should stop breast-feeding, or 

stop using Brintellix taking into account the benefit of breast-feeding for your child, and the benefit of 

therapy for you 

 

Driving and using machines 

 

Brintellix has no or negligible influence on the ability to drive and use machines. However, as adverse 

reactions such as diziness have been reported, caution is advised during such activities when 

beginning Brintellix treatment or changing the dose. 

 

Brintellix contains ethanol 

 

This medicine contains 85 mg of alcohol (ethanol 96%) in each ml which is equivalent to 10.1 % v/v. 

The amount in 1 ml of this medicine is equivalent to less than 3 ml of beer or 1 ml of wine.  

The small amount of alcohol in this medicine will not have any noticeable effects.  

 

 

3. How to take Brintellix 

 

Always take this medicine exactly as your doctor has told you. Check with your doctor or pharmacist 

if you are not sure. 

 

The recommended dose of Brintellix is 10 mg vortioxetine taken as one daily dosein adults less than 

65 years of age. The dose may be increased by your doctor to a maximum of 20 mg vortioxetine per 

day or lowered to a minimum of 5 mg vortioxetine per day depending on your response to treatment. 

 

For elderly people 65 years of age or older the starting dose is 5 mg vortioxetine taken once daily. 

 

5 mg corresponding to 5 drops. 

10 mg corresponding to 10 drops. 

15 mg corresponding to 15 drops. 

20 mg corresponding to 20 drops. 

 

Method of administration 

 

Brintellix can be taken with or without food.  

The drops can be mixed with water, juice or other non-alcoholic drinks. 

Brintellix oral drops are not to be mixed with other medicinal products. 

 

Turn the bottle completely upside down. If no drops come out, tap the bottle lightly to start the flow. 

 

 
 

 



107 

Duration of treatment 

 

Take Brintellix for as long as your doctor recommends. 

 

Continue to take Brintellix even if it takes some time before you feel any improvement in your 

condition. 

 

Treatment should be continued for at least 6 months after you feel well again. 

 

If you take more Brintellix than you should 

 

If you take more than the prescribed dose of Brintellix, contact your doctor or nearest hospital 

emergency department immediately. Have the bottle and any remaining solution available. Do this 

even if there are no signs of discomfort. Overdose signs could be dizziness, nausea, diarrhoea, 

stomach discomfort, itching of the whole body, sleepiness and flushing.  

 

Following intake of dosages several times higher than the prescribed dose, fits (seizures) and a rare 

condition called serotonin syndrome have been reported. 

 

If you forget to take Brintellix 

 

Take the next dose at the usual time. Do not take a double dose to make up for a forgotten dose. 

 

If you stop taking Brintellix 

 

Do not stop taking Brintellix without talking with your doctor.  

 

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. 

 

In general, the observed side effects were mild to moderate and occurred within the first two weeks of 

treatment. The reactions were usually temporary and did not lead to cessation of therapy. 

 

Side effects listed below have been reported in the following frequencies. 

 

Very common: may affect more than 1 in 10 people  

- nausea  

 

Common: may affect up to 1 in 10 people  

- diarrhoea, constipation, vomiting 

- dizziness 

- itching of the whole body  

- abnormal dreams 

 

Uncommon: may affect up to1 in 100 people 

- flushing 

- night sweats 

 

Rare: may affect up to 1 in 1,000 people 

- enlarged pupils (mydriasis), which can increase the risk of glaucoma (see section 2) 

 

 



108 

Not known: frequency cannot be estimated from available data 

- low levels of sodium in the blood (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) 

- serotonin syndrome (see section 2) 

- allergic reactions, that may be serious, causing swelling of the face, lips, tongue or throat, 

difficulties breathing or swallowing, and/or a sudden drop in blood pressure (making you feel 

dizzy or lightheaded) 

- hives 

- excessive or unexplained bleeding (including bruising, nose bleeding, gastrointestinal and 

vaginal bleeding) 

- rash  

- sleep disorders (insomnia) 

- agitation and aggression. If you experience these side effects, contact your doctor (see section 

2). 

 

An increased risk of bone fractures has been observed in patients taking this type of medicines. 

 

Additional side effects in adolescents 

 

Side effects observed with vortioxetine in adolescents were similar to those seen for adults except for 

abdominal pain related events and suicidal thoughts that were observed more often in adolescents than 

in adults.  

 

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. 

 

 

5. How to store Brintellix 

 

Keep this medicine out of the sight and reach of children. 

 

Do not use this medicine after the expiry date that is stated on the packaging after EXP. The expiry 

date refers to the last day of that month.  

 

This medicine does not require any special storage conditions. 

 

After first opening the drops should be used within 8 weeks. 

 

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 Brintellix contains  

 

- The active substance is vortioxetine. Each drop of solution contains 1 mg vortioxetine (as (D,L)-

lactate). 

- The other ingredients are hydroxypropylbetadex, ethanol (96 percent) and purified water 

 

 

 

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


109 

What Brintellix looks like and contents of the pack 

 

Oral drops, solution 

Clear, nearly colourless to yellowish solution. 

 

Brintellix oral drops, solution, are available in 20 ml amber glass bottle including screw cap with 

dropper (child-resistant closure). 

 

Each bottle contains 15 ml Brintellix oral drops, solution. 

 

Marketing Authorisation Holder and Manufacturer 

 

H. Lundbeck A/S 

Ottiliavej 9 

2500 Valby 

Denmark 

 

For any information about this medicine, please contact the local representative of the Marketing 

Authorisation Holder: 

 

Belgique/België/Belgien 

Lundbeck S.A./N.V. 

Tél/Tel: +32 2 535 7979 

Lietuva 

H. Lundbeck A/S 

Tel: +45 36301311(Danija)  

lietuva@lundbeck.com 

 

България 

Lundbeck Export A/S Representative Office 

Tel: +359 2 962 4696 

 

Luxembourg/Luxemburg 

Lundbeck S.A. 

Tél: +32 2 535 7979 

 

Česká republika  

Lundbeck Česká republika s.r.o. 

Tel: +420 225 275 600 

 

Magyarország 

Lundbeck Hungaria Kft. 

Tel: +36 1 4369980 

Danmark 

Lundbeck Pharma A/S 

Tlf: +45 4371 4270 

 

Malta 

H. Lundbeck A/S 

Tel: + 45 36301311 

 

Deutschland 

Lundbeck GmbH 

Tel: +49 40 23649 0 

Nederland 

Lundbeck B.V. 

Tel: +31 20 697 1901 

 

Eesti 

Lundbeck Eesti AS 

Tel: + 372 605 9350 

 

Norge 

H. Lundbeck AS  

Tlf: +47 91 300 800 

 

Ελλάδα 

Lundbeck Hellas S.A. 

Τηλ: +30 210 610 5036 

 

Österreich 

Lundbeck Austria GmbH 

Tel: +43 1 253 621 6033  

 

España 

Lundbeck España S.A. 

Tel: +34 93 494 9620 

Polska 

Lundbeck Poland Sp. z o. o.  

Tel.: + 48 22 626 93 00 

 

France 

Lundbeck SAS 

Tél: + 33 1 79 41 29 00 

 

Portugal 

Lundbeck Portugal Lda 

Tel: +351 21 00 45 900 

 



110 

Hrvatska 

Lundbeck Croatia d.o.o. 

Tel.: + 385 1 6448263 

 

România 

Lundbeck Romania SRL 

Tel: +40 21319 88 26 

 

Ireland 

Lundbeck (Ireland) Limited 

Tel: +353 468 9800 

 

 

Slovenija 

Lundbeck Pharma d.o.o. 

Tel.: +386 2 229 4500 

Ísland 

Vistor hf. 

Tel: +354 535 7000  

 

Slovenská republika 

Lundbeck Slovensko s.r.o. 

Tel: +421 2 5341 42 18 

 

Italia 

Lundbeck Italia S.p.A. 

Tel: +39 02 677 4171 

 

Suomi/Finland 

Oy H. Lundbeck Ab 

Puh/Tel: +358 2 276 5000 

 

Κύπρος 

Lundbeck Hellas A.E 

Τηλ.: +357 22490305 

 

Sverige 

H. Lundbeck AB 

Tel: +46 40 699 82 00 

 

Latvija 

H. Lundbeck A/S 

Tel: +45 36301311(Dānija) 

latvia@lundbeck.com 

 

United Kingdom 

Lundbeck Limited 

Tel: +44 1908 64 9966 

 

 

This leaflet was last revised in MM/YYYY 

 

Other sources of information 

 

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 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