Brintellix pills 20mg, 28pcs

Composition

The Active ingredient is vortioxetine hydrobromide 25.420 mg, which is equivalent to 20 mg of vortioxetine. Excipients:

• mannitol 91.58 mg,
• microcrystalline cellulose 22.5 mg,
• hyprolose 4.5 mg,
• sodium carboxymethyl starch (type A) 4.5 mg,
• magnesium stearate 1.5 mg.

Film shell:

• Opadray red 3.0 mg (hypromellose 1.875 mg,
• titanium dioxide (E 171) 0.449 mg,
• macrogol 400 0.188 mg,
• iron oxide red dye (E 172) 0.488 mg).

Pharmacological action

Mechanism of action The mechanism of action of vortioxetine appears to be related to its direct modulating serotonergic activity and inhibition of the serotonin transporter protein. Preclinical studies show that vorticity acts as the antagonist of the 5-HT₃,5-HT₇ and 5-HT_1D receptors, a partial agonist of 5-HT_1B receptors and a full agonist 5-HT _1Areceptors and also inhibits 5-HT Transporter, thereby modulating neurotransmission in multiple systems, primarily serotonergic, but probably also the noradrenergic, dopaminergic, neurotransmission, mediated by histamine, acetylcholine, GABA and glutamate. This multimodal pharmacological activity appears to underlie the antidepressant and anxiolytic properties of vortioxetine, and also determines the improvements in cognitive function, learning, and memory observed in animal studies. However, since the individual contribution of each pharmacological target to the observed pharmacodynamic profile of vortioxetine remains unclear, extrapolation of these preclinical data to humans should be performed with caution.

In two studies using positron emission tomography (PET) people with the goal of quantifying the degree of employment of carriers of the 5-HT (using the ligand 11C-MADAM, or 11C-DASB), at different dose level of vorticity obtained the following data: the average number of carriers of the 5-HT-related vorticities was approximately 50% at a dose of 5 mg/day,65% at a dose of 10 mg/day and increased to 80% with increasing doses up to 20 mg/day.

Clinical efficacy and safety

The efficacy and safety of vortioxetine were studied in a number of clinical trials involving more than 6,700 patients, of which more than 3,700 patients participated in short-term (≤12 weeks) studies for major depressive disorder (MDD).

Twelve double-blind, placebo-controlled,6/8-week, fixed-dose studies were conducted to determine the short-term efficacy of vortioxetine for MDD in adult patients (including elderly patients).

The efficacy of vortioxetine was demonstrated in at least the single-dose group in 9 out of 12 studies that showed a change of at least 2 points from placebo on the Montgomery-Asberg Depression Scale (MADRS) and Hamilton Depression Scale (HAM-D24).

This was clinically confirmed by the number of patients who responded to therapy and achieved remission, as well as improvement on the Overall Clinical Impression Scale (CGI-I). The effectiveness of vortioxetine increased with increasing dose.

The effectiveness of individual studies was confirmed by a meta-analysis (MMRM) of mean changes in the overall MADRS score at 6/8 weeks in short-term placebo-controlled studies in adults.

According to the results of a meta-analysis of these studies, the differences from placebo were statistically significant: -2.3 points (p=0.007); -3.6 points (p<0.001); -4.6 points (p

The efficacy of vortioxetine is also confirmed in the summary analysis, in which the percentage of respondents ranged from 46% to 49% with vortioxetine compared to 34% with placebo (p

In addition, vortioxetine in the dose range 5-20 mg/day demonstrated efficacy against a wide range of depressive symptoms (assessed by changes in scores for all individual MADRS subscales).

The efficacy of vortioxetine at doses of 10 or 20 mg/day was also shown in a 12-week, double-blind, variable-dose comparative study with agomelatine at doses of 25 or 50 mg/day in patients with MDD. Vortioxetine showed a statistically significant superiority over agomelatine in the overall MADRS score, which was also clinically significant in the number of patients who responded to therapy, achieved remission and improved on the CGI-I scale.

Maintenance therapy

The persistence of the antidepressant effect with maintenance therapy is shown in a study on relapse prevention.

Patients who were in remission after initial vortioxetine therapy during a 12-week open-label trial were randomly assigned to vortioxetine 5 or 10 mg/day or placebo groups and monitored for relapses during a double-blind follow-up period of at least 24 weeks (24 to 64 weeks).

Vortioxetine was superior to placebo (p=0.004) by the main evaluation criterion – time elapsed before relapse of MDD, with a risk ratio of 2.0; this means that the risk of relapse was twice as high in the placebo group as in the vortioxetine group.

Elderly patients

In a double-blind, placebo-controlled,8-week, fixed-dose study in elderly patients with depression (≥65 years, n=452,156 of them were treated with vortioxetine), vortioxetine at a dose of 5 mg / day was superior to placebo when evaluating the overall score on the MADRS and HAM-D24 scales. The difference between vortioxetine and placebo was 4.7 points on the MADRS scale at week 8 of therapy (MMRM analysis).

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

The efficacy of vortioxetine was also demonstrated in patients with severe depression (baseline MADRS score ≥30) and in patients with depression with concomitant high anxiety (baseline HAM-A score ≥20) in short-term studies of adult patients (the mean difference from placebo on the MADRS scale at weeks 6 and 8 ranged from 2.8 to 7.3 points and from 3.6 to 7.3 points, respectively (MMRM analysis)).

In a separate study in the elderly, vortioxetine showed its effectiveness in this group of patients as well. The persistence of the antidepressant effect in this category of patients was also shown in a long-term study on relapse prevention.

Effects of vortioxetine on the Digital Symbol Substitution Test (DSST), the University of California San Diego (UPSA) Quality of Basic Life Skills (objective measures), as well as the number of points in the Perceived Deficiencies Questionnaire (PDQ) and the number of points in the Cognitive and Physical Functioning Questionnaire (CPFQ) (subjective indicators).

The efficacy of vortioxetine (at a dose of 5-20 mg / day) in patients with MDD was studied in two short-term placebo – controlled studies in adults and in one in elderly patients.

Vortioxetine had a statistically significant effect on the Digital Character Replacement Test (DSST) compared to placebo, with Δ = 1.75 (p = 0.019) to 4.26 (p

In a meta-analysis (ANCOVA, LOCF), the mean change from the number of correct characters in the DSST compared to the baseline value in all three studies, vortioxetine was different from placebo (p When adjusted for change in MADRS, the total score in a meta-analysis of the same studies showed that vortioxetine was different from placebo (p < 0.05) with a standardized effect value of 0.24.

One study evaluated the effect of vortioxetine on functional ability using the University of California, San Diego (UPSA) Basic Life Skills Quality Score.

Vortioxetine was statistically significantly different from placebo with results of 8.0 points for vortioxetine versus 5.1 points for placebo (p = 0.0003).

In one study, vortioxetine was superior to placebo in terms of subjective scores measured using the subjective deficiency questionnaire, with results of -14.6 for vortioxetine and -10.5 for placebo (p = 0.002).

Vortioxetine did not differ from placebo in terms of subjective measures measured by the cognitive and physical functioning assessment questionnaire, with results of -8.1 for vortioxetine versus -6.9 for placebo (p = 0.086).

Portability and security

The safety and tolerability of vortioxetine have been established in short-and long-term studies in the dose range from 5 to 20 mg / day. For information on undesirable side effects, see the “Side Effects” section.

Vortioxetine did not increase the incidence of insomnia or drowsiness compared to placebo.

Short – term and long-term placebo-controlled clinical trials consistently evaluated possible withdrawal symptoms after abrupt discontinuation of vortioxetine treatment.

There was no clinically significant difference with placebo in the frequency or quality of withdrawal symptoms after either short-term (6-12 weeks) or long-term (24-64 weeks) vortioxetine therapy.

The frequency of spontaneous complaints of sexual adverse reactions was low and similar to placebo in both short-and long-term studies of vortioxetine. In studies using the Arizona Sexual Function Scale (ASEX), the incidence of therapy-induced sexual dysfunction (TESD) and the overall ASEX score did not differ clinically significantly from placebo when vortioxetine was administered at doses of 5-15 mg / day.

When using vortioxetine at a dose of 20 mg / day, an increase in the incidence of sexual dysfunction was observed compared to placebo (a difference in frequency of 14.2%,95% CI (1.4; 27.0)).

In both short-and long-term studies, vortioxetine compared with placebo had no effect on body weight, heart rate, or blood pressure.

Vortioxetine did not have a clinically significant effect on liver and kidney function parameters in clinical studies.

In patients with MDD, vortioxetine did not have a clinically significant effect on ECG parameters, including QT, QTc, PR, and QRS intervals. In a thorough study of the QTc interval in healthy subjects, vortioxetine at doses up to 40 mg / day did not affect its duration.

Pharmacokinetics

Suction

Vortioxetine is slowly but well absorbed after oral use. The maximum plasma concentration is reached in 7-11 hours. After repeated use at doses of 5,10 or 20 mg/day, the average maximum plasma concentration (Cmax) is 9-33 ng / ml. Absolute bioavailability is 75%. Food intake does not affect the pharmacokinetics of the drug (see the section “Dosage and use”).

Distribution

The average volume of distribution (Vss) is 2600 L, indicating extensive extravascular distribution. The degree of binding to plasma proteins is high (98-99%) and, apparently, does not depend on the concentration of vortioxetine in plasma.

Biotransformation

Vortioxetine is extensively metabolized in the liver, mainly due to oxidation by the CYP2D6 isoenzyme and to a lesser extent by the CYP3A4/5 and CYP2C9 isoenzymes and subsequent conjugation with glucuronic acid.

In drug interaction studies, no inhibitory or inducing effect of vortioxetine on the isoenzymes CYP1A2, CYP2A6, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP2E1 or CYP3A4/5 was found (see the section “Interaction with other drugs”). Vortioxetine is a weak inhibitor and substrate of P-glycoprotein. The main metabolite of vortioxetine is pharmacologically inactive.

Elimination The mean elimination half-life and oral clearance are 66 h and 33 l / h, respectively. About 2/3 of the inactive vortioxetine metabolite is excreted in the urine and about 1/3 in the feces. Only a small amount of vortioxetine is excreted unchanged in the faeces. Steady-state plasma concentrations are reached after approximately 2 weeks.

Linearity / non-linearity

The pharmacokinetics are linear and independent of time in the dose range studied (2.5-60 mg / day). In accordance with the half-life based on AUC_{o-24 hours} after multiple doses of 5-20 mg/day, the accumulation index is from 5 to 6.

Special patient groups

Elderly patients

In elderly healthy subjects (≥65 years; n=20), vortioxetine exposure increased by 27% (Cmax and AUC) compared to the control group of young healthy subjects (≤45 years) after multiple doses of 10 mg/day.

The minimum effective dose of vortioxetine 5 mg / day should always be used as a starting dose in patients aged ≥65 years (see section “Dosage and use”). Vortioxetine should be administered with caution in elderly patients at a dose higher than 10 mg / day (see section “Special instructions”).

Renal insufficiency After a single dose of vortioxetine 10 mg, renal insufficiency assessed by the Cockcroft-Gault formula (mild, moderate, or severe; n=8 in the group) resulted in a moderate (up to 30%) increase in exposure to vortioxetine compared to the control group of healthy subjects.

In patients with end-stage renal disease, dialysis resulted in only a slight decrease in exposure (AUC and Cmax decreased by 13% and 27%, respectively; n=8) after a single dose of vortioxetine 10 mg. No dose adjustment is required (see section “Special instructions”).

Liver failure

After a single dose of vortioxetine 10 mg in patients with mild or moderate hepatic insufficiency (Child-Pugh criteria A or B; n=8 in the group), no changes in the pharmacokinetics of vortioxetine were observed (AUC change of less than 10%). No dose adjustment is required (see section “Dosage and use”).

Vortioxetine has not been studied in patients with severe hepatic insufficiency, so the drug should be used with caution in such patients (see the section “Special instructions”).

Types of CYP2D6 isoenzyme genes

The plasma concentration of vortioxetine was approximately twice as high in patients with reduced metabolic activity of the CYP2D6 isoenzyme compared with extensive metabolizers. Concomitant use of strong inhibitors of the CYP3A4/2C9 isoenzyme in patients with reduced metabolic activity of the CYP2D6 isoenzyme may potentially lead to increased exposure to vortioxetine (see section “Interaction with other drugs”).

In patients with extremely rapid metabolism of the CYP2D6 isoenzyme, the plasma concentration of vortioxetine 10 mg / day was within the values obtained from extensive metabolizers at doses of 5 mg / day and 10 mg/day. As with all patients, depending on the individual response, the possibility of adjusting the dose of the drug should be considered (see the section “Dosage and use”).

Preclinical safety data sheet

In general toxicity studies, the use of vortioxetine in mice, rats, and dogs was accompanied by effects mainly from the central nervous system, which included such manifestations as salivation (rats and dogs), pupil dilation (dogs), and two episodes of convulsions in dogs.

When the drug was administered at the maximum recommended therapeutic dose of 20 mg/day, no convulsive activity was recorded, taking into account the fact that the safety limit was determined at 5%. Organ toxicity was limited to the kidneys (rats) and liver (mice and rats).

Changes in the kidneys in rats (glomerulonephritis, tubular obstruction, crystals in the renal tubules) and liver in mice and rats (hepatocellular hypertrophy, hepatocyte necrosis, bile duct hyperplasia, crystals in the bile ducts) were observed at exposures more than 2 times (rats) and 10 times (mice) higher than human exposure at the maximum recommended dose of 20 mg/day. These cases were mainly associated with rodent-specific obstruction by crystals of the renal tubules and bile ducts and are considered unlikely in humans.

Vortioxetine had no genotoxic effect in a standard battery of in vitro and in vivo tests.

Based on the results of standard two-year studies of carcinogenicity in mice or rats, vortioxetine does not have a risk of carcinogenicity in humans.

Vortioxetine had no effect on fertility, mating ability, reproductive organ function, or sperm morphology and motility in rats.

Vortioxetine did not have a teratogenic effect in rats or rabbits, although the effect on fetal weight and delayed ossification were observed in rats exposed to doses of vortioxetine exceeding 10 times the maximum daily dose for humans of 20 mg/day. Similar effects were observed in rabbits with subtherapeutic exposure.

In pre-and postnatal studies in rats, the use of vortioxetine in doses that did not have a toxic effect on the mother and corresponded to a dose of 20 mg/day in humans was associated with increased mortality of pups, a decrease in the rate of weight gain and a slowdown in their development (see the section “Use during pregnancy and lactation”).

Vortioxetine penetrated into the milk of lactating rats (see the section “Use during pregnancy and lactation”).

In studies of juvenile toxicity in rats, the data obtained on vortioxetine therapy correlated with those obtained in adult animals.

The Active ingredient vortioxetine hydrobromide is classified as SBT-substance (persistent, bioaccumulative and toxic; risk to fish). However, at the recommended doses for patients, vortioxetine poses little risk to the aquatic and terrestrial environment.

Indications

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

Use during pregnancy and lactation

Pregnancy Data on the use of vortioxetine in pregnant women are limited. Animal studies have revealed the reproductive toxicity of vortioxetine (see section “Pharmacological properties”).

Newborns whose mothers receive serotonergic drugs in late pregnancy may experience the following symptoms: respiratory distress, cyanosis, apnea, seizures, temperature instability, difficulty eating, vomiting, hypoglycemia, hypertension, hypotension, hyperreflexia, tremor, increased neuro-reflex excitability, irritability, lethargic sleep, constant crying, drowsiness, and poor sleep. These symptoms can be associated with both withdrawal symptoms and excessive serotonergic activity. In most cases, such complications begin immediately or soon (

Data from epidemiological studies suggest that the use of SSRIs during pregnancy, especially in the late stages, may increase the risk of developing persistent pulmonary hypertension in newborns (PPHN). Although to date, the possibility of a relationship between this condition and the use of vortioxetine has not been studied, taking into account the mechanism of its action (increased serotonin concentration), a possible risk cannot be excluded.

Brintellix should not be used during pregnancy, unless the clinical condition of the woman herself requires it.

Breast-feeding Available pharmacodynamic and toxicological data in animals have shown that vortioxetine and its metabolites are excreted in breast milk. It is likely that vortioxetine also passes into human breast milk (see section “Pharmacological properties”).

The risk to the baby during breastfeeding cannot be excluded.

The decision to stop breastfeeding or refrain from using Brintellix should be made taking into account the assessment of the relative benefits of breastfeeding for the child and the need for therapy for the mother.

Fertility Studies in male and female rats have shown that vortioxetine has no effect on fertility, sperm quality, or mating ability (see section “Pharmacological properties”).

Cases of human use of drugs belonging to the corresponding pharmacological class of antidepressants (SSRIs) have shown the presence of effects on sperm quality, which is reversible. No effect on human fertility has been observed to date.

Contraindications

• Hypersensitivity to the Active ingredient or any component of the drug.
• Concomitant use with non-selective monoamine oxidase inhibitors (MAOIs) or with selective MAOIs A inhibitors (see section “Interaction with other medicinal products”).
• Children and adolescents under 18 years of age (safety and efficacy have not been established).

Interaction

Vortioxetine undergoes extensive metabolism in the liver, mainly due to oxidation catalyzed by the CYP2D6 isoenzyme, and to a lesser extent by the CYP3A4/5 and CYP2C9 isoenzymes (see the section “Pharmacological properties”).

Possible effect of other drugs on the pharmacological action of vortioxetine Non-reversible non-selective MAO inhibitors Due to the risk of serotonin syndrome, vortioxetine is contraindicated in combination with irreversible non-selective MAO inhibitors. Vortioxetine can be prescribed no earlier than 14 days after discontinuation of irreversible non-selective MAO inhibitors. Vortioxetine should be discontinued at least 14 days before the start of irreversible non-selective MAO inhibitors (see section “Contraindications”).

Reversible selective MAO A inhibitors (moclobemide)Concomitant use of vortioxetine with reversible selective MAO A inhibitors, such as moclobemide, is contraindicated (see section “Contraindications”). In case of proven need for simultaneous use, the drug to be added should be used in minimal doses and with careful clinical monitoring for the occurrence of serotonin syndrome (see the section “Special instructions”).

Reversible non-selective MAO inhibitors (linezolid)Concomitant use of vortioxetine with a weak reversible nonselective MAO inhibitor, such as the antibiotic linezolid, is contraindicated (see section “Contraindications”). In case of proven need for simultaneous use, the drug to be added should be used in minimal doses with careful clinical monitoring for the occurrence of serotonin syndrome (see the section “Special instructions”).

Irreversible selective MAO B inhibitors (selegiline, rasagiline)Although the risk of serotonin syndrome with concomitant use of vortioxetine and selective MAO B inhibitors is lower than with concomitant use of vortioxetine and selective MAO A inhibitors, the combined use of vortioxetine with irreversible MAO B inhibitors, such as selegiline or rasagiline, should be carried out with caution. In case of simultaneous use, the patient should be carefully monitored for serotonin syndrome (see the section “Special instructions”).

Serotonergic drugs Simultaneous use of vortioxetine and other drugs with a serotonergic effect (for example, tramadol, sumatriptan and other triptans) may lead to the development of serotonin syndrome (see the section “Special instructions”).

Simultaneous use of antidepressants with a serotonergic effect with drugs containing St. John’s wort (Hypericum perforatum) may lead to an increase in the frequency of adverse reactions, including serotonin syndrome (see the section “Special instructions”).

Drugs that lower the threshold of convulsive alertidepressants with serotonergic effects can lower the threshold of convulsive alertity. Concomitant use with drugs that reduce the threshold of convulsive readiness (for example, antidepressants (TCAS, SSRIs, SSRIs), neuroleptics (phenothiazines, thioxanthenes, butyrophenones), mefloquine, bupropion, tramadol) should be carried out with caution (see the section “Special instructions”).

ECT (electroconvulsive therapy)Currently, there is no clinical experience with the simultaneous use of vortioxetine and ECT, so caution should be exercised when using it.

Inhibitors of the CYP2D6 isoenzyme When vortioxetine was administered at a dose of 10 mg/day simultaneously with bupropion (a strong inhibitor of the CYP2D6 isoenzyme) at a dose of 150 mg twice a day for 14 days in healthy subjects, vortioxetine exposure (AUC) increased 2.3 times. Adverse reactions were more often observed when bupropion was added to current vortioxetine therapy than when vortioxetine was added to current bupropion therapy. Depending on the individual response of the patient, when a strong inhibitor of the CYP2D6 isoenzyme (for example, bupropion, quinidine, fluoxetine, paroxetine) is added to current therapy with vortioxetine, the possibility of reducing the dose of vortioxetine should be considered (see the section “Dosage and use”).

CYP3A4 and CYP2C9 inhibitors Addition of vortioxetine 6 days after initiation of ketoconazole 400 mg/day (inhibitor of CYP3A4/5 and P-glycoprotein isoenzymes) or 6 days after initiation of fluconazole 200 mg/day (inhibitor of CYP2C9, CYP2C19 and CYP3A4/5 isoenzymes) in healthy subjects exposure (AUC) of vortioxetine increased by 1.3 and 1.5 times, respectively. No dose adjustment is required.

Interactions in patients with weak CYP2D6 isoenzyme activity Special studies of the use of vortioxetine simultaneously with strong inhibitors of the CYP3A4 isoenzyme (such as itraconazole, voriconazole, clarithromycin, telithromycin, nefazodone, conivaptan and many HIV protease inhibitors) and inhibitors of the CYP2C9 isoenzyme (such as fluconazole and amiodarone) in patients with reduced activity of the CYP2D6 isoenzyme (see section “Pharmacological properties”), it has not been performed, however, it can be expected that in these patients such use will lead to a more pronounced exposure to vortioxetine compared to the moderate action described above. Taking a single dose of omeprazole 40 mg (an inhibitor of the CYP2C19 isoenzyme) against the background of repeated doses of vortioxetine did not change the pharmacokinetics of the latter in healthy subjects.

Cytochrome P450 inducers When a single dose of vortioxetine 20 mg was administered 10 days after the start of rifampicin 600 mg/day (a broad-spectrum CYP isoenzyme inducer) in healthy subjects, vortioxetine exposure (AUC) decreased by 72%. Depending on the individual response of the patient, when a strong inducer of broad-spectrum cytochrome P450 isoenzymes (e. g. rifampicin, carbamazepine, phenytoin) is added to current therapy with vortioxetine, the possibility of adjusting the dose of vortioxetine should be considered (see the section “Dosage and use”).

Alcohol Concomitant use of single doses of vortioxetine (20 mg and 40 mg) and ethanol (0.6 g/kg) to healthy subjects showed no changes in the pharmacokinetics of vortioxetine or ethanol and no significant cognitive impairment compared to placebo. However, alcohol intake is not recommended during antidepressant therapy.

Acetylsalicylic acid: A single use of acetylsalicylic acid at a dose of 150 mg / day did not alter the pharmacokinetics of multiple doses of vortioxetine in healthy subjects.

Possible effect of vortioxetine on the pharmacological effects of other drugs anticoagulants and antiplatelet agents There was no significant effect of vortioxetine compared to placebo on prothrombin parameters, international normalized ratio (INR), or the ratio of R-R-/S-warfarin in blood plasma when multiple doses of vortioxetine were administered simultaneously with a fixed dose of warfarin in healthy subjects. There was also no significant inhibitory effect of vortioxetine on platelet aggregation and the pharmacokinetics of acetylsalicylic acid and salicylic acid compared to placebo when acetylsalicylic acid was co-administered at a dose of 150 mg / day after multiple doses of vortioxetine in healthy subjects. However, as with other serotonergic medications, caution should be exercised when using vortioxetine concomitantly with oral anticoagulants or antiplatelet agents due to the potential risk of bleeding caused by pharmacodynamic interactions (see section “Special Instructions”).

Cytochrome P450 substrates In vitro studies have not shown vortioxetine to inhibit or induce cytochrome P450 isoenzymes (seesection “Pharmacological properties”).

After multiple doses of vortioxetine in healthy subjects, no inhibitory effect was found on the activity of cytochrome P450 isoenzymes CYP2C19 (omeprazole, diazepam), CYP3A4/5 (ethinylestradiol, midazolam), CYP2B6 (bupropion), CYP2C9 (tolbutamide, S-warfarin), CYP1A2 (caffeine) or CYP2D6 (dextromethorphan).

Pharmacodynamic interactions were also not observed. There was no significant cognitive impairment compared to placebo when vortioxetine was used in combination with a single dose of diazepam 10 mg. There was no significant effect of vortioxetine compared to placebo on the level of sex hormones after its use in combination with a combined oral contraceptive (ethinyl estradiol 30 mcg + levonorgestrel 150 mcg).

Lithium, tryptopha N in healthy subjects, no clinically significant changes were observed with the simultaneous use of lithium and multiple doses of vortioxetine. However, due to the fact that cases of increased serotonergic antidepressant effects have been reported when used concomitantly with lithium or tryptophan, the use of vortioxetine in combination with these drugs should be carried out with caution.

How to take, course of use and dosage

Dosage regimen The initial and recommended dose of Brintellix in adult patients under 65 years of age is 10 mg once daily. Depending on the individual response of the patient, the daily dose may be increased to a maximum dose of 20 mg of vortioxetine once a day or reduced to a minimum dose of 5 mg of vortioxetine once a day.

After the symptoms of depression have fully resolved, it is recommended to continue treatment for at least 6 months to consolidate the antidepressant effect.

Discontinuation of treatment Patients receiving treatment with Brintellix may discontinue Brintellix at one time without the need for a gradual dose reduction (see section “Pharmacological properties”).

Special patient groupspri Vileged patients in patients ≥ 65 years of age, the minimum effective dose of Brintellix 5 mg once daily should always be used as the initial dose. Caution should be exercised when treating patients ≥ 65 years of age with doses higher than 10 mg of vortioxetine once a day, as data on the use of the drug in this group of patients are limited (see the section “Special instructions”).

Cytochrome P450 inhibitors Depending on the individual response of the patient, it may be necessary to reduce the dose of Brintellix in case of joining therapy with strong inhibitors of the CYP2D6 isoenzyme (for example, bupropion, quinidine, fluoxetine, paroxetine) (see the section “Interaction with other drugs”).

Cytochrome P450 inducers Depending on the individual response of the patient, a dose adjustment of Brintellix may be required if therapy with broad-spectrum cytochrome P450 inducers (for example, rifampicin, carbamazepine, phenytoin) is initiated (see the section “Interaction with other drugs”).

Children and adolescents (under 18 years of age)The safety and efficacy of Brintellix in children and adolescents under 18 years of age have not been established. There are no data available for this group of patients (see the section “Special instructions”).

Method of applicatio Nbrintellix is intended for oral use. Film-coated tablets can be taken regardless of food intake.

Overdose

Currently, there is only limited experience with vortioxetine overdose.

Symptoms: Oral use of vortioxetine at a dose of 40 to 75 mg led to an increase in the following adverse reactions: nausea, postural dizziness, diarrhea, abdominal discomfort, generalized itching, drowsiness and hot flashes.

Treatment: In case of overdose, it is necessary to monitor the patient and conduct symptomatic treatment. It is also recommended to carry out follow-up medical supervision in specialized settings.

Special instructions

Use in children and adolescents under 18 years of age

Brintellix is not recommended for the treatment of depression in patients under 18 years of age, as the safety and efficacy of vortioxetine in this age group has not been established (see section “Dosage and use”).

In clinical studies, children and adolescents treated with other antidepressants were more likely to experience suicidal behavior (suicidal attempts and suicidal thoughts) and hostility (with a predominance of aggressive behavior, confrontational tendencies, and irritability) compared to those treated with placebo.

Suicide / suicidal thoughts or clinical deterioration

Depression is associated with an increased risk of suicidal thoughts, self-harm, and suicide (suicidal behavior).

This risk persists until a pronounced remission occurs. Since there may be no improvement during the first few weeks of therapy or even longer, patients should be constantly monitored until their condition improves.

General clinical practice shows that in the early stages of recovery, the risk of suicide may increase.

Patients with a history of suicidal behavior or patients with a significant level of suicidal thoughts prior to treatment are more at risk of suicidal thoughts or suicide attempts, so they should be closely monitored during treatment. A meta-analysis of placebo-controlled clinical trials of antidepressants involving adult patients with psychiatric disorders showed that when using antidepressants in patients younger than 25 years of age, there is an increased risk of suicidal behavior compared to placebo.

Patients should be carefully monitored, especially those who show a high risk of suicide, especially at the beginning of treatment or when changing the dose of the drug. Patients (and their caregivers) should be warned to monitor for signs of any clinical deterioration, suicidal behavior or thoughts, or unusual behavioral changes, and to seek immediate medical attention if such symptoms occur.

Convulsive seizures

There is a possible risk of developing seizures when taking antidepressants. Therefore, Brintellix should be used with caution in patients with a history of convulsive seizures or in patients with unstable epilepsy (see the section “Interaction with other drugs”). If convulsive seizures occur or their frequency increases, treatment with vortioxetine should be discontinued.

Serotonin syndrome or neuroleptic malignant syndrome

Serotonin syndrome (SS) or neuroleptic malignant syndrome (NMS) are potentially life-threatening conditions that may occur with the use of Brintellix.

The risk of SS or NMS is increased when co-administered with serotonergic drugs (including triptans), drugs that affect serotonin metabolism (including MAOIs), antipsychotics, or other dopamine antagonists. Patients should be monitored for objective and subjective symptoms of SS and NMS (see sections “Contraindications” and “Interactions with other medications”).

Symptoms of serotonin syndrome include changes in mental state (e. g., agitation, hallucinations, coma), autonomic instability (e. g., tachycardia, blood pressure lability, hyperthermia), neuromuscular abnormalities (e. g., hyperreflexia, coordination disorders), and/or gastrointestinal symptoms (e. g., nausea, vomiting, diarrhea). If such symptoms occur, Brintellix therapy should be discontinued immediately and symptomatic treatment should be initiated.

Mania / Hypomania Brintellix should be used with caution in patients with a history of mania/hypomania episodes. The drug should be discontinued if a manic state develops.

Angle-closure glaucoma The dilation of the pupils that occurs after taking many antidepressants, including Brintellix, can trigger an attack of angle-closure glaucoma in patients with an anatomically narrow angle of the anterior chamber of the eye who have not undergone peripheral iridectomy.

Bleeding

Against the background of the use of serotonergic antidepressants (SSRIs, SSRIs), there were rare cases of hemorrhagic disorders, such as ecchymosis, purpura, gastrointestinal and gynecological bleeding.

The drug is recommended to be used with caution in patients taking anticoagulants and/or drugs that affect platelet function (for example, atypical antipsychotics, phenothiazines, most tricyclic antidepressants, nonsteroidal anti-inflammatory drugs (NSAIDs) and acetylsalicylic acid) (see the section “Interaction with other drugs”), as well as in patients with a known tendency to bleeding / clotting disorders.

Hyponatremia

Rare cases of hyponatremia have been reported with the use of antidepressants with serotonergic effects (SSRIs, SSRIs), probably due to the syndrome of inadequate secretion of antidiuretic hormone.

Caution should be exercised when using vortioxetine in patients from high-risk groups, such as elderly patients, patients with cirrhosis of the liver, or patients receiving concomitant therapy with drugs that may cause hyponatremia.

If possible, Brintellix should be discontinued in patients with symptomatic hyponatremia and appropriate medical interventions should be performed to correct their condition.

Elderly patients Data on the use of Brintellix in elderly patients with a major depressive episode are limited. Therefore, caution should be exercised when treating patients ≥ 65 years of age with doses of vortioxetine above 10 mg once a day (see sections “Pharmacological properties” and “Side effects”).

Renal dysfunction There are only limited data on the use of the drug in patients with severe renal insufficiency. Therefore, caution should be exercised when treating these patients (see section “Pharmacological properties”).

Hepatic impairment Vortioxetine has not been studied in patients with severe hepatic insufficiency, so the drug should be used with caution in such patients (see the section “Pharmacological properties”).

Influence on the ability to drive vehicles and work with mechanisms

Brintellix has no or very little effect on the ability to drive a car or use machinery. However, patients should exercise caution when driving vehicles or working with dangerous machinery, especially when starting treatment with vortioxetine or when changing its dose.

Active ingredient

Vortioxetine

Conditions of release from pharmacies

By prescription

Dosage form

Tablets

Purpose

For adults as directed by your doctor

Indications

Depression