Brintellix pills 5mg, 28pcs

Composition

Current broadcastvo: 5 mg of vortioxetine in the form of vortioxetine hydrochloride. Auxiliary substances: mannitol (E 421), microcrystalline cellulose, hydroxypropylcellulose, sodium starch (type A), magnesium stearate, hypromellose, macrogol 400, titanium dioxide (E 171);tablets 5 mg iron oxide red (E 172); tablets 10 mg iron oxide yellow (E 172).

Pharmacological action

pharmacokineticabsorption. Vortioxetine is slowly but well absorbed after oral use and peak plasma concentrations are reached within 7-11 hours. After multiple doses of 5,10, or 20 mg per day, an average Cmax of 9-33 ng/ml was observed. Bioavailability is 75%. The effect of food intake on pharmacokinetics was not observed. Distribution. The mean volume of distribution (VSS) is 2600 L, indicating a voluminous extravascular distribution. Vortioxetine binds strongly to plasma proteins (98-99%) and binding appears to be independent of vortioxetine plasma concentrations. Metabolism. Vortioxetine is extensively metabolized in the liver, mainly by oxidation and subsequent conjugation with glucuronic acid. In vitro cytochrome P450 isoenzymes CYP2D6, CYP3A4 / 5, CYP2C19, CYP2C9, CYP2A6, CYP2C8 and CYP2B6 are involved in the metabolism of vortioxetine. No inhibitory or inducing effect of vortioxetine in vitro on the CYP isoenzymes CYP1A2, CYP2A6, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP2E1 or CYP3A4 / 5 was observed. Vortioxetine is a weak P-gp substrate and inhibitor. The main metabolite of vortioxetine is pharmacologically inactive. Elimination half-life is 66 hours. Approximately 2/3 of the inactive vortioxetine metabolite is excreted in the urine and about 1/3 in the faeces. Only a small amount of vortioxetine is excreted in the faeces. A stable concentration in the blood plasma is reached after 2 weeks. Linearity/non-linearity. The pharmacokinetics are linear and do not depend on time in the range of studied doses (2.5-60 mg per day). According to the half-life, the accumulation index is 5 to 6 based on an AUC of 0-24 after multiple doses of 5 to 20 mg per day. Elderly patients. In elderly healthy volunteers (aged ≥ 65 years, n = 20), the effect of vortioxetine increased by 27% (Cmax and AUC) compared to young healthy control volunteers (aged ≤ 45 years) after several doses of 10 mg per day. No dose adjustment is required. Kidney failure. After a single dose of 10 mg of vortioxetine, renal failure (according to the Cockcroft-Gault formula, mild, moderate or severe, n = 8 in the group) caused a slight increase in exposure (up to 30%) compared to that in the control group of healthy volunteers. In patients with end-stage renal failure, only a small fraction of vortioxetine was lost during the dialysis process (AUC and Cmax were 13% and 27% lower; n = 8) after a single dose of 10 mg of vortioxetine. No dose adjustment is required. Liver failure. After a single dose of 10 mg of vortioxetine, no effect of mild or moderate hepatic insufficiency (Child-Pugh, criteria A and B; n=8 in each group) on the pharmacokinetics of vortioxetine was observed (AUC changes were less than 10%). No dose adjustment is required. Vortioxetine has not been studied in patients with severe hepatic insufficiency, and caution should be exercised when prescribing it to these patients. Weak metabolizers of CYP2D6. In weak CYP2D6 metabolizers, the plasma concentration of vortioxetine was approximately twice as high as in extensive metabolizers. In the presence of potent CYP3A4/2C9 inhibitors, the effect can potentially be higher. Dose adjustment may be necessary, as for all patients, depending on the individual response. Pharmacodynamics Mechanism of action. The mechanism of action of vortioxetine is believed to be related to its multimodal activity, which is a combination of two pharmacological mechanisms: direct modulation of receptor activity and inhibition of the serotonin transporter (5-HT). Preclinical data show that vortioxetine is an antagonist of the 5-HT3,5-HT7 and 5-HT1D receptors, a partial agonist of the 5-HT1B receptors, an agonist of the 5-HT1A receptors and an inhibitor of the 5-HT transporter, and modulates neurotransmission in several systems, including serotonin, norepinephrine, dopamine, histamine, acetylcholine, GABA and glutamate. Such multimodal activity is believed to provide antidepressant and anxiolytic effects, as well as improvements in cognitive function, learning, and memory in preclinical studies of vortioxetine. In addition, preclinical studies indicate that vortioxetine does not cause sexual dysfunction. The exact contribution of each component of this mechanism to the observed pharmacodynamic profile remains unclear, so attention should be paid to extrapolating preclinical data directly to humans. It was found that the uptake of the serotonin transporter by various daily doses of vortioxetine was approximately 50% – at a dose of 5 mg,65% – at a dose of 10 mg, and more than 80% – at a dose of 20 mg. Vortioxetine clinically showed an antidepressant effect when capturing the 5-HT transporter by 50%. Clinical efficacy and safety. The effectiveness of vortioxetine increases with increasing dose. In addition, vortioxetine in the 5-20 mg dose range demonstrated efficacy in a wide range of depressive (MADRS) and anxious (HAM-A) symptoms of depression. Prevention of relapses. The duration of the antidepressant effect was demonstrated in a relapse prevention study, in which twice the risk of relapse was determined in the placebo group than in the vortioxetine group. Elderly patients. In the dose range of vortioxetine from 5 to 20 mg per day, the efficacy and tolerability in the elderly corresponded to the results of studies in the adult population. Patients with severe depression or high levels of anxiety symptoms. Antidepressant efficacy has also been demonstrated in patients with severe depression (≥30 MADRS points) and in depressed patients with high levels of anxiety symptoms (≥ 20 HAM-A points) in short-term studies, including studies in elderly patients, and long-term relapse prevention studies. Patients with inadequate response to SSRI / SIZZD treatment. In a comparative study of flexible doses in patients with depression after an inadequate response to treatment of an existing SSRI / SIZZD episode, vortioxetine at a daily dose of 10-20 mg was statistically significantly more effective than agomelatine at a dose of 25-50 mg (on the MADRS scale), the clinical significance was proved on the CGI-I and SDS scales. Cognitive dysfunction in depression. In studies of the drug’s effect on cognitive processes, it turned out that the effect of vortioxetine is mainly due to direct effects on cognitive function, rather than indirect effects through improving symptoms of depression. Quality of life and overall functioning. Vortioxetine was superior to placebo in terms of quality of life, clinically significantly improved overall health (on the EQ-5D scale) and overall functioning (on the SDS scale – work, social and family life) compared to placebo or the active comparator (agomelatine). Moreover, the best quality-of-life effects compared to placebo were maintained during the long-term relapse prevention trial. Portability and security. The safety and tolerability of vortioxetine were evaluated in short – and long-term studies at doses of 5-20 mg per day. Vortioxetine did NOT increase the incidence of insomnia or drowsiness compared to placebo. In a systematic evaluation of potential withdrawal symptoms, there was no clinically significant difference between vortioxetine and placebo in the frequency and nature of withdrawal symptoms, either after a short-term (6-12 weeks) or after a long-term (24-64 weeks) treatment period. In clinical trials with vortioxetine, the frequency of reported unwanted sexual reactions was low and similar to placebo, the frequency of therapy-related sexual dysfunction and overall ASEX scores did not have clinically significant differences with placebo in terms of symptoms of sexual dysfunction when using the recommended dose of vortioxetine, but high doses were associated with a numerical increase in cases of dysfunction. Similar to placebo, vortioxetine had no effect on body weight, heart rate, or blood pressure in clinical trials. There were no clinically significant changes in liver and kidney function scores during clinical trials. Vortioxetine did not have any clinically significant effect on ECG parameters, including QT, QTc, PR, and QRS intervals, in patients with major depressive disorder. In a thorough QTc study among healthy volunteers, no potential for an increase in the QTc interval was observed at doses up to 40 mg per day. Children’s age. No clinical studies have been conducted in paediatric patients, hence the safety and efficacy of the drug. Brintellix for patients under 18 years of age have not been established.

Indications

Treatment of major depressive disorder in adults.

Recommendations for use

Inside, regardless of the meal. Dosage regimen. The initial and recommended dose of Brintellix in adult patients under 65 years of age is 10 mg once a day. Depending on the individual response of the patient, the daily dose of vortioxetine can be increased to a maximum dose of 20 mg once a day or reduced to a minimum dose of 5 mg 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 can stop taking it at once without the need for a gradual dose reduction.

Side effects

The most common adverse reaction was nausea. Adverse reactions were usually mild or moderate and were observed during the first two weeks of treatment. Reactions were usually transient and usually did not lead to discontinuation of therapy. Digestive disorders (such as nausea) were more common in women than in men.

Interaction

Vortioxetine is metabolized in the liver mainly by oxidation and subsequent conjugation with glucuronic acid. In vitro, cytochrome P 450 isoenzymes CYP2D6, CYP3A4/5, CYP2C19, CYP2C9, CYP2A6, CYP2C8, and CYP2B6 are involved in the metabolism of vortioxetine. The effect of other drugs on the action of vortioxetine. Irreversible non-selective MAO inhibitors Due to the risk of serotonin syndrome, vortioxetine is contraindicated in any combination with irreversible non-selective MAO inhibitors. Treatment with vortioxetine should not be started earlier than at least 14 days after discontinuation of treatment with irreversible non-selective MAO inhibitors. Vortioxetine should be discontinued at least 14 days before starting treatment with irreversible non-selective MAO inhibitors. Reverse selective MAO-A inhibitor (moclobemide). The combination of vortioxetine with a reverse selective MAO-A inhibitor, such as moclobemide, is contraindicated. Careful monitoring of serotonin syndrome with simultaneous use is necessary. Reverse nonselective MAO inhibitor (linezolid). The combination of vortioxetine with a weak reversible and non-selective MAO inhibitor, such as the antibiotic linezolid, is contraindicated. Careful monitoring of serotonin syndrome with simultaneous use is necessary. Non-current selective MAO-B inhibitors (selegiline, rasagiline). Although the expected risk of serotonin syndrome is lower (than with MAO-A inhibitors), the combination of vortioxetine with irreversible MAO-B inhibitors, such as selegiline or rasagiline, should be carried out with caution. Careful monitoring of serotonin syndrome with simultaneous use is necessary. Serotonergic drugs. Concomitant use with serotonergic medications (such as tramadol, sumatriptan, and other triptans) may lead to serotonin syndrome. St. John’s wort. Concomitant use of serotonergic antidepressants and herbal remedies containing St. John’s wort may increase the frequency of adverse reactions, including serotonin syndrome. Medications that lower the seizure threshold. Serotonergic antidepressants may lower the seizure alert threshold. Caution is recommended when concomitantly using other medications that can lower the seizure threshold (such as antidepressants (TCAS, SSRIs, SIZZLS), neuroleptics (phenothiazines, thioxanthenes, butyrophenones), mefloquine, bupropion, and tramadol). ECT (Electroconvulsive therapy). There is no clinical experience of concomitant use of vortioxetine with ECT, so caution is advisable. Cytochrome P 450 inhibitors. When administered together with 150 mg of bupropion (a strong CYP2D6 inhibitor) twice daily for 14 days in healthy volunteers, the effect of vortioxetine increased 2.3-fold for AUC. Co-use was more likely to increase the frequency of side effects when bupropion was added to vortioxetine than when vortioxetine was added to bupropion. Depending on the individual sensitivity of the patient, when adding strong CYP2D6 inhibitors (for example, bupropion, quinidine, fluoxetine, paroxetine) to therapy, the use of low doses of vortioxetine may be considered. When vortioxetine was co-administered after 6 days of ketoconazole 400 mg / day (a CYP3A4/5 and P-glycoprotein inhibitor) or fluconazole 200 mg / day (a CYP2C9, CYP2C19, and CYP3A4 / 5 inhibitor), a 1.3-and 1.5-fold increase in vortioxetine AUC was observed in healthy volunteers, respectively. No dose adjustment is required. The effect of a single 40 mg dose of omeprazole (a CYP2C19 inhibitor) on the pharmacokinetics of long-term use of vortioxetine in healthy volunteers was not observed. The combination of potent CYP3A4 and CYP2C9 inhibitors in patients with low CYP2D6 metabolism has not been studied, but an increased effect of vortioxetine on such patients is likely to be expected. Cytochrome P 450 inducers. With a single dose of 20 mg of vortioxetine co-administered after 10 days of rifampicin 600 mg per day (an inducer of CYP isoenzymes), a 72% decrease in vortioxetine AUC was observed in healthy volunteers. Depending on the individual patient response, a dose adjustment may be necessary if a cytochrome P450 inducer (e. g. rifampicin, carbamazepine, phenytoin) is added to treatment with vortioxetine. Acetylsalicylic acid. The effect of repeated use of acetylsalicylic acid 150 mg per day on the pharmacokinetics of vortioxetine in healthy volunteers was not observed. The effect of vortioxetine on the action of other drugs. Anticoagulants and antiplatelet agents. There were no significant effects on the international normalized ratio, prothrombin or R- / S-warfarin plasma values compared to placebo when vortioxetine was co-administered with a fixed dose of warfarin in healthy volunteers. In addition, there was no significant inhibitory effect on platelet aggregation compared to placebo when co-administered aspirin at a dose of 150 mg per day after taking vortioxetine in healthy volunteers. However, as with other serotonergic agents, caution should be exercised when using vortioxetine in combination with oral anticoagulants or antiplatelet agents due to the potential increased risk of bleeding due to pharmacodynamic interactions. Alcohol. No effect on the pharmacokinetics of vortioxetine or ethanol, as well as a significant impairment of cognitive function compared to placebo after the use of vortioxetine in doses of 20 mg or 40 mg with simultaneous single use of ethanol 0.6 g/kg in healthy volunteers was found. However, like other drugs acting on the central nervous system, it is not recommended to use vortioxetine in combination with alcohol. Cytochrome P450 substrates. In vitro, vortioxetine showed no potential for inhibition or induction of cytochrome P450 isoenzymes. The inhibitory effect of vortioxetine on cytochrome P 450 isoenzymes CYP2C19 (omeprazole, diazepam), CYP3A4/5 (ethinyl estradiol, midazolam), CYP2B6 (bupropion), CYP2C9 (tolbutamide, S-warfarin), CYP1A2 (caffeine) or CYP2D6 (dextromethorphan) in healthy volunteers was found. There was no significant cognitive impairment compared to placebo after using vortioxetine concomitantly with 10 mg of diazepam. There was no significant effect on sex hormone levels compared to placebo after concomitant use of vortioxetine with a combined oral contraceptive (ethinyl estradiol 30 mcg / levonorgestrel 150 mcg). Lithium, tryptophan. There was no clinically significant effect of exposure to stable lithium concentrations after concomitant use with vortioxetine in healthy volunteers. However, there have been reports of increased effects when using serotonergic antidepressants together with lithium or tryptophan, so the simultaneous use of vortioxetine with these drugs should be carried out with caution.

Overdose

Experience is limited. Taking vortioxetine in the dose range from 40 to 75 mg caused an exacerbation of the following side effects: nausea, postural dizziness, diarrhea, abdominal discomfort, generalized itching, drowsiness and blushing. Treatment should be symptomatic and include appropriate monitoring. Medical supervision in specialized settings is recommended.

Active ingredient

Vortioxetine

Conditions of release from pharmacies

By prescription

Dosage form

Tablets

Purpose

For adults as directed by your doctor

Indications

Depression