Index of drugs

Treatment of major depressive episodes in adults.

1 tabl powl. contains 10 mg vortioxetine in the form of hydrobromide.

Antidepressant. The mechanism of action of vortioxetine is believed to be associated with the modulation of serotoninergic receptor activity and inhibition of serotonin (5-HT) carrier activity. Vortioxetine is an antagonist of 5-HT receptors₃, 5-HT₇ and 5-HT_1D, a partial agonist of the 5-HT receptor_1B, a 5-HT receptor agonist_1A and a 5-HT transporter inhibitor, leading to the modulation of neurotransmission in several systems, including mainly in the serotonin system, but probably also norepinephrine, Dopamine, histamine, acetylcholine, GABA and glutamate. It is believed that this multiple activity of vortioxetine is responsible for its antidepressant and anxiolytic activity and for improving the cognitive functions, learning and memory observed under the influence of vortioxetine in animal studies. However, the exact contribution of individual target sites to its observed pharmacodynamic profile remains unclear and care should be taken extrapolating the results obtained in animal studies directly on humans. After oral administration, vortioxetine is well absorbed, although slowly absorbed, and C_maxoccurs within 7-11 h. Absolute bioavailability is 75%. Vortioxetine is highly bound to plasma proteins (98-99%). It is extensively metabolised in the liver, mainly by oxidation catalyzed by CYP2D6, and to a lesser extent by CYP3A4 / 5 and CYP2C9, followed by conjugation with glucuronic acid. The main metabolite is pharmacologically inactive. Medium T_0,5 elimination is 66 h. Approx. 2/3 of the inactive metabolites of vortioxetine are excreted in the urine and about 1/3 in the faeces. Plasma concentrations at steady-state are achieved after approximately 2 weeks.

Hypersensitivity to the active substance or to any of the excipients. Concomitant use of non-selective MAO inhibitors or selective MAO-A inhibitors.

The drug is not recommended in patients under 18 years of age, because the safety and efficacy of vortioxetine have not been established in this age group. In clinical trials in children and adolescents treated with other antidepressants, suicidal behavior (suicide attempts and suicidal thoughts) and hostility (mainly aggression, rebellious behavior, anger) were observed more frequently than in patients treated with placebo. Depression is associated with an increased risk of suicidal thoughts, self-harm and suicide (events related to suicide). This risk persists until significant remission. Patients should remain under strict control until improvement occurs and at an early stage of recovery (increased risk of suicide). In patients with a history of suicide-related events or those with severe suicidal thoughts, the risk of suicidal thoughts or attempts is higher before commencing treatment, and therefore should be closely monitored during treatment, particularly patients under 25 years of age. During treatment, especially at an early stage and after dose changes, close supervision of patients, especially those at high risk, should be ensured. Due to the risk of seizures, care should be taken when initiating therapy with patients with a history of seizures or patients with unstable epilepsy. Treatment should always be discontinued if the patient has fits or if their incidence increases. The use of the drug may result in serotonin syndrome (SS) or neuroleptic malignant syndrome (NMS), potentially life-threatening diseases. The risk of SS or NMS increases with concomitant use of serotonergic active substances (including triptans), drugs that interfere with serotonin metabolism (including MAO inhibitors), antipsychotics and other Dopamine antagonists. Patients should be monitored for signs and symptoms of SS or NMS.If these symptoms occur, treatment should be discontinued immediately and symptomatic treatment initiated. It should be used with caution in patients with a history of mania / mild manic episode and should be discontinued if the patient enters the manic phase. Because of the risk of abnormal bleeding, caution is advised in patients taking anticoagulants and / or drugs with known effects on platelet function (eg, atypical antipsychotics and phenothiazines, most tricyclic antidepressants, NSAIDs, acetylsalicylic acid) and in patients with known bleeding tendency / bleeding disorders. Caution should be exercised in patients with risk factors for hyponatremia, such as the elderly, cirrhotic patients or patients taking medications known to induce hyponatremia. Discontinuation of the preparation should be considered in patients with symptoms of hyponatremia and appropriate medical treatment should be instituted. Due to limited data, caution should be used when treating patients ≥65 years old with doses greater than 10 mg once a day. Caution is required in patients with severe renal impairment and in patients with severe hepatic impairment (limited data).

It should not be used during pregnancy unless the mother's clinical condition requires treatment with vortioxetine. After the use of serotonergic drugs by the mother in late pregnancy, the following symptoms may occur in the newborn: respiratory distress syndrome, cyanosis, apnea, convulsions, unstable body temperature, difficulty in taking food, vomiting, hypoglycaemia, hypertonia, hypotension, hyperreflexia, tremor, jitter , irritability, lethargy, constant crying, drowsiness and difficulty sleeping. These symptoms may be due to drug discontinuation or excessive serotoninergic effects. In most cases, these complications occur directly or soon (<24 h) after delivery. Epidemiological data suggest that the use of SSR inhibitors in pregnancy, especially at a later stage, may increase the risk of persistent pulmonary hypertension in newborns (PPHN) - this risk can not be excluded for vortioxetine. It is to be expected that vortioxetine will be excreted in human milk. A danger for breastfed babies can not be excluded. A decision should be made whether to discontinue breast-feeding or discontinue the drug, taking into account the benefits of breastfeeding for the child and the benefits of treatment for the mother. There have been reports of isolated cases of transient effects on sperm quality of a related class of antidepressants (SSRIs). So far, the effect of vortioxetine on human fertility has not been observed.

Very often: nausea. Common: decreased appetite, unusual dreams, dizziness, diarrhea, constipation, vomiting, generalized pruritus. Uncommon: bruxism, redness of the face, night sweats. After 20 mg once daily, the incidence of nausea and constipation was higher in patients ≥65 years of age than in patients <65 years of age. In clinical trials, sexual dysfunction was assessed using the ASEX scale. Doses of 5 to 15 mg showed no difference with placebo. However, the 20 mg dose was associated with an increase in sexual dysfunction resulting from treatment. Epidemiological studies, mainly in patients aged 50 years and older, show an increased risk of bone fractures in people receiving medicines of the related class of antidepressants (SSRI or TCA). The mechanism of occurrence of this risk is unknown and it is not known whether this risk also occurs after the use of vortioxetine.

Orally. Adults (under 65 years of age): The initial recommended dose is 10 mg once a day. Depending on the patient's individual response to treatment, the dose can be increased to a maximum of 20 mg once a day or reduced to a minimum dose of 5 mg once a day. After the depressive symptoms have resolved, it is recommended to continue treatment for at least 6 months to consolidate the antidepressant response. Patients treated with the product may discontinue its use in an urgent manner, without the need to gradually reduce the dose. In patients ≥65 years of age, the lowest effective dose - 5 mg once a day - should always be used as the starting dose.Caution should be exercised when treating patients ≥65 years old with doses greater than 10 mg once a day, due to limited data. Depending on the patient's individual response to treatment, a lower dose of vortioxantine may be considered if a strong CYP2D6 inhibitor (eg bupropion, quinidine, Fluoxetine, paroxetine) is added to the treatment. Depending on the patient's individual response to treatment, dose adjustment of vortioxetine may be considered if a broad range of cytochrome P450 inducer (eg rifampicin, carbamazepine, phenytoin) is added to the treatment. Table. powl. can be taken regardless of the meal.