1 tabl powl. contains 25 mg of agomelatine. The preparation contains lactose.
Action:
Antidepressant - a melatonergic agonist (MT receptors1 and MT2) and a 5-HT receptor antagonist2C. Studies show that agomelatine has no effect on monoamine uptake and has no affinity for the α- and β-adrenergic, histaminergic, cholinergic, dopaminergic and benzodiazepine receptors. The drug restores the circadian rhythm in animal models of disturbed circadian rhythm. Agomelatine increases the release of norepinephrine and Dopamine, especially in the frontal cortex, and has no effect on extracellular serotonin levels. The effect of agomelatine similar to the antidepressant effect in animal models of depression (learned helplessness test, despair test, chronic moderate stress), as well as in circadian rhythm desynchronization models and in models related to stress and anxiety has been demonstrated. In humans, the preparation exhibits positive phase shifts, induces an accelerated sleep phase, a decrease in body temperature and the onset of melatonin. After oral administration, the drug is absorbed quickly and well (≥80%) from the gastrointestinal tract. Total bioavailability is low (<5% of the oral dose) and interindividual variability is significant. Biological availability is higher in women than in men. Bioavailability increases the use of oral contraceptives, and reduces smoking. The maximum plasma concentration is reached within 1-2 h. The degree of binding to plasma proteins is 95%. Following oral administration, agomelatine is rapidly metabolised primarily by the hepatic CYP1A2 isoenzyme; CYP2C9 and CYP2C19 are also involved in metabolism, but to a lesser extent. The main metabolites, hydroxylated and demethylated agomelatine derivatives are inactive and are rapidly coupled and excreted in the urine. Medium T0,5 in the plasma is 1-2 h. Excretion occurs mainly in the urine (80%) and in the form of metabolites.
Contraindications:
Hypersensitivity to the active substance or to any of the excipients. Hepatic impairment (ie cirrhosis or active liver disease); patients with serum transaminases above 3-fold ULN. Co-administration with strong CYP1A2 inhibitors (eg fluvoxamine, ciprofloxacin).
Precautions:
Due to the risk of liver damage, caution should be exercised before starting treatment, and all patients should be carefully monitored throughout the course of therapy, especially if there are risk factors for liver damage or if there are medicines used to treat liver damage at the same time. In patients with risk factors for liver damage, e.g. obesity, overweight, non-alcoholic steatohepatitis, diabetes, high alcohol intake or concomitant medications, the use of which may lead to liver damage, treatment with the preparation may only be recommended after careful consideration of benefits and risks. Liver function tests should be performed in all patients and treatment should not be initiated in patients with ALT and / or AST> 3-fold GGN. Caution should be exercised when administering the preparation to patients with elevated aminotransferase levels prior to treatment (> GGN values and ≤ 3-fold GGN values). Liver function should be investigated: before starting treatment; then: about 3 weeks, after about 6 weeks (the end of the acute phase), after about 12 and 24 weeks (end of the maintenance phase) and later, when it is clinically indicated. When increasing the dosage, liver function tests should be performed again at the same frequency as when starting treatment. In any patient who develops serum transaminases, hepatic function tests should be repeated within 48 h. Treatment should be discontinued immediately if: signs or symptoms of potential liver damage (such as dark urine, light faeces, yellowing of the skin or eyes, pain in the right upper abdomen, persistent and unexplained fatigue); serum transaminase activity is 3-fold higher than ULN. After discontinuation of treatment with the product, liver function tests should be repeated until serum aminotransferase levels return to normal. The preparation is not recommended for the treatment of depression in patients under 18 years of age because the safety and efficacy of the medicine in this age group has not been established.In clinical trials of children and adolescents treated with other antidepressants, suicide-related behaviors (suicide attempts and suicidal thoughts) and hostility (mainly aggression, opposition and anger) were more frequently observed than patients receiving placebo. No effect has been documented in patients ≥75 years, therefore agomelatine should not be used by patients in this age group. It should not be used in the treatment of major depressive episodes in elderly patients with dementia, as the safety and efficacy of the medicine have not been established. It should be used with caution in patients with a history of bipolar disorder, mania or hypomania, and treatment should be discontinued if the patient develops symptoms of mania. Depression is associated with an increased risk of suicidal thoughts, self-injury and suicide. The risk persists until significant remission is achieved. Patients should be closely monitored until significant improvement is achieved and in the early stages of recovery (increased risk of suicide). Patients with a history of suicide or a history of significant suicidal ideation are considered to be at increased risk of suicidal thoughts or suicide attempts and should be closely monitored during treatment, especially those under 25 years of age. During treatment, especially at the beginning of therapy and after dose changes, patients should be closely monitored, particularly those at high risk. Caution should be exercised in patients with severe or moderate renal impairment, as only limited clinical data regarding them are available. The preparation contains lactose - should not be used in patients with rare inherited disorders associated with galactose intolerance, Lapp lactase deficiency or malabsorption of Glucose and galactose.
Pregnancy and lactation:
It is recommended to avoid the use during pregnancy. You should decide whether to stop breastfeeding, to stop the treatment or not to use the preparation, taking into account the benefit of breastfeeding for a child and the benefit of treatment for a woman.
Side effects:
Common: anxiety, headache and dizziness, drowsiness, insomnia, migraine, nausea, diarrhea, constipation, abdominal pain, vomiting, increased ALT and / or AST (increase> 3-fold GGN for ALT and / or AST) in 1.4% of patients taking a dose of 25 mg / day and in 2.5% of patients taking a dose of 50 mg / day), increased sweating, back pain, tiredness. Uncommon: agitation and related symptoms (such as irritability and anxiety), aggression, nightmares, unusual dreams, paresthesia, blurred vision, eczema, pruritus, urticaria. Rare: mania / hypomania (may also be caused by the underlying disease), hepatitis, increased GGT (> 3-fold GGN), increased alkaline phosphatase (> 3-fold GGN), hepatic failure (several cases have been reported) death or requiring liver transplantation regarding patients with risk factors for liver damage), jaundice, erythematous rash, facial edema and angioneurotic edema, weight gain, weight loss. Frequency unknown: suicidal thoughts and behaviors.
Dosage:
Orally. Adults: the recommended dose is 25 mg once a day, in the evening before bedtime. After 2 weeks of treatment, if there is no improvement, the dose may be increased to 50 mg once a day (2 tables before bedtime). When deciding to increase the dose, the higher risk of transaminase elevation should be considered. Any increase in the dose to 50 mg should be based on an individual patient's risk-benefit assessment and strict adherence to monitoring of liver function tests. Patients with depression should be treated for at least 6 months. No gradual dose reduction is required to discontinue treatment. Change in treatment with an SSRI / SNRI antidepressant to agomelatine: discontinuation symptoms may occur in patients after discontinuation of SSRI / SNRI antidepressants. To avoid them, check the currently used SSRI / SNRI group in the SmPC, how to stop it. Administration of agomelatine can be started immediately while reducing the SSRI / SNRI dose.The efficacy and safety of agomelatine (25-50 mg / day) in elderly patients (<75 years) with depression has been established; drug effects are not documented in patients ≥75 years - do not use the drug in this age group. The preparation can be taken regardless of the meal.
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