Agomelatine - instructions for use, dose, side effects, contraindications

Clinical and pharmacological group: & nbsp

Antidepressants

Included in the formulation

Valdoxane®

pills inwards

Servier Laboratories France

Included in the list (Order of the Government of the Russian Federation No. 2782-r of 30.12.2014):

VED

АТХ:

N.06.A.X Other antidepressants

Pharmacodynamics:

Stimulates melatonin (both types: MT1 and MT2) and blocks serotonin 5-HT2C receptors.

Due to the antagonistic effect on serotonin receptors, the drug causes the release of dopamine and norepinephrine, especially in the prefrontal cortex, which causes an antidepressant effect. Influence on melatonin receptors provides restoration of circadian (daily) rhythms of an organism, improves quality of a dream at a chronic stress and depression, eliminates insomnia. The drug does not interfere with the normal structure of sleep.

Pharmacokinetics:Quickly and almost completely (more than 80%) is absorbed when taken orally, reaching a maximum concentration in the blood after 1-2 hours, but quickly breaks down in the liver. The total bioavailability is 3-5%. Binding to plasma proteins - 95%. Metabolites of agomelatine are pharmacologically inactive and are excreted from the body by the kidneys (with urine). Half-life is 1-2 hours.

Indications:Treatment of major depressive disorder in adults.

ICD-10

V.F30-F39.F31 Bipolar affective disorder

V.F30-F39.F32 Depressive episode

V.F40-F48.F41.2 Mixed anxiety and depressive disorder

V.F30-F39.F33 Recurrent depressive disorder

Contraindications:Hepatic insufficiency, cirrhosis, liver disease in the active phase; simultaneous use of strong inhibitors of cytochrome CYP1A2 (such as fluvoxamine, ciprofloxacin); alcohol abuse, children and adolescence under 18; hypersensitivity to agomelatine or any of the excipients of the drug; patients with lactose intolerance: lactase deficiency, galactosemia and glucosogalactose malabsorption.

Carefully:

For the elderly (over 65 years), the amount of clinical data is limited, and the effectiveness of the drug has not been reliably shown, therefore, agomelatine carefully.

In the treatment of bipolar disease, the drug can provoke a hypomanic episode, so caution is needed in the treatment of such patients.

Because of limited clinical experience, caution should be exercised in prescribing agomelatine to patients with moderate and severe renal failure.

Patients who consume alcohol in significant quantities or who take drugs that can cause liver dysfunction.

Pregnancy and lactation:

The action category for fetus by FDA is B.

Data on the use of agomelatine in pregnancy are absent. If necessary, use in pregnancy requires caution and careful evaluation of the expected benefit of therapy for the mother and the possible risk to the fetus.

If it is necessary to use agomelatine during lactation, breastfeeding should be discontinued.

In experimental animal studies, there was no direct or indirect adverse effect on the course of pregnancy, embryo and fetus development, labor and postnatal development. It was shown that agomelatine and its metabolites are excreted in breast milk.

Dosing and Administration:

Inside, regardless of food intake, the tablet should be swallowed whole, without chewing. The recommended dose is 25 mg once a day (in the evening). The maximum daily dose is 50 mg 1 time (in the evening).

With mild and moderate hepatic insufficiency, the daily dose is 25 mg.

If you skip the next dose of the drug, during the next dose, its dose should not be increased.The drug is discontinued on the recommendation of the doctor after the patient's condition is normalized.

Drug therapy for depression should be carried out at least for another 6 months after the complete cessation of symptoms.

To stop treatment, there is no need for a gradual dose reduction.

Side effects:

From the side of the central nervous system: often - anxiety, headache, dizziness, drowsiness, insomnia, migraine; infrequently paresthesia; unspecified frequency - suicidal thoughts and behavior.

From the digestive system: often - nausea, diarrhea, constipation, epigastric pain, increased ALT and / or ACT activity more than 3 times compared with VGN; rarely - hepatitis.

Dermatological reactions: often - sweating; infrequently eczema; rarely erythematous rash.

From the side of the organ of vision: infrequently - indistinct vision.

From the organ of hearing: infrequently, noise in the ears.

From the musculoskeletal system: often - pain in the region back.

Other: often fatigue.

Overdose:

Data on an overdose of agomelatine are limited.

Symptoms: drowsiness, epigastric pain, anxiety, weakness, anxiety, agitation, stress, dizziness, cyanosis, malaise.

Treatment: Specific antidotes for agomelatine are unknown.Symptomatic treatment and monitoring in specialized departments with follow-up is recommended.

Interaction:

Agomelatine is metabolized in the liver with the participation of predominantly isoenzymes CYP1A2 (90%) and with the participation of CYP2C9 / 19 (10%). Therefore, any drugs whose metabolism depends on these isoenzymes (grapafloxacin, propranolol, fluvoxamine, ciprofloxacin, enoxacin and others), may increase or decrease the bioavailability of agomelatine.

Simultaneous use of agomelatine and estrogens, which are moderate inhibitors of the isoenzyme CYP1A2, leads to an increase in the concentration of agomelatine by several times. Rifampicin, as an inducer of both cytochromes involved in the metabolism of agomelatine, can lower the bioavailability of agomelatine.

Bioavailability of agomelatine increases with oral contraceptives and decreases with smoking.

It is not recommended to use agomelatine together with ethanol.

Special instructions:

There have been reports of liver damage, including liver failure (leading to death in exceptional cases or requiring liver transplantation in patients with pre-existingrisk factors for liver damage), increase in the level of hepatic enzymes by more than 10 times relative to VGN, hepatitis and jaundice in patients taking agomelatine, in the post-registration period. Most of these disorders occurred during the first months of treatment. The nature of the liver lesion is mainly hepatocellular. As a rule, after discontinuation of therapy, transaminase levels returned to normal values. It is recommended to monitor liver function at the beginning of therapy and then periodically, at 3, 6 (end of the period of therapy), 12 and 24 weeks (end of maintenance period) after initiation of therapy, and subsequently in accordance with the clinical situation. With increasing doses, liver function should be monitored at the same frequency as at the beginning of the drug.

When the activity of transaminases in the blood serum increases, a re-examination should be carried out within 48 hours. If the activity of transaminases is more than 3 times higher than UGN, the drug should be discontinued. In the future, it is necessary to regularly monitor the functional state of the liver prior to the normalization of transaminase activity.

If symptoms and signs of possible violations of the liver function (such as dark urine, discolored stool, yellowness of the skin / eye, pain in the right upper abdomen, recently appeared permanent and unexplained fatigue), the drug should be stopped immediately.

Care should be taken when prescribing the drug to patients with risk factors for liver dysfunction, such as obesity (overweight), non-alcoholic fatty hepatosis, diabetes, the use of alcohol in significant quantities or the taking of drugs that can cause a violation of liver function.

Efficacy of the drug in elderly patients (aged 75 years and older) is not established. Concerning agomelatine Do not prescribe to patients of this age group.

Do not prescribe a drug to treat major depressive episodes in elderly patients with dementia (due to lack of data on the efficacy and safety of the drug in this group of patients).

In patients with severe renal insufficiency no significant change in pharmacokinetic parameters was noted.However, experience with the use of agomelatine in large depressive episodes in patients with moderate to severe renal failure is limited. When prescribing the drug, such patients should be careful.

Caution should be exercised when using agomelatine in patients with bipolar disorder, manic or hypomanic episodes in the anamnesis. When symptoms of mania appear, stop taking the drug.

In a depressed state, the risk of suicidal thoughts, self-harm and suicide (events associated with suicide) is increased. The risk persists until a distinct remission occurs. Patients should be under medical supervision until the condition improves (after the start of therapy, it may take several weeks before the condition improves). Clinical experience indicates that the risk of suicide may increase in the early stages of the onset of remission.

Studies to study the effect of agomelatine on the ability to drive and other mechanisms have not been carried out. It should be remembered that dizziness and drowsiness are frequent side effects of agomelatine.

Instructions

Agomelatine (Agomelatinum)