Mirzaten Ku-tab - instructions for use, dose, side effects, contraindications

Excipients: lactose monohydrate, ethylcellulose, pharmacistur Cl (SP1 Pharma) (mixture: 65% -82% mannitol (Ph.Eur.), 5-14% sorbitol (Ph.Eur.), 8% -20% crospovidone (Ph.Eur.) and 0.1% to 2% of silicon dioxide colloidal (NF)), aroma orange, aspartame, magnesium stearate.

Description:

Tablets 15 mg, 30 mg and 45 mg: round, slightly biconvex tablets of white color with a bevel.

Pharmacotherapeutic group:antidepressant

ATX: & nbsp

N.06.A.X.11 Mirtazapine

Pharmacodynamics:

Mirtazapine is a drug from the group of antidepressants, is an antagonist of presynaptic α₂-adrenoceptors of central action, enhancing central noradrenergic and serotonergic (through 5-HT₁ serotonin receptors) transmission of nerve impulses. Mirtazapine blocks 5-HT₂ and 5-HT₃-serotonin receptors. In the manifestation of antidepressant activity both spatial enantiomers participate: S (+) - enantiomer blocks α₂-adreno and 5-HT₂-serotonin receptors, R(-) - enantiomer - 5-HT₃-serotonin receptors.

Sedative properties of mirtazapine are due to its antagonistic activity in relation to H₁-histamine receptors.

Mirtazapine is usually well tolerated. In therapeutic doses, it has almost no anticholinergic effect and practically no effect on the cardiovascular system.

There are also anxiolytic and hypnotic properties, so mirtazapine is most effective in anxiety depressions of different genesis.

Antidepressant effect is manifested after 1-2 weeks of treatment.

Pharmacokinetics:

After taking mirtazapine quickly absorbed (bioavailability of about 50%), reaching a maximum concentration in the blood plasma after about 2 hours. About 85% of mirtazapine binds to plasma proteins. The mean half-life (T_1/2) is from 20 to 40 hours (rarely up to 65 hours), which allows you to take the drug 1 time per day. A shorter T_1/2 observed in young people. The equilibrium concentration is established after 3-5 days. In the recommended dosage range, the pharmacokinetic parameters of mirtazapine are linear.

Mirtazapine is actively metabolized and excreted by the kidneys and intestines for several days. The main ways of its metabolism in the body are demethylation and oxidation followed by conjugation. Cytochrome P450-dependent enzymes CYP2D6 and CYP1A2 participate in the formation of 8-hydroxy metabolite mirtazapine, while CYP3A4 presumably determines education N-detylated and Noxidized metabolites. Demethyl-mirtazapine is pharmacologically active and appears to be pharmacokinetically similar to the parent compound.

The clearance of mirtazapine decreases with renal or hepatic insufficiency.

Indications:

Depressive states of various etiologies.

Contraindications:

- Hypersensitivity to mirtazapine or other components of the drug;

- simultaneous administration with monoamine oxidase (MAO) inhibitors and within 2 weeks after their withdrawal;

- age under 18 years (effectiveness and safety not established);

- lactation period;

- patients with galactosemia, with deficiency of Lapta lactase or glucose-galactose malabsorption syndrome;

- patients with intolerance to fructose, sucrase-isomaltase deficiency;

- phenylketonuria.

Carefully:

- Epilepsy and organic lesions of the brain (against the background of drug therapy mirtazapine, in rare cases, the development of convulsive conditions is possible);

- hepatic or renal insufficiency (of moderate and severe severity);

- heart disease (ciliary tachyarrhythmia, conduction disorders, stress angina or recent myocardial infarction);

- arterial hypotension and conditions predisposing to hypotension (including dehydration and hypovolemia);

- drug dependence and propensity to abuse psychoactive drugs (in the anamnesis), depressive phase of manic-depressive psychosis, hypomania;

- schizophrenia or other psychotic disorders;

- obstructive disorders of the intestine and violation of urination, including with prostatic hyperplasia;

- acute angle-closure glaucoma and increased intraocular pressure;

- diabetes;

- elderly patients;

- suicidal events in the anamnesis;

- pregnancy.

Pregnancy and lactation:

The safety of the use of the drug mirtazapine in pregnancy is not established, so it can be used during pregnancy only if the benefit to the mother exceeds the potential risk to the fetus and under the supervision of the doctor.

The use of the drug during lactation and breast-feeding is not recommended (there is no data on excretion of the drug with breast milk).

Dosing and Administration:

Inside, resorption tablets. Mirzaten® Ku-tab, resorption tablets are brittle, they should not be squeezed out through the foil packaging, they can break. The package is opened by gently pulling the labeled edge of the foil of the blister and the tablet is removed, then it should be immediately put on the tongue. The tablet begins to dissolve in the mouth for a few seconds and can be swallowed with water and without water, and do not mix the drug in the mouth with food.The tablet should not be cracked or chewed.

The daily dose should be taken at one time, at night. Also, if necessary, it is possible to take equal doses, twice a day (in the morning and in the evening).

Adults: the initial dose is 15 mg per day, in the future, usually the dose is increased to achieve the optimal clinical effect. Effective daily dose: from 15 mg to 45 mg.

Elderly Patients: the recommended dose is the same as for adults. To achieve a satisfactory effect and to ensure safety, an increase in the dose should be carried out under close medical supervision.

In severe and moderate severity of renal and severe severity of liver failure: clearance of mirtazapine decreases (see section Special instructions). Therefore, the drug should be administered with caution, reducing the prescribed dose.

The duration of treatment is 4-6 months until the symptoms disappear completely. Treatment is canceled gradually. The effect of taking adequate doses of the drug is expected within 2-4 weeks. In the absence of effect, the dose may be increased to a maximum daily dose of 45 mg. If there is no effect on the maximum dose after 2-4 weeks, the drug should be stopped.

Side effects:

Classification of incidence of adverse events (World Health Organization (WHO)):

very frequent> 1/10

Frequent from> 1/100 to <1/10

infrequent from> 1/1000 to <1/100

rare from> 1/10000 to <1/1000

very rare from <1/10000, or at an unidentified frequency (the frequency can not be established according to available data).

From the central (CNS) and peripheral nervous system: often - drowsiness, impaired concentration, is more common in the first weeks of treatment (lowering the dose usually does not lead to a decrease in sedation, but can reduce the antidepressant effect), dizziness, headache; rarely - psychomotor retardation, confusion, hallucinations, hyperkinesis, restless legs syndrome, akathisia, hypokinesia, apathy, tremor, convulsive syndrome, myoclonus, hyperesthesia, paresthesia, fainting, mania, nightmares / bright dreams, excitement; very rarely - aggravation of anxiety and insomnia (which may be symptoms of depression), suicidal behavior and thoughts, serotonin syndrome, paresthesia of the oral mucosa.

On the part of the organs of hematopoiesis: rarely - oppression hemopoiesis (granulocytopenia, neutropenia, agranulocytosis, aplastic anemia and thrombocytopenia), eosinophilia.

From the cardiovascular system: rarely - arterial hypotension, incl. orthostatic.

From the digestive system: often - increased appetite, rarely - dry mouth, thirst.

From the skin and subcutaneous tissue: rarely - exanthema.

Allergic reactions: hives.

Laboratory data: rarely - hyponatremia (more often in the elderly), increased activity of "liver" transaminases.

Other: often - weight gain; generalized or local edematous syndrome; rarely: weakness, back pain, flu-like syndrome, dysmenorrhea, dysuria. With the sudden cessation of long-term therapy, the development of the "withdrawal" syndrome is possible (see section "Special instructions").

Overdose:

Symptoms: oppression of the central nervous system, accompanied by disorientation and prolonged sedation in combination with tachycardia and weak hyper- or hypotension. At doses far exceeding the therapeutic dose, especially with mixed overdoses, there is a probability of heavier conditions (including a fatal outcome).

Treatment: gastric lavage, Activated carbon and symptomatic therapy.

Interaction:

Pharmacodynamic interactions

Mirtazapine may enhance the depressant effect alcohol on the central nervous system. Therefore, during treatment it is necessary to exclude the use of alcohol.

Do not take from MAO inhibitors or within 2 weeks after their cancellation.

Can potentiate sedation benzodiazepines.

With simultaneous admission to other serotonergic drugs (for example,, selective serotonin reuptake inhibitors and venlafaxine) - risk of developing serotonin syndrome; recommended thorough medical supervision of the patient.

Mirtazapine at a dose of 30 mg / day caused a slight increase in the international normalized ratio (INR) in patients taking warfarin; It is recommended that INR.

Pharmacokinetic interactions

Caution is required in cases where inhibitors CYP3A4, HIV protease inhibitors, antifungal agents of the azole group, erythromycin and nefazodone simultaneously with mirtazapine.

Simultaneous appointment with ketoconazole increased FROM_mOhand the area under the "concentration-time" curve (AUC) mirtazapine by 40 and 50%, respectively.

Inductors CYP3A4 (incl. carbamazepine, phenytoin) increased the clearance of mirtazapine by about 2 times, which is accompanied by a decrease in its plasma concentrations by 45-60%. Against the background of taking inducers of hepatic metabolism, it is necessary to increase the dose of mirtazapine, and at its end - to reduce.

With simultaneous reception with cimetidine - the bioavailability of mirtazapine may increase by more than 50%; it is recommended to reduce the dose of mirtazapine.

There were no significant clinical effects or pharmacokinetic changes in the background of simultaneous prescription with drugs lithium.

Special instructions:

When prescribing antidepressants, patients with concomitant schizophrenia or other psychotic disorders may experience psychotic symptoms or potentiate; paranoid thoughts aggravate; The depressive phase of manic-depressive psychosis can be replaced by a manic one.

With caution, it is recommended to appoint patients with epilepsy and organic syndrome (the risk of developing convulsive syndrome); When there is a spasm or an increase in their frequency, the drug should be discarded.

With a single administration of 15 mg of mirtazapine against a background hepatic insufficiency The clearance of mirtazapine and the average concentration of mirtazapine in plasma are reduced by 35% and 55%, respectively. When taking 15 mg of mirtazapine against a background of moderate renal insufficiency (QC 10-39 ml / min) clearance of mirtazapine reduced by 30%; with a severe degree (CC <10 ml / min) - by 50%; at an easy degree (SC from <80 ml / min) - the changes are minor. The average concentration of mirtazapine in plasma with an average and severe degree of renal failure is reduced by 55% and 115%, respectively. Therefore, the drug should be administered with caution to patients with hepatic and / or renal (moderate to severe) insufficiency.

Caution should be given to patients with: obstructive bowel disorders and urinary disorders (eg, with prostatic hyperplasia), acute angle-closure glaucoma, increased intraocular pressure (mild anticholinergic effect).

Since there is a risk of suicide, especially at the beginning of treatment, patients should be given only a small amount of tablets. Patients with a history of suicidal events or with suicidal ideals require special control during the treatment period.

Patients with diabetes are recommended to control the level of glycemia, if necessary, correcting the dose of insulin and / or oral hypoglycemic agents.

Abrupt cancellation of therapy can cause withdrawal syndrome (nausea, headache, dizziness, agitation, anxiety and general malaise); the symptoms are mild and stop on their own. It is recommended that the dose be gradually reduced when the drug is withdrawn.

Elderly patients are often more sensitive, especially with regard to adverse effects of antidepressants.

When there are signs of jaundice, treatment should be discontinued.

Oppression of bone marrow functions, manifested in the form of granulocytopenia or agranulocytosis, is rare and usually occurs after 4-6 weeks of treatment and is restored after discontinuing treatment on its own.

The physician should inform the patient that if symptoms such as fever, sore throat, stomatitis, and other signs of the flu-like syndrome are manifested, it is necessary to stop treatment, consult a doctor, and make a blood test.

Mirzaten® Ku-Tab contains lactose, so the drug should not be taken in patients with galactosemia,with Lactase Lactase deficiency or glucose-galactose malabsorption syndrome.

Since Mirzaten® Cu-tab tablets also contain sorbitol, the drug should not be taken to patients with rare hereditary problems of fructose intolerance, with glucose-galactose malabsorption or sucrase-isomaltase deficiency.

Mirzaten® Cu-Tab tablets contain aspartame, which is a source of phenylalanine. The drug is not recommended for patients with phenylketonuria.

Effect on the ability to drive transp. cf. and fur:In The time of treatment with mirtazapine should avoid performing potentially hazardous activities requiring high rates of psychomotor reactions, such as driving a car or controlling machinery.

Form release / dosage:

Tablets for resorption, 15 mg, 30 mg and 45 mg.

Packaging:

10 tablets per blister.

By 3, 6 or 9 blisters in a pack of cardboard along with instructions for use.

Storage conditions:

Store at a temperature not exceeding 30 ° C.

Keep out of the reach of children.

Shelf life:

2 years.

Do not use the drug after the expiration date.

Terms of leave from pharmacies:On prescription

Registration number:LSR-005233/09

Date of registration:30.06.2009

Expiration Date:Unlimited

The owner of the registration certificate:KRKA, dd, Novo mesto, AOKRKA, dd, Novo mesto, AO

Manufacturer: & nbsp

KRKA, d.d. Slovenia

Representation: & nbspKRKA KRKA Slovenia

Information update date: & nbsp06.09.2016

Illustrated instructions

Instructions

Mirzaten® Ku-Tab (Mirzaten Q-Tab®)