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

Excipients: lactose monohydrate 101.8 mg, starch corn pregelatinized starch (starch 1500) 21.8 mg, silicon dioxide 2.2 mg, croscarmellose sodium 2.9 mg, magnesium stearate 1.3 mg, Opadrai 03F22322 yellow 2.9 mg: hypromellose 6 cp 1.8125 mg, titanium dioxide 0.807621 mg macrogol / PEG 8000 0.8125 mg, iron dye oxide yellow 0.0986 mg, ferric oxide red oxide 0.000029 mg ;

1 tablet, film-coated, 30 mg contains:

active substance: mirtazapine 30 mg;

Excipients: lactose monohydrate 203.6 mg, starch corn pregelatinized starch (starch 1500) 43.6 mg, silicon dioxide 4.4 mg, croscarmellose sodium 5.8 mg, magnesium stearate 2.6 mg, Opadrai 03F23252 orange 5.8 mg: hypromellose 6 cp 3,625 mg, titanium dioxide 1,32472 mg, macrogol / PEG 8000 0.3625 mg, iron oxide dye yellow 0.35554 mg, iron oxide dye red 0.13224 mg;

1 tablet, film-coated, 45 mg contains:

active substance: mirtazapine 45 mg;

Excipients: lactose monohydrate 305.4 mg, corn starch pregelatinized starch (starch 1500) 65.4 mg, silicon dioxide 6.6 mg, croscarmellose sodium 8.7 mg, magnesium stearate 3.9 mg, Opadrai 03F28635 white 8,7 mg: hypromellose 6 cp 5.4375 mg, titanium dioxide 2.71875 mg, macrogol / PEG 8000 0.54375 mg.

Description:

Tablets 15 mg: oval, biconvex film-coated tablets of brownish-yellow color with a risk on both sides and labeling "I" on one side.

Tablets 30 mg: oval, biconvex film-coated tablets of pink-brown color with a risk on both sides and marking "I" on one side.

Tablets 45 mg: oval, biconvex film-coated tablets of white color with the label "I" on one side.

Pharmacotherapeutic group:Antidepressant

ATX: & nbsp

N.06.A.X.11 Mirtazapine

Pharmacodynamics:

Pharmacological properties

Mirtazapine is an antidepressant of a four-ring structure with predominantly sedative effect. The drug is most effective in depressive states with symptoms in the clinical picture such as inability to experience pleasure and joy, loss of interest (anhedonia), psychomotor retardation, sleep disorders (especially in the form of early awakenings) and weight loss, as well as other symptoms: suicidal thoughts and daily mood swings.

The antidepressant effect of the drug usually comes in 1-2 weeks of treatment.

Pharmacodynamics

Mirtazapine is an antagonist of presynaptic α₂adrenoreceptors in the central nervous system and enhances central noradrenergic and serotonergic transmission of nerve impulses. In this case, the increase in serotoninergic transmission is realized only through 5-HT₁-receptors, since mirtazapine blocks 5-HT₂ and 5-HT₃-receptors. It is believed that both enantiomers of mirtazapine have antidepressant activity, S(+) enantiomer - by blocking α₂and 5-HT₂-receptors, a R(-) enantiomer - by blocking 5-HT₃-receptors.

Sedative properties of mirtazapine are due to its antagonistic activity with respect 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.

Pharmacokinetics:

After oral administration of the drug 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 average half-life is between 20 and 40 hours (rarely up to 65 hours). A shorter half-life is observed in young people. Stable concentration of the substance is achieved after 3-4 days and in the future it does not change. In the recommended dosage range, the pharmacokinetic parameters of mirtazapine are linearly dependent on the administered dose of the drug. Eating does not affect the pharmacokinetics of the drug.

Mirtazapine is actively metabolized and excreted in urine and feces 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- demethylated 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.

Contraindications:

Hypersensitivity to mirtazapine or to any of the excipients.

Since safety and efficacy for children under 18 years of age have not been established, it is not recommended to use Mirtazonal for the treatment of children.

Carefully:

Correction of the dosage regimen and regular medical supervision are necessary for the following categories of patients:

- patients with epilepsy and organic lesions of the brain (against the background of therapy with Mirtazonal, in rare cases, the development of convulsive conditions);

- patients with hepatic or renal insufficiency;

- patients with heart disease (conduction disorder, angina pectoris or recent myocardial infarction);

- patients with cerebrovascular diseases (including with ischemic attacks in the anamnesis);

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

- patients who abuse drugs, with drug dependence, mania, hypomania;

Like other antidepressants, Mirtazonal should be used with caution in the following cases:

- Violation of urination, including with prostatic hyperplasia;

- acute angle-closure glaucoma and increased intraocular pressure;

- diabetes.

Pregnancy and lactation:

The safety of the drug during pregnancy in humans is not established, so it can be used during pregnancy only if the benefit to the mother exceeds the potential risk to the fetus.

The use of the drug Mirtazonal during lactation is not recommended because of the lack of data on its excretion in human milk.

Dosing and Administration:

Tablets should be taken orally, if necessary, washed down with liquid, and swallowed without chewing.

Adults:

Effective daily is usually between 15 and 45 mg; the initial dose is 15 or 30 mg (a higher dose should be taken at night).

Elderly:

The recommended dose is the same as for adults. In elderly patients, in order to achieve a satisfactory and safe response to treatment, an increase in the dose should be made under the direct supervision of a physician.

Children and teenagers under 18 years of age:

The safety and effectiveness of Mirtazonal in the treatment of children and adolescents under the age of 18 with major depressive disorder in placebo-controlled trials have not been established. Safety and efficacy in this population can not be extrapolated based on data from adults. Therefore, the drug Mirtazonal should not be used in children and adolescents under the age of 18 years.

In patients with renal or hepatic insufficiency clearance of mirtazapine may be reduced. This should be taken into account when prescribing a drug in this category of patients. The half-life of mirtazapine is 20-40 hours and thereforethe drug is suitable for reception once a day. It is preferable to take the drug as a single dose before bedtime. The drug Mirtazonal can also be prescribed for admission twice a day, dividing the daily dose in half (once in the morning and once a night).

Treatment should be continued as far as possible until the patient has no symptoms in 4-6 months. After this treatment can be gradually canceled. Mirtazapine usually begins after 1-2 weeks of treatment. Treatment with an adequate dose should result in a positive response in 2-4 weeks. If the response to treatment is insufficient, the dose can be increased to the maximum dose. If there is no response to treatment after another 2-4 weeks, treatment should be discontinued.

Side effects:

Patients with depression experience a number of symptoms due to the disease, so sometimes it is difficult to distinguish between symptoms associated with the disease and symptoms caused by the use of the drug.

The following side effects may occur.

From the nervous system: drowsiness (which can lead to impaired concentration),is more common in the first days of the week of treatment (NB: lowering the dose usually does not lead to a decrease in sedation, but may adversely affect the effectiveness of the antidepressant); in rare cases: psychomotor retardation, anxiety, hyperkinesia, myoclonus, hypokinesia, apathy, hyperesthesia, tremor, convulsive syndrome, restless legs syndrome, fatigue, mania, nightmares / bright dreams.

On the part of the organs of hematopoiesis: In rare cases, the following side effects are possible: oppression hemopoiesis (granulocytopenia, neutropenia, eosinophilia, agranulocytosis, aplastic anemia and thrombocytopenia); increased activity of transaminases in blood plasma.

From the digestive system: nausea, vomiting, constipation, abdominal pain.

From the genitourinary system: dismenorrhea

From the side of the cardiovascular system: rarely orthostatic hypotension, lowering blood pressure.

Other: increased appetite and weight gain, dizziness, headache, edematous syndrome; rarely: urticaria, back pain, arthralgia, myalgia, dysuria, withdrawal syndrome, dry mouth, thirst.

Overdose:

The clinical safety of Mirtazonal in overdose has not been investigated. Toxicity studies indicate that there is no clinically significant cardiotoxic effect with drug overdose.

Symptoms: oppression of the central nervous system, accompanied by disorientation and prolonged sedation in combination with tachycardia and weak hyper- or hypotension. However, there is a possibility of more severe violations of the physiological functions of the body, which can lead to a fatal outcome at doses far exceeding the therapeutic dose, especially with mixed overdoses.

In the event of an overdose, symptomatic therapy should be used to maintain the vital functions of the body. It is recommended to take activated charcoal or wash the stomach.

Interaction:

Pharmacokinetic interaction

- Mirtazapine is extensively metabolized with CYP2D6 and CYP3A4, and to a lesser extent with participation CYP1A2. The study of interaction in healthy volunteers showed that paroxetine, an inhibitor CYP2D6, does not affect the pharmacokinetics of mirtazapine in a stationarycondition. Introduction in combination with a powerful inhibitor CYP3A4, ketoconazole increased the maximum levels in plasma and AUC mirtazapine by approximately 40% and 50%, respectively. Caution should be exercised when using mirtazapine in combination with potent inhibitors CYP3A4, inhibitors of HIV proteases, azole antifungal drugs, erythromycin or nefazodone.

- Carbamazepine and phenytoin, inductors CYP3A4, increased the clearance of mirtazapine approximately twice, which resulted in a 45-60% decrease in the concentrations of mirtazapine in plasma. When adding carbamazepine or another inducer of liver metabolism (eg rifampicin) to mirtazapine therapy, the dose of mirtazapine may need to be increased. When discontinuing treatment with such a drug, it may be necessary to reduce the dose of mirtazapine.

- When used in conjunction with cimetidine, the bioavailability of mirtazapine may increase by more than 50%. The dose of mirtazapine may be reduced at the start of treatment in combination with cimetidine or increased with cimetidine discontinuation of treatment.

- AT in vivo research interactions mirtazapine did not influence the pharmacokinetics of risperidone or paroxetine (CYP2D6 substrates), carbamazepine and phenytoin (CYP3A4 substrates), amitriptyline and cimetidine.

- There were no significant clinical effects or changes in pharmacokinetics in humans when treated with mirtazapine in combination with lithium.

Pharmacodynamic interaction

- Mirtazapine should not be used in combination with MAO inhibitors or within two weeks after discontinuation of treatment with an MAO inhibitor.

- Mirtazapine can enhance the sedative properties of benzodiazepines and other sedatives. Caution should be exercised when prescribing these medicines together with mirtazapine.

- Mirtazapine can enhance the depressant effect of alcohol on the central nervous system. Therefore, patients should be warned about the need to avoid drinking alcohol.

- In the case of other serotonergic drugs (for example, selective serotonin reuptake inhibitors and venlafaxine) in combination with mirtazapine, there is a risk of interaction that may lead to the development of serotonin syndrome.Based on the post-registration experience of the drug, it turned out that serotonin cider appears very rarely in patients receiving treatment with mirtazapine in combination with selective serotonin reuptake inhibitors or venlafaxine. If this combination is thought to be therapeutically necessary, then the dose should be carefully changed and the signs of the onset of serotonergic up-regulation should be directly monitored.

- Mirtazapine at a dose of 30 mg once a day caused a small but statistically significant increase in INR (International Normalized Ratio) in subjects treated with warfarin. You can not rule out a more pronounced effect with a higher dose of mirtazapine. It is recommended to monitor INR in case of treatment with warfarin in combination with mirtazapine.

Special instructions:

When combined with other drugs should be borne in mind:

- worsening of psychotic symptoms can occur with the use of antidepressants for the treatment of patients with schizophrenia or other psychotic disorders; Paranoid ideas can intensify;

- the depressive phase of manic-depressive psychosis on the background of treatment can be transformed into a manic phase;

- taking into account the risk of suicide, especially at the beginning of treatment, the patient should be given only a limited number of tablets;

- a sharp cessation of treatment after prolonged use can cause nausea, headache and malaise;

- Elderly patients are usually more sensitive, especially with regard to side effects. In clinical studies of the drug Mirtazonal it was not noted that in elderly patients side effects are more frequent than in other age groups, but they can be more pronounced; but the data is still limited;

- when there are signs of jaundice, treatment should be interrupted;

- patients are advised to avoid the use of alcohol in drug treatment;

- caution should be exercised when prescribing benzodiazepines concurrently with the drug;

- oppression of bone marrow functions, usually manifested in the form of granulocytopenia or agranulocytosis, is rarely observed with the use of Mirtazonal. Appears mostly after 4-6 weeks of treatment and reversibly after discontinuation of treatment.The doctor should carefully consider (and inform the patient) symptoms such as fever, sore throat, stomatitis, and other signs of flu-like syndrome; when such symptoms appear, you must stop treatment and make a blood test;

- based on the post-registration experience, it turned out that serotonin syndrome occurs very rarely in patients receiving treatment with Mirtazonal alone. Interaction with other serotonergic drugs (see section "Interaction");

- patients with such rare hereditary diseases as galactose intolerance, Lappa lactase deficiency or glucose-galactose malabsorption should not be prescribed Mirtazapine.

Effect on the ability to drive transp. cf. and fur:

Mirtazonal can reduce concentration of attention. In the treatment of antidepressants, patients should avoid performing potentially dangerous activities requiring high rates of psychomotor reactions, such as driving a car or controlling machinery.

Form release / dosage:

Film-coated tablets, 15 mg, 30 mg and 45 mg.

Packaging:

For 10 or 14 tablets in PVC / Aluminum foil blisters.

For 1, 2, 3, 5, 10 blisters for 10 tablets or 2, 4, 10 blisters for 14 tablets together with instructions for use in a cardboard pack.

Storage conditions:

At a temperature of no higher than 30 ° C.

Keep out of the reach of children.

Shelf life:

3 years.

Do not use after the expiry date printed on the package.

Terms of leave from pharmacies:On prescription

Registration number:LSR-002281/08

Date of registration:01.04.2008 / 18.05.2009

Expiration Date:Unlimited

The owner of the registration certificate:AKTAVIS GROUP, AO AKTAVIS GROUP, AO Iceland

Manufacturer: & nbsp

ACTAVIS, Ltd. Iceland

Representation: & nbspAktavis, Open Company Aktavis, Open Company

Information update date: & nbsp09.06.2018

Illustrated instructions

Instructions

Mirtazonal (Mirtazonal)