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

Excipients: mannitol DC (Perlitol 200) 57.975 mg, microcrystalline cellulose (Avicel PH 102) 30,375 mg, magnesium carbonate 7.5 mg, hypromellose with a low degree of substitution (L-HPC, LH-11) 6 mg; crospovidone (Polyplasdone XL-10) 6 mg, microcrystalline cellulose + guar gum (Avicel CE-15) 7.5 mg, silicon colloidal dioxide (Aerosil 200) 1.5 mg, L-methionine 0.15 mg, aspartame 6 mg, flavoring orange Silesia 1209603133 3.75 mg, magnesium stearate 2.25 mg.

1 tablet for resorption of 30 mg contains:

Active substance: mirtazapine 30 mg;

Excipients mannitol DC (Perlitol 200) 115.95 mg, microcrystalline cellulose (Avicel PH 102) 60.75 mg, magnesium carbonate 15 mg, hypromellose with a low degree of substitution (L-HPC, LH-11) 12 mg, crospovidone (Polyplasdone XL- 12 mg, cellulose microcrystalline + guar gum (Avicel CE-15) 15 mg, silicon dioxide colloid (Aerosil 200) 3 mg, L-methionine 0.3 mg, aspartame 12 mg, orange flavor Silesia 1209603133 7.5 mg, magnesium stearate 4.5 mg.

1 tablet for resorption of 45 mg contains:

Active substance: mirtazapine 45 mg;

Excipients Mannitol DC (Perlitol 200) 173.925 mg, microcrystalline cellulose (Avicel PH 102) 91,125 mg, magnesium carbonate 22.5 mg, low-substituted hypromellose (L-HPC, LH-11) 18 mg, crospovidone (Polyplasdone XL-10) 18 mg, microcrystalline cellulose + guar gum (Avicel CE-15) 22.5 mg, silicon dioxide colloid (Aerosil 200) 4.5 mg, L-methionine 0.45 mg, aspartame 18 mg, orange flavor Silesia 12096.03133 11 , 25 mg, magnesium stearate 6.75 mg.

Description:

Round, biconvex tablets white or almost white with the smell of orange with engraving M1 (tablets 15 mg), M2 (tablets 30 mg) or M4 (tablets 45 mg) 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 enhancement of serotonergic 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 α₂ and 5-HT₂-receptors, a R(-) enantiomer - by blocking 5-HT₃-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.

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 by the kidneys and through the intestine for several days. The main ways of its metabolism in the body are demethylation and oxidation followed by conjugation. Cytochrome P450-dependent isozymes CYP2D6 and CYP1A2 are involved in the formation of the 8-hydroxy metabolite mirtazapine, while the isoenzyme 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 conditions (including anhedonia, psychomotor retardation, insomnia, early awakening, weight loss, loss of interest in life, suicidal thoughts and mood lability).

Contraindications:

- Hypersensitivity to mirtazapine or 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;

- BVariability and lactation period (efficacy and safety not established).

Carefully:

Correction of the dosing regimen and regular medical control 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 hyperplasia of the prostate;

- acute angle-closure glaucoma and increased intraocular pressure;

- diabetes.

Dosing and Administration:

The tablet for resorption should be put on the tongue and dissolve until it completely disintegrates. Tablets for resorption of Mirtazonal are rapidly destroyed in the tongue, no liquid is required to receive them. Before taking the drug and during its resorption, do not try to destroy the tablet (chew, break, etc.).

Adults:

The recommended initial daily dose is 15 or 30 mg / day, which is gradually increased if necessary to 45 mg / day. The dose should be taken once a day 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:

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.

Have patients with renal or hepatic impairment 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 therefore the drug is suitable for admission 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 that, the 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 can occur with frequency: often (> 1/100); sometimes (> 1/1000, but <1/100); rarely (> 1/10000, but <1/1000); very rarely (<1/10000), including individual cases.

From the nervous system: often - drowsiness (which can lead to impaired concentration), is more common in the first weeks of treatment (N.B.: lowering the dose usually does not lead to a reduction in sedation, but may adversely affect the effectiveness of the antidepressant); dizziness and headache.

Rarely - agitation, confusion, insomnia, psychomotor agitation (including akathisia, hyperkinesis), anxiety, myoclonus, hypokinesia, apathy, hyperesthesia, tremor, convulsive syndrome, restless legs syndrome, paresthesia, fatigue, mania, hallucinations, nightmares / bright dreams.

Very rarely - serotonin syndrome, paresthesia of the oral mucosa.

The frequency is unknown - suicidal thoughts and the risk of suicide;

From the hematopoiesis: rarely - oppression hemopoiesis (granulocytopenia, neutropenia, agranulocytosis, aplastic anemia and thrombocytopenia), eosinophilia.

From the digestive system: sometimes - nausea; rarely - diarrhea, dry mouth, increased transaminase activity in the blood plasma, vomiting, constipation, abdominal pain; very rarely - edema of the oral mucosa.

From the genitourinary system: dysmenorrhea, dysuria.

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

From the skin: rarely - exanthema.

From the side of the musculoskeletal system: rarely - arthralgia, myalgia.

Other: often - increased appetite and weight gain, swollen syndrome; rarely hives, back pain, withdrawal syndrome, 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 minor 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 case of an overdose, symptomatic therapy should be conducted, aimed at maintaining 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 the participation of isoenzymes CYP2D6 and CYP3A4, and to a lesser extent with the participation of isoenzyme CYP1A2. The study of interaction in healthy volunteers showed that paroxetine, inhibitor of isoenzyme CYP2D6, does not affect the pharmacokinetics of mirtazapine in the equilibrium state. Introduction in combination with a potent inhibitor of isoenzyme CYP3A4, ketoconazole increased the maximum plasma concentration levels and the area under the concentration-time curve of mirtazapine by approximately 40% and 50%, respectively. Caution should be exercised when using mirtazapine in combination with potent inhibitors of isoenzyme CYP3A4, HIV protease inhibitors, azole antifungal drugs, erythromycin or nefazodone.

- Carbamazepine and phenytoin, isoenzyme inducers 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 studies of interactions mirtazapine did not influence the pharmacokinetics of risperidone or paroxetine (isozyme CYP2D6 substrate), carbamazepine and phenytoin (isoenzyme CYP3A4 substrate), 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 monoamine oxidase (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, venlafaxine) in combination with mirtazapine, there is a risk of interaction that may lead to the development of serotonin syndrome, which should be taken into account when selecting joint doses of the drugs. Based on the post-registration experience of the drug, it turned out that serotonin syndrome occurs very rarely in patients treated with mirtazapine in combination with selective serotonin reuptake inhibitors or venlafaxine.

- 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 exclude 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:

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

In the treatment of the depressive phase of bipolar affective psychosis, an affect inversion with the development of mania can be observed.

- Depression can be accompanied by an increased incidence of suicidal thoughts and suicide attempts. This risk persists until the onset of remission of the disease. Since the improvement in the condition may not occur during the first weeks of treatment, the patient should be carefully monitored before improving his condition. Clinical experience shows that the risk of suicide attempts may increase in the early stages of recovery.

Patients with cases of suicidal attempts in the history of the disease or patients who have an increased incidence of suicidal thoughts before starting treatment, there is an increased risk of suicide attempts, such patients need careful monitoring. A meta-analysis of placebo-controlled clinical trials of antidepressant drug products in adult patients with mental disorders showed an increased risk of suicidal events with antidepressant medications compared with placebo in a group of individuals younger than 25 years of age.

Patients (and people caring for patients) should be warned about the need to monitor the clinical signs of mental deterioration, the occurrence of suicidal attempts or thoughts and the appearance of unusual changes in behavior. If these symptoms appear, consult your doctor immediately.

- Given the risk of suicide, the patient should be given only a limited number of tablets.

- A sharp cessation of treatment after prolonged use can cause nausea, headache, malaise, anxiety and anxiety.

- 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 discontinued.

- Patients are advised to avoid the use of alcohol in the treatment of the drug.

- Caution should be used when prescribing benzodiazepines simultaneously with the drug.

- Oppression of bone marrow functions, usually manifested in the form of granulocytopenia or agranulocytosis, is rarely observed with 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 with other drugs").

- Women of reproductive age should be treated only if reliable contraception is used.

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

Mirtazonal can reduce concentration of attention.In the process of treatment with 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:

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

Packaging:

For 6 tablets in Al / Al strips or blisters.

By 1, 3, 5, 6, 15 or 16 strips or blisters together with instructions for use in cardboard pack.

Storage conditions:

At a temperature of no higher than 25 ° C.

Keep out of the reach of children.

Shelf life:

2 years.

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

Terms of leave from pharmacies:On prescription

Registration number:LSR-004851/10

Date of registration:28.05.2010

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)