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

Excipients: cellulose (this is a spray-dried compound consisting of 75% lactose monohydrate and 25% cellulose), sodium carboxymethyl starch, pregelatinized starch, silicon dioxide colloidal anhydrous, magnesium stearate;

Film sheath: hypromellose, titanium dioxide, E 171, talc, macrogol 6000; for a dosage of 30 mg: Iron Oxide Red Dye, Iron Oxide Yellow Dye.

Description:

Tablets with a dosage of 30 mg: oval, biconvex tablets of orange-brown color, film-coated, with a risk on one side.

Cross-sectional view *: rough mass of white with orange-brown shell.

Tablets with a dosage of 45 mg: oval, biconvex tablets of white color, covered with a film membrane.

Cross-sectional view *: Rough white mass with a white sheath.

Pharmacotherapeutic group:antidepressant

ATX: & nbsp

N.06.A.X.11 Mirtazapine

Pharmacodynamics:

Mirtazapine is a drug from the group of tetracyclic antidepressants with predominantly sedative effect. Is an antagonist of presynaptic alpha₂-adrenoceptors of central action, which enhance central noradrenergic and serotonergic transmission of nerve impulses. Serotonergic transmission is intensified only through serotonin 5-HT₁receptors, while 5-HT₂ and 5-HT₃ receptors are blocked by mirtazapine. In the development of antidepressant effect, both enantiomers of mirtazapine, S(+) enantiomer blocks alpha₂- and 5-HT₂ receptors, a R(-) enantiomer blocks 5-HT₃receptors.

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

Mirtazapine weakens symptoms such as anhedonia (inability to experience pleasure and joy), psychomotor retardation, sleep disturbances (especially in the form of early awakenings) and weight loss, and can also be used to treat other symptoms: loss of interest, suicidal thoughts and diurnal mood swings .

Mirtazapine is usually well tolerated. When used in therapeutic doses, it is practically devoid of anticholinergic action and has practically no effect on the cardiovascular system (CCC).

It has anxiolytic and hypnotic properties, which is why it is most effective in anxious depressions of various genesis. The antidepressant effect usually manifests itself after 1-2 weeks of treatment.

Pharmacokinetics:

After oral administration mirtazapine quickly absorbed (bioavailability of about 50%), reaching a maximum concentration in the blood plasma (C_mOh) after about 2 hours.Food does not affect the pharmacokinetics of mirtazapine.

About 85% of mirtazapine binds to plasma proteins. The mean half-life (T_1/2) is from 20 to 40 hours, which allows you to take the drug 1 time per day. In rare cases, a longer T_1/2> (up to 65 hours). A shorter T_1/2 observed in young people. R(-) - enantiomer is deduced 2 times more slowly. Equilibrium concentrations are achieved after 3-4 days. Pharmacokinetics when taken in therapeutic doses is linear.

Mirtazapine is actively metabolized and excreted by the kidneys (75%) and the intestine (15%) for several days. The main ways of its metabolism in the body are demethylation and oxidation followed by conjugation. Isozymes CYP2D6 and CYP1A2 cytochrome P450 are involved in the formation of 8-hydroxymetabolite mirtazapine, while CYP3A4 is supposedly involved in education N-detylated and Noxidized metabolites. Demethylmirtazapine is pharmacologically active and appears to be pharmacokinetically similar to the parent compound.

With renal or hepatic insufficiency, a decrease in the clearance of mirtazapine is possible.

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;

- intolerance to galactose, lactase deficiency, glucose-galactose malabsorption syndrome.

Carefully:

- Epilepsy and organic lesions of the brain;

- hepatic or renal failure (severe and moderate severity);

- heart disease (including atrial fibrillation, conduction disorders, angina pectoris, recent myocardial infarction);

- arterial hypotension;

- drug addiction and a propensity to abuse psychoactive drugs (in the anamnesis);

- schizophrenia or other psychotic disorders, depressive phase of manic-depressive psychosis;

- obstructive bowel disease;

- disturbances of urination (including hyperplasia of the prostate gland);

- closed angle glaucoma and ophthalmic hypertension;

- diabetes;

- elderly age;

- suicidal events in the anamnesis;

- pregnancy, lactation;

- age 18-24 years, due to the risk of developing suicidal behavior.

Pregnancy and lactation:

The safety of mirtazapine during pregnancy is not established, so it can only be prescribed for absolute indications, when the benefit to the mother exceeds the potential risk to the fetus.

The use of the drug in the period of breastfeeding is not recommended (there is no data on the allocation of the drug in breast milk).

Dosing and Administration:

Inside, not liquid, squeezed a little water.

The daily dose should be taken once, at night. Also, reception in equal doses is possible, 2 times a day (in the morning and in the evening).

Adults: the initial dose is 15 mg per day, after 4 days it can be increased to 30 mg per day, after 10 days in the absence of effect - up to 45 mg per day.

Effective daily dose: from 15 mg to 45 mg.

The maximum daily dose is 45 mg. In the absence of effect after 2-4 weeks of taking the drug at the maximum daily dose, the drug should be stopped.

Older patients: correction of the dose is not required.

To achieve the desired effect and to ensure safety, the dose increase should be carried out under close medical supervision.

With renal and hepatic insufficiency possibly reducing the clearance of mirtazapine; it is recommended to reduce the daily dose by about 1/3.

Treatment is carried out until the symptoms disappear completely (usually 4-6 months). Treatment is stopped gradually, in order to avoid the development of the "withdrawal" syndrome.

Side effects:

The distribution of side effects by frequency is given in accordance with recommendations of the World Health Organization (WHO):

very often> 1/10

often from> 1/100 to <1/10

infrequently from> 1/1000 to <1/100

rarely from> 1/10000 to <1/1000

very rarely from <1/10000, or at an unidentified frequency (the frequency can not be determined from the available data).

From the 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, akathisia, hypokinesia, apathy, tremor, convulsive syndrome, myoclonus, hyperesthesia, paresthesia, fainting, mania, nightmares / bright dreams, agitation, agitation; 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 hematopoiesis system: rarely - oppression of hematopoiesis (granulocytopenia, neutropenia, agranulocytosis, aplastic anemia and thrombocytopenia), eosinophilia.

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

From the digestive system: often - increased appetite; infrequently - nausea; rarely dry mouth, diarrhea, vomiting; very rarely - hypoesthesia of the oral mucosa, edema of the oral mucosa, constipation, abdominal pain.

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

From the skin: rarely - exanthema.

From the genitourinary system: dysmenorrhea, dysuria.

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 - general weakness, back pain, "flu-like" syndrome. With the sudden cessation of long-term therapy, the development of the syndrome of "withdrawal" is possible.section "Special instructions").

Overdose:

Symptoms: oppression of the central nervous system, accompanied by disorientation, prolonged sedation, hallucinations; tachycardia, moderate increase or decrease in blood pressure. Clinically significant cardiotoxic effects were not observed. When taking high doses, significantly exceeding therapeutic, more serious consequences (including fatal ones) are possible.

Treatment: gastric lavage, the use of activated charcoal and symptomatic therapy.

Interaction:

Pharmacodynamic interactions

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

Do not take at the same time mirtazapine from MAO inhibitors or within 2 weeks after their withdrawal, due to the possibility of the occurrence of undesirable phenomena such as nausea, vomiting, facial hyperemia, dizziness, muscle stiffness, increased sweating, hyperthermia, epileptic seizures, changes in mental status, coma.

Can potentiate sedation benzodiazepines.

With simultaneous admission to other serotonergic drugs (for example, selective serotonin reuptake inhibitors (SSRIs) and venlafaxine) there is a risk of developing a serotonin syndrome; when it is necessary to use such a combination, careful medical observation of the patient is recommended for the early detection of symptoms of serotonergic hyperstimulation. Mirtazapine at a dose of 30 mg / day caused a slight increase in the International Normalized Ratio (INR) in patients taking warfarin; since it is impossible to exclude the increase of this effect at high doses of the drug, it is recommended to monitor INR with simultaneous therapy with warfarin and mirtazapine.

Pharmacokinetic interactions

Mirtazapine should be administered with caution at the same time as inhibitors isoenzyme CYP3A4, HIV protease inhibitors, antifungal agents of the azole group, erythromycin and nefazodone. Simultaneous administration with ketoconazole increased FROM_mOh and the area under the concentration-time curve (AUC) of mirtazapine by 40 and 50%, respectively.

Inductors of isoenzyme CYP3A4 (e.g., carbamazepine, phenytoin) increased the clearance of mirtazapine by about 2 times, which was 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.

In studies of drug interactions in vivo mirtazapine had no effect on the pharmacokinetics risperidone (isoenzymatic substrate CYP2D6) and paroxetine (substrate and inhibitor of isoenzyme CYP2D6), carbamazepine (substrate and isoenzyme inducer CYP3A4) and amitriptyline, cimetidine or phenytoin.

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

Special instructions:

Suicide and suicidal thoughts, or worsening of the clinical condition

Depression is accompanied by an increased risk of suicidal thoughts, self-harm and the risk of suicide (suicidal events). This risk persists until stable remission is achieved.Because significant improvement in the condition may not occur in the first few weeks of therapy, patients should be monitored until it occurs. According to general clinical experience, the risk of suicide may increase in the early stages of recovery. Patients with a history of suicidal events or suicidal thoughts require special control during the treatment period. In connection with the risk of suicidal thoughts and the development of suicidal behavior, Mirzaten® should be used with extreme caution in persons aged 18-24 years.

During drug therapy, Mirzaten® requires close monitoring of patients, especially those at high risk, at the beginning of treatment and when changing the doses of the drugs. Patients (and caregivers) should be warned about the need for increased attention to any manifestations of impairment, suicidal behavior, thoughts or unusual behavior; when these symptoms appear, seek medical help immediately.

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

It is necessary to inform the patient that if symptoms such as fever, sore throat, stomatitis and other signs of an infectious disease appear, stop treatment and consult a doctor.

Carefully it is recommended that patients with epilepsy and the risk of convulsive syndrome develop; When there is a spasm or an increase in their frequency, it is necessary to cancel the drug.

Patients with diabetes mellitus are recommended to control blood glucose concentration, if necessary, dose adjustment of insulin and / or oral hypoglycemic agents.

When jaundice should immediately stop treatment.

With the simultaneous use of SSRIs and other serotonergic drugs may develop serotonin syndrome, which is usually reversible and passes within 24 hours after drug withdrawal.

According to the postmarketing experience, serotonin syndrome rarely develops with monotherapy with Mirzaten®.

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

In the treatment of the depressive phase of manic-depressive psychosis, the depressive phase can become manic; patients with a mania or hypomania in a history require increased attention; When the disease passes into the manic phase, therapy with Mirzaten® should be discontinued.

Since there is a risk of suicide, especially at the beginning of treatment, patients should be given only a small amount of tablets.

Despite the fact that antidepressants are not addictive, abrupt withdrawal 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.

The preparation Mirzaten® contains lactose, therefore the drug should not be taken to patients with intolerance to galactose, lactase deficiency or glucose-galactose malabsorption syndrome.

Effect on the ability to drive transp. cf.and fur:In The time of treatment with Mirzaten® should avoid the management of motor vehicles and other technical devices that require concentration of attention and speed of psychomotor reactions.

Form release / dosage:

The film-coated tablets are 30 mg and 45 mg.

Packaging:

For 10 tablets in a blister of PVC / PVDC - aluminum foil.

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

Storage conditions:

At a temperature of no higher than 30 ° C.

Keep out of the reach of children.

Shelf life:

5 years.

Do not use the drug after the expiration date.

Terms of leave from pharmacies:On prescription

Registration number:LS-000347

Date of registration:05.05.2010

Expiration Date:Unlimited

Date of cancellation:2018-04-12

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: & nbsp12.04.2018

Illustrated instructions

Instructions

Mirzaten (Mirzaten)