Composition, form of production and packaging
The tablets covered with a cover 1 tab.
mirtazapine 15 mg
10 pieces. - blisters (1) - packs of cardboard.
10 pieces. - blisters (3) - packs of cardboard.
The tablets covered with a cover 1 tab.
mirtazapine 30 mg
10 pieces. - blisters (1) - packs of cardboard.
10 pieces. - blisters (3) - packs of cardboard.
The tablets covered with a cover 1 tab.
mirtazapine 45 mg
10 pieces. - blisters (1) - packs of cardboard.
10 pieces. - blisters (3) - packs of cardboard.
INSTRUCTION FOR THE SPECIALIST.
Description of the drug approved by the manufacturer for the printed edition of 2013.
PHARMACHOLOGIC EFFECT
The drug Remeron (mirtazapine) is a tetracyclic antidepressant 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 disturbances (especially in the form of early awakenings) and weight loss, as well as other symptoms: suicidal thoughts and diurnal mood swings.
Antidepressant effect of the drug Remeron usually comes in 1-2 weeks of treatment.
Mirtazapine is a presynaptic antagonist? 2- adrenoreceptors in the central nervous system and enhances central noradrenergic and serotonergic transmission of nerve impulses. In this case, the increase in serotonergic transmission is realized only through serotonin 5-HT 1 -receptors, since mirtazapine blocks serotonin 5-HT 2 - and 5-HT 3 -receptors. It is believed that both enantiomers of mirtazapine have antidepressant activity, S (+) enantiomer - blocking? 2- adreno-and serotonin 5-HT 2 -receptors, and R (-) enantiomer - blocking serotonin 5-HT 3 -receptors.
Sedative properties of mirtazapine are due to its antagonistic activity against H 1 -histamine receptors.
Mirtazapine is usually well tolerated. In therapeutic doses, it has almost no m-holinoblokiruyuschego effect and almost no effect on the cardiovascular system.
PHARMACOKINETICS
After oral administration, mirtazapine is rapidly absorbed (bioavailability of about 50%), reaching Cmax in blood plasma after about 2 hours. About 85% of mirtazapine binds to plasma proteins. The average T 1/2 is between 20 and 40 hours (rarely up to 65 hours). A shorter T 1/2 is observed in young people. The equilibrium concentration of the substance is reached 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. Isozymes of cytochrome P450 (CYP2D6 and CYP1A2) are involved in the formation of mirtazapine 8-hydroxymetabolide, while CYP3A4 presumably determines the formation of N-demethylated and N-oxidized metabolites. Demethylmirtazapine is pharmacologically active.
The clearance of mirtazapine decreases with renal or hepatic insufficiency.
INDICATIONS
- Depression.
DOSING MODE
Tablets should be taken orally, if necessary, washed down with liquid, and swallowed without chewing.
Adults: The effective daily dose is usually between 15 and 45 mg; the initial dose is 15 or 30 mg.
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.
In patients with renal or hepatic insufficiency, the clearance of mirtazapine may be reduced. This should be taken into account when prescribing Remeron for this category of patients.
The drug Remeron can be taken 1 time per day, preferably at the same time, before night sleep. The drug Remeron can also be prescribed for reception 2 times a day, dividing the daily dose in half (1 time in the morning and 1 time at night, a higher dose should be taken at night).
Treatment should, if possible, continue for 4-6 months until the symptoms disappear completely. After that, the treatment can be gradually canceled. Mirtazapine begins to act normally 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 (up to 45 mg). In the absence of response to treatment after 2-4 weeks treatment should be discontinued.
SIDE EFFECT
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. To indicate the frequency of side effects, the following classification is used: very often (? 1/10), often (? 1/100 and? 1/10), infrequently (> 1/1000 and? 1/100), rarely (> 1/10000 and? 1/1000), the frequency is not set (? 1/10000).
Violations from the blood and lymphatic system: the frequency is not established - bone marrow depression (granulocytopenia, agranulocytosis, aplastic anemia and thrombocytopenia), eosinophilia.
Disturbances from the nervous system: very often - drowsiness (which can lead to impaired concentration), usually occurring during the first weeks of treatment. (NB reduction of the dose usually does not lead to less sedation, but may decrease the effectiveness of the antidepressant), sedation, headache; often - lethargy, dizziness, tremor; infrequently - paresthesia, restless legs syndrome, fainting; rarely - myoclonus, very rarely - convulsions (stroke), serotonin syndrome, paresthesia of the oral mucosa.
Disorders from the gastrointestinal tract: very often - dry mouth; often - nausea, diarrhea, vomiting; infrequent - a decrease in the sensitivity of the oral mucosa;frequency is not established - edema of the oral mucosa.
Disturbances from the skin and subcutaneous tissues: often - skin rash.
Disorders from the musculoskeletal and connective tissue: often - arthralgia, myalgia, back pain.
Disorders from the endocrine system: the frequency is not established - a violation of the secretion of antidiuretic hormone;
Disorders from the metabolism and nutrition: very often - increased appetite.
Violations from the vessels: often - orthostatic hypotension; infrequently - arterial hypotension.
General disorders and disorders at the injection site: often - local edema; infrequently - fatigue.
Disorders from the liver and bile ducts: rarely - increased serum transaminase activity.
Disorders of the psyche: often - unusual dreams, confusion, anxiety *, insomnia *; infrequently - nightmares, mania, agitation, hallucinations, psychomotor agitation (including acacia and hyperkinesia); frequency not established - suicidal ideation, suicidal behavior.
Laboratory and instrumental data (according to the results of post-registration studies): very often - weight gain.
* - usually in the treatment of antidepressants anxiety and insomnia (which may be symptoms of depression) may develop or worsen. When treated with Remeron, the development or worsening of anxiety and insomnia was reported very rarely.
CONTRAINDICATIONS
- hypersensitivity to mirtazapine or to any of the excipients.
Patients with such rare hereditary problems as lactose intolerance, lactase deficiency or glucose-galactose malabsorption, Remeron should not be prescribed.
Since the safety and efficacy of Remeron for children under 18 years of age have not been established, it is not recommended to use Remeron for children.
Carefully
Correction of the dosing regimen and regular medical control are necessary for the following categories of patients:
- patients with epilepsy and organic brain lesions (on the background of therapy with Remeron in rare cases, the development of seizures);
- patients with hepatic or renal insufficiency;
- Patients with heart diseases (conduction disorders, angina pectoris or recent myocardial infarction);
- Patients with cerebrovascular diseases (including with an ischemic stroke in the anamnesis);
- Patients with arterial hypotension and with conditions predisposing to hypotension (including with dehydration and hypovolemia);
- patients who abuse drugs, with dependence on drugs that affect the central nervous system, with mania, hypomania.
Like other antidepressants, Remeron should be used with caution in the following cases:
- violation of urination, incl. with hyperplasia of the prostate;
- acute angle-closure glaucoma and increased intraocular pressure;
- diabetes;
- with the simultaneous administration of benzodiazepines with the drug Remeron.
PREGNANCY AND LACTATION
Safety of application of the drug Remeron in pregnancy in humans is not established, however, the animals have no teratogenic effect, therefore it can be used during pregnancy only if the benefit to the mother exceeds the potential risk to the fetus.
The use of Remeron during lactation is not recommended because of the lack of data on its excretion in human milk.
APPLICATION FOR FUNCTIONS OF THE LIVER
Use with caution in patients with renal insufficiency.
In patients with renal failure, the clearance of mirtazapine may be reduced. This should be taken into account when prescribing Remeron for this category of patients.
APPLICATION FOR VIOLATIONS OF THE FUNCTION OF KIDNEYS
Use with caution in patients with hepatic insufficiency.
In patients with hepatic insufficiency, the clearance of mirtazapine may be reduced. This should be taken into account when prescribing Remeron for this category of patients.
APPLICATION FOR CHILDREN
Since the safety and efficacy of Remeron for children under 18 years of age have not been established, it is not recommended to use Remeron for children.
APPLICATION IN ELDERLY PATIENTS
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.
Elderly patients are usually more sensitive to side effects. In clinical studies of the drug Remeron 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.
SPECIAL INSTRUCTIONS
When using Remeron, it should be borne in mind that the 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.
In young people (under 24 years) with depression and other mental disorders, antidepressants, compared with placebo, increase the risk of suicidal thoughts and suicidal behavior. Therefore, when prescribing Remeron in young people (younger than 24 years), the risk of suicide and the benefits of using the drug should be correlated. In short-term studies in people over 24 years of age, the risk of suicide did not increase, but in people older than 65 years, it declined slightly. Any depressive disorder in itself increases the risk of suicide. Therefore, during the treatment for the patient, surveillance should be established to detect abnormalities or changes in behavior, as well as suicidal tendencies.
Hohhotya drug Remeron is not addictive, based on the post-experience, it turned out that a sharp cessation of treatment after prolonged use can sometimes cause withdrawal symptoms. Most cancellation reactions are weak and self-limiting. The most commonly reported symptoms were: dizziness, agitation, anxiety, headache and nausea. Although they have been reported as symptoms of withdrawal, it should be understood that these symptoms can be associated with underlying disease. It is recommended to stop treatment with mirtazapine gradually.
Elderly patients are usually more sensitive, especially with regard to side effects. In clinical studies of the drug Remeron 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 when treated with Remeron.
Oppression of bone marrow functions, usually manifested in the form of granulocytopenia or agranulocytosis, is rarely observed with the use of Remeron. 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 only with Remeron.
Influence on the ability to drive and work with machinery. The drug Remeron В® can reduce the 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.
OVERDOSE
The experience with an overdose of only the Remeron drug indicates that the symptoms are usually mild. Reported CNS depression, accompanied by disorientation and prolonged sedation in combination with tachycardia and a slight increase or decrease in blood pressure. However, there is a possibility of more severe results (including death) at doses far exceeding the therapeutic dose, especially with overdoses of several drugs taken simultaneously. In case of an overdose, symptomatic therapy should be used to maintain the vital functions of the body. You must enter activated charcoal or rinse the stomach.
DRUG INTERACTION
Pharmacokinetic interaction
- Mirtazapine is extensively metabolized with the participation of CYP2D6 and CYP3A4 isoenzymes, and to a lesser extent with the participation of the CYP1A2 isoenzyme. The study of interaction in healthy volunteers showed that paroxetine, an inhibitor of the isoenzyme CYP2D6, does not affect the pharmacokinetics of mirtazapine in the equilibrium state. Introduction in combination with a potent inhibitor of the isoenzyme CYP3A4, ketoconazole increased the maximum plasma concentration and AUC of mirtazapine by approximately 40% and 50%, respectively. Caution should be exercised when using mirtazapine in combination with potent inhibitors of the CYP3A4 isoenzyme, HIV protease inhibitors, azole antifungal drugs, erythromycin or nefazodone.
- carbamazepine and phenytoin, inductors of the CYP3A4 isoenzyme, increased the clearance of mirtazapine approximately twice, which resulted in a 45-60% decrease in the plasma mirtazapine concentrations. When adding carbamazepine or another inducer of liver metabolism (eg rifampicin) to mirtazapine therapy, the dose of mirtazapine should be increased if necessary. 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, if necessary, should be reduced at the beginning of treatment in combination with cimetidine or increased when cimetidine is discontinued.
- In studies on in vivo interactions, mirtazapine had no effect on the pharmacokinetics of risperidone or paroxetine (substrate of the isoenzyme CYP2D6), carbamazepine (substrate of the isoenzyme CYP3A4), amitriptyline, cimetidine or phenytoin.
- 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 may enhance the sedative properties of benzodiazepines and other sedatives. Caution should be exercised when prescribing these medicines together with mirtazapine.
- Mirtazapine can enhance the depressive 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 syndrome occurs very rarely in patients receiving myrtleapparin 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 sustained serotonergic overstimulation should be directly monitored.
- Mirtazapine at a dose of 30 mg once a day caused a small but statistically significant increase in MHO (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 MHO in case of treatment with warfarin in combination with mirtazapine.
TERMS OF RELEASE FROM PHARMACY
The drug is released by prescription.
TERMS AND CONDITIONS OF STORAGE
At a temperature of 2-30 В° C, protected from light and moisture, inaccessible to children. Shelf life - 3 years. Do not use after the expiration date printed on the package
