Description
Release form
tablets
Packing
30 pcs.
Pharmacological action of
Mirtazapine is an antagonist of presynaptic 2-adrenergic receptors in the central nervous system and enhances central noradrenergic and serotonergic transmission of nerve impulses. In this case, increased serotonergic transmission is realized only through serotonin 5-HT1 receptors, since mirtazapine blocks serotonin 5-HT2 and 5-HT3 receptors. Both enantiomers of mirtazapine are believed to have antidepressant activity, S (+) enantiomer – blocking 2-adreno- and serotonin 5-HT2 receptors, aR (-) enantiomer – blocking serotonin 5-HT3 receptors.
The 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 practically does not have an m-cholinergic blocking effect and practically does not affect the cardiovascular system.
Pharmacokinetics of
After oral administration of the drug, mirtazapine is rapidly absorbed (bioavailability of about 50%), reaching Cmax in plasma after about 2 hours. About 85% of mirtazapine binds to plasma proteins.
Average T1 / 2 is 20 to 40 hours (rarely up to 65 hours). Shorter T1 / 2 is observed in young people. The equilibrium concentration of the substance is achieved after 3-4 days and in the future it does not change. In the recommended dose 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 isoenzymes (CYP2D6 and CYP1A2) are involved in the formation of mirtazapine 8-hydroxymetabolite, while CYP3A4 presumably determines the formation of N-demethylated and N-oxidized metabolites. Demethylmirtazapine is pharmacologically active. Mirtazapine clearance decreases with renal or liver failure.
Indications
Depression.
Contraindications
hypersensitivity to mirtazapine or to any of
excipients in patients with rare hereditary problems such as lactose intolerance, lactase deficiency or glucose-galactose malabsorption, Calixta drug should not be taken for the sldlk ² ¢s safety age is not established, then the use of Calixta for the treatment of children under 18 years of age is not recommended.
With caution
Correction of the dosage regimen and regular medical supervision are necessary for the following categories of patients:
patients with epilepsy and organic brain lesions (seizures may occur in rare cases with Calixta therapy)
patients with hepatic or renal failure
patients with heart disease (conduction disturbance, angina pectoris or recent myocardial infarction)
patients with cerebrovascular disease including with a history of ischemic stroke)
patients with arterial hypotension and with conditions predisposing to arterial hypotension (including with dehydration and hypothyroidism volaemia)
patients abusing drugs, dependency on drugs that affect the central nervous system, with mania, hypomania.
Like other antidepressants, Calixta should be used with caution in the following cases:
impaired urination, including with prostatic hyperplasia
acute angle-closure glaucoma and increased intraocular pressure
diabetes mellitus
with the simultaneous use of benzodiazepines with Calixta.
Use during pregnancy and lactation
The safety of Calixta during pregnancy has not been established in humans, however, animals have no teratogenic effect, therefore, the drug can be used during pregnancy only when the mother’s benefit outweighs the potential risk to the fetus .
The use of Calixta during lactation is not recommended due to the lack of data on its excretion in human milk.
Special instructions
When using the Calixt drug, it should be borne in mind:
Deterioration of psychotic symptoms can occur when antidepressants are used to treat patients with schizophrenia or other psychotic disorders, paranoid ideas may intensify.
The depressive phase of manic-depressive psychosis during treatment can transform into the manic phase.
In young people (under 24 years old) with depression and other mental disorders, antidepressants, compared with placebo, increase the risk of suicidal thoughts and suicidal behavior. Therefore, when prescribing Calixta in young people (under 24 years of age), 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, and in people over 65 years old, it decreased slightly. Any depressive disorder in itself increases the risk of suicide. Therefore, during treatment, the patient should be monitored to detect violations or changes in behavior, as well as suicidal tendencies.
even though that Calixta is not addictive, based on their post-registration experience, it turned out that a sharp cessation of treatment after prolonged use can sometimes cause withdrawal symptoms. Most withdrawal reactions are weak and self-limiting. The most commonly reported withdrawal symptoms were dizziness, agitation, anxiety, headache, and nausea. Although they have been reported as withdrawal symptoms, it should be understood that these symptoms may be associated with the underlying disease. It is recommended to discontinue treatment with mirtazapine gradually.
Elderly patients are usually more sensitive, especially with regard to side effects. In clinical trials of the drug Calixta, it was not noted that in elderly patients, side effects are more likely than in other age groups, but they may be more pronounced, but the data is still limited.
If signs of jaundice appear, treatment should be discontinued.
Patients are advised to avoid alcohol during treatment with Calixta.
Inhibition of bone marrow function, usually appearing as granulocytopenia or agranulocytosis, is rarely observed with the use of Calixta. Appears mostly after 4-6 weeks of treatment and reversible after discontinuation of treatment. The doctor should carefully consider symptoms such as fever, sore throat, stomatitis, and other signs of the flu-like syndrome, and inform the patient if such symptoms appear, stop treatment and do a blood test.
Effects on ability to drive vehicles and mechanisms
Calixta may decrease attention span. In the process of antidepressant treatment, patients should avoid performing potentially dangerous activities that require a high speed of psychomotor reactions, such as driving a car or operating machinery.
Composition
1 film-coated tablet contains:
active substance:
mirtazapine 45 mg,
excipients:
lactose monohydrate – 133.2 mg
corn starch – 84 mg
srlkp 45 mg mrd
gprol Pregelatinized starch – 45 mg
talc – 4.2 mg
magnesium stearate – 2, 1 mg
silicon dioxide – 1.5 mg
film sheath:
hypromellose-5 CPS – 7.2 mg
macrogol 6000 – 0.6 mg
titanium dioxide – 1.05 mg.
Dosage and administration
Tablets should be taken orally, washed down with liquid if necessary, and swallowed without chewing.
Adults:
The effective daily dose is usually between 15 mg and 45 mg, the initial dose is 15 mg or 30 mg.
Elderly patients:
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 done under the direct supervision of a physician.
Hepatic and renal impairment:
In patients with renal or hepatic insufficiency, mirtazapine clearance may be reduced. This should be taken into account when prescribing the drug Kalikstav this category of patients.
Calixta can be taken 1 time / day, preferably at the same time, before bedtime. Calixta can also be prescribed for administration 2 times / day, dividing the daily dose in half (once in the morning and once at night, a higher dose should be taken at night).
If possible, treatment should be continued for 4-6 months until the patient completely disappears. After that, treatment can be gradually canceled. Mirtazapine begins to exert its effect usually after 1-2 weeks of treatment. Treatment with an adequate dose should lead to a positive result after 2-4 weeks. If necessary, the dose can be increased to the maximum dose (up to 45 mg). In the absence of positive dynamics of treatment after another 2-4 weeks, treatment should be discontinued.
Drug interaction
Pharmacokinetic interaction
Mirtazapine is extensively metabolized with the participation of the isoenzymes CYP2D6 and CYP3A4, and to a lesser extent, with the participation of the isoenzyme CYP1A2. A study of the interaction in healthy volunteers showed that paroxetine, a CYP2D6 isoenzyme inhibitor, does not affect the pharmacokinetics of mirtazapine in equilibrium. The introduction in combination with a powerful 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, inducers of the CYP3A4 isoenzyme, increased approximately two-fold the clearance of mirtazapine, resulting in a 45 60% decrease in plasma concentrations of mirtazapine. When carbamazepine or another inducer of microsomal liver enzymes (for example, rifampicin) is added to mirtazapine therapy, the dose of mirtazapine should be increased if necessary. When treatment with such a drug is discontinued, it may be necessary to reduce the dose of mirtazapine.
When using mirtazapine in combination with cimetidine, the bioavailability of mirtazapine may increase by more than 50%. If necessary, the dose of mirtazapine should be reduced at the beginning of treatment in combination with cimetidine or increased when cimetidine is discontinued.
In studies of in vivo interactions, mirtazapine did not affect the pharmacokinetics of risperidone or paroxetine (a substrate for the isoenzyme CYP2D6), carbamazepine (a substrate for the isoenzyme CYP3A4), amitriptyline, cimetidine, or phenytoin.
No important clinical effects or pharmacokinetic changes in humans have been observed with mirtazapine in combination with lithium.
Pharmacodynamic interaction
Mirtazapine should not be used in combination with MAO inhibitors or within two weeks after cessation of treatment with an MAO inhibitor.
Mirtazapine may enhance the sedative properties of benzodiazepines and other sedatives. Caution should be exercised when prescribing these drugs with mirtazapine.
Mirtazapine may enhance the depressive effect of alcohol on the central nervous system. Therefore, patients should be warned about the need to avoid drinking alcohol.
If other serotonergic drugs are used (for example, selective serotonin and venlafaxine uptake inhibitors) in combination with mirtazapine, there is a risk of interaction that can lead to the development of serotonin syndrome.
Mirtazapine at a dose of 30 mg 1 time / day caused a small, but statistically significant increase in MHO (international normalized ratio) in subjects treated with warfarin. A more pronounced effect cannot be ruled out with a higher dose of mirtazapine. It is recommended that MHO be monitored in case of treatment with warfarin in combination with mirtazapine.
overdose
Current experience with overdose with Kaliksta alone indicates that symptoms are usually mild. CNS depression was reported, accompanied by disorientation and prolonged sedation in combination with tachycardia and a slight increase or decrease in BP. However, there is a likelihood of more severe outcomes (including death) at doses well in excess of the therapeutic dose, especially with overdoses of several drugs taken at the same time.
In case of overdose, symptomatic therapy should be carried out to maintain vital functions of the body. Activated charcoal or gastric lavage should be given.
Storage conditions
Store the product out of the reach of children at a temperature not exceeding 25 ° C.
Shelf life
2 years.
Active ingredient
Mirtazapine
drugstore conditions
drugstore
dosage form
tablets
Possible product names
KALIKSTA TAB. P / O CAPTURE. 45MG No. 30 (BLISTERS)
Calixta tablets 45 mg, 30 pcs.
