Calixta, pills 30mg, 30pcs

Composition

Active ingredient:

mirtazapine 15 mg.

Auxiliary substances:  

lactose monohydrate – 44.4 mg,

corn starch-28 mg,

hyprolose-15 mg,

microcrystalline cellulose-15 mg,

pregelatinized starch-15 mg,

talc-1.4 mg,

magnesium stearate-0.7 mg,

silicon dioxide-0.5 mg.

Shell composition:  

hypromellose-5 CPS-2.4 mg, macrogol 6000-0.2 mg, titanium dioxide-0.25 mg, iron oxide yellow (E 172) dye-0.1 mg, talc-0.05 mg

Pharmacological action

Mirtazapine is an antagonist of presynaptic α2-adrenergic receptors in the central nervous system and increases the central noradrenergic and serotonergic transmission of nerve impulses. At the same time, 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: the S (+) enantiomer blocks α2-adreno-and serotonin 5-HT2-receptors, and the aR ( -) enantiomer blocks serotonin 5-HT3-receptors.

The sedative properties of Mirtazapine are due to its antagonistic activity against H1-histamine receptors.

Mirtazapine is usually well tolerated. In therapeutic doses, it has practically no m-cholinoblocking effect and practically does not affect the cardiovascular system.

Pharmacokinetics

After oral use, Mirtazapine is rapidly absorbed (bioavailability is about 50%), reaching Cmax in blood plasma after approximately 2 hours. About 85% of Mirtazapine binds to plasma proteins. The average T1 / 2 is from 20 to 40 hours (rarely up to 65 hours). A shorter T1 / 2 is observed in young people. The equilibrium concentration of the substance is reached after 3-4 days and does not change in the future.

In the recommended dose range, the pharmacokinetic parameters of Mirtazapine have a linear relationship with the administered dose of the drug. Food intake does not affect the pharmacokinetics of the drug. Mirtazapine is actively metabolized and excreted in the urine and feces within a few days. The main routes 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 the 8-hydroxymetabolite Mirtazapine, while CYP3A4 presumably determines the formation of N-demethylated and N-oxidized metabolites.

Demethylmirtazapine is pharmacologically active.

Mirtazapine clearance decreases in patients with renal or hepatic insufficiency.

Indications

Depression.

Use during pregnancy and lactation

The safety of using Calixta during pregnancy in humans has not been established, but no teratogenic effect has been detected in animals, so the drug can be used during pregnancy only if the benefit to the mother exceeds 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 breast milk.

Contraindications

-patients with rare hereditary problems such as lactose intolerance, lactase deficiency or glucose-galactose malabsorption should not be prescribed the drug Calixta;

– hypersensitivity to mirtazapine or to any of the excipients; 

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

With caution:

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

— acute angle-closure glaucoma and increased intraocular pressure;

– diabetes mellitus;

– violation of urination, including with prostatic hyperplasia;

– with simultaneous use of benzodiazepines with the drug Calixta.

The correction mode and regular medical monitoring is required for the following categories of patients:

patients with epilepsy and organic brain lesions (on the background of drug therapy Calixtus in rare cases may develop convulsions);

— patients with hepatic or renal insufficiency;

patients with diseases of the heart (conduction disorder, angina or recent myocardial infarction);

— patients with cerebrovascular disease (including ischemic stroke in anamnesis);

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

— patients who abuse drugs with addiction to drugs affecting the Central nervous system, with delusions, hypomania.

Side effects

From the gastrointestinal tract: very often-dry mouth; often-nausea, diarrhea, vomiting; infrequently-decreased sensitivity of the oral mucosa; frequency is not established-swelling of the oral mucosa.

From the blood and lymphatic system: frequency not established-bone marrow depression (granulocytopenia, agranulocytosis, aplastic anemia and thrombocytopenia), eosinophilia.

From the nervous system: very often – drowsiness (which can lead to impaired concentration), usually occurs during the first weeks of treatment. (N. B. dose reduction usually does not lead to less sedation, but may reduce the effectiveness of an 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.

From the skin and subcutaneous tissues: often-skin rash.

Musculoskeletal and connective tissue disorders: often-arthralgia, myalgia, back pain.

From the endocrine system: frequency not established-violation of antidiuretic hormone secretion.

From the side of metabolism and nutrition: very often – increased appetite.

From the cardiovascular system: often-orthostatic hypotension; infrequently-a decrease in blood pressure.

General disorders and disorders at the injection site: often-local edema; infrequently-fatigue.

From the liver and biliary tract: rarely-increased activity of serum transaminases.

Mental disorders: often-unusual dreams, confusion, anxiety*, insomnia*, infrequently-nightmares, mania, agitation, hallucinations, psychomotor agitation (including akatasia and hyperkinesia); frequency not established – suicidal ideation, suicidal behavior. * usually, when treated with antidepressants, anxiety and insomnia, which may be symptoms of depression, may develop or worsen.

The development or worsening of anxiety and insomnia has been reported very rarely during treatment with Calixta.

Interaction

Pharmacodynamic interaction

Mirtazapine should not be used in combination with MAO inhibitors or for 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 medications together with mirtazapine.

Mirtazapine may increase the depressive effect of alcohol on the central nervous system. Therefore, patients should be warned to avoid drinking alcoholic beverages.

If other serotonergic drugs (such as selective serotonin reuptake inhibitors and venlafaxine) are used in combination with mirtazapine, there is a risk of interaction that may 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 excluded with a higher dose of mirtazapine. It is recommended to monitor MHO in the case of treatment with warfarin in combination with mirtazapine.

Mirtazapine is extensively metabolized by the CYP2D6 and CYP3A4 isoenzymes, and to a lesser extent by the CYP1A2 isoenzyme. Interaction studies in healthy volunteers showed that paroxetine, an inhibitor of the CYP2D6 isoenzyme, does not affect the pharmacokinetics of mirtazapine at steady state. use in combination with a potent inhibitor of the CYP3A4 isoenzyme, 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 the clearance of mirtazapine approximately twice, which led to 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 stopping treatment with such a drug, it may be necessary to reduce the dose of mirtazapine.When mirtazapine is used 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 at the end of treatment with cimetidine.

In in vivo interaction studies, mirtazapine did not affect the pharmacokinetics of risperidone or paroxetine (a substrate of the CYP2D6 isoenzyme), carbamazepine (a substrate of the CYP3A4 isoenzyme), amitriptyline, cimetidine, or phenytoin. No significant clinical effects or pharmacokinetic changes were observed in humans when treated with mirtazapine in combination with lithium.

How to take, course of use and dosage

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:

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 doctor.

Impaired liver and kidney function:

In patients with renal or hepatic insufficiency, mirtazapine clearance may be reduced. This should be taken into account when prescribing the drug Calixta in this category of patients.

The drug Calixta can be taken 1 time / day, preferably at the same time, before bedtime. The drug Calixta can also be prescribed for taking 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’s symptoms completely disappear. After that, the treatment can be gradually canceled. Mirtazapine usually begins to exert its effect after 1-2 weeks of treatment. Treatment with an adequate dose should lead to a positive result in 2-4 weeks. If necessary, the dose can be increased to the maximum dose (up to 45 mg). If there is no positive dynamics of treatment after another 2-4 weeks, treatment should be discontinued.

Overdose

In case of overdose, symptomatic therapy should be performed to maintain vital body functions.

You should inject activated charcoal or flush your stomach. Experience with overdose with Calixta alone indicates that symptoms are usually mild. CNS depression has been reported, accompanied by disorientation and prolonged sedation in combination with tachycardia and a slight increase or decrease in blood pressure.

However, there is a potential for more severe outcomes (including death) at doses much higher than the therapeutic dose, especially with overdoses of several drugs taken simultaneously.

Special instructions

When using the drug Calixta, you should keep in mind:

– Worsening of psychotic symptoms may occur with the use of antidepressants for the treatment of patients with schizophrenia or other psychotic disorders; paranoid ideas may increase.

– The depressive phase of manic-depressive psychosis during treatment can transform into a manic phase.

– In young people (under 24 years of age) with depression and other mental disorders, antidepressants, compared with placebo, increase the risk of suicidal thoughts and suicidal behavior. Therefore, when prescribing the drug 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, the risk of suicide did not increase in people over 24 years of age, and in people over 65 years of age – slightly decreased. Any depressive disorder itself increases the risk of suicide. Therefore, during treatment, the patient should be monitored for violations or changes in behavior, as well as suicidal tendencies.

— Despite the fact that the drug Calixta is not addictive, based on their post-marketing experience, it turned out that abrupt discontinuation of treatment after prolonged use can sometimes cause withdrawal symptoms. Most withdrawal reactions are mild and self-limiting. The most frequently reported withdrawal symptoms were dizziness, restlessness, anxiety, headache, and nausea. Although they have been reported as withdrawal symptoms, it should be understood that these symptoms may be related to the underlying medical condition. It is recommended to stop mirtazapine treatment gradually.

– Older patients are usually more sensitive, especially with regard to side effects. In clinical studies of the drug Calixta, it was not noted that in elderly patients, side effects are more common than in other age groups, but they may be more pronounced, but data are still limited.

– If signs of jaundice appear, treatment should be discontinued.

– Patients are advised to avoid the use of alcohol during treatment with Calixta.

– Inhibition of bone marrow functions, usually appearing in the form of granulocytopenia or agranulocytosis, is rarely observed with the use of Calixta. It appears mostly after 4-6 weeks of treatment and is reversible after discontinuation of treatment. The doctor should pay close attention to symptoms such as fever, sore throat, stomatitis, and other signs of flu-like syndrome and inform the patient about this; if such symptoms occur, stop treatment and perform a blood test.

Influence on the ability to drive vehicles and mechanisms

The drug Calixta may reduce the concentration of attention. During treatment with antidepressants, patients should avoid performing potentially dangerous activities that require a high rate of psychomotor reactions, such as driving a car or operating machinery.

Form of production

Tablets covered with a yellow film-coated color, oblong, with a risk on one side.

Storage conditions

Keep the drug out of the reach of children at a temperature not exceeding 25°C.

Shelf

life is 2 years.

Active ingredient

Mirtazapine

Conditions of release from pharmacies

By prescription

Dosage form

Tablets